Sunday 09 June
08:00

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B11
08:00 - 10:00

ISRS SRS/SBRT EDUCATIONAL COURSE
INTRACRANIAL SRS: THE BASICS

Moderators: Guilherme ESPOSITO QUERELLI (Physicist) (Brasília, Brazil), Matthew FOOTE (Deputy Director / Co-Director) (Brisbane, Australia), Crystian SARAIVA (Medical Physicist) (São Paulo, Brazil)
08:00 - 08:10 Introduction & Course Objectives. Antonio DE SALLES (Professor - Chief) (Speaker, SÃO PAULO, Brazil)
08:10 - 08:30 Principles of Radiosurgery. Laura FARISELLI (director) (Speaker, milan, Italy)
08:30 - 08:50 Radiobiology of Radiosurgery. Dennis SHRIEVE (Professor and Chair) (Speaker, NY, USA)
08:50 - 09:10 QA and Imaging. Ian PADDICK (Consultant Physicist) (Speaker, London, United Kingdom)
09:10 - 09:30 Imaging for Radiosurgery. Stephen HOLMES (Imaging Consultant and Conference Organizer) (Speaker, honolulu, USA)
09:00 - 10:00 Discussion.
Segovia Break Out
10:00 COFFEE BREAK Segovia Break Out
10:20

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B13
10:20 - 12:00

ISRS SRS/SBRT EDUCATIONAL COURSE
INTRACRANIAL SRS: CLINICAL INDICATIONS

Moderators: Julio ANTICO (Argentina), Paul SPERDUTO (Radiation Oncology) (Durham, USA), John SUH (Radiation Oncologist) (Cleveland, USA)
10:20 - 10:40 Brain Metastases. Patrick HANSSENS (Radiation Oncologist) (Speaker, Tilburg, The Netherlands)
10:40 - 11:00 Brain Protection with Repeat SRS : Making Whole Brain Radiation Obsolete. Iris GIBBS (Professor) (Speaker, Stanford, USA)
11:00 - 11:20 Intracranial Benign Lesions. Samuel CHAO (Radiation Oncologist) (Speaker, Cleveland, OH, USA)
11:20 - 11:40 Stereotactic Radiosurgery for AVMs. Bruce POLLOCK (Physician) (Speaker, Rochester, USA)
11:40 - 12:00 Trigeminal Neuralgia and Functional Disorders. Alessandra GORGULHO (Director) (Speaker, SÃO PAULO, Brazil)
Segovia Break Out
12:00 LUNCH - Oceanico's Restaurant Segovia Break Out
13:00

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B15
13:00 - 14:30

ISRS SRS/SBRT EDUCATIONAL COURSE
SBRT: THE BASICS

Moderators: Francine Xavier DOS SANTOS (Medical Physicist) (porto alegre, Brazil), Uriel NOVICK (Chief Medical Physicist) (CABA, Argentina), Marta SCORSETTI (Director Department) (Rozzano-Milan, Italy)
13:00 - 13:20 Contouring. Caroline CHUNG (Associate Professor, Radiation Oncology) (Speaker, Houston, USA)
13:20 - 13:40 Treatment planning considerations for SBRT: from optimization to dose calculation. Andrea GIRARDI (Medical Physicist) (Speaker, Brussels, Belgium)
13:40 - 14:00 Immobilization and Positioning Considerations. Paul MEDIN (Radiation Oncology) (Speaker, Dallas, USA)
14:00 - 14:20 Motion Management Techniques. Fang-Fang YIN (Medical Physicist/Professor) (Speaker, Durham, NC, USA)
14:20 - 14:30 Discussion.
Segovia Break Out

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C15
13:00 - 14:30

LGKS AFTERNOON SESSION - Part I
Radiosurgery - What we can expect in the future?

13:00 - 13:05 Welcome. Dan LEKSELL (Chairman) (Speaker, Stockholm, Sweden)
13:05 - 13:30 Personalized machine learning - AI based segmentation & plan generation. Kenneth LAU (Speaker, Stockholm, Sweden)
13:30 - 14:00 Sunnybrook approach to multiple metastases – SPARE technique and workflow. Arjun SAHGAL (Professor) (Speaker, Toronto, Canada)
14:00 - 14:30 Radiosurgery & Immunotherapy--A Good Bet? Jonathan KNISELY (Faculty) (Speaker, New York, USA)
El Pardo I
14:30 COFFEE BREAK Segovia Break Out
14:50

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C17
14:50 - 18:00

LGKS AFTERNOON SESSION - Part II
Radiosurgery - What we can expect in the future?

14:50 - 15:20 Increased visualization in CBCT imaging – How far can we get? Kenneth LAU (Speaker, Stockholm, Sweden)
15:20 - 15:50 MR guided RT with Unity – Potential applications and benefits. Caroline CHUNG (Associate Professor, Radiation Oncology) (Speaker, Houston, USA)
15:05 - 16:10 Foresee outcome using pathology, blood biomarkers, genomics & radiomics. Hakan NORDSTROM (Physicist) (Speaker, Stockholm, Sweden)
16:10 - 16:40 Radiosurgery for OCD and major depression. Antonio Carlos LOPES (Collaborating Professor) (Speaker, São Paulo, Brazil)
16:40 - 17:10 What can we learn from dose planning comparison studies? Ian PADDICK (Consultant Physicist) (Speaker, London, United Kingdom)
17:10 - 17:20 Next generation inverse planner. Bjorn SOMELL (Product Manager Treatment Planning) (Speaker, Stockholm, Sweden)
17:20 - 17:30 Intuitive interactive inverse planning for Gamma Knife radiosurgery. Marc LEVIVIER (Chef de Service) (Speaker, Lausanne, Switzerland)
17:30 - 17:55 Fast and comprehensive plan adaptation. Hakan NORDSTROM (Physicist) (Speaker, Stockholm, Sweden)
17:55 - 18:00 Concluding remarks. Dan LEKSELL (Chairman) (Speaker, Stockholm, Sweden)
El Pardo I

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B17
14:50 - 17:00

ISRS SRS/SBRT EDUCATIONAL COURSE
SBRT: CLINICAL INDICATIONS

Moderators: Laura FARISELLI (director) (milan, Italy), Samuel RYU (Professor) (Stony Brook, NY, USA), Kita SALLABANDA (Medical Direcor) (Madrid, Spain)
14:50 - 15:10 Lung. Ben SLOTMAN (Professor) (Speaker, AMSTERDAM, The Netherlands)
15:10 - 15:30 The evolving role of SBRT in the management of liver metastases. Marta SCORSETTI (Director Department) (Speaker, Rozzano-Milan, Italy)
15:30 - 15:50 Prostate SBRT. Patrick KUPELIAN (Professor) (Speaker, Palo Alto, USA)
15:50 - 16:10 Spine. Arjun SAHGAL (Professor) (Speaker, Toronto, Canada)
16:10 - 16:30 Oligometastases. Rupesh KOTECHA (Radiation Oncologist and Chief of Radiosurgery) (Speaker, Miami, USA)
16:30 - 16:50 Other and Emerging Indications. Lauren HENKE (Radiation Oncologist) (Speaker, St. Louis, USA)
16:50 - 17:00 Discussion.
Segovia Break Out
18:00

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A18
18:00 - 19:00

OPENING LECTURES

18:00 - 18:05 Welcome By Antonio De Salles and Brazil-Latin American Presentation Congress Chairman. Antonio DE SALLES (Professor - Chief) (Speaker, SÃO PAULO, Brazil)
18:05 - 18:25 Welcome and Lecture from Ministry of Science, Technology, Innovation and Communications - MCTIC. Marcello MORALES (Speaker, Brasilia, Brazil)
18:00 - 19:00 Define your Brand. Edmour SAIANI (Speaker, Brazil)
18:00 - 19:00 Words of Welcome. Ian PADDICK (Consultant Physicist) (Speaker, London, United Kingdom)
18:00 - 19:00 Words of Logistics. Antonio DE SALLES (Professor - Chief) (Speaker, SÃO PAULO, Brazil)
Segovia Plenary
19:00 OPENING RECEPTION - EXHIBITION AREA
Monday 10 June
07:30

"Monday 10 June"

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A21
07:30 - 09:00

BREAKFAST SEMINAR
ISRS GUIDELINES OVERVIEW

Moderators: Randy JENSEN (Professor) (Salt Lake City, USA), Daniel PAZ (Brazil), Arjun SAHGAL (Professor) (Toronto, Canada)
07:30 - 07:40 ISRS Guidelines for Multiple Brain Metastases. Steve BRAUNSTEIN (Faculty) (Speaker, San Francisco, USA)
Antonio DE SALLES, Laura FARISELLI, Marc LEVIVIER, Ian PADDICK, Bruce POLLOCK, Jean REGIS, Jason SHEEHAN, John SUH, Shoji YOMO, Lijun Ma
07:40 - 07:50 Technological Considerations for Small Brain Metastases. Alexis DIMITRIADIS (Physicist) (Speaker, London, Austria)
Antonio DE SALLES, Laura FARISELLI, Marc LEVIVIER, Lijun MA, Bruce POLLOCK, Jean REGIS, Jason SHEEHAN, John SUH, Shoji YOMO, Ian Paddick
07:50 - 08:00 #17901 - Stereotactic radiosurgery for post-operative metastatic surgical cavities : International Society of Stereotactic Radiosurgery (ISRS) practice guideline.
Stereotactic radiosurgery for post-operative metastatic surgical cavities : International Society of Stereotactic Radiosurgery (ISRS) practice guideline.

The historical standard of care in patients who have undergone surgical resection of brain metastases is whole brain radiation therapy (WBRT) based on data that resection alone is associated with high rates of local recurrence.  Unfortunately, WBRT is associated with long term cognitive toxicity and as such SRS to the resection cavity has been increasingly utilized.  As part of the ISRS Guideline Committee, the purpose of this project is to summarize the current literature for stereotactic radiosurgery (SRS) for post-operative brain metastases resection cavities.  Medline and Embase databases were utilized to search for manuscripts reporting outcomes following SRS for post-operative brain metastases tumor bed resection cavities with a search end date of July 20, 2018.  Prospective studies, consensus guidelines, and retrospective series that included exclusively post-operative brain metastases, had at minimum 100 patients were considered eligible. Embase search revealed a total of 157 manuscripts of which 77 were selected for full text screening. Pubmed search revealed a total of 55 manuscripts of which 23 were selected for full text screening.  After excluding articles that did not meet eligibility criteria or present data specific for resection cavity SRS as well as eliminating duplicates, a total of 12 articles were deemed appropriate for inclusion.  Specifically, results of 9 retrospective series, a single phase II prospective study, 3 randomized controlled trials, and a consensus contouring manuscript were included.  Overall, these data suggest that SRS to brain metastases resection cavities is associated with excellent local control as high as 91%.  Randomized data suggests improved local control with SRS compared to observation and improved cognitive outcomes compared to WBRT.  Toxicity of SRS in the post-operative setting were limited, although development of leptomeningeal disease was reported to be higher than 10% in the 5 studies in which it was investigated.  To conclude,  SRS for post-operative brain metastases resection cavities demonstrates excellent local control and low toxicity.  Future investigations aiming to reduce the risk of leptomeningeal disease will be important. 


Kristin REDMOND (Baltimore, MD, USA), Arjun SAHGAL
08:00 - 08:10 #17541 - Stereotactic radiosurgery for post-operative spinal metastases: International Society of Stereotactic Radiosurgery (ISRS) practice guideline.
Stereotactic radiosurgery for post-operative spinal metastases: International Society of Stereotactic Radiosurgery (ISRS) practice guideline.

Objective: Spine stereotactic body radiation therapy (SBRT) is increasingly utilized as a treatment option for patients after surgery for spinal metastatic disease. The purpose of this review was to determine the efficacy and toxicity of spine SBRT post-operatively as well as to determine the surgical and radiosurgical techniques most commonly reported in the literature.

Methods: A systematic literature review was conducted using PubMed and Embase according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Keywords used included “postoperative spine radiosurgery”, “postoperative spine SBRT”, “postoperative spine stereotactic body radiotherapy” and “postoperative spine stereotactic body radiation therapy”.

Results: A total of 557 articles were identified, of which 54 were selected for in-depth review. 18 publications met all of the inclusion criteria of which 8 were retrospective, 4 were retrospective of prospective databases, 3 were prospective, 2 were phase I/II studies and 1 had a mixed design of phase I/II study and retrospective patients. A total of 665 spinal segments were treated across these studies. In the 9 studies that reported it 1yr local control ranged from 70% to 100%. 13 studies commented on toxicity and only one patient was documented with myelopathy of a previously irradiated spinal segment retreated with post-operative spine SBRT. Guidelines based on this systematic review are in development.

Conclusion: Spine SBRT is a safe and effective treatment option for patients post-surgery and can be considered in select cases based on mostly low-quality data.


Salman FARUQI (Calgary, Canada), Arjun SAHGAL, Laura FARISELLI, Marc LEVIVIER, Lijun MA, Ian PADDICK, Bruce POLLOCK, Jean RÉGIS, Jason SHEEHAN, John SUH, Shoji YOMO, Antonio DE SALLES
08:10 - 08:20 #17635 - a21-5 Stereotactic Radiosurgery for Spetzler Grade I and II AVM: Systematic Review for the Formation of International Society of Stereotactic Radiosurgery (ISRS) Practice Guideline.
Stereotactic Radiosurgery for Spetzler Grade I and II AVM: Systematic Review for the Formation of International Society of Stereotactic Radiosurgery (ISRS) Practice Guideline.

Background: The role of stereotactic radiosurgery (SRS) in the management of Spetzler-Martin Grade I and II arteriovenous malformations (AVM) is controversial, with no consensus guidelines available to inform treatment recommendations.

Objective: Systematic literature review for development of objective SRS practice guidelines.

Methods: Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines were employed. We searched Medline, Embase, and Scopus, 1986-2018, identifying English language publications reporting post-SRS outcomes in ≥10 Grade I-II patients with median follow-up ≥24 months. Primary endpoints were AVM obliteration and hemorrhage; publications not reporting both were excluded. Initial search identified 447 candidate records; 71 underwent full-text screening; 8 publications reporting 1102 patients were included.

Results: Of 1102 AVM, 836 were Grade II. Obliteration was achieved in 884 (80%) at a median 37 months; 66 hemorrhages (6%) occurred during a median follow-up of 68 months. Excellent outcomes were achieved in 743 of 952 patients with requisite data reported (78%). Among 680 Grade II lesions with Spetzler-Martin parameters reported, 377 were located in eloquent brain, and 178 had deep venous drainage, indicating that 82% of Grade II AVM treated with SRS had a high risk feature.

Conclusions: SRS is a safe, effective treatment for Spetzler-Martin Grade I-II AVM, and should be considered front-line for many low-grade AVM—in particular, those with eloquent location or deep venous drainage. Systematic selection bias appears to have influenced referral patterns, with favorable AVM typically recommended for resection, while lesions that carry a higher resection risk—and a lower probability of obliteration—are disproportionately referred for SRS.


Christopher GRAFFEO (Oklahoma City, USA), Arjun SAHGAL, Antonio DE SALLES, Laura FARISELLI, Marc LEVIVIER, Lijun MA, Ian PADDICK, Jean REGIS, Jason SHEEHAN, John SUH, Shoji YOMO, Bruce POLLOCK
08:20 - 08:30 #17639 - Stereotactic radiosurgery for non-functioning pituitary adenomas: International Society of Stereotactic Radiosurgery (ISRS) practice guideline.
Stereotactic radiosurgery for non-functioning pituitary adenomas: International Society of Stereotactic Radiosurgery (ISRS) practice guideline.

Purpose/Objectives: Stereotactic radiosurgery (SRS) has become an established treatment for patients with non-functioning pituitary adenomas (NFAs) in the definitive, adjuvant, or recurrent setting. This review of the published literature regarding patient selection, dose and fractionation, and treatment-related outcomes and toxicities was performed to develop consensus guidelines. 

 

Materials/Methods: Using the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines, a systematic review of the published English literature was performed using articles describing clinical outcomes of at least 10 patients with NFAs published prior to May 2018 using the Medline database and the following key words: “radiosurgery” and “pituitary” and/or “adenoma.”

 

Results: Of the 678 abstracts reviewed, a total of 35 full-text articles were included in this analysis describing the clinical outcomes of 2671 patients treated between 1971-2017. All included studies were retrospective. A majority of patients had undergone surgery (Median: 95%, Range: 0-100%) prior to SRS, and a small proportion had received prior radiotherapy (Range: 0-17%). The median tumor volume at the time of SRS was 3.5 cc. Single fraction treatment was used in 27 studies (Median dose: 15 Gy, Range: 5-35 Gy) and hypofractionated treatments were used in 8 studies (Median total dose: 21 Gy, Range: 12-25 Gy delivered in 3-5 fractions). Tumor control was favorable across studies (Range: 90-100%). Post-treatment hypopituitarism was the most common treatment-related toxicity observed (Range: 0-32%), whereas visual dysfunction or cranial nerve injury rarely occurred (Range: 0-7%).

 

Conclusions: Based on these retrospective studies, practice guidelines were developed with consensus from the International Stereotactic Radiosurgery Society. We conclude SRS is an effective treatment option for patients with NFAs with limited treatment-related toxicities.


Rupesh KOTECHA (Miami, USA), Arjun SAHGAL, Antonio DE SALLES, Laura FARISELLI, Bruce POLLOCK, Marc LEVIVIER, Lijun MA, Ian PADDICK, Jean REGIS, Jason SHEEHAN, Shoji YOMO, John SUH
08:30 - 08:40 #17725 - a21-4 Stereotactic radiosurgery for secretory pituitary adenomas: systematic review and development of ISRS guidelines.
Stereotactic radiosurgery for secretory pituitary adenomas: systematic review and development of ISRS guidelines.

A systematic review was performed to provide objective evidence on the use of stereotactic radiosurgery in the management of secretory pituitary adenomas and develop consensus guidelines recommendations.

The authors performed a systematic review of English-language literature up until June 2018 using the Pubmed, Medline, Embase and Cochrane databases. The following MeSH terms were used to search for relevant articles: (Gamma Knife OR Radiosurgery OR LINAC OR Cyberknife) AND (pituitary adenoma OR Cushing’s disease OR acromegaly OR prolactinoma). The initial search provided 1045 articles whose title and abstract were screened, retaining 134 articles. Full text screening of those articles was performed, using the following inclusion criteria: single institution study, more than 10 patients reported, both tumor and endocrine control data reported. Proton SRS, FSRT and studies only reporting Nelson syndromes were excluded. In cases of multiple studies from the same institution, only the most recent was included. 

A total of 49 articles were selected for the analysis. All studies were retrospective case series. Many studies reported the outcomes of all pituitary adenomas treated at that institution. From those, only the data reporting the outcomes of Cushing’s disease, acromegaly or prolactinoma was extracted.

Data analysis is ongoing at the moment and will be completed at the time of the meeting.


David MATHIEU (Sherbrooke, Canada)
08:40 - 08:50 #16742 - Stereotactic radiosurgery for intracranial, non-cavernous sinus, benign meningiomas: international society of stereotactic radiosurgery (isrs), practice guideline.
Stereotactic radiosurgery for intracranial, non-cavernous sinus, benign meningiomas: international society of stereotactic radiosurgery (isrs), practice guideline.

Objective. Radiosurgery (RS) for benign intracranial meningiomas is increasingly being used. Considering this, the aim of the present review is to define practice guidelines to support the clinicians in the radiosurgical management of such lesions.

Methods. Articles published from January 1964 to April 2018 were systemically reviewed. Three electronic databases, PubMed, EMBASE, and The Cochrane Central Register were searched. Publications in English about benign meningiomas’ radiosurgery.

Results. Of 2844 studies, 306 studies had a full text evaluation and 42 studies met the above mentioned criteria and were then include in the present analysis. All but two are retrospective studies. The 10 local control (LC) range from 85 to 100%. The ten years progression free survival (PFS) range from 52 to 97 %. The median post-RS symptoms worsening rate is near 9 %. The most common treatment dose range from 12 to 15 Gy delivered in a single fraction.

Conclusions. The current literature lacks of level I and II evidences. Despite this, due to the large consensus of level III evidences, sRS represents an effective treatment paradigm for benign intracranial meningioma (recommendation level II). The ideal treatment time has to be better investigated as well as the potential advantages of the mRS.


Marcello MARCHETTI (Milano, Italy), Arjun SAHGAL, Antonio DE SALLES, Marc LEVIVIER, Lijun MA, Ian PADDICK, Bruce POLLOCK, Jean REGIS, Jason SHEEHAN, John SUH, Shoji YOMO, Laura FARISELLI
Segovia Plenary

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B21
07:30 - 09:00

BREAKFAST SEMINAR
SBRT IN OPERABLE LUNG

Moderators: Hilde KLEIVEN (radiation oncologist) (Canberra, Australia), Patrick KUPELIAN (Professor) (Palo Alto, USA), Lisa MORIKAWA (Brazil)
07:30 - 07:48 Patient Selection. Simon CHENG (Assistant Professor) (Speaker, New York, USA)
07:48 - 08:06 Motion Management. Anderson PASSARO (Medical Physicist) (Speaker, São Paulo, Brazil)
08:06 - 08:24 Evidence Review. Jin Ho KIM (Associate Clinical Professor) (Speaker, Seoul, Korea)
08:24 - 08:42 Resection of Thoracic Metastases. Rui HADDAD (Speaker, Brazil)
08:42 - 09:00 MR Guided SBRT for Lung Tumors. Ben SLOTMAN (Professor) (Speaker, AMSTERDAM, The Netherlands)
Segovia Break Out

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C21
07:30 - 09:00

BREAKFAST SEMINAR
MACHINE LEARNING AND AI IN SRS/SBRT

Moderators: Guilherme BULGRAEN DOS SANTOS (Brazil), Renan SERRANO RAMOS (Brazil), Fang-Fang YIN (Medical Physicist/Professor) (Durham, NC, USA)
07:30 - 07:52 The Potential of AI in SBRT. Fang-Fang YIN (Medical Physicist/Professor) (Speaker, Durham, NC, USA)
07:52 - 08:14 Inverse Treatment Planning. Marc LEVIVIER (Chef de Service) (Speaker, Lausanne, Switzerland)
08:14 - 08:36 Dose Painting/Delivery Automation. Richard POPPLE (Medical Physicist) (Speaker, Birmingham, USA)
08:36 - 09:00 Automatic Segmentation of Structures in the Brain. Crystian SARAIVA (Medical Physicist) (Speaker, São Paulo, Brazil)
El Pardo I
09:00

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A21b
09:00 - 09:05

OPENING ADDRESS

Speakers: Antonio DE SALLES (Professor - Chief) (Speaker, SÃO PAULO, Brazil), Ian PADDICK (Consultant Physicist) (Speaker, London, United Kingdom)
Segovia Plenary
09:05

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A22
09:05 - 10:20

PLENARY SESSION
WHAT IS REALLY HAPPENING WHEN WE TREAT?

Moderators: Antonio DE SALLES (Professor - Chief) (SÃO PAULO, Brazil), John P. KIRKPATRICK (Professor - Radiation Oncology & Neurosurgey) (Durham, NC, USA), Ian PADDICK (Consultant Physicist) (London, United Kingdom)
09:05 - 09:20 #17820 - A22-1 Basic radiobiology of high-dose SBRT and SRS.
Basic radiobiology of high-dose SBRT and SRS.

We have observed that, in experimental tumors, significant additional tumor cell death occurs during several days after irradiation with >10 Gy, most likely due to the radiation-induced vascular destruction. We then found that treating the host animals with hypoxic cytotoxins, such as PR-104, further increases death or residual hypoxic cells. We recently observed that fractions of the surviving hypoxic cells in tumors after 10-20 Gy irradiations undergo reoxygenation in 2-5 days. It appeared that the oxygen supply via a small proportion of blood vessels that escaped total occlusion by irradiation together with the significant decrease in oxygen consumption induced the reoxygenation of hypoxic tumor cells. In recent years, numerous reports indicated that high-dose irradiation evoked anti-tumor immunity by increasing the cytotoxic T-cell population, and that inhibition of anti-immune checkpoints such as PD-L1 and PD-1 improved the anti-cancer immunity.  On the other hand, in our recent study, high-dose irradiation significantly upregulated HIF-1α and increased the anti- immune PD-L1 and PD-1. It has been known that HIF-1α directly controls the PD-L1: PD-1 axis. We have previously reported that anti-diabetes drug metformin effectively suppressed  the radiation-induced upregulation of  HIF-1α. Together, it appeared that HIF-1 α inhibitors such as metformin may block the radiation-induced upregulation of the anti-immune PD-L1: PD-1 axis thereby they increase the antitumor immunity.

In summary, (i) Additional tumor cell death due to vascular injury plays an important role in the response of tumors to high-dose SBRT/SRS. (ii) The efficacy of SBRT/SRS may be markedly improved by increasing the post-irradiation death of hypoxic cells with hypoxia cytotoxin. (iii) Allowing 2-5 days between irradiations in fractionated SBRT/SRS may render hypoxic tumor cells reoxygenated. (iii) Suppressing the radiation-induced upregulation of PD-L1: PD1 axis using HIF-1α inhibitors may significantly improve the anti-cancer immunity after SRRT/SRS.  


Chang SONG (Minneapolis, USA), Kathryn E. DUSENBERY, Stephanie TEREZAKIS, L. Chinsoo CHO
09:20 - 09:35 The Concept of BED in SRS. John HOPEWELL (invited speaker) (Speaker, Oxford, United Kingdom)
09:35 - 09:50 Can Radiobiology help us further refine SRS treatments? John P. KIRKPATRICK (Professor - Radiation Oncology & Neurosurgey) (Speaker, Durham, NC, USA)
09:50 - 10:05 Imaging of Radiation Necrosis. Yael MARDOR (Research) (Speaker, Ramat-Gan, Israel)
10:05 - 10:20 Oncogenesis & Stereotactic Radiation: What We Know. Jonathan KNISELY (Faculty) (Speaker, New York, USA)
Segovia Plenary
10:20 COFFEE BREAK - POSTERS & EXHIBITION
10:45

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A24
10:45 - 12:00

PARALLEL SESSION
MR GUIDED SRS/SBRT: CURRENT STATE & FUTURE DIRECTIONS

Moderators: John ADLER (neurosurgery) (San Francisco, USA), Patrick KUPELIAN (Professor) (Palo Alto, USA), Ben SLOTMAN (Professor) (AMSTERDAM, The Netherlands)
10:45 - 11:00 MR GUIDED SRS/SBRT: Technical Overview. Ben SLOTMAN (Professor) (Speaker, AMSTERDAM, The Netherlands)
11:00 - 11:15 Realtime Adaptive Therapy: Workflow Considerations. Frank LAGERWAARD (Radiation Oncologist) (Speaker, Amsterdam, The Netherlands)
11:15 - 11:30 Beyond Anatomical Imaging: The Promise and Challenges. Caroline CHUNG (Associate Professor, Radiation Oncology) (Speaker, Houston, USA)
11:30 - 11:45 Clinical Indications & Results. Lauren HENKE (Radiation Oncologist) (Speaker, St. Louis, USA)
11:45 - 12:00 Clinical Trials and Research Overview. Arjun SAHGAL (Professor) (Speaker, Toronto, Canada)
Segovia Plenary

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B24
10:45 - 12:00

Oral Session
FUNCTIONAL #1 - OCD/PAIN

Moderators: Eduardo ALHO (Neurosurgeon) (São Paulo, Brazil), Carlos CIAROLO (Argentina), Jean REGIS (PROFESSEUR) (MARSEILLE, France)
10:45 - 10:55 #17863 - b24-1 Deterministic Diffusion Tensor Imaging Tractography and Gamma Ventral Capsulotomy for Obsessive-compulsive disorder.
b24-1 Deterministic Diffusion Tensor Imaging Tractography and Gamma Ventral Capsulotomy for Obsessive-compulsive disorder.

BACKGROUND: The role of tractography in Gamma Ventral Capsulotomy (GVC) is unclear. Herein we describe spatial distributions of medial-orbitofrontal cortex (OFC) and lateral-OFC fibers through the anterior limb of internal capsule (ALIC), analyzing quantitative tractography parameters, differentiating OCD individuals from controls.

METHODS: Five Obsessive-compulsive disorders (OCD) patients underwent GVC (single-shot 150Gy, 4mm collimators) between 2013-2016. Five controls were randomly selected matching factors such as age, sex and DTI protocol (Diffusion-sensitizing gradient-encoding was applied in 33 directions by using a diffusion-weighted factor b=750s/mm2). Diffusion tensor image (DTI) tractography was reconstructed using Brainlab Elements (Brainlab AG, Feldkirchen, Germany). Deterministic fiber tracking (fractional anisotropy=0.15, minimum fiber-length=50 mm, maximal angulation=13) was used in all cases to reconstruct fibers from OFC.

RESULTS: Five OCD patients and five controls were included, mean age respectively, 28 ± 4.4 and 31 ± 5.8 (p=0,33). Four (80%) were men in each group. Twenty hemispheres were analyzed. Medial-OFC fibers are localized more ventral in the ALIC than lateral-OFC fibers in all hemispheres, the level of intersection and exact topography of fiber bundles are variable among individuals, especially among controls where intersection seems more prominent.  Medial- and lateral-OFC fiber tracts from right control hemispheres have lower volume than medial and lateral counterparts of OCD patients (p=0,003 and p=0,046, respectively). On the left side, only control lateral-OFC fiber bundles have lower volume than OCD patients. There are no significant differences between OCD and control concerning mean fractional anisotropy and mean fiber length.

CONCLUSIONS: Medial and lateral OFC tract fibers have a general standard distribution, lateral-OFC more dorsal than medial-OFC fibers. There are differences between OCD and control patients regarding fiber tracts volume, supporting OCD fiber tracking singularities justifying studies to identify specific targets based on DTI tractography. This needs to be validated in large clinical series.


Bruno FERNANDES DE OLIVEIRA SANTOS (Aracaju, Brazil), Alessandra AUGUSTA GORGULHO, Rafael COSTA LIMA MAIA, Antonio CARLOS LOPES, Crystian WILIAN CHAGAS SARAIVA, Anderson MARTINS PASSARO, Euripedes CONSTANTINO MIGUEL, Antônio AFONSO FERREIRA DE SALLES
10:55 - 11:05 #17837 - b24-2 Tractography-based targeting of the ventral capsule/ventral striatum for obsessive compulsive disorder.
b24-2 Tractography-based targeting of the ventral capsule/ventral striatum for obsessive compulsive disorder.

Objectives

Obsessive compulsive disorder (OCD) is refractory to conventional therapies in 10% of the cases, requiring procedural interventions. In a recent meta-analytic study, our group found superiority of neuroablation procedures (i.e. capsulotomy) over deep brain stimulation. Here, we (1) use ventral capsule-ventral striatum (VC/VS) probabilistic tractography to optimize targeting for neuroablation and (2) merge our tractography results to postoperative images of our gamma-knife capsulotomy patients.

Methods

Probabilistic tractography was used to analyze diffusion MRI from 40 healthy Human Connectome Project subjects to assess which portion of the VC/VS has higher streamline probability to brain regions thought to mediate obsessions, compulsions, and other motivated behaviors, namely the ventromedial prefrontal cortex (vmPFC), insula, amygdala, hippocampus, orbitofrontal cortex (OFC), dorsolateral prefrontal cortex (dlPFC, divided in middle and superior frontal gyri) and inferior frontal gyrus (IFG). The VC/VS was used as seed, and each region of interest (ROI) as target. A tractography-based atlas of the VC/VS was derived from our results for targeting purposes. Our atlas was overlaid to the post-operative MRI images of non-responders as well as a responder treated with gamma-knife capsulotomy.

Results

Probabilistic tractography allowed identification of subregion-specific VC/VS connections. Subregions were visualized within the human VC/VS according to its streamline probability to either the vmPFC, amygdala, insula, hippocampus, OFC, dlPFC, or IFG. The dorsal-most VC region presented high streamline probability to these ROIs, except middle frontal gyrus, and this pattern was similar in the ventral VS. Notably, post-procedure imaging of responders revealed that incorporation of this dorsal-most VC subregion was required. Conversely, the ventral-most VC and dorsal VS presented lower streamline probability to these ROIs, and non-responders received a single shot targeting this ventral-most VC.

Conclusions

Probabilistic tractography allows targeting connections relevant to OCD within the VC/VS. Poorer outcomes occurred when gamma-knife failed to target dorsal VC connections. Augmenting capsulotomy with ventral VS targeting warrants further investigation. We will leverage this methodology in trials using radiosurgery and high-intensity focused ultrasound.


Daniel ALVES NEIVA BARBOSA (Stanford, USA), Alessandra A. GORGULHO, Bruno F. O. SANTOS, Rafael C. L. MAIA, Antônio C. LOPES, Eurípedes MIGUEL, Jennifer MCNAB, Sameer SHETH, Antônio A. F. DE SALLES, Casey HALPERN
11:05 - 11:15 #17834 - b24-3 Asymmetries in Bilateral Gamma Ventral Capsulotomy for Obsessive Compulsive Disorder.
b24-3 Asymmetries in Bilateral Gamma Ventral Capsulotomy for Obsessive Compulsive Disorder.

Introduction: Despite of both hemispheres being treated in the same day under identical protocol, Gamma-Knife Capsulotomy (GKC) lesions are asymmetrical in the same patient.

Objective: Evaluate lesion volume discrepancies between hemispheres after GKC for Obsessive Compulsive Disorder (OCD).

Methodology: Eight OCD-patients were treated from Dec/2014 to Oct/2017 receiving bilateral ventral-GKC (Perfexion, Elekta AB, Sweden). Treatment protocol was 150Gy delivered with a 4mm collimator. Six patients were complemented with a more dorsal GKC 14 to 27 months later. T1-MRIs were used for lesion-volume calculations (Elements®, Brainlab, Feldkirchen). Twelve-months average reduction in Yale-Brown Obsessive Compulsive Scores was 5.6 %, none achieved the expected 35% YBOCS reduction. Post–GKR MRIs were analyzed, 2 patients didn’t reach 12 months follow-up, 3 had a 2nd MRI between 7-16 months apart initial imaging. Final sample was 6 patients, 9 MRI’s and 18 lesion-volumes.

Results: Hemispheres had same treatment time, target definition and GKC parameters. The interval between first MRI and ventral-GKC was 12-21months, average 14.5months. Lesion-volumes were 0.01-0.13cm³, average: 0.045cm³. The right-side lesion was larger, average: 0.05cm³ in four cases compared to left, average: 0.03cm³. Asymmetries were 40%-500%, average: 228%. Three patients were treated first on the right side. There was no correlation between the initially treated hemisphere and lesion-volume. All lesion-volumes reduced later, range: 14.3%-100%; one disappeared. At mean 22months post-GKC lesion-volumes ranged from zero to 0.06cm³, average: 0.02cm³. The initial reported asymmetry persisted. Average volume difference was 0.023 cm³, range: 100-200%. These single isocenter lesion-volumes were insufficient to achieve the expected clinical outcomes.

Conclusion: Asymmetry was noticed in all cases during the 2-years post-GKC. Inter-hemispheric discrepancies became less prominent as the final volume established. The causes of these discrepancies are poorly understood. Larger lesions and/or in more strategic locations in the internal-capsule appear necessary for substantial decreases in YBOCS.


Rafael COSTA LIMA MAIA (São Paulo, Brazil), Antonio DE SALLES, Bruno FERNANDES DE OLIVEIRA SANTOS, Antônio CARLOS LOPES, Marcelo CAMARGO BATISTUZZO, Crystian WILIAN CHAGAS SARAIVA, Anderson MARTINS PASSARO, Euripedes CONSTANTINO MIGUEL, Alessandra GORGULHO
11:15 - 11:25 #17833 - b24-4 TREATMENT IMPROVEMENT FOLLOWING SINGLE-SHOT GAMMA VENTRAL CAPSULOTOMY FOR OBSESSIVE COMPULSIVE DISORDER.
b24-4 TREATMENT IMPROVEMENT FOLLOWING SINGLE-SHOT GAMMA VENTRAL CAPSULOTOMY FOR OBSESSIVE COMPULSIVE DISORDER.

Background:

Treatment refractory obsessive-compulsive disorder (OCD) is a precise indication for Gamma Knife radiosurgery, using an approach named Gamma Ventral Capsulotomy (GVC). A prior study suggested that bilateral single-shot (ss) GVC could be as efficacious as double-shot targets, but safer. In our report, we describe symptoms changes for our patients that received ssGVC. 

Methods:

Refractory OCD patients (n=5) received bilateral ssGVC (150 Gy, targeted at the ventral anterior limb of the internal capsule, with 4 mm collimator at each hemisphere). Subjects who showed to be unresponsive to ssGVC (after a minimum follow-up of 12 months) were allowed to receive additional dorsal lesions. Longitudinal assessments with psychiatric rating scales were repeated along the study.

Results:

For ssGVC, the median reductions of Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) scores after 12 months and 20 months of follow-up were, respectively, 13.5% and 8.1% only. There were no treatment responders. All subjects were submitted to retreatment, which consisted on adding an adjacent dorsal shot to the initial ventral one. After second shot, symptoms scores decreased by 24.1% in a median follow-up of 15 months, and two patients became partial responders. No severe or permanent side effects were described. 

Conclusion:

In this report, single-shot GVC did not show treatment efficacy in OCD. Furthermore, only the addition of adjacent dorsal shots contributed to higher rates of symptom improvement. However, treatment response remained sub-optimal in comparison to our prior cohort results, using the double shot approach. Until the last follow-up assessment of this cohort of patients, GVC showed to be safe.


Antônio CARLOS LOPES (São Paulo, Brazil), Stephanie KASABKOJIAN, Antônio DE SALLES, Alessandra GORGULHO, Marcelo BATISTUZZO, Marcelo HOEXTER, Marinês JOAQUIM, Maria COPETTI, Juliete MELO DINIZ, Nicole MCLAUGHLIN, Benjamin GREENBERG, Georg NORÉN, Eurípedes MIGUEL
11:25 - 11:35 #16764 - b24-5 Intracranial radiosurgery in refractory oncological and non-oncological pain.
b24-5 Intracranial radiosurgery in refractory oncological and non-oncological pain.

Introduction.

We present a series of 17 patients that have been treated with radiosurgical hypophysectomy for medically refractory oncological pain, and patients that were treated via medial radiosurgical thalamotomy for refractory trigeminal neuralgia pain, using a Rotating Gamma Ray Unit.

Radiosurgical technique.

Stereotactic frame was placed under local anesthesia, images were acquired with a 1.5 tesla MRI T1MPR 1mm slices of the zone of interest hypophysis, brainstem, optic apparatus, and thalamus region for thalamotomy. For hypophysectomy procedure a single 8mm shot was placed in the neurohypophysis and a prescription dose of 150 Gy was delivered. In the cases of medial thalamotomy a 4 mm shot was placed 4 mm anterior to PC (Y) and 4 to 6 mm lateral to the thalamic border (X) and 3 to 5 mm cephalic in Z, the prescription dose was 140 Gy.

Patient series and results.

Hypophysectomy.

11 patients have been treated thus far, follow up has been 106 days on average until the death of the patient (14-393). Positive pain response (VAS of 5 or more) was 81.8% 9/11 patients. Median VAS 3 (1-4) from the scale of 10 pretreatment. Time to response 4.8 days. No complications to report.

Medial Thalamotomy.

6 patients have been treated thus far, on average follow up has been 32 weeks (1-84), 1 patient died at 4 weeks of unrelated causes with a 70% response to his pain. Average VAS is 2.4 (1-4) for the whole series, response has been 100%. Average time to sustained response (more than 15 days) is 4.8 weeks (1-10), there are no complications to report. 3 (50%) patients recurred, one at 24 months with full installment of her pain, the two others had an 80% response in VAS at at week 20 and 16 all though pain remains in 6 in one and 10 in the other.

Conclusion.

Hypophysectomy for alleviating pain in oncological terminal patients has proven to be effective and safe. Medial thalamotomy for “central” facial pain is effective and safe although lasting effect and recurrence are yet unknown.


Eduardo LOVO (San Salvador, El Salvador), Fidel CAMPOS, Victor CACEROS, William REYES, Claudia CRUZ, Juan ARIAS ROSA
11:35 - 11:45 #16940 - b24-6 Biologically effective dose (BED) is a stronger predictor compared with the dose in classical trigeminal neuralgia treated with Gamma Knife surgery.
b24-6 Biologically effective dose (BED) is a stronger predictor compared with the dose in classical trigeminal neuralgia treated with Gamma Knife surgery.

Object:To determine the impact of the biologically effective dose (BED) on the clinical outcome for cases of classical trigeminal neuralgia (CTN) treated with Gamma Knife radiosurgery (GKS), as compared with the physical prescription dose delivered over variable overall treatment times. 

Methods:Between July 1992 and November 2010, 408 CTN cases, with more than one-year follow-up, had the appropriate clinical and dosimetric (including BED) data available for analysis. The median follow-up period was 43 months (12-156.7 months). The median BED was 2243.95 Gy2.47 (mean 2232.7 Gy2.47; range 1539.4 – 2665.5 Gy2.47, showing a 75 % increase). The impact of these BED values on patient outcome were analyzed and compared with the effect of the total physical prescribed dose alone. 

Results:No significant increase in the initial pain cessation was associated with escalating BED values. However, the onset of new hypoesthesia was highly correlated with BED. For this specific outcome, BED was a strong predictor of the risk of this effect, while the physical prescribed dose was not. Maintenance of pain relief up to 2 years after GKS was again not associated with higher BED values. The data suggested that a BED value of around 1820 Gy2.47represented a good therapeutic windowsince this was associated with a ~ 5% risk of hypoesthesia, while maintaining long term pain freedom relief rate of ~90%. 

Conclusion:Dose prescription has been classically considered the best predictor for efficacy (and in some cases for toxicity). In the present analysis,physically prescribed dose showed no effect on pain relief or hypoesthesia rates. BED showed no difference for immediate or long-term pain relief, which was maintained at a high level of ~ 90%. However, the analysis revealed an increase of hypoesthesia rates for higher BED values.


Constantin TULEASCA (Lausanne, Switzerland), Ian PADDICK, John HOPEWELL, William T MILLAR, Hussein HAMDI, Marc LEVIVIER, Jean RÉGIS
11:45 - 11:55 #17724 - b24-7 Gamma knife stereotactic radiosurgery for trigeminal neuralgia secondary to multiple sclerosis: a matched case-control study.
b24-7 Gamma knife stereotactic radiosurgery for trigeminal neuralgia secondary to multiple sclerosis: a matched case-control study.

Context

The efficacy of stereotactic radiosurgery (SRS) for idiopathic trigeminal neuralgia (TN) is well established, with a meta-analysis of 65 studies reporting a rate of pain-free response of 85%. The benefit of SRS for TN in the setting of multiple sclerosis (MS) remains uncertain. Such cases are often excluded from TN SRS studies and are felt to have a less favorable outcome. We performed a case-control study of patients who underwent SRS for MS-associated vs. idiopathic TN to compare pain evolution in both entities and identify risk factors for failure.

Methods

Patients treated by SRS for TN secondary to MS were retrospectively identified. The control cohort was generated using a propensity score (PS) matching algorithm. Briefly, the PS was calculated by performing a logistic regression on the complete dataset of 909 patients who underwent Gamma Knife SRS for trigeminal neuralgia at our center. The model used 11 prospectively collected variables (sex, year of treatment, age at SRS, pain level, frequency of crises, number of medications, burning sensation, electric shock sensation, loss of sensation, previous MVD and previous rhizotomy) to predict the probability of a patient having a diagnosis of MS. Then, MS patients (cases) were matched to 2 non-MS patients (controls) having a propensity score within 0.15. This yielded a final control cohort of 131 patients for 76 cases. For each patient, basic demographic data, past management, medication, subsequent treatment as well as pain characteristics at baseline and at each follow-up were collected. The primary outcome was the change in BNI pain scale distribution at last follow-up.

Results

Data collection is now complete and the results will be presented at the ISRS 2019 meeting.

Conclusion

This study will provide high level evidence on the efficacy of SRS for MS-associated TN and should improve patient selection and outcomes in this challenging population.


William LEDUC, Christian IORIO-MORIN, David MATHIEU (Sherbrooke, Canada)
Segovia Break Out

"Monday 10 June"

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C24
10:45 - 12:00

Oral Session
OTHER BENIGN TUMORS

Moderators: Joao Gabriel GOMES (Neurosurgeon) (Recife, Brazil), Samuel RYU (Professor) (Stony Brook, NY, USA), Isaac YANG (Associate Professor) (Los Angeles, USA)
10:45 - 10:55 #17899 - C24-1 A modified disease specific graded prognostic assessment (ds-GPA) scale for melanoma consisting of age, karnofsky performance score (KPS), cumulative intracranial tumor volume (CITV), and BRAF mutation status.
C24-1 A modified disease specific graded prognostic assessment (ds-GPA) scale for melanoma consisting of age, karnofsky performance score (KPS), cumulative intracranial tumor volume (CITV), and BRAF mutation status.

ABSTRACT

Introduction:  Survival prognostication is an important aspect of personalizing oncologic care for patients with melanoma brain metastasis (BM).  We previous demonstrated the utility of a cumulative intracranial tumor volume modified diagnosis-specific graded prognostic assessment scale (CITV-dsGPA) for SRS-treated melanoma BM patients. Pertinent prognostic variables in this model included age, Karnofsky performance status (KPS), and CITV.  Here we determined whether the incorporation of BRAF mutation status into this CITV-modified scale further enhanced its prognostic accuracy.   

Methods:  We collated the survival pattern of 331 melanoma BM patients with known BRAF mutation status treated with stereotactic radiosurgery (SRS) and validated our findings in an independent cohort of 174 patients. All patients with BRAF mutation were treated with BRAF inhibitors. The prognostic utility of the model with and without BRAF mutation information was compared using the net reclassification index (NRI > 0) and integrated discrimination improvement (IDI) metric.

Results:   BRAF mutation status is an important determinant of clinical survival in both univariate analysis (Hazard Ratio for death for BRAF mutated melanomas (HR) = 0.74, p<0.001 as well as a multi-variate Cox proportional hazard model that included age, KPS, and CITV (HR for BRAF mutated melanoma = 0.72, p < 0.001).  Addition of BRAF mutation status to the CITV-ds-GPA model for melanoma significantly improved its prognostic value, with NRI > 0 of 0.294 (p=0.01) and IDI of 0.017 (p=0.02). We validated these the prognostic utility of this model in an independent cohort of 174 melanoma patients.  

Conclusions:  Optimal survival prognostication for SRS-treated patients with melanoma BM requires an integrated assessment of age, KPS, CITV, and BRAF mutation status.


Ahluwalia MANMEET, Clark CHEN (Minneapolis, USA)
10:55 - 11:05 #17750 - c24-2 Management of Trigeminal Schwannoma with Gamma Knife Radiosurgery.
c24-2 Management of Trigeminal Schwannoma with Gamma Knife Radiosurgery.

Objective:

Trigeminal Schwannomas are second most common intracranial Schwannomas. They have been traditionally treated by microsurgery which is associated with significant morbidity, and complete excision is challenging. Gamma knife radiosurgery (GKRS) is a minimally invasive alternative. This study evaluates the radiological and clinical outcome in a series of Trigeminal schwannomas’ patients treated with Gamma Knife radiosurgery.

Material and Methods:

Thirty patients were treated with Leksell Gamma Knife between May 2008 till  Dec.2018. Mean age at treatment was 43.4 yrs (Range 21-65Yrs).GKRS was used as initial treatment in 24 patients (80%) after initial subtotal resection in 4 patients(20%).The tumor volume ranged from 0.5 cc to19.3 cc (Men, 3.8cc).Mean prescription  dose was 13.2 Gy at 50 % isodose line (range. 12.5Gy to 14 Gy).

Results:

Average follow up was 48.4months ( range 6-124 months).Tumor size remained static in 16 (53.3%) and showed radiological evidence of shrinkage in 12 (40%).Tumor progression occurred in 2 (6%) patients. No patient had worsening of pre-existing neurologic symptoms or development of new cranial nerves deficits at the last follow up.

Conclusion:

GKRS is a safe and effective treatment alternative for patients with Trigeminal nerve schwannoma. There is not only long term tumor control but also functional preservation.


M Abid SALEEM (Karachi, Pakistan), A Sattar M HASHIM, Azhar RASHID
11:05 - 11:15 #17727 - c24-3 Stereotactic radiosurgery for oculomotor nerves schwannomas: an international multicenter study.
c24-3 Stereotactic radiosurgery for oculomotor nerves schwannomas: an international multicenter study.

Cranial nerve schwannomas are radiosensitive tumors that are commonly managed by stereotactic radiosurgery (SRS). There is a large body of literature supporting the use of SRS for vestibular and trigeminal schwannomas. Schwannomas affecting the oculomotor nerves (cranial nerves III, IV and VI) are rare tumors. They are skull base tumors in close proximity the brainstem and often involving the cavernous sinus, for which resection can cause significant morbidity. As for other schwannomas, SRS can be used to manage these tumors, but only a handful of cases have been published so far, often among other uncommon schwannoma location reports. 

The goal of this study was to collect retrospective multicenter data on tumor control, clinical evolution and morbidity after SRS. This study was performed through the International Radiosurgery Research Foundation (IRRF). To be included, patients had to be treated with single fraction SRS for an oculomotor nerve schwannoma. The diagnosis was based on either diplopia or ptosis as the main presenting symptom as well as anatomic location on the trajectory of the presumed cranial nerve of origin, or prior surgical resection confirming diagnosis.

7 institutions submitted data for a total of 25 patients. There were 11 CN III schwannomas, 11 CN IV schwannomas and 3 CN VI schwannomas. Data analysis is ongoing, and further results will be available at the meeting.


Anne-Marie LANGLOIS, Christian IORIO-MORIN, Andrew FARAMAND, Ajay NIRANJAN, L.dade LUNSFORD, Nasser MOHAMMED, Jason SHEEHAN, Roman LISCAK, Dusan URGOSIK, Douglas KONDZIOLKA, Cheng-Chia LEE, Huai-Che YANG, Atik AHMET, David MATHIEU (Sherbrooke, Canada)
11:15 - 11:25 #17758 - c24-4 Long-Term Outcome of Gamma Knife radiosurgery for cavernous hemangioma of the orbital apex.
c24-4 Long-Term Outcome of Gamma Knife radiosurgery for cavernous hemangioma of the orbital apex.

Objective  This study was performed to analyze the long-term outcome of Gamma Knife radiosurgery (GKRS) in a series of 28 patients with cavernous hemangioma of the orbital apex. Methods  Twenty-eight patients with cavernous hemangioma of the orbital apex were treated with GKRS between March 2005 and June 2014. The series included 11 male and 17 female patients with an average age of 40.5 years (range 22–65 years). The diagnoses were confirmed by histology in 1 cases and presumed in accordance with clinical and radiological findings in 27 cases. The mean volume of the lesion at GKRS was 1.9±1.1cm3 (range 0.2~8.9cm3). The prescription peripheral dose ranged from 10.0 to 14.0 Gy. All patients had no history of radiation therapy. Results The median duration of follow-up was 52.5 months (range 24–120 months).Periodically scheduled MRI/CT and clinical follow-up showed evidence of tumor shrinkage in 26 patients (92.9%). Visual acuity (VA) was preserved in all cases. Thirteen patients (46.4%) experienced vision improvement of varying degrees, and VA was stable in 12 cases (42.9%) . Deterioration in VA was observed in only 3 cases (10.7%), including 2 patients had transient visual impairment within two weeks after GKRS. Exophthalmos disappeared on clinical ophthalmic examination in 14 cases. Only 4 cases (14.3%) had a transient chemosis. No recurrence was found during the follow-up examinations.  Conclusions This retrospective investigation indicates that GKRS provides an long-term effective management strategy in patients with cavernous hemangioma of the orbital apex, with a high rate of visual function preservation.


Dong LIU (Tianjin, China), Desheng XU
11:25 - 11:35 #17721 - c24-5 Multi-fraction stereotactic radiosurgery for large cavernous sinus hemangiomas: 10 years outcomes of 88 cases.
c24-5 Multi-fraction stereotactic radiosurgery for large cavernous sinus hemangiomas: 10 years outcomes of 88 cases.

Objective: Cavernous sinus hemangiomas (CSHs) are rare vascular tumors. This study aimed to clarify the 10 year  outcomes of multi-fraction stereotactic radiosurgery  for the treatment of large CSHs(10 cm3 <tumor volume</=40 cm3).  Methods: Between January 2008 and January 2018,  Eighty-eight patients with large CSHs (10 cm3 < tumor volume</=40cm3) underwent multi-fraction Cyberknife radiosurgery . Eighty-five(96%) patients underwent multi-fraction stereotactic radiosurgery as the primary management for their CSHs based on clinical and imaging criteria, and the other three patients had previous operation before multi-fraction stereotactic radiosurgery. The median volume of the CSHs was 23.9  cm3 (range, 10.3-40.0 cm3). Multi-fraction stereotactic radiosurgery was delivered in 3 fractions. The median marginal dose was 20.3 Gy (range, 19.5–21 Gy) prescribed to a median 64% isodose line. Results:  The median follow-up period was 56 months (range, 12–123 months). Tumor control was achieved in all patients (100%) during the follow-up period. At 12 months after cyberknife radiosurgery, MRI revealed a mean of 80% tumor volume reduction (range, 60%-99%). The last MRI showed a mean of 90% tumor volume reduction. Sixty-six( 75%)patients who had cranial neuropathies before radiosurgery demonstrated improvements in their neurological deficits (improvement of vision, facial numbness), 16(18%) patients initially asymptomatic kept the same clinical status, 4 patients developed mild facial numbness.  One patient reported a stroke 3 years post radiosurgery because of hypertension. One elder patient felt reduction of memory post radiosurgery. No patient had visual function deterioration, and other adverse radiation effects during the follow-up period. Conclusion: Our experience confirms that multi-fraction stereotactic radiosurgery is a safe and an effective management strategy for large CSHs. Considering the risk involved in microsurgery, multi-fraction SRS may serve as the primary treatment option for patients with large CSHs.


Enmin WANG, Enmin WANG (Shanghai, China), Xin WANG, Li PAN, Huaguang ZHU, Xiaoxia LIU, Yang WANG
11:35 - 11:45 #17771 - c24-6 Cyberknife radiosurgery for jugular foramen schwannomas: long-term outcomes.
c24-6 Cyberknife radiosurgery for jugular foramen schwannomas: long-term outcomes.

OBJECTIVE  Jugular foramen schwannomas (JFSs) are rare lesions and controversy regarding their management still exists. Complete resection is possible but may be associated with significant morbidity. Stereotactic radiosurgery (SRS) is a minimally invasive alternative or adjunct to microsurgery. The authors reviewed clinical and imaging outcomes of Cyberknife SRS for patients with these tumors.

METHODS   Fifty-nine patients with JFSs underwent hypofractionated Cyberknife radiosurgery between January 2008 and January 2015. Thirteen patients had previous microsurgical resection, one patient had recurrent tumor post Gamma Knife radiosurgery, the rest 45 patients underwent Cyberknife radiosurgery based on their neuroimaging and clinical manifestations. Fifty-four patients had preexisting cranial nerve (CN) symptoms and signs. The median tumor volume was 15.1 cm3 (range 2.6-36.0 cm3), and 39 of them was larger than 10cm3 in volume. The radiation dose prescribed to the tumor margin and the number of fractions depend on the tumor volume. Twelve patients with large tumors were treated in 4 fractions, 31 patients were treated in three fractions and 16 patients in two fractions. The median margin dose was 19.2 Gy/2 Fx ( fractions),  21.1Gy/3Fx  and 24.5Gy/4Fx. Patients with neurofibromatosis were excluded from this study.

RESULTS  The median follow-up was 58 months (range 24-105 months). Tumors regressed in 41(69%) patients, remained stable in 14 and progressed in 4. The progression-free survival (PFS) was 93% at 5 years, Preexisting cranial neuropathies improved in 32 patients, remained stable in 10 patients, and worsened in 17 patients.  Four patients underwent resection at a median of 14 months after Cyberknife SRS (range 8-30 months).

CONCLUSIONS  Cyberknife radiosurgery proved to be a safe and effective primary or adjuvant management approach for JFSs. Long-term tumor control rates and stability or improvement in CN function were confirmed.


Enmin WANG, Enmin WANG (Shanghai, China), Xin WANG, Huaguang ZHU, Xiaoxia LIU, Yang WANG, Li PAN
11:45 - 11:55 #17860 - b28-6 Postoperative Stereotactic Radiosurgery for Spinal Metastases: Clinical Outcomes, Failures, and Analysis of Local Control.
Postoperative Stereotactic Radiosurgery for Spinal Metastases: Clinical Outcomes, Failures, and Analysis of Local Control.

Stereotactic radiosurgery (SRS) is a viable treatment modality for spine metastases. SRS is increasingly being used in the multimodal management of these patients. Results of post-operative stereotactic radiosurgery following separation surgery has been reported but clinical outcomes and local control for a more heterogenous surgical sample (i.e., anterior approaches, anterior column reconstruction, revision surgery after previous SRS) is lacking in the literature. We present data on clinical outcomes and local tumor control at a major cancer center following contemporary surgical approaches for spine metastases.

After IRB approval, retrospective review of patients between 2012 and 2017. Demographic information, tumor histology, survival rates, recurrence rates, clinical outcomes and complications were recorded and analyzed

 

The mean age of patients in our cohort was 64 years (range 44 to 85 years), with 32% female.The radiation dose was 18 Gy in 1 fraction using 6 MV photons with a 24Gy boost to the gross tumor volume.The follow up period range was 3-84 months, with average time between surgery (11.1% anterior approach, 88.9% posterior approach) and SRS 3 weeks. Radiographic evaluation following SRS was every 3 months after treatment with CT or MRI. The 1- and 2-year survival rates were 57% and 38% respectively. The overall rate of local recurrence was 12.7% within the follow up period. Multivariate analysis revealed tumor location (thoracic) and histology (lung carcinoma, colon adenocarcinoma, or melanoma) as significant prognostic factors for local control and overall survival. The overall surgical and medical complication rates were 14.3% and 19.0% respectively.  The most common complication after SRS was an acute pain flare. The rate of hardware failure was 6.3%, with 3 patients developing procedure-related neurological deficits, but there were no cases of radiation myelopathy. Eighteen patients required additional surgery for metastatic disease at adjacent or distant spinal levels. There were no differences in local control if a patient had anterior column reconstruction or not.

 

SRS is an effective treatment modality following all types of surgery for metastases, not just separation surgery. SRS should be considered in the post-operative management for spinal metastases given the low complications, and local control roughly 87% irrespective of histology.


John SHIN (Boston, USA), Muhamed HADZIPASIC, Laura VAN BEAVER, Caroline AYINON, Robert KOFFIE, Brian WINEY, Thomas BOTTICELLO, Ganesh SHANKAR, Joseph SCHWAB, Kevin OH
El Pardo I
12:00

"Monday 10 June"

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B25
12:00 - 13:00

Oral Session
GENITOURINARY

Moderators: Patrick KUPELIAN (Professor) (Palo Alto, USA), Ernesto ROESLER (Head of the Department) (Recife, Brazil), Deivid Augusto SILVA (Brazil)
12:00 - 12:10 #17634 - b25-1 CyberKnife based radioablation of 500 LR and IR prostate cancer patients - single center results.
b25-1 CyberKnife based radioablation of 500 LR and IR prostate cancer patients - single center results.

Objectives: An evaluation of effectiveness and toxicity of LR and IR prostate cancer patients (PCP) CyberKnife (CK) based radioablation.

Methods: Consecutive 500 PCP (LR 264  and IR 236) were irradiated with fd 7.25 Gy to TD 36.25 Gy. Median FU was 31.3 months. PSA, ADT uptake and toxicity using EORTC/RTOG scoring system were checked (acute effects to 4 months, next, late ones). ROC curves were created and appropriate AUC were calculated for different PSA values as predictors of failures. Two-way analysis of variances was used for PSA course evaluation.

Results: During FU 15 failures appeared (6 biochemical failures, 2 local relapses, 5 locoregional-pelvic  nodal disseminations and 2 bone metastasis). Median time to failure was 19.9 months (22.5 to relapse and 17.5 to dissemination). Percentage of patients without ADT increased from 44.6% before RT to 100% 56 months later. In this period PSA median decreased from 2.8 to 0.12. Percentage of patients without gastrointestinal (GI) toxicity varied from 90.2% at the RT end to 100% 56 months later. There was one G4 toxicity: rectourethral fistula revealed 26 months after RT. Percentage of patients without genitourinary (GU) toxicity was smaller and varied from 74.5% 1 month after RT to 97.9% 44 months after RT. No G4 GU toxicity was noted.  Higher PSA values during FU (even not filled Phoenix criterion), before failure appearance were connected to high risk of failure later on. PSA concentration during FU was significantly higher for IR patients without ADT.

Conclusions: CK based radioablation of LR and IR PCP is safe, effective treatment. Higher PSA during first part of FU is strong predictive factor for a treatment failure. Lack of ADT in the group of IR patients results in higher PSA, so ADT administration for these patients may benefit with lower PSA and, finally with better treatment results.


Leszek MISZCZYK (Gliwice, Poland), Aleksandra NAPIERALSKA, Malgorzata KRASZKIEWICZ, Agnieszka NAMYSL-KALETKA, Grzegorz WOZNIAK, Malgorzata STAPOR-FUDZINSKA MALGORZATA, Marcin MISZCZYK, Andrzej TUKIENDORF
12:10 - 12:20 #17666 - b25-2 CyberKnife robotic radiosurgery for intermediate unfavorable and high-risk prostate cancer patients: initial results.
b25-2 CyberKnife robotic radiosurgery for intermediate unfavorable and high-risk prostate cancer patients: initial results.

Introduction: The role of radiosurgery for intermediate unfavorable-risk (IUFR) and high-risk (HR) prostate cancer (pCa) patients is not clear. Patients which refuse other treatment methods might benefit from local application of radiosurgery if involvement of pelvic lymph nodes is excluded.

Materials and methods: From June y.2016 to January 2019 12 IUFR and 11 HR prostate cancer patients were treated with local application of robotic radiosurgery with CyberKnife M6 system to prostate and seminal vesicles. All patients whose risk of pelvic lymph node involvement were above 7% according to MSKCC risk calculator were advised to undergo  PSMA PET-CT. 4 fiducial markers were implanted according Accuray recommendations. CT and MRI topometry was done with following delineation of prostate and 1-2cm proximal seminal vesicles (CTV). Safety margin of 5mm in all directions except 3mm posteriorly were added for PTV. Dose of 35-36.25 Gy were prescribed to PTV with focal increase of the dose to dominant lesion (GTV) visible on MRI and PET-CT. Median pretreatment PSA was 7.98 ng/ml [range 0.21, 60]. PSA level was evaluated before treatment and every 3 months after treatment. 6 patients received ADT before treatment or short term (3-6 months) after SRS. Follow-up ranged from 3 months to 30 months (median 11.5 months). Minimal dose to GTV was applied 36.22 Gy, maximal 53.62Gy (median 42.32 Gy). Early toxicity was evaluated according RTOG/EORTC toxicity scale.

Results:  PSA values decreased for all patients reaching values of 0.1 - 4.58 (median 1.385) ng/ml. There were no biochemical relapse detected according Phoenix criteria (nadir+2) however 1 high-risk patient had PSA increase from 0.231 ng/ml (nadir) to 1.4 ng/ml during follow-up of 9 months. For one high-risk patient ADT was prescribed after minor PSA increase - from 0.13 ng/ml (nadir) to 0.259 ng/ml in 6 months. All patients (96%) had Grade 0-2 toxicity, except one (4%) who had grade 3 rectal toxicity due to inflammation in rectal wall.

Conclusions: Initial data suggests that FSRS provides significant PSA decrease for all IUFR and HR prostate cancer patients. Focal increase of radiation dose does not increase Grade 3 toxicity comparing to published data. Longer follow-up and larger number of patients in multi-institutional data registries might help clarify the role of FSRS for these groups of patients.


Maris MEZECKIS (Sigulda, Latvia), Kirils IVANOVS, Egils VJATERS, Sandra LEDINA, Vladislav BURYK
12:20 - 12:30 #17689 - b25-3 Pattern of progression after stereotactic body radiotherapy of oligorecurrent prostate cancer patients.
b25-3 Pattern of progression after stereotactic body radiotherapy of oligorecurrent prostate cancer patients.

Purpose

To determine the pattern of progression after stereotactic body radiotherapy (SBRT) of oligorecurrent prostate cancer patients.

Material and Methods

Study group consisted of 86 patients(pts) with 120 metastatic lesions – 77 in lymph nodes (LN) and 43 in bones (BM) treated with SBRT (mean total dose of 36 Gy in 3 fractions). Primary treatment was surgery (16pts), surgery+ RT (28pts, in 9 with elective nodal irradiation–ENI), prostate only RT (24pts), prostate RT+ENI (18pts). PET-CT was used in diagnosis in 84% of pts. Oligorecurrence was diagnosed in 29 pts (34%) during hormonal treatment (HT), remaining 66% were not on HT at that time. Oligorecurrence in LN was regional (defined as LN below L5) in 28 pts (48 LN) and distant in 23 pts (29 LN). Among 59 patients without ENI, oligorecurrence in regional LN occurred in 19 pts, as compared to 5 pts with ENI. 

Results

Median follow-up was 3 years after SBRT. One-, 2- and 3-year overall survival (OS) was 95%, 87% and 78%, respectively. Progression after SBRT was observed in 45 pts (still oligometastatic in 26 pts, disseminated in 19 pts) and 1-, 2- and 3-year progression-free survival (PFS) was 67%, 45% and 36%, respectively. Majority of  pts with LN oligorecurrence who had clinical progression after SBRT developed LN metastases (83%), while majority of  pts with BM oligorecurrence developed BM (89%). Among 28 pts diagnosed with oligorecurrence in regional LN there were 13 pts with nodal recurrence after SBRT: regional LN in 5, regional and distant in 6 and distant LN in 2 pts. Almost all pts with oligorecurrence in distant LN had progression in distant LN (majority in common iliac above L5 – 11 pts or retroperitoneal/paraaortic LN – 9 pts). Progression after SBRT in pts without previous ENI was within regional LN in 61% in contrast to only 1 pts given previous ENI with progression in regional LN after SBRT. Patients with oligorecurrence diagnosed during HT compared to those who were not on HT while diagnosed with oligorecurrence had worse PFS (p=0.0008) and worse overall survival (p=0.001).

Conclusions

Pattern of progression after SBRT in oligorecurrent prostate cancer pts is strongly associated with previous metastasis location. Patients with previous ENI tend to progress outside regional lymph nodes. Progression during HT predicts worse outcome despite of applied further treatment.


Aleksandra NAPIERALSKA (Gliwice, Poland), Wojciech MAJEWSKI, Małgorzata STĄPÓR-FUDZIŃSKA, Leszek MISZCZYK
12:30 - 12:40 #17765 - b25-4 Evaluation of outcomes after stereotactic hypofractionated radiotherapy for prostate cancer.
b25-4 Evaluation of outcomes after stereotactic hypofractionated radiotherapy for prostate cancer.

Aims: Several randomized trials support the use of high doses of radiation for localized prostate cancer. We retrospectively report collected data from a cohort of localized prostate cancer patients treated with Cyberknife (CK) in our Center.
Methods: From July 2007 through June 2016 a retrospective analysis was carried out on 217 pts with a median age of 75 years (range 52 – 86), median prostate volume of 75.6 cc (range 37.03-163.16)and clinically localized prostate cancer. CK was used to deliver fiducials based image guided Stereotactic Body Radiotherapy Treatment . The majority of pts 116 (53%) were low risk , 60 pts (28%) were intermediate risk and 41 patients (19%) were high risk (according to the NCCN criteria). Median pre-treatment PSA was 8.51 ng/ml (range 1.51- 51 ng/ml) .17 (41%) of 41 high risk pts received Androgen Deprivation Therapy. The course of radiotherapy consisted of 38 Gy over 4 fractions (9.5 Gy per fraction) given daily to the PTV. Heterogenous dose planning was used, dose was normalized to the 75% isodose line in order for the prescription dose to cover at least 95% of PTV. Real-time intrafractional motion tracking was used.
Results: With a median follow up of 61 months (range 12 – 120), the six years actuarial PSA relapse free survival rate is 94.4% (CI: 90.8%-98.2%) with 98.2% for low risk, 94.5% for intermediate and 85.6% for high risk. 23 (10.5%) pts died during the follow up for unrelated causes, only one (0.5%) died for prostate cancer. Limited acute urinary symptoms(grade I - II) were common (46.5% of pts), no one experienced grade III or worse acute urinary symptoms. 20.3% of pts reported grade I or II acute GI symptoms, only one experienced a grade III acute proctitis. No grade IV rectal toxicity was observed. The majority of pts (78.3%) experienced grade 0 GU late toxicity, 39 (18 %) experienced grade I or II GU symptoms, 7 (3%) pts reported grade III toxicity. In one patient (0.5%) a grade IV bladder fistula was observed. The majority of pts (95%) did not experienced late GI toxicity, only Grade I or II symptoms were observed in 10 patients (4.6%),higher was not reported.
Conclusions: Cyberknife SBRT represents a non invasive method for the definitive treatment of localized prostate cancer with results not inferior to standard fractionated radiotherapy in terms of biochemical control rates at up to 6 years and toxicities.


Giancarlo BELTRAMO, Giovanni LONGO, Isa BOSSI ZANETTI (Milano, Italy), Achille BERGANTIN, Anna Stefania MARTINOTTI, Irene REDAELLI, Paolo BONFANTI, Chiara SPADAVECCHIA, Livia Corinna BIANCHI, Matteo MAGGIONI, Guido DORMIA
12:40 - 12:50 #17787 - b25-5 Phase 2 multicentre study of gantry-based SBRT boost for intermediate and high risk prostate cancer.
b25-5 Phase 2 multicentre study of gantry-based SBRT boost for intermediate and high risk prostate cancer.

Objectives: To report feasibility, early toxicity and PSA kinetics following gantry linac-based, stereotactic radiotherapy (SBRT) boost within a prospective, phase 2, multicentre study (PROMETHEUS: ACTRN12615000223538)

Methods: Patients were treated with gantry-based SBRT, 19-20Gy in 2 fractions delivered one week apart, followed by conventional IMRT (46Gy in 23 fractions). The study mandated MRI fusion for planning, rectal displacement and intrafraction image guidance. Toxicity was prospectively graded using CTCAE v4.  

Results: Between March 2014 and July 2018, 135 patients (76% intermediate, 24% high-risk), median age 70 years (range 53–81) were treated across five centres. Short course (≤6 months) androgen deprivation therapy (ADT) was used in 36%, long course in 18%. Rectal displacement method was SpaceOAR in 59% and Rectafix in 41%. Median follow-up was 24 months.Acute grade 2 gastrointestinal (GI) and urinary toxicity occurred in 4.4% and 26.6% with no acute grade 3 toxicity. At 6, 12, 18, 24 and 36 months post-treatment the prevalence of late grade ≥2 GI toxicity was 1.6%, 3.7%, 2.2%, 0% and 0% respectively and the prevalence of late grade ≥2 urinary toxicity was 0.8%, 11%, 12%, 7.1% and 6.3% respectively. Three patients experienced grade 3 late toxicity at 12 to 18 months which subsequently resolved to grade 2 or less. For patients not receiving ADT, median PSA pre-treatment was 7.6ug/L (1.1 – 20) and at 12, 24 and 36 months post-treatment was 0.86, 0.36 and 0.20ug/L. 

Conclusions: Delivery of a gantry-based SBRT boost is feasible in a multicentre setting, is well tolerated with low rates of early toxicity and is associated with promising PSA responses. A second transient peak in urinary toxicity was observed at 18 months which subsequently resolved. Follow-up is ongoing to document late toxicity, long-term patient reported outcomes and tumour control with this approach.


David PRYOR (Brisbane, Australia), Mark SIDHOM, Sankar ARUMUGAM, Joseph BUCCI, Sarah GALLAGHER, Joanne SMART, Greer PETER, Sarah KEATS, Lee WILTON, Jarad MARTIN
Segovia Break Out

"Monday 10 June"

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A25
12:00 - 13:00

Oral Session
METASTASES #1

Moderators: Eduardo LOVO IGLESIAS (Brain and Spine Radiosurgery Program) (San Salvador, El Salvador), Edilmar MOURA (DIRECTOR) (NATAL, Brazil), John SUH (Radiation Oncologist) (Cleveland, USA)
12:00 - 12:10 #17640 - a25-1 United States radiotherapy practice patterns for brain metastases in the era of stereotactic radiosurgery.
United States radiotherapy practice patterns for brain metastases in the era of stereotactic radiosurgery.

Background: Stereotactic radiosurgery (SRS) effectively treats brain metastases (BM) while minimizing treatment-related morbidity, prompting reassessment of whole brain radiotherapy (WBRT) indications. A patterns of care analysis between SRS and WBRT was performed.

Materials/Methods: Adults in the National Cancer Database (NCDB) with BM at diagnosis from a lung, breast, skin, urogenital, gastrointestinal, or head/neck primary tumor between 2010-2015 and no prior malignancy were identified. WBRT was defined as 20-50Gy in 4-44 fractions (fx) at 1.6-6Gy/fx totaling 60-100Gy2 biologically equivalent dose delivered in ≤60 days using non-SRS external beam modality. SRS was defined as radiosurgery modality, 12-24Gy/1fx, 18-30Gy/2fx, 21-36Gy/3fx, 21-36Gy/4fx, or 25-40Gy/5fx to the brain. Radioresistant histology was defined as melanoma, renal cell carcinoma (RCC), sarcoma/spindle cell, or gastrointestinal (GI) primary. Odds ratios (OR, 95% confidence interval) of SRS receipt compared to WBRT were calculated from multivariate logistic regression. OS was estimated via the Kaplan-Meier method. The substantial limitations in using the NCDB for these analyses were critically reviewed.

Results: 90,388 subjects were identified, the majority with BM from primary lung cancer (83.0%). Of these, 11,486 (12.7%) received SRS and 24,262 (26.8%) WBRT. Annual use of WBRT decreased from 27.8% to 23.5%, while use of SRS increased from 8.7% to 17.9% in 2010 and 2015, respectively. The most common SRS and WBRT dose-fractionations were 20Gy/1fx (13.0%) and 30Gy/10fx (56.8%), respectively. Factors significantly associated with SRS receipt on multivariate analysis were later year of diagnosis (2015 vs 2010, OR 2.4, 2.2-2.6), radioresistant histology (OR 2.0, 1.9-2.2), academic facility (OR 1.9, 1.8-2.0), highest income quartile (OR 1.6, 1.4-1.7), chemotherapy receipt (OR 1.4, 1.4-1.5), and further travel distance (>15 vs ≤15 miles, OR 1.4, 1.3-1.5). Median OS was 11.7mo for SRS (OS 72% @6mo, 19% @36mo) and 5.7mo for WBRT (OS 49% @6mo, 6% @36mo).

Conclusions: WBRT utilization appears to be decreasing while SRS utilization is increasing in the U.S. to treat BM at diagnosis. BM from melanoma, RCC, sarcoma, or GI primaries are more likely to receive SRS. The data in the NCDB are inadequate to infer the efficacy of SRS over WBRT, particularly in the absence of performance status and number of BM.


Andrew BARBOUR (Seattle, USA), Corbin JACOBS, Gita SUNEJA, Scott FLOYD, Jordan TOROK, John KIRKPATRICK
12:10 - 12:20 #17703 - a25-2 Stereotactic radiosurgery (SRS) for brain metastases – time trend and variation in practice in Australia.
Stereotactic radiosurgery (SRS) for brain metastases – time trend and variation in practice in Australia.

Introduction: To evaluate the trend in utilisation of stereotactic radiosurgery (SRS) for management of brain metastases (BM) in Australia

Methods: The Victorian Radiotherapy Minimum Data Set (VRMDS) captures vital details of radiotherapy (RT) delivered in the state of Victoria, Australia. This study comprise all patients in VRMDS with solid tumour (excluding primary brain malignancies) who underwent brain RT between January 2012 and December 2017. The primary outcome was any documented use of SRS. Differences in patient-, tumour-, sociodemographic and institutional factors between patients who had SRS vs. no SRS were compared using Pearson’s chi-squared test for categorical variables. The Cochrane-Armitage test for trend was used to evaluate the use of SRS over time. Multivariable logistic regression was used to identify factors associated with SRS use.

Results: Of the 3,964 patients who had brain RT included in this study, 1,348 (34%) were documented to have SRS. There was an increase in uptake of SRS from 31% in 2012 to 41% in 2017 among patients who had RT for BM (P<0.001). Patients who had SRS were younger – mean age was 63.2 (SD=12.8) in those who had SRS vs. 65.5 (SD=12.3) in those who did not have SRS (P<0.001). There were no differences in SRS use between men (34%) and women (34%) (P=0.8). Patients who had melanoma were significantly more likely to have SRS  (50%), compared to other tumour types e.g. lung cancer (26%), breast cancer (33%), or gastrointestinal cancers (31%) (P<0.001). Patients from the most disadvantaged residential areas were less likely to have SRS (29%) compared to those from least disadvantaged residential areas (45%) (P<0.001). Patients treated in public institutions were more likely to have SRS compared to private institutions (36% vs. 30%, P=0.001). Patients treated in metropolitan centres were also more likely to have SRS compared to those treated in regional centres (41% vs. 8%, P<0.001). In multivariate analysis, patients’ age, tumour type, sociodemographic factors, treatment centres, and year of RT were all independently associated with SRS use.

Conclusion: This is the largest Australian population-based cohort of patients who had RT for BM, with increasing use of SRS observed over time. There is marked variation in SRS use, depending on tumour type as well as sociodemographic and institutional factors.


Wee Loon ONG (Melbourne, Australia, Australia), Therese KANG, Gishan RATNAYAKE, Morikatsu WADA, Jeremy RUBEN, Sashendra SENTHI, Jeremy MILLAR, Farshad FOROUDI
12:20 - 12:30 #17560 - a25-3 Safety and efficacy of dose escalation for neoadjuvant stereotactic radiosurgery for large brain metastases: results from a prospective trial.
a25-3 Safety and efficacy of dose escalation for neoadjuvant stereotactic radiosurgery for large brain metastases: results from a prospective trial.

Background: Single session stereotacic radiosurgery (SRS) alone for brain metastases larger than 2cm in maximal dimension results in local control of only 50%. Surgical resection followed by SRS to the resection cavity can result in leptomeningeal failure (LMD).

Objectives: To determine the safety, feasibility, and efficacy of neoadjuvant SRS at escalating doses followed by surgical resection of brain metastases greater than 2 cm in maximal dimension.

Methods: Patients underwent Gamma Knife SRS followed by surgical resection of brain metastases within 2 week as part of an IRB-approved trial. SRS dose was escalated based on maximal lesion dimension at 3 Gy increments from currently accepted RTOG dosing; and cohorts of 2-6 patients were treated at each dose. Initially, 2 patients were treated at a particular dose and followed for 4 months. If no dose-limiting toxicities (DLT) were observed, the dose was escalated and a new cohort of 4 patients were treated.

Results: A total of 27 patients enrolled on the trial. For tumor size >2.0 - 3.0 cm, 2 patients completed treatment at 18 Gy and 3 patients at 21Gy. For tumor size >3.0 - 4.0 cm, 4 patients were treated at 15 Gy and 9 patients were treated at 18 Gy and 1 patient at 21 Gy. For tumor size > 4.0 - 5.0 cm, 1 patient was treated at 12 Gy and 7 patients at 15 Gy.  Thirteen patients have died at time of analysis. Two patients have experienced local failure. After a median and mean follow up of 9.2 and 15.2 months, respectively, the 6 and 12 month local control was 94.7% and 94.7%, respectively. Six and 12 month distant brain control was 71.7% and 49.6% respectively. Overall survival at 6 and 12 months was 81.5% and 54.9%, respectively. One patient developed localized LMD 5 months following SRS. Twenty-six patients were evaluable for acute toxicity. No DLT have occurred. Twenty-two patients (85%) had no adverse events related to protocol treatment.

Conclusions: Neoadjuvant SRS with dose escalation followed by surgical resection for brain metastases greater than 2 cm in size results in excellent local control, acceptable acute toxicity, and very low rate of LMD failure. The maximum safe dose has not yet been reached. 


Erin MURPHY (Cleveland, USA), Kailin YANG, John SUH, Jennifer YU, Cathy SCHILERO, Alireza MOHAMMADI, Glen STEVENS, Lilyana ANGELOV, Michael VOGELBAUM, Gene BARNETT, Gennady NEYMAN, Sam CHAO
12:30 - 12:40 #17735 - a25-4 A natural history of melanoma brain metastases on MRI: Recommendations for interval from imaging to treatment delivery.
A natural history of melanoma brain metastases on MRI: Recommendations for interval from imaging to treatment delivery.

Background:

Stereotactic radiation surgery (SRS) is increasingly being used to treat brain metastases to minimize the neurocognitive side effects associated with whole-brain radiation therapy and provide good intracranial disease control. Previous studies have shown that time between pretreatment magnetic resonance imaging (MRI) and SRS is associated with intracranial progression and reduced local control. However, there are no formal recommendations regarding the timing between pretreatment MRI and SRS delivery based on a natural radiographic history of individual brain metastases.

Methods:

Retrospective review of all patients diagnosed with melanoma brain metastases between 2003 and 2018. All MRI scans, including those from outside institutions, were reviewed for radiographic change. Individual brain metastases were tracked for growth before treatment. Number of new metastases was recorded between scans. Kaplan-Meier analysis was used to evaluate frequency of radiographic change.

 

Results:

A total of 561 MRI scans were reviewed and revealed 384 brain metastases in 65 patients with metastatic melanoma. Each patient had 8.6 MRI scans and 5.9 metastases on average. Ninety metastases (23.4%) grew before treatment, 223 (58.3%) were treated before displaying any growth, and 70 (18.2%) showed no growth during observation. The median time interval between MRI scans, diagnosis and metastatic growth, and diagnosis and treatment was 73 days (IQR 28-99), 33 days (IQR 27-71), and 19 days (IQR 0-38), respectively. Seventy-two (14.8%) MRI scans displayed growth relative to the previous MRI, with a median interval of 33 days, while 98 (20.1%) MRI scans showed new metastases relative to the previous MRI, with a median interval of 70 days.

 

Conclusion:

Roughly a quarter of the observed metastases showed growth before treatment with most of the observed growth occurring between 1 and 3 months after diagnosis. This suggests that SRS delivery within 1 month of diagnosis would minimize risk of metastatic growth.


Alon KASHANIAN (Los Angeles, USA), Collin PRICE, Rebecca LEVIN-EPSTEIN, Tania KAPREALIAN, Nader POURATIAN
12:40 - 12:50 #17777 - a25-5 Stereotactic radiosurgery for small cell lung cancer brain metastases.
Stereotactic radiosurgery for small cell lung cancer brain metastases.

Purpose:

Brain metastases from small cell lung cancer (SCLC), either when newly diagnosed or recurrent following prior prophylactic cranial irradiation (PCI) or whole brain radiotherapy (WBRT), are traditionally thought to be widely disseminated and unsuited for focal stereotactic radiosurgery (SRS). For newly diagnosed metastases, we hypothesized that the rate of new distant failure (DF) elsewhere in the brain and neurologic death rate following SRS for SCLC is similar to historical controls for non-SCLC brain metastases and that SRS is suitable for salvage following prior PCI/WBRT.  

Materials & Methods:

In this IRB-approved retrospective study, we identified 59 patients with 236 total metastases treated from 2000-2017 with SRS in 90 total courses for SCLC brain metastases. Twenty-one patients had inadequate follow-up, yielding 38 evaluable patients with 153 metastases. SRS was indicated for salvage after prior PCI (12 patients (32%)) or WBRT (15 patients (32%)) or for upfront initial treatment in 11 (29%) patients. The cumulative incidences, with death and salvage WBRT as competing risks, were estimated for local (LF), distant (DF) failure, and adverse radiation effect (ARE) as were the Kaplan-Meier estimates of overall (OS) from the time of SRS.

Results:

With a median follow up of 6.2 months (range 0.1 - 91.3 months), the 1-year cumulative incidence of LF was 21% [95%CI 15%, 27%]. The rate of LF was 4% for upfront SRS compared to 27% for salvage SRS after PCI/WBRT (p=0.01). The 1-year cumulative incidence of DF was 49% [95%CI 31%, 64%]. There was no difference in DF for patient treated with upfront SRS (57% [95% CI 21%, 85%]) and salvage SRS (44% [95%CI 25%, 63%]) (p=0.36). In patients treated with upfront SRS, 46% ultimately received salvage WBRT following SRS compared to 13% with prior PCI or WBRT (13%) (p=0.08).  The 1-year rates of ARE per patient were 17% for upfront SRS and 20% for salvage SRS (p=1.00). The median OS was 5.9 months, with a crude incidence of neurologic death of 14%.

Conclusion:

Patients with SCLC treated with SRS appear to have similar rates of local failure, distant failure and neurologic death compared to historical controls of SRS for non-SCLC.    In the era of controversy regarding PCI for SCLC as well as the deferral of WBRT for NSCLC given concerns of neurotoxicity, the role of upfront SRS alone for SCLC should be re-evaluated.


Scott SOLTYS (Stanford, CA, USA), Rohil TAGGARSI, Everett MODING, Ziad FAWAZ, Rie VON EYBEN, Erqi POLLOM, Steven CHANG, Iris GIBBS, Steven HANCOCK, Hilary BAGSHAW
12:50 - 13:00 #16763 - a25-6 Symptomatic brain metastases larger than 8.5cc managed with upfront radiosurgery.
a25-6 Symptomatic brain metastases larger than 8.5cc managed with upfront radiosurgery.

Introduction.

Current recommendations in accordance with NCCN guidelines regarding management of metastases larger than 2.5 cm in symptomatic patients suggest surgery as a first choice. We analyze the role of upfront radiosurgery in such patients.

Methods.

37 symptomatic patients that harbored metastatic tumors mainly from breast histology that were greater than 8.5 cc in volume were treated from 2011 to January 2018.

Results.

The median tumor volume was 12.5 cc (8.5-78.4), 9 (24%) patients were treated with LINAC with a volume of 20 cc (9.2-70 cc). The treatments with Gamma Ray were administrated to the remaining 28 (76%) patients, 9 (32%) of them with adaptive (Staged) radiosurgery protocol. The prescription dose for the gamma group was 13.8 Gy (7.5-18Gy) mean dose of 17.9 Gy (13.2-23.3 Gy) with a mean volume of 16.3 cc (8.5-78.4 cc) for single dose and 14.5 Gy (10-18) for the first treatment of adaptive SRS to a volume of 12.8 cc (8.5-78.4) and 13.5 Gy (10-18) for the second treatment 30 days after to a 4.3cc (0.4-70) volume.

Karnofsky score was 60 (50-70) the day of treatment and 80 (60-100) at 30 days (P=0.0001). At 30 days 95% of the tumors available for scanning (20 out of 21 tumors) had reduced in size in a 74% (11-95%). Median survival was 19 months (4-34), with an accumulative risk of death from central nervous progression of 4.5%. We had reports of disease progression in 7 (18.9%) patients (RECIST), Two of them were adequately managed by steroids (Radiation necrosis). Four patients meet criteria for surgery at 7 months (4-34), 3 were operated. Of the whole series 6 (16.2%) Patients required new treatments with radiosurgery for new lesions, 3 for progression.

Conclusion.

Radiosurgery in our experience has shown to be effective in controlling large metastases in the brain, it requires a careful monitoring and neurosurgical collaboration to provide patient safety.


Eduardo LOVO (San Salvador, El Salvador), Victor CACEROS, Mario MINERVINI, William REYES, Fidel CAMPOS
Segovia Plenary

"Monday 10 June"

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C25
12:00 - 13:10

Oral Session
PHYSICS #1

Moderators: Francine Xavier DOS SANTOS (Medical Physicist) (porto alegre, Brazil), Josef NOVOTNY (Head of department) (Prague, Czech Republic), David SCHLESINGER (Medical Physics) (Charlottesville, VA, USA, USA)
12:00 - 12:10 #17812 - C25-1 Interactive inverse planning system for radiosurgery by convex optimization.
C25-1 Interactive inverse planning system for radiosurgery by convex optimization.

We developed a new interactive inverse planning approach based on a fully convex framework. The system has been first implemented to be used with Gamma Knife (GK) radiosurgery.

The convex framework is based on the precomputation of a dictionary composed of the individual dose distributions of all possible shots, considering all their possible locations, sizes, and shapes inside the target volume. The convex problem is solved to determine the plan, i.e., which shots and with which weights, that will actually be used, considering a sparsity constraint on the shots to fulfill the constraints while minimizing the beam-on time. The system is called IntuitivePlan and allows data from the generated dose plans to be transferred into the GK treatment planning software for further dosimetry evaluation and treatment.

The system has been very efficiently implemented and an optimal plan is usually obtained in less than 1 minute, depending on the complexity of the problem, on a desktop computer or in only a few minutes on a high-end laptop. Dosimetry data from clinical cases were generated with IntuitivePlan. The dosimetry characteristics are very satisfactory and adequate in terms of conformity, selectivity, gradient, protection of organs at risk, and yield to much shorter beam-on (treatment) time. Moreover the system allows to interact and move intuitively, in a very user-friendly manner, the isodose lines and modify them directly, to relax or increase constraints, and automaically generate a new optimal plan.

The possibility of using optimal interactive real-time inverse planning in conjunction with GK opens new perspectives in radiosurgery, especially considering the potential use of the full capabilities of its latest generations. This approach gives new users the possibility of using the system for easier and quicker access to good-quality plans with a shorter technical training period and opens avenues for new planning strategies for expert users. The use of a convex optimization approach allows an optimal plan to be provided in a very short processing time. The versatility of the system will allow to develop similar approaches for other radiosurgery/radiotherapy plateforms. Independent quantitative prospective evaluation comparing inverse planned and expert planned cases are underway to validate this novel and promising treatment planning approach. 


Marc LEVIVIER (Lausanne, Switzerland), Rafael E. CARRILLO, Rémi CHARRIER, Jean-Philippe THIRAN
12:10 - 12:20 #17671 - c25-2a The impact of unscheduled gaps and shot ordering on the biologically effective dose (BED) in Gamma Knife Radiosurgery.
c25-2a The impact of unscheduled gaps and shot ordering on the biologically effective dose (BED) in Gamma Knife Radiosurgery.

Purpose: Historically, Leksell Gamma Knife® (LGK) procedures have been regarded as single fraction exposures with no account taken as to the potential influence of the repair of sub-lethal radiation damage during treatment. However, given the large variations in treatment time and dose-rate during treatment delivery, this basic assumption has to be re-evaluated. This study aims at quantifying two possible sources of variations: unscheduled gaps during treatment and the order in which the individual shots are delivered.

Methods: An established biologically effective dose (BED) model, which includes bi-exponential repair parameters, has been used to analyse LGK treatments in a cohort of 15 patients with vestibular schwannomas. These patients were treated using a prescription dose of either 12 or 13 Gy with the LGK model Perfexion® (PFX). For comparisons, the BED values were evaluated for the physical prescription dose iso-surface.

A single gap of 15 minutes was introduced at different times throughout the course of treatment to assess the impact on BED. After evaluating all possible combinations of shot sequences for a subset of the cohort, a heuristic approach was taken to estimate the achievable range of BED values when determining the order of delivery of the individual iso-centres. This is achieved by either grouping or distributing shots according to their average dose-rate on the prescription dose iso-surface.

Results: In regard to the temporal position of the gap in the treatment delivery, mean BED values were shown to decrease between 0.1% and 9.9%, depending on the individual average dose-rate profiles. Depending on the number of iso-centres used for the treatment, the application of a heuristic approach to sorting the shots results in BED variations of up to 14.2%, relative to the mean BED for the original sequence.

Conclusions: The influence of treatment variables, like dose-rate profiles and shot sequence, on the BED should be considered during treatment planning for LGK radiosurgery. Further studies on the predictive value of BED in treatment outcome should be carried out.


Thomas KLINGE (London, United Kingdom), Marc MODAT, Jamie MCCLELLAND, Alexis DIMITRIADIS, Ian PADDICK, John W. HOPEWELL, Neil KITCHEN, Sébastien OURSELIN
12:20 - 12:30 #17674 - c25-2b Calculation of biologically effective dose (BED) distribution matrices for Gamma Knife Radiosurgery.
c25-2b Calculation of biologically effective dose (BED) distribution matrices for Gamma Knife Radiosurgery.

Purpose: Historically, Leksell Gamma Knife® (LGK) procedures were regarded as single fraction exposures with no account taken as to the potential influence of the repair of sub-lethal radiation damage during treatment. However, given the large variations in treatment time and dose-rate distributions, this basic assumption needs to be re-evaluated. This study aims at demonstrating the feasibility of efficiently calculating biologically effective dose (BED) distributions to aid with the treatment planning process.

Methods: An established biologically effective dose (BED) model [1], which includes bi-exponential repair parameters, has been implemented in MATLAB [2]. A custom version of the treatment planning system (TPS) Leksell GammaPlan® 10.1 (LGP) was used to export the physical dose distribution matrices and the corresponding beam-on times for every iso-centre. Using the parameters for the BED model (alpha/beta ratio, repair rates, partition coefficient) allows for the calculation of 3D BED distribution matrices from the 4D dose distribution matrices (combination of one 3D matrix per iso-centre).

Results: The processing time in MATLAB for a single 31×31×31 BED matrix calculation, as it is used in LGP for the physical dose, does not exceed 0.05 s on a regular laptop (Intel® Core™ i7-7700HQ, 16 GB RAM). This was measured using the MATLAB built-in function timeit() for a 20-iso-centre treatment plan. The resulting BED distributions can be visualised side-by-side with the corresponding physical dose distribution.

Conclusions: Calculating the BED distribution for a given physical dose treatment plan could be implemented into the TPS to better estimate the effectiveness of a treatment and its dependence on parameters like the treatment time, the number, location and shape of iso-centres and their order of delivery. Since the additional computational cost is limited, the BED could be updated and visualised in real time, similar to the physical dose visualisation that is used in LGP now.

References:

[1] W. T. Millar et al., ‘The role of the concept of biologically effective dose (BED) in treatment planning in radiosurgery.’, Phys. Medica PM Int. J. Devoted Appl. Phys. Med. Biol. Off. J. Ital. Assoc. Biomed. Phys. AIFB, vol. 31, no. 6, pp. 627–33, Sep. 2015, http://dx.doi.org/10.1016/j.ejmp.2015.04.008

[2] BED model on GitHub: https://github.com/klinge-th/modelBED


Thomas KLINGE (London, United Kingdom), Marc MODAT, Jamie MCCLELLAND, Alexis DIMITRIADIS, Ian PADDICK, John W. HOPEWELL, Neil KITCHEN, Sébastien OURSELIN
12:30 - 12:40 #17677 - c25-3 A linear programming approach to inverse planning in gamma knife radiosurgery.
c25-3 A linear programming approach to inverse planning in gamma knife radiosurgery.

Purpose:  The Leksell Gamma Knife® radiosurgery platform has excellent dose characteristics that admits the delivery of high quality plans. To utilize its full potential, a new inverse planning approach has been developed that both resolves the shortcomings of earlier approaches and unlocks new capabilities.

Methods: We present an inverse planning approach, where the isocenter positions are determined and fixed prior to the sector-duration optimization step, which is done using linear programming. In sector duration optimization irradiation times for each sector and collimator at each isocenter are the optimization variables. In the framework of  linear programming, we describe two methods for problem size reduction: dualization and representative subsampling. Furthermore, we propose an efficient penalization of beam-on-time promoting the total irradiation time of each sector to be equally long, which is advantageous since they can irradiate simultaneously.  We can constrain dose to organs at risk and we study the effect of beam-on time penalization on the trade-off between plan quality and beam-on time.

Results:  Compared to a naïve beam-on time penalization, we find that our efficient beam-on time penalization reduces the beam-on time by a factor 2-3. Both explicit dualization and representative subsampling lead to optimization time-savings by a factor 5-20. Overall, in a comparison on 75 clinical plans we find that it is always possible to find plans with similar coverage and better selectivity and beam-on time. In addition, in 44 of these cases, the plans have an improved gradient index. On a standard Leksell GammaPlan® workstation, the optimization times for typical cases are less than a minute. 

Conclusion: We present a combination of techniques that enables sector-duration optimization, which renders clinically acceptable plans, in a clinically feasible time frame. 


Stella RIAD, Jens SJOLUND, Haakan NORDSTROEM (Stockholm, Sweden), Haakan NORDSTROEM
12:40 - 12:50 #17803 - c25-5 Effects of variations in treatment time on clonogenic survival of V79 cells: Implications for Radiosurgery.
c25-5 Effects of variations in treatment time on clonogenic survival of V79 cells: Implications for Radiosurgery.

Purpose: The major importance of the effects, related to the repair of sublethal radiation damage - as treatment duration varies, are a current controversy in radiosurgery. Cell survival studies have been performed to verify the importance of this effect in relation to established models. 

Methods: Mammalian V79-4 cells were irradiated in vitro with γ-rays, either as an acute exposure, where the effects of sublethal irradiation damage repair can be ignored, or as protracted exposures over 15 – 120 min.  Protraction was achieved either by introducing a variable time gap between two doses of 7 Gy, or as a continuous exposure at lower dose rates so that a range of doses were delivered in fixed times of 30, 60 or 120 min. 

Results: For all doses there was a progressive reduction in efficacy with increasing overall treatment time. This was illustrated by the progressive increase in clonogenic cell survival with the progressive increase in exposure time, with a resulting shift of the cell survival curves.  Cell survival curves for irradiations given either as an acute exposure (6.1 Gy/min), over fixed times (30, 60 and 120 min) were well fitted by the LQ model, giving an α/β ratio of  4.0 Gy and because of the limited data set a single repair half-time of 31.5 min.

Conclusions: The present results are consistent with published data with respect to the response of solid tumors and normal tissues, whose response to both continuous and fractionated irradiation is also well described by the LQ model. This suggests the need for dose compensation in radio-surgical treatments, where dose is delivered over a similar range of protracted overall treatment times, perhaps as a prerequisite to full Biological Effective Dose treatment planning.


John W HOPEWELL (Oxford, United Kingdom), Steven HALLGREN, Mark A HILL, Ian PADDICK, James M THOMPSON, Amy ELLIOTT, Bleddyn JONES
12:50 - 13:00 #17749 - c25-5 Application of Machine Learning Techniques for Accurate Dose Verification of MLC-based Cyberknife SRS and SBRT.
c25-5 Application of Machine Learning Techniques for Accurate Dose Verification of MLC-based Cyberknife SRS and SBRT.

Objectives: Cyberknife treatments with Small and Irregular MLC-formed fields are widely used in SRS and SBRT. The current technique is to perform film or ion chamber measurements to confirm the dose accuracy, which is time-consuming and prone to errors. The purpose of this study is to apply state-of-the-art machine learning techniques for accurate dose verification of MLC-based SRS and SBRT treatments.

Methods: The commissioning and clinical measurement data were collected from our institution and the datasets were randomly split into training and testing data. The measured dose distributions were treated as outcomes of a deep neuro network (DNN) based estimator with inputs of different fields with detailed MLC positions. Dose results for different MLC fields were predicted using models trained with regularization added to the cost functions. The predicted dose distributions for small and irregular fields were evaluated using percentage relative error regarding measured data at the depth of 1.5cm and 5cm.

Results: The packages we used were Tensorflow and scikit-learn in python. With augmentation techniques, datasets of field sizes ranging from 7mm x 7mm up to 115mm x 100mm were tested for model training and dose output prediction. The dose of small and irregular SRS treatment field was accurately predicted with the proposed machine learning methods.  The mean relative error between the predicted and the measured dose is 0.11% with a maximum error of 0.4%.

Conclusions: The proposed method could potentially be used for dose reconstruction with recorded MLC and robot positions during the delivery which will shorten the patient QA time and enhance treatment efficacy. 


Bin HAN (Stanford, USA), Lei XING, Yong YANG, Scott SOLTYS, Lei WANG
13:00 - 13:10 #17759 - c25-6 Deep learning for tumor contouring in neuroradiosurgery: an evaluation of time savings.
c25-6 Deep learning for tumor contouring in neuroradiosurgery: an evaluation of time savings.

Target delineation is an important step in radiosurgery (RS)  treatment planning. Routinely the targets are delineated through slice-by-slice manual segmentation on MR images. This process is time-consuming, operator - dependent and could lead to treatment delays. The aim of this study was to investigate the speed up of the tumor delineation within the radiosurgery treatment planning using contours generated by a deep convolutional neural network (CNN).

The MR images of ten patients treated with Gamma Knife RS  were selected from routine clinical practice. The dataset consisted of four cases of meningioma, two cases of vestibular schwannoma and four cases of multiple brain metastases. We compared the times needed for two contouring techniques: manual delineation of the tumors and a user adjustment of the CNN generated contours of the tumors. The time spent on each task was recorded. The tasks were performed in Leksell Gamma Plan (version 11.1, Elekta AB) and iPlan (version 4.5, BrainLab) by four experts. The 3D - Unet architecture with residual connections, trained with custom loss function and sampling procedure [Krivov et al, 2018], optimized for metastases segmentation was used for automatic brain tumor segmentation. The automatic contours were generated within five seconds.  The time required to import these contours to the treatment planning systems was less than one minute.

The generated contours were acceptable with no or minor corrections.The total median time needed to delineate a tumor manually was 9.15 min. (ranged from 3.15 min. to 29.18 min). The median times saved were 6.54 min. (range 40 sec. - 17.06 min.), 2.16 min. (range 48 sec.- 8.20 min.), 9 min. (range 1 min. -  26 min.), 5.27 min. (range 3 min - 17.35 min) for User 1, User 2, User 3, User 4 respectively. The Wilcoxon signed-rank test was used to compare results (p < 0.05, r > 0.6). On average, the automatic algorithm speeds up the process of the delineation in 2.30 times.

The usage of deep learning generated contours accelerates delineation more than twofold. Though the automatically generated contours were almost identical to the manual ones,  further investigation is needed to quantify these differences and compare it with inter-rater reliability.

1.   Krivov E. et al. Tumor Delineation For Brain RS by a ConvNet and Non-Uniform Patch Generation // 3rd Int. Workshop Patch - MI . 2018. 8p.


Alexandra DALECHINA (Moscow, Russia), Valery KOSTJUCHENKO, Egor KRIVOV, Boris SHIROKIKH, Alexey SHEVTSOV, Mikhail BELYAEV, Andrey GOLANOV, Mikhail GALKIN, Amayak DURGARYAN, Ivan OSINOV
El Pardo I
13:00 LUNCH (exhibition area), VISIT OF THE EXHIBITION & POSTERS
13:15

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B26
13:15 - 14:15

ELEKTA SPONSORED SESSION
Precision Radiation Medicine: Moments that Matter

13:15 - 13:20 Welcome and Introduction. Aaron OAKS (Vice President Marketing) (PLATINUM PARTNERS, France)
13:20 - 13:35 Elekta Unity™ Installation and Initial Clinical Usage at the University of Iowa. Mark SMITH (PLATINUM PARTNERS, Iowa City, USA)
13:35 - 13:50 Managing the Increasing Demand for Intracranial Radiosurgery Treatments in an integrated Oncology and Neurosurgical Setting. Matthew FOOTE (Deputy Director / Co-Director) (PLATINUM PARTNERS, Brisbane, Australia)
13:50 - 14:05 4D Image Guidance and Other Motion Management Techniques for Lung SBRT. Farkhad MANAPOV (PLATINUM PARTNERS, Munich, Germany)
14:05 - 14:15 Discussion.
Segovia Break Out
14:30

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A27
14:30 - 15:30

PARALLEL SESSION
BENIGN BRAIN TUMORS UPDATE

Moderators: Laura FARISELLI (director) (milan, Italy), Leonardo FRIGHETTO (Neurosurgeon) (Passo Fundo, Brazil), Eduardo LOVO IGLESIAS (Brain and Spine Radiosurgery Program) (San Salvador, El Salvador)
14:30 - 14:45 Long Term Outcomes. Zhiyuan XU (Gamma Knife) (Speaker, Charlottesville, USA)
14:45 - 15:00 Combination Therapy. Bruce POLLOCK (Physician) (Speaker, Rochester, USA)
15:00 - 15:15 Repeat Radiosurgery. Gus BEUTE (Neurosurgeon) (Speaker, Tilburg, The Netherlands)
15:15 - 15:30 Is Earlier Better? Jean REGIS (PROFESSEUR) (Speaker, MARSEILLE, France)
Segovia Plenary

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B27
14:30 - 15:30

PARALLEL SESSION
SPINE

Moderators: Lilyana ANGELOV (Staff Neurosurgeon) (Cleveland, USA), Lucas Ignacio CAUSSA (MD) (Córdoba, Argentina), Scott SOLTYS (ISRS 2023) (Stanford, CA, USA)
14:30 - 14:40 Patient Selection for Spine SBRT. Matthew FOOTE (Deputy Director / Co-Director) (Speaker, Brisbane, Australia)
14:40 - 14:50 Status of clinical trials for de novo metastases. Samuel RYU (Professor) (Speaker, Stony Brook, NY, USA)
14:50 - 15:00 Re-irradiation Spine SBRT. Sten MYREHAUG (Radiation Oncologist) (Speaker, Toronto, Canada)
15:00 - 15:10 Consensus Contouring Guidelines for Spine SRS. Kristin J REDMOND (Associate Professor of Radiation Oncology and Molecular Radiation Sciences) (Speaker, Baltimore, MD, USA)
15:10 - 15:20 Radiation for spinal chordoma. Scott SOLTYS (ISRS 2023) (Speaker, Stanford, CA, USA)
15:20 - 15:30 Radiosurgery for Benign Pathologies. Kita SALLABANDA (Medical Direcor) (Speaker, Madrid, Spain)
Segovia Break Out

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C27
14:30 - 15:30

Oral Session
METASTASES #2a

Moderators: Luis Gustavo GUIMARÃES (Brazil), Harley OLIVEIRA (Brazil), John SUH (Radiation Oncologist) (Cleveland, USA)
14:30 - 14:40 #17621 - c27-1 Clinical risk assessment score to estimate the likelihood of pseudoprogression versus tumor recurrence following stereotactic radiosurgery for brain metastases.
c27-1 Clinical risk assessment score to estimate the likelihood of pseudoprogression versus tumor recurrence following stereotactic radiosurgery for brain metastases.

Objective: A major challenge in the follow-up of patients managed with stereotactic radiosurgery (SRS) for brain metastases (BM) is to differentiate pseudoprogression (PP) from tumor recurrence (TR). A clinical score based on tumor and treatment related factors would be valuable when selecting appropriate treatment.

Material and methods: Follow-up images of 97 consecutive patients treated with SRS for 406 BM were analyzed. Of these 100 (24.6 %) BM in 48 (49.5 %) patients responded either with TR (delayed growth; 53 (13.1 %) BM) or PP (temporary volume increase; 47 (11.5 %) BM). Differences between the 2 groups were analyzed and used to develop a PP risk assessment score (PP-RAS).

Results: Significant factors associated with a higher incidence of PP versus TR were: prior radiation SRS or WBRT (p = 0.001, π = 13.7), target cover ratio > 98 % (p = 0.031, π = 4.7), BM volume ≤ 2cc (or BM ≤ 1.5 cm in diameter, p = 0.039, π = 4.3), and primary lung cancer vs. other primaries (p = 0.084, π = 3.0). Based on the presence (0) or not (1) of these 5 parameters, a risk assessment score for PP versus TR was established. A PP-RAS score of 0 corresponds with high likelihood of PP vs. TR, whereas a score of 5 corresponds with a high risk of TR.

A score of ≤ 1 point was associated with 100 % PP, 2 points with 57 % PP  and 43 % TR, 3 points with 57 % TR and 43 % PP, whereas ≥ 4 points were associated with 84 % TR and 16 % PP , π=24.6, df =4, p < 0.001).

Conclusion: Based on 5 readily available parameters at the time of SRS our risk assessment score could robustly differentiate between PP versus growth following SRS. The score is user-friendly, intuitive and cost-free. It may be a useful tool to guide the decision making whether to retreat or observe at appropriate follow-up intervals.


Bente Sandvei SKEIE (Bergen, Norway), Per Øyvind ENGER, Paal-Henning PEDERSEN, Jan Ingemann HEGGDAL, Geir Olve SKEIE
14:40 - 14:50 #17641 - c27-2 Single-fraction versus hypofractionated stereotactic radiosurgery for medium-sized (2.5 to 3 cm) brain metastases.
c27-2 Single-fraction versus hypofractionated stereotactic radiosurgery for medium-sized (2.5 to 3 cm) brain metastases.

The aim of this study was to investigate the clinical relevance of hypofractionated stereotactic radiosurgery (SRS) specifically in treating medium-sized brain metastases (BMs) of 2.5 to 3 cm compared with single-fraction SRS.

Between 2011 and 2015, a total of 100 patients with newly diagnosed BMs (n=105) of 2.5 to 3 cm had been treated with either single-fraction SRS using the Gamma Knife (GK; n=67; median 58 years) or hypofractionated SRS using the CyberKnife (CK; n=38; median 64 years) at our institution. Primary cancers originated from the lung (n=56, 53.3%), the breast (n=22, 21.0%), the gastrointestinal tract (n=14, 13.3%), and others (n=13, 12.4%). A median marginal dose 21 Gy (range, 18-23 Gy) was delivered for single-fraction GK and a median cumulative dose 35 Gy (range, 27-41 Gy) was delivered in median 5 daily fractions (range, 3-5 fractions) for hypofractionated CK. None of the patients received any prior or upfront whole brain radiotherapy. In each patient, treatment outcome was measured by local tumor control (LTC), overall and progression-free survival (OS and PFS), and the occurrence of radionecrosis (RN).

With a median follow-up of 14 months (3-59 months), significant differences were observed in the incidence of RN (29.9% versus 5.3%, P=0.004) and LTC (LTC rates at 1 year 66.6% versus 92.4%, P=0.035) between the single-fraction versus hypofractionated SRS groups. There were no differences in PFS (median 6 months versus 6 months, P=0.368) and OS (median 13 months versus 18 months, P=0.234) between the groups. Treatment related adverse events (≥ grade 2 toxicity by CTCAE ver 4.0) were more frequently occurred in single-fraction group than hypofractionated group, but the difference was not statistically significant (56.3% versus 36.1%, P=0.084).

These findings suggest a better safety and efficacy profile of hypofractionated SRS compared with single-fraction SRS for the treatment of medium-sized BMs. Further prospective studies are needed to address definitive conclusions.


Young Hyun CHO (SEOUL, Korea), Kyoungjun YOON, Eun Suk PARK, Do Hee LEE, Do Hoon KWON
14:50 - 15:00 #17662 - c27-3 Multi-fraction stereotactic radiosurgery in giant brain oligometastases.
c27-3 Multi-fraction stereotactic radiosurgery in giant brain oligometastases.

Purpose: To evaluate the efficacy and safety of multi-fraction stereotactic radiosurgery(MF-SRS) in patients with giant oligometastatic brain metastases.

Methods: All patients with giant (defined as ≥20 cm3) brain oligometastases who had been referred for MF-SRS at the Huashan Hospital between July 2009 until December 2016 were identified. The radiosurgical dose, isodose curve and fraction selection were based on various factors including tumor volume, tumor characteristic, location and original pathology. The BED of MF-SRS was higher than 40 Gy, corresponding to a single dose of about 16 Gy. All patients had routine clinical and radiologic follow-up at 30 days next to the last fraction and then 3-month intervals. Overall survival was evaluated using the Kaplan-Meier method. Multivariate analyses were performed with the multivariate Cox proportional hazard model.

Results: Between July 2009 and December 2016, 27 patients with 29 intracranial giant metastases were included in this study.The radiosurgical margin dose (median 30 Gy, range 26.1–36 Gy) was prescribed at an isodose curve of 64%–75% (median 68%) with multiple fractions (median 3 fractions, range 3-5), targeting a median tumor volume of 35.51 cm3 (range, 20.7-98.1 cm3). The overall median survival time (MST) was 20 months. The 1-, 2-, and 5-year survival rates were 66.7%, 43.7%, and 23.6%, respectively.Local tumor control rates were 85.7%, 66.9% and 50.2% at 1-, 2-, and 3-year, respectively.On multivariate analysis extracranial metastasis (p = 0.021, HR: 3.76, 95% CI:1.22–11.56), was confirmed as associated with worsened overall survival.The median KPS improved significantly from 40 to 70 (p<0.05, paired t test).No patient obtained a worsened KPS.

Conlusion: MF-SRS is a safe and effective option for patients with giant brain oligometastases and poor performance status.  Prospective studies are required to confirm the findings in this study.


Hua Guang ZHU (Shanghai, China), Xin WANG, Enmin WANG
15:00 - 15:10 #17688 - c27-4 Stereotactic radiosurgery as primary management of intracranial germ cell metastases.
c27-4 Stereotactic radiosurgery as primary management of intracranial germ cell metastases.

Purpose/Objectives: Brain metastases from germ cell tumors (GCTs) are rare and mainly occur in young men whose functional status is otherwise unimpaired. Standard of care in GCT patients with brain metastases remains WBRT, but radiation-induced neurocognitive deficits have been reported in patients with germ cell metastases to the brain treated with whole brain radiation (WBRT). To the authors’ knowledge, there are no published reports evaluating the efficacy of stereotactic radiosurgery (SRS) as the primary treatment of GCT brain metastases. We hypothesize that SRS alone is a feasible alternative for the treatment of limited GCT brain metastases.

Materials/Methods: The records of 14 male patients with various GCT histologies treated between 2012 and 2017 at a single institution were retrospectively reviewed. All of the patients received gammaknife radiosurgery without WBRT. Two of the patients underwent SRS to a post-surgical resection cavity.

Results: The median follow-up of the cohort was 24 months (range 1-50 months) with a median age of 29 years (range, 17-56) and a median of 1.5 (range, 1-7) lesions treated. The 1-year OS was 71% with a median survival of 23 months. There were no local recurrences among the SRS-treated lesions resulting in a 1-year LC of 100%. Only one neurologically related death occurred, leading to a neuro-specific mortality rate of 7%. A total of 35% of patients experienced distant brain recurrence at a median time of 2.7 months, which resulted in a 1-year distant brain control of 71%. Of the 5 patients with distant failure, 3 were successfully salvaged with repeat SRS treatment without additional relapse on follow-up imaging. Only one patient received salvage WBRT 19 months post initial SRS, leading to a 2-year WBRT free survival of 93%.

Conclusions: Given that GCT brain metastases are often limited in number, and mainly affect young men with good functional status, avoidance of WBRT may provide control of intracranial disease with the goal of preserving neurocognitive function in these young patients. Our preliminary results suggest that SRS may safely replace WBRT as an initial treatment of choice patients with GCT brain metastases.


Moaaz SOLIMAN, Yan WANG, Ahsan FAROOQI, Andrew BISHOP, Debra YEBOA, Kristina WOODHOUSE, Susan MCGOVERN, Tina BRIERE, Caroline CHUNG, Mary MCALEER, Matthew CAMPBELL, Shi-Ming TU, Yago NIETO, Ganesh RAO, Sherise FERGUSON, Jing LI (Houston, USA)
15:10 - 15:20 #17818 - c27-5 Outcomes after 2-fractions dose-staged Gammaknife Surgery for large or brainstem located metastases.
c27-5 Outcomes after 2-fractions dose-staged Gammaknife Surgery for large or brainstem located metastases.

Objectives: The aim of this study is to evaluate the outcome after 2 fraction dose stage gammaknife radiosurgery (GKS) for large brain metastases.

Methods: A total of 53 large brain metastases in 42 patients were treated by 2 fraction dose stage GKS. The inclusion criterion was “large” brainstem located lesions or large lesions with a 12 Gy isodose volume of normal brain parenchyma exceeding 10 cm3. The mean tumor volume for the first ones was 4.4 cm3, for the latter ones was 12.7 cm3. For both fractions, the prescription margin dose was 12Gy on the 50% isodose line, with 2 weeks between them. Local control failure was define as an increase of more than 20% between initial and last tumor volume. The primary cancer was melanoma (8), pulmonary (19), breast (8), kidney (2), other (5). The mean age was 62 years old (31-88). The median Karnofsky score was 90. Nine patients had GPA (0-1), 20 patients had GPA (1.5-2), 7 patients had GPA (2.5-3), 6 patients had GPA (3.5-4).

Results: At the second fraction, mean tumor volume was 8.2 cm3. The mean percentage of volume variation for decreasing lesions was 29%. Only 3 lesions increased their volume. At last follow-up, mean tumor volume was 6.0 cm3; 46 lesions decreased volume with a mean percentage of volume variation of 68%; only 7 lesions increased volume. There was a significant correlation (p=0.05) regarding volume variation between 1rst and 2nd GKS and between 1rst GKS and last follow-up. Rate local control at 6 months and 1 year was 87.3% and 68.3% respectively. The rate of adverse radiation effect (ARE) was 14.3%. No predictive factor of local control or ARE was found in an univariate analysis.

Conclusion: The new 2-fraction-dose-staged GKS concept seems to be a well-tolerated and effective treatment option for large BMs.


Pierre-Yves BORIUS (Paris), Aymeric AMELOT, Eli BOUSTANY, Jean Jacques MAZERON, Charles Ambroise VALERY
15:20 - 15:30 #17858 - c27-6 Randomized phase III trial comparing gamma knife and linac based (EDGE) approaches for brain metastases radiosurgery: results from the Gadget trial.
c27-6 Randomized phase III trial comparing gamma knife and linac based (EDGE) approaches for brain metastases radiosurgery: results from the Gadget trial.

Introduction: Brain metastases (BMs) from solid tumors represent a topic of increasing interest for the higher incidence in the last years. Stereotactic radiosurgery (SRS) is the main effective local therapeutic approach used. We draw a phase III trial comparing Gammaknife (GK) and Linac based (Edge) SRS.

Materials and Methods: Patients with a maximum of 4 BMs up to ≤30 mm were included. Randomization was stratified according to age, presence of extracranial metastases, and number of BMs. For Arm A (GK) single dose of 20-24 Gy at 50% isodose was prescribed. For Arm B single dose of 24 Gy was prescribed to PTV. Radionecrosis was assessed mismatching T1/T2 MRI images, perfusion MRI, and in doubt cases Methionine-CT/PET.

Results: From October 2014 to September 2018, 202 patients for 354 BMs treated were included, 96 in Arm A and 106 in Arm B, for 182 and 172 metastases, respectively.  RN occurred in 28 (7.8%) cases, 12 in Arm A and 16 in Arm B; grade II in 9 cases of GK arm at a median time of 7 months and in 15 cases of Edge arm at a median time of 9 months; grade III RN was recorded in 4 cases, in 3 of GK arm, at a median time of 3 months, and in 1 of Edge arm at 37.5 months. The 12, and 18  months local control (LC) rates were 98.8% and 90.9% for arm  and 96.2% and 96.2% for Arm B (p=0.96).  The median, 12, and 18 months OS rates were 17.8  months, 74.1%, and 48.9%. The volume of BMs was impacting on radionecrosis occurrence (p value=0.005; p value=0.03).

Conclusions: Gamma-knife and LINAC based SRS for BMs were comparable in terms of LC. The occurrence of GIII radionecrosis was greater and earlier in the GK arm respect to Edge arm.


Ciro FRANZESE (Milano, Italy), Pierina NAVARRIA, Elena CLERICI, Ilaria RENNA, Salvatore COZZI, Piero PICOZZI, Pietro MANCOSU, Stefano TOMATIS, Marta SCORSETTI
El Pardo I
15:30

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A28
15:30 - 16:30

Oral Session
VESTIBULAR SCHWANNOMA #1

Moderators: Steven CHANG (Member) (Stanford, USA), Marc LEVIVIER (Chef de Service) (Lausanne, Switzerland), Jânio NOGUEIRA (Brazil)
15:30 - 15:40 #17683 - a28-2 Gamma knife radiosurgery for residual and recurrent vestibular schwannomas after previous surgery: clinical results in a series of 90 patients and review of the literature.
a28-2 Gamma knife radiosurgery for residual and recurrent vestibular schwannomas after previous surgery: clinical results in a series of 90 patients and review of the literature.

OBJECTIVE: Complete removal of vestibular schwannomas (VS) is not always achievable without any risk of disabling postoperative complications, especially in terms of facial nerve function. Moreover, even after gross total removal, a relevant rate of recurrence has been reported. The aim of this study is to validate Gamma Knife radiosurgery (GKRS) as an effective strategy to treat tumor regrowth after previous surgery.

METHODS: Ninety patients treated with GKRS for VS after previous microsurgery were included in the present study. GKRS was performed at a median of 31 months (range, 4-174 months) postoperatively. Mean tumor volume was 3.35 cm3 (median, 2.5 cm3; range, 0.027-13 cm3) and median marginal dose was 13 Gy.

RESULTS: At a mean follow-up of 77.2 months, tumor control was achieved in 90% of patients: 2 patients underwent repeated GKRS, and 7 patients underwent further microsurgery. Tumor shrinkage at last follow-up was recorded in 80.3% of cases. The complication rate was low and many consisted of a transient worsening of preexisting symptoms. The overall incidence of persisting facial nerve deficit and trigeminal nerve impairment was, in both cases, 3.3%. Two of 5 patients (40%) preserved functional hearing at last follow-up. One patient (1.1%) underwent ventriculoperitoneal shunting 12 months after GKRS.

CONCLUSIONS: GKRS is a safe and effective treatment for growing residual and recurrent VSs, with tumor control obtained in 90% of cases and a low morbidity rate. Moreover, the possibility of treating patients with major medical comorbidities constitutes a significant advantage over repeated surgery.


Michele BAILO (Milan, Italy), Nicola BOARI, Filippo GAGLIARDI, Martina PILONI, Alfio SPINA, Marco GEMMA, Antonella DEL VECCHIO, Angelo BOLOGNESI, Pietro MORTINI
15:40 - 15:50 #17698 - a28-3 Gamma Knife Radiosurgery in the management of intracanalicular vestibular schwannomas: experiences of a single high-volume center.
a28-3 Gamma Knife Radiosurgery in the management of intracanalicular vestibular schwannomas: experiences of a single high-volume center.

OBJECTIVE According to literature, gamma knife radiosurgery (GKS) is a promising method for intracanalicular vestibular schwannoma (IVS) management, providing excellent tumor growth control rates (91-100%) and good hearing preservation rates (41-76%), but this evidence originates primarily from small series of patients. The aim of this study was to present the outcomes of GKS in the largest group of patients with IVS that has been studied to date, with particular emphasis on the long-term outcomes of the treatment.

METHODS The study included 112 consecutive patients with unilateral IVS, who underwent GKS in 2011-2014. Mean age of the patients was 50±14.6 years. All patients were operated on with a 192-source cobalt-60 gamma knife unit. All patients had complete follow-up documentation and mean duration of the follow-up was 42±11.8 months (range 6-69 months). Neurological status (facial and trigeminal nerve function) and hearing (vestibulocochlear nerve function) were determined prior to GKS, immediately after the procedure and during the follow-up visits. In order to maximize neurological safety of radiosurgery authors have proposed new concept of directional gradient index (DGI).

RESULTS Tumor growth control was obtained in 104/112 (92.8%) patients. At the end of the follow-up, 24 patients presented with hearing improvement, whereas 76 patients presented with a stable hearing, and 12 showed deterioration of hearing (>20 dB). Four patients developed facial nerve dysfunction including in 3 periodic hemifacial spasm and 1 partial paresis which resolved spontaneously within 12 months of GKS. None of the operated patients showed new, debilitating neurological deficits including trigeminal sensory disturbances.

CONCLUSIONS GKS is a highly effective treatment for IVS, associated with low morbidity and good tumor growth control. Highly conformal planning with steep dose falloff at organs-at-risk is crucial for the best facial and hearing outcome. The results of this study imply that GKS is superior to the “wait-and-see” strategy and may constitute a good alternative for conventional surgical resection of IVS.


Sebastian DZIERZECKI (Warsaw, Poland), Grzegorz TUREK, Katarzyna DYTTUS-CEBULOK, Maciej HARAT, Miroslaw ZABEK
15:50 - 16:00 #17730 - a28-4 Basic pretreatment RADIOMIC features to predict SRS outcome of vestibular schwannomas.
a28-4 Basic pretreatment RADIOMIC features to predict SRS outcome of vestibular schwannomas.

Objectives:

To search for parameters of routine Magnetic Resonance Imaging (MRI) to predict tumor volume reduction and transient versus permanent tumor progression of vestibular schwannomas treated by Gamma Knife stereotactic radiosurgery.

 

Material and methods:

Included were 24 patients with vestibular schwannomas treated in our center and followed over a period of 21.9 to 80.3 months (mean 41.8). MRI was performed on a 3 Tesla scanner and included T1-weigheted images with and without contrast enhancement, T2-weighted and FLAIR images. Volumetric results measured on the Gamma Plan workstation were followed longitudinally over time and correlated to basic RADIOMIC features as mean, minimum, maximum, standard deviation, skewness and kurtosis of corresponding signals taken from regions of interest covering the total tumor volume, and were normalized with parameters measured from volumes of the corpus callosum.

 

Results:

The most significant correlation between imaging parameters and reduction of tumor volume per month was found as minimum of normalized T2 values (CC=-0.640) followed by the standard deviation of T2 values (CC=0.574), both p<0.05 after correction for False Discovery Rate (FDR). 15 tumors showed progression after treatment, which was permanent in only 2 cases, but transient in 13 cases, whereas 9 tumors regressed immediately after SRS. Kurtosis of T2 turned out to predict progression with a sensitivity and specificity of 86% and 78%. A trend of macro-cystic tumors towards higher regression rates was observed, as expected from previous studies.

 

Conclusions:

Prediction of unfavorable transient or permanent volumetric changes of schwannomas after GKRS could help to consider alternative treatment strategies, mainly in large tumors, where further clinical deterioration cannot be excluded. To confirm these results and to work out predictive parameters differentiating between pseudo-progression and permanent enlargement, a prospective study including more cases and a longer follow-up period is necessary.


Herwin SPECKTER (Santo Domingo, Dominican Republic), Jairo SANTANA, Jose BIDO, Giancarlo HERNANDEZ, Diones RIVERA, Luis SUAZO, Santiago VALENZUELA, Peter STOETER
16:00 - 16:10 #17764 - a28-5 Predictability of transient tumor enlargement following gamma knife radiosurgery on vestibular schwannoma.
a28-5 Predictability of transient tumor enlargement following gamma knife radiosurgery on vestibular schwannoma.

Introduction
Gamma Knife radiosurgery (GKRS) is a well-established treatment for small- to medium-sized vestibular schwannomas (VS). However, this treatment is controversial for larger VS. One of its drawbacks is that VS can present a radiation-induced transient tumor enlargement (TTE). For larger VS, such a swelling may cause symptoms related to mass effect, necessitating microsurgery. Currently, it is not possible to predict this adverse effect. We evaluated the predictability of TTE by quantitatively analyzing the tumor appearance on MRI. The goal is to determine the optimal treatment strategy, i.e. radiosurgery or microsurgery, on an individual basis.

Methods
From our database, patients with large VS (>4cc) and minimum follow-up of three years, were identified. The TTE classification was based on evaluation of MRI scans at 6, 12, 24 and 36 months, according to strict volumetric criteria. We evaluated the influence of MRI tumor texture characteristics on TTE. These texture characteristics were quantified by calculating features based on gray-level co-occurrence matrices (GLCM), computed on T1-weighted, T2-weighted, and T1-weighted contrast-enhanced MRIs. Correlation was determined between these characteristics and TTE using machine-learning methods.

Results
Between 2002 and 2015, 795 VS patients received GKRS as primary treatment at our center. The strict criteria for TTE and non-TTE led to the inclusion of 67 patients, of which 26 exhibited TTE. By employing GLCM-based features, we developed a model to predict TTE. We obtained a prediction sensitivity and specificity of 83% and 79%, respectively, using Support Vector Machines. These results improved for larger tumor volumes, i.e. in 7cc or larger, the results obtained were 85% and 87%, respectively.

Conclusion
Results from this research clearly show that MRI differences in VS tumor texture can be exploited to predict TTE in large VS. The developed prediction model can lead to an optimal treatment strategy selection on an individual basis.


Patrick LANGENHUIZEN (Tilburg, The Netherlands), Sander SEBREGTS, Svetlana ZINGER, Sieger LEENSTRA, Patrick HANSSENS, Peter DE WITH, Jeroen VERHEUL
16:10 - 16:20 #17856 - a28-6 Gamma Knife radiosurgery following partial resection of large vestibular schwannomas: evaluation of long-term tumor control.
a28-6 Gamma Knife radiosurgery following partial resection of large vestibular schwannomas: evaluation of long-term tumor control.

Introduction

Recently, we have reported the influence of pretreatment growth rates on Gamma Knife radiosurgery (GKRS) of vestibular schwannomas (VS): fast growing tumors are less likely to obtain tumor control.1 This indicates that biological aspects intrinsic to VS are influencing the GKRS treatment outcome. Also, various papers have reported that GKRS treatment for large VS is significantly less effective compared to small-to-medium-sized VS. These findings suggest that large VS may have biological properties similar to those of fast-growing VS. To evaluate this, we assessed the long-term GKRS tumor control of remnants of large VS after partial resection. Furthermore, we compared this to the outcome of large tumors (>10cc) that were not resected, but received primary GKRS.

Methods

Patients with a minimum follow-up of 4 years were included. Loss of tumor control was defined as radiological progression. All patients were uniformly treated according to protocol. We employed Kaplan-Meier survival analyses to determine differences in tumor control probability rates following GKRS between small-to-medium-sized VS and large VS, either after partial resection or after primary GKRS treatment.

Results

In our center, 736 patients received primary GKRS treatment, while 77 patients were first subjected to partial resection. Kaplan-Meier analyses showed significantly lower tumor control rates for large tumors, both after partial resection and after primary treatment, compared to the small-to-medium-sized VS (log-rank, p<0.001). The obtained 10-year tumor control rates were 78.5%, 73.6%, and 89.7%, respectively. These control rates observed in large VS are even worse than the rates observed in fast growing small-to-medium-sized tumors (85.1%).1

Conclusions

Results from this research clearly show that tumor control rates of large VS, either after partial resection or primary treatment, show lower tumor control rates following GKRS. The survival curves of these tumors resemble the curve of extremely fast growing VS, suggesting that the intrinsic tumor biology is indeed an important factor influencing tumor control rates of VS after GKRS.

References

1. Langenhuizen PPJH, Zinger S, Hanssens PEJ, Kunst HPM, Mulder JJS, Leenstra S, et al. (2018). Influence of pretreatment growth rate on Gamma Knife treatment response for vestibular schwannoma: a volumetric analysis. J Neurosurg, ,1-8.


Patrick LANGENHUIZEN (Tilburg, The Netherlands), Victor FU, Svetlana ZINGER, Sieger LEENSTRA, Patrick HANSSENS, Peter DE WITH, Jeroen VERHEUL
Segovia Plenary

"Monday 10 June"

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B28
15:30 - 16:30

Oral Session
SPINE

Moderators: Sebastiao CORREA (RADIO-Oncologist) (São Paulo, Brazil), Kita SALLABANDA (Medical Direcor) (Madrid, Spain)
15:30 - 15:40 #17631 - b28-1 Phase I study of spinal cord constraint relaxation with single session spine stereotactic radiosurgery (SSRS) in the primary management in patients with inoperable, previously irradiated metastastic epidural spinal cord compression (MESCC).
b28-1 Phase I study of spinal cord constraint relaxation with single session spine stereotactic radiosurgery (SSRS) in the primary management in patients with inoperable, previously irradiated metastastic epidural spinal cord compression (MESCC).

Objectives:  We seek to establish the feasibility of using salvage SSRS allowing for spinal cord dose constraint relaxation as the primary management of MESCC in inoperable patients monitoring for radiation related toxicity and radiographic local control (LC).

Methods: Patients with MESCC in the thoracic spine deemed inoperable with a history of radiation at the site of interest at least 3 months prior were enrolled on this prospective Phase 1 single institution protocol.  Single fraction SSRS was delivered to a prescription dose of 18 Gy.  Spinal cord constraint relaxation was performed from an initial allowable Dmax cohort of 8 Gy only if tumor progression (TP) occurred.  If the risk of radiation induced spinal cord myelopathy (RM) remained lower than the risk of TP, then the cord Dmax was elevated in 2 Gy increments to a maximum of 14 Gy in the final planned cohort. Patients were monitored every 3 months with follow-up visits and MRI scans.  The planned accrual was 32 patients.

Results:  The trial was closed early due to slow accrual.  From 2011 to 2014, 9 patients received SSRS on the trial of which 5 were in the 8 Gy cord Dmax cohort and 4 in the 10 Gy cord Dmax cohort.  The most common histology was adenocarcinoma of the lung (n=3).  The median age was 58 years (range 39-68 years).  At baseline, 4 patients had MESCC Grade 2 disease, 2 patients had MESCC Grade 1C disease and 2 patients had MESCC Grade 1B disease. 

The median overall survival was 8.4 months (95% CI 6.1, 10.7 months).  The 1-year KM estimated OS was 33%.  Of the 9 patients treated with SSRS, 1 died prior to post-SSRS evaluation.  Of the remaining 8 patients, 5 experienced a local failure.  Three of the five were treated with surgery while two received systemic therapy.  Two of the five failures ultimately resulted on loss of neurologic function.  The KM estimated median LC was 8.1 months (95%CI 5.5, 10.7 months).  With a median clinical follow-up of 7.2 months (range 1.1-28.5 months), there were no cases of RM.

Conclusions: SSRS is a safe tool for previously irradiated patients with inoperable MESCC.  Despite the limited life expectancy in this high-risk cohort of patients, strategies to optimize local control are necessary to prevent neurologic deterioration. Larger prospective trials exploring optimal dose/fractionation and cord constraints are required.


Amol GHIA (Houston, USA), Nandita GUHA-THAKURTA, Kenneth HESS, Stephen SETTLE, Erik SULMAN, Hadley SHARP, Mary Francis MCALEER, Jing LI, Xin WANG, Eric CHANG, Claudio TATSUI, Paul BROWN, Lawrence RHINES
15:40 - 15:50 #17685 - b28-2 PREST: Pain REduction with bone metastases STereotactic radiotherapy: A phase III randomized multicentric trial.
b28-2 PREST: Pain REduction with bone metastases STereotactic radiotherapy: A phase III randomized multicentric trial.

Objectives Palliative antalgic treatments represent an issue for clinical management and a challenge for scientific research. Radiotherapy (RT) plays a central role. Techniques such as stereotactic body radiotherapy (SBRT) were largely investigated in several phase 2 studies with good symptom response at 3 months, becoming widely adopted.The efficacy of standard RT for pain management is consolidated. Still is lacking evidence from randomized, direct comparison of RT and SBRT. Methods The PREST trial primarily investigates efficacy of SBRT in pain control versus standard RT. IMRT-Simultaneous Integrated Boost (SIB) approach was adopted. Personalization of treatment is included in pt selection: performed by both prognosis prediction through a clinically validated prognostic score (Mizumoto prognostic score) and adequate spinal stability is defined according to Spine Instability Neoplastic Score (SINS). Mandatory MRI of the spinal tract is required for planning and imaging response, at baseline and 3 month after treatment. Results The PREST trial (NCT03597984) was designed as an interventional study without medicinal, randomized 1:1, open-label, multicentric, phase 3. It enrols pt with painful (Numeric Rating Scale -NRS- <4) spinal bone metastases. Pt at expected prognosis superior to 6 months according to the Mizumoto prognostic score, and SINS sores ConclusionThe PREST trial will provide insight on efficacy of an hypofractionated SBRT IMRT-SIB in pain control respect to a standard fractionation. Preliminary results will be available on May 2019.


Valeria MASIELLO, Stefania MANFRIDA, Ernesto MARANZANO, Paolo MUTO, Silvia CHIESA, Stefano PERGOLIZZI, Francesco DEODATO, Savino CILLA, Vincenzo VALENTINI, Francesco CELLINI (Rome, Italy)
15:50 - 16:00 #17694 - b28-3 RADIOSURGERY IN SPINE TUMORS, COMBINE TREATMENT.
b28-3 RADIOSURGERY IN SPINE TUMORS, COMBINE TREATMENT.

As far as in surgery, in the last decade ,the evolution of technology in Radiotheraphy give us the posibility to treat successfully spine tomors, beningn and malignant one.

We have transfere all our knowledge and experience about brain radiosurgery in spine and medulla tumor pathiology. It is clear that the spine and medulla are diferente, we have diferent anatomic structure, different constrains, different way of localization of the target and we have to use a special technology to treat those lessions.

The introduction of Cybeknife,Tomotheraphy, GammKnife Icon, high level Linac make posible with some kind of difference to treat quite well.

From 2011 we began to treat spine tumors in the Cyberknife Unit of Genescare Madrid, we have a long term follow up, 5-6 years with very good tumor control, 98% in bening tumors. 30 patient median follow-up 5 years, 16 neurinomas, 10 meningiomas, 4 Chordomas.

In the majority of the cases we make combine treatment, surgery and Radiosurgery, to separete the tumor from the medulla and to give us the posibility of correct treatmen The doses use was 3x7 Gy and 14 Gy for meningioma, 3x6  and 12-13 Gy for neurinoma. we found no toxicty grade II RTOG.


Kita SALLABANADA DIAZ (Madrid, Spain), Rafel GARCIA, Iciar SANTAOLALIA
16:00 - 16:10 #17729 - b28-4 Management of chordomas: an evolving paradigm shift from a Brazilian tertiary center.
b28-4 Management of chordomas: an evolving paradigm shift from a Brazilian tertiary center.

Background: Chordoma is a rare neoplasm arising from cellular remnants of the notochord. In Brazil, most surgeons consider aggressive surgery as the only curative treatment option. Patients are referred to Radiation Therapy (RT) with palliative intent.

Objective: To report local control (LC) and survival of chordoma patients treated with Radiation Therapy at ICESP, a tertiary referral cancer center in Brazil.

Methods: We retrospectively analyzed patients with histologically confirmed diagnosis of chordoma treated in a Multidisciplinary Chordoma Management Program with high dose image guided, intensity modulated radiation therapy (IG-IMRT) or stereotactic radiosurgery (SRS).

Results: From July 2014 to June 2018, 13 patients were treated (IG-IMRT n=9; SRS n=4).  Median age was 58 years (range 37-73 y). Median Gross Tumor Volume for IG-IMRT was 75.5 cc (range 2.5-1471.2 cc) and for SRS was 88.5 cc (range 33.1-316.2 cc). Median dose was 78Gy/39fx for IG-IMRT and 24Gy/1fx for SRS. Location was as follows: sacrum n=9; cervical spine n=3; clivus + cavernous sinus n=1; lumbar spine n=1. 2y-LC was 80% (1 local failure), 2-y regional failure-free survival was 58%, and 2-y distant metastasis-free survival was 91%. 2-y cause specific survival was 92%.   

Conclusion: Chordoma patients managed by a multidiciplinary expert team with high dose RT can achieve excellent local control and survival.

 


Andre CHEN (Sao Paulo, Brazil), Douglas NARAZAKI, Virginio RUBIN, Bruno ALBARICCI, Hugo STERMAN, Sergio GONCALVES, Alexandre CRISTANTE, William TEIXEIRA
16:10 - 16:20 #17855 - b28-5 Estimation of achievable control probabilities of microscopic disease of the epidural space in spinal stereotactic body radiation therapy.
b28-5 Estimation of achievable control probabilities of microscopic disease of the epidural space in spinal stereotactic body radiation therapy.

Local recurrence for spinal stereotactic body radiation therapy (SBRT) often occurs in the epidural space immediately adjacent to the planning target volume (PTV). It is unknown if a clinically significant reduction in local recurrence could be achieved safely by imposing dose coverage on the epidural space near the PTV. The purpose of this study is to theoretically investigate the achievable dose coverage and control probability for the epidural space, using the linear-quadratic model of cell survival undergoing radiation. Previous spinal SBRT cases were retrospectively replanned for analysis in this study. For each case, a contour was drawn of the subset of the epidural space next to the PTV for targeting. These cases were re-planned using three coplanar volumetric modulated arc therapy beams centered on the PTV with collimator angles of 0, 45, and 315 degrees.  Prescriptions for the new plans were 1800 cGy to the PTV in one fraction, with the D95% and D5% PTV constraints being 1750 cGy and 1950 cGy, respectively. The D10% and Dmax spinal cord constraints were 1000 cGy and 1400 cGy, respectively. Priority was given to the spinal cord constraints when the objectives could not all be met. The resulting plans yielded dose-volume histograms, which were used for estimating control probabilities. An approximate alpha/beta value of 3 was taken from previous studies, and clonogen density in the epidural space was conservatively estimated to be at most 10,000 cells/cc. The average achievable epidural space D95% is about 13 Gy +/- 1 Gy, while the achievable control probabilities are all greater than 99%. These results suggest that a clinically significant dose can be delivered to the epidural space while preserving spinal cord constraints. A clinical trial is needed to confirm the clinical significance of this coverage.


P. James JENSEN, John KIRKPATRICK, Scott FLOYD, Jordan TOROK (Durham, NC, USA), C. Rory GOODWIN, Elizabeth HOWELL, Will GILES, Fang-Fang YIN, Q. Jackie WU
Segovia Break Out

"Monday 10 June"

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C28
15:30 - 16:30

Oral Session
METASTASES #2b

Moderators: Lilyana ANGELOV (Staff Neurosurgeon) (Cleveland, USA), Sergio DANTAS (Neurosurgeon) (Natal, Brazil), Yoshiaysu IWAI (Neurosurgery, Radiosurgery) (Osaka, Japan)
15:30 - 15:40 #16803 - c28-1 The Effect of Gamma Knife Radiosurgery on Large Posterior Fossa Metastases (LPFM) and the associated peritumoral edema and 4th ventricle volume.
c28-1 The Effect of Gamma Knife Radiosurgery on Large Posterior Fossa Metastases (LPFM) and the associated peritumoral edema and 4th ventricle volume.

 

ABSTRACT

Introduction

Gamma Knife Radiosurgery (GKRS) as monotherapy is often avoided for the treatment of large (≥ 2cm) posterior fossa brain metastasis (LPFM) based on a theoretical risk of increased peritumoral edema (PTE) and associated compression of the 4th ventricle (4V) related to the treatment.

Methods

A single center, IRB approved, retrospective review of LPFM treated with GKRS from 2009-2017 was performed. Brainlab® iPlan software was used to evaluate the tumor, 4V and PTE volumes at initial treatment and all subsequent follow-ups. Statistical analysis was performed using Wilcoxon Signed Rank test and McNemar test.

Results

We identified 49 lesions in 47 consecutive patients; 55% males, median age 61.5 years, median KPS was 90 at the time of GKRS. Median number of LPFM and overall brain metastases was 1 and 2.5 respectively. The median overall tumor, PTE, and 4V volumes at diagnosis were 5.37 cm3, 17.11 cm3, 1.23 cm3 respectively with a median study follow-up of 7.28 months (range 1.87-56.23). At first follow-up, 2 months post treatment, median tumor volume decreased by 54.04 % [range -96.95, 48.69] (p <0.001), median PTE decreased by 55.66 % [range -99.92, 143.36] (p <0.001) and 4V increased (23.89 [range -50.16, 545.76] p 0.31). No patient required surgical intervention, external ventricular drainage or shunting between treatment and first follow-up. Post treatment, 65.95 % receive our routine steroid taper, 4.25% received no steroids and 29.78% required prolonged steroid treatment.  

Conclusions

Patients with LPFM treated with GKRS had in a significant reduction in tumor size and PTE (p <0.001) and marked opening of the 4V post treatment. This study suggests that GKRS was well tolerated and can be considered in the management of LPFM especially in patients for whom surgery in contraindicated.  

 


Baha'eddin MUHSEN, Lilyana Angelov Md ANGELOV (Cleveland, USA), Michael VOGELBAUM, John SUH, Alireza MOHAMMADI, Samuel CHAO, Gene H BARNETT, Hamid BORGHEI-RAZAVI, Krishna JOSHI, Bicky THAPA, Bryan LEE
15:40 - 15:50 #17679 - c28-2 Reducing ctv-ptv margin from 2mm to 0mm in stereotactic radiotherapy of single brain metastasis.
c28-2 Reducing ctv-ptv margin from 2mm to 0mm in stereotactic radiotherapy of single brain metastasis.

Purpose: To compare the incidence of pseudoprogression (PP), local tumor control (LC) and overall survival (OS) in patients treated with stereotactic radiotherapy (SRT) for a solitary brain metastasis using a 2mm Planning Target Volume (PTV) margin versus a 0mm margin. The development of pseudoprogression and the volume of the brain receiving 12Gy (V12) was assessed for single fraction treatment while V18 was assessed for treatment with 3 fractions.

Patients and methods: Patients were treated on the Novalis LINAC and had a minimal follow-up of 24 months. Dose was prescribed according to the PTV-volume: 1x21Gy, 1x18Gy or 3x8.5Gy. A 2mm CTV-PTV margin was used in 93 patients while a 0mm margin was used from 2015 onwards in 37 patients. Follow-up included a 3-monthly MRI-scan including a perfusion MRI-scan when PP was suspected. The V10-V18Gy of the brain was calculated.

Results: The mean CTV-volume was similar (p=0.3) while the mean PTV-volume was significantly larger in the 2mm group (15.2cc versus 7.6cc P<0.01). There was no significant difference in the incidence of PP between the 2mm and 0mm group at 1 year (31% versus 33%) and at 2 years (43% and 33% P=0.6). Symptomatic PP was significantly more frequent in the 0mm arm (4.1% vs 1.6%, P=0.02). The 2-year LC rate was similar in the 2mm and the 0mm group (78% and 82%, P=0.4) while the 2-year OS was significant better in the 0mm group (29% versus 13%, P=0.01). The V10-V18 of the brain was not predictive for PP.

Conclusion: PTV margin reduction from 2mm to 0mm did not reduce the incidence of PP in linac-SRT for single brain metastases. LC and OS rates were similar, indicating margin reduction is safe. V10-V18Gy were not associated for the incidence of pseudoprogression.


Justine BADLOE (The Hague, The Netherlands), Mirjam MAST, Anna PETOUKHOVA, Jan-Huib FRANSSEN, Elyas GHARIQ, Ruud WIGGENRAAD
15:50 - 16:00 #17704 - c28-3 Impact of the number of metastatic brain lesions on survival after gamma knife radiosurgery.
c28-3 Impact of the number of metastatic brain lesions on survival after gamma knife radiosurgery.

Objective: The number of brain metastases (BMs) plays an important role in the decision making between stereotactic radiosurgery (SRS) and whole-brain radiation therapy
Methods: We analyzed the survival of 457 SRS-treated patients with BM as a function of BM number. 113 (24.7%) patients were treated with repeat SRS for local recurrence and distant brain relapse. Survival analyses were performed with Kaplan-Meier analysis as well as univariate and multivariate Cox proportional hazards models.
Results: The median survival for all patients was 9.8 months (95% CI 8.5-11.3). Patients with BMs were categorized as those with 1, 2-4, 5-9 and ≥10 BMs. Median overall survival for patients with 1 BM was superior to those with 2-4, 5-10 and >10 BMs (14.3 months vs. 10.5 months vs. 6.6 months vs. 7.2 months, р= 0,0001). Survival of patients with 5-9 BMs did not differ from those with >10 BMs (6.6 months vs. 7.2 months, p=0.8288).
Аccording to multivariate analysis, age younger than 50 years (p = 0.005, HR 0.59, 95% CI 0.41 - 0.86), number of lesions ≥5 (p = 0.02, HR 1,44, 95% CI 1,05 - 1.95), Karnofsky performance status ≥80 (p < 0.0001, HR 0.52, 95% CI 0.38 - 0.69) аnd absence of extracranial metastases (p < 0.01, HR 0.56, 95% CI 0.35 - 0.90) had significant impacts on overall survival.
Conclusions: The contribution of BM number to overall survival is modest and should be considered as one of the many variables considered in the decision between SRS and whole-brain radiation therapy. Our finding confirm correlation between the survival outcome and the number of lesions treated SRS. According to our data, the median survival of patients with 2-4 metastases in the brain is significantly higher compared with a group of patients who have 5-10 or more lesions.


Sergey BANOV, Andrey GOLANOV (Moscow, Russia), Elena VETLOVA, Alexandra DALECHINA, Valery KOSTJUCHENKO, Ivan OSINOV
16:00 - 16:10 #17720 - c28-4 Stereotactic radiosurgery versus whole brain with simultaneous integrated boost using VMAT for multiple brain metastases.
c28-4 Stereotactic radiosurgery versus whole brain with simultaneous integrated boost using VMAT for multiple brain metastases.

Introduction: Local control of brain metastases reduces risk of death from intracranial progression and improves survival, which can be extended by 6 months with whole brain radiation therapy (WBRT), but this treatment has a greater risk of a significant neurological decline compared with patients who receive more focal treatments, like stereotactic radiosurgery(SRS). The widespread of the volumetric modulated arc technique therapy (VMAT) which can deliver a fraction of WBRT and a simultaneous integrated boost (WBIB) to multiple brain metastases in a few minutes suspected possible advantages of local and regional control for this treatment and the studies are controversial about the real impact in neurocognition

Methods: Patients with confirmed one to six brain metastases submitted to either WBIB or SRS alone using VMAT were selected. WBIB group patients received WBRT in daily 4 Gy to a total of 20 Gy over one week and the boost reached the total dose of 40Gy with daily 8 Gy in each evident metastasis. For the SRS alone group, doses varied according to the metastasis sizes, based on the RTOG. We retrospectively accessed patient clinical and radiological data until death registration.

Results: 31 patients were selected, 20 in SRS group and 11 in the WBIB group, mean age of 63 years old. Majority of patients have secondary lung central nervous system metastasis. The mean overall survival after the radiotherapy treatment was 11,4 months in the SRS group and 8,2 months in the WBIB group (p =0,001). There was no difference in local control after 3 and 6 months between the groups, but the was a significantly greater incidence of new leasons in the group that received only SRS compared with WBIB( 38,1 versus 27,3 %  p<0,001). Subgroup analysis of the SRS group showed that 47,6% needed to receive WB treatment after a mean time of 6,8 months. Grade I and II toxicity incidence was greater in the WBIB and there was also a greater decreasement in the KPS status of theses patients after the 6 months reassessment

Conclusions: WBIB seems to achieve a similar local control to focal SNS leasons and better regional control to subclinical leasons compared with patients who receive only SRS, despite a greater toxicity. Afterwards, WB would be needed in almost 50% of the patients who received SRS and therefore the WBIB  treatment could propitiate a best cost effectiveness choice 


Jose REGIS NETO (São Paulo, Brazil), Wellington Pimenta NEVES JUNIOR, Anselmo MANCINI, Sebastião Francisco Miranda CORREA
16:10 - 16:20 #17800 - c28-5 Stereotactic radiosurgery for resected brain metastases – does the surgical corridor need to be treated?
c28-5 Stereotactic radiosurgery for resected brain metastases – does the surgical corridor need to be treated?

Background

Post-operative stereotactic radiosurgery (SRS) is the standard of care for resected brain metastases, but SRS techniques are not standardized. Although expert consensus guidelines recommend that the surgical corridor leading to resection cavity be included in SRS plan, this statement is not evidence-based. We analyzed failures and toxicity with post-resection SRS, with the hypothesis that the corridor needs not be targeted with SRS. 

Methods

In this IRB-approved retrospective review, from 428 lesions treated from 2005-2018 with post-resection SRS, 58 evaluable lesions had a ‘deep’ tumor with a surgical corridor, defined as ≥1.0cm from surface pre-operatively. SRS targeted the surgical corridor, defined as the surgical tract uninvolved by tumor on pre-operative imaging, in 33 (57%). Failure was defined as local (LF) if within the surgical cavity involved with tumor pre-resection, corridor (CF) if within the surgical tract leading to the cavity, distant (DF) if a new parenchymal tumor, or leptomeningeal (LMD) if new nodular/classical leptomeningeal enhancement. The cumulative incidences of failure and adverse radiation effect (ARE) were analyzed with death and whole brain radiotherapy as competing risks, with 95% confidence intervals.

Results

The median follow-up was 14 months. Not targeting the surgical corridor was associated with prior SRS or resection for other brain metastases (23% vs. 0%, p=0.01), deeper tumors (median 2.1 cm vs. 1.4 cm, p<0.01), and systemic treatment within 3 months (p =0.01), but not other factors (p>0.10). The 12-month failure rates, if the surgical corridor was not treated vs. was treated, respectively, were: CF 8% (1-24%) vs. 0% (p=0.12), LF 4% (0-17%) vs. 13% (4-27%) (p=0.32), LMD 40% (19-61%) vs. 10% (2-23%) (p=0.03), DF 65% (43-81%) vs. 35% (19-52%) (p=0.02), and ARE 8% (1-22%) vs. 13% (4-28%) (p=0.35). After adjusting for use of systemic therapy, all differences were not statistically significant (p>0.05).

 Conclusion

Omitting the surgical corridor in post-operative SRS for resected brain metastases was not independently associated with statistically significant differences in recurrences or adverse radiation effect.


Scott SOLTYS (Stanford, CA, USA), Siyu SHI, Joseph ABI JAOUDE, Navjot SANDHU, Kirsten SCHOFIELD, Elyn WANG, Michael JIN, Carrie ZHANG, Steven CHANG, Erqi POLLOM
16:20 - 16:30 #17900 - c28-6 Adverse radiation effect after stereotactic radiosurgery for brain metastases: an international multi-center retrospective analysis.
c28-6 Adverse radiation effect after stereotactic radiosurgery for brain metastases: an international multi-center retrospective analysis.

Stereotactic radiosurgery (SRS) is a cornerstone treatment for brain metastases (BM). Despite its notably efficacy in tumor control, adverse radiation effect (ARE) remains a dreaded complication. Here, we perform a quantitative analysis to examine the relative contribution of various clinical and dosimetric factors to ARE.

We identified 214 patients with 1,106 BM who were treated with SRS at University of California San Diego (2007-17) and 148 patients with 1,760 BM who were SRS treated at Karolinska Institutet who had  >3 months of MRI follow-up. ARE was defined by post-SRS FLAIR involving >25% of the cross-sectional area of the centrum semiovale, third ventricle, temporal horns, or the fourth ventricle. Standard statistical measures were used to identify risk factors for ARE.

In the UCSD cohort, 62 patients (29%) suffered post-SRS ARE. In univariate models, the risk of ARE increased with 1) the number of treated tumors (OR 1.061 per additional tumor, p<0.001), 2) cumulative intracranial tumor volume (CITV) (OR 1.016 per cm3, p= 0.03), 3) the number of SRS sessions (OR 1.425 per additional session, p<0.001), and 4) previous WBRT (OR 4.601, p<0.001). In a multivariate model, ARE risk was associated with the number of SRS sessions (p=0.002) and prior WBRT (p=0.02). These findings were recapitulated in the cohort of 148 Karolinska patients. In a combined multivariable model accounting for the length of follow-up, the associations with number of SRS and WBRT remained robust: number of SRS (p=0.002), history of WBRT (p< 0.001). Variance analysis indicated that a history of WBRT contributes more to the risk of ARE than the number of SRS sessions.

In this analysis of our decade-long experience, we demonstrate that the number of SRS sessions and prior WBRT independently contribute to the odds of developing ARE, and that prior WBRT is the biggest contributor to ARE.


Ali ALATTAR, Jiri BARTEK, JR., Brian HIRSHMAN, Clark CHEN (Minneapolis, USA)
El Pardo I
16:30 COFFEE BREAK - POSTERS & EXHIBITION
17:00

"Monday 10 June"

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A291
17:00 - 18:00

YOUNG INVESTIGATOR SEMINAR

Moderators: Christopher GRAFFEO (Neurologic surgery) (Oklahoma City, USA), Paulo OPPITZ (Neurosurgeon) (Porto Alegre, Brazil), Scott SOLTYS (ISRS 2023) (Stanford, CA, USA)
17:00 - 17:15 Designing Studies. Debra Nana YEBOA (Radiation Oncologist) (Speaker, Houston, USA)
17:15 - 17:30 Perfecting Article Writing and Publication. Isaac YANG (Associate Professor) (Speaker, Los Angeles, USA)
17:30 - 17:45 Interpreting Statistics: Common Pitfalls to Avoid. David PRYOR (Radiation Oncologist) (Speaker, Brisbane, Australia)
17:45 - 18:00 Remember the Patient. Lilyana ANGELOV (Staff Neurosurgeon) (Speaker, Cleveland, USA)
Segovia Plenary

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B291
17:00 - 18:00

BREAST SYMPOSIUM

Moderators: Laura FARISELLI (director) (milan, Italy), Karina MOUTINHO (neurosurgery) (Santa Paula, Brazil), Mariza TUNMER (Radiation Oncologist) (Johannesburg, South Africa)
17:00 - 17:20 Influence of Molecular Subgroups and Systemic Therapy on Outcomes of Metastatic Breast Cancer Patients Receiving Stereotactic Radiosurgery for Brain Metastases. Steve BRAUNSTEIN (Faculty) (Speaker, San Francisco, USA)
17:20 - 17:40 Focal Radiation Techniques (incl. IORT). Lorenzo LIVI (Full Professor, Head of Radiation Oncology Unit) (Speaker, Florence, Italy)
17:40 - 18:00 SBRT Clinical Trials and Research Overview. Allisson Barcelos BORGES (Radiation Oncologist) (Speaker, Brasilia-DF, Brazil)
Segovia Break Out

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C291
17:00 - 18:30

VARIAN SPONSORED SESSION
Cutting EDGE Radiosurgery from Varian

17:00 - 17:15 Implementing HyperArc™ SRS in Scotland: Clinical Experience with over 70 Patients. Suzanne CURRIE (Physicst) (PLATINUM PARTNERS, Glasgow, United Kingdom)
17:15 - 17:30 HyperArc™ for Cranial SRS: First Year Indications & Outcomes on the EDGE® at UAB. Evan THOMAS (BALLER) (PLATINUM PARTNERS, BIRMINGHAM, USA)
17:30 - 17:45 RapidArc™ Radiosurgery and SGRS – The Brazilian Experience. Samir HANNA (PLATINUM PARTNERS, São Paulo, Brazil)
17:45 - 18:00 VMAT on the EDGE® for H&N and other Extracranial Targets: The Henry Ford Experience. Farzan SIDDIQUI (PLATINUM PARTNERS, Detroit, USA)
18:00 - 18:15 Frameless Functional Linac-Based Radiosurgery: Focus on Essential Tremor. Evan THOMAS (BALLER) (PLATINUM PARTNERS, BIRMINGHAM, USA)
18:15 - 18:30 Immunotherapy plus SRS/SBRT: Increasing the Probability of the Abscopal Effect. James WELSH (PLATINUM PARTNERS, Chicago, USA)
El Pardo I
Tuesday 11 June
07:30

"Tuesday 11 June"

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B31
07:30 - 09:00

BREAKFAST SEMINAR
QUALITY OF LIFE: WHAT THE DATA SHOWS

Moderators: Allisson Barcelos BORGES (Radiation Oncologist) (Brasilia-DF, Brazil), Joao Gabriel GOMES (Neurosurgeon) (Recife, Brazil), Jonathan KNISELY (Faculty) (New York, USA)
07:30 - 07:50 Gliomas: What is Best for the Patient. Bente Sandvei SKEIE (MD, PhD) (Speaker, Bergen, Norway)
07:50 - 08:10 Metastases & Neurocognition: An Update. Jeff WEFEL (Associate Professor, Chief, Section of Neuropsychology) (Speaker, Houston, USA)
08:10 - 08:30 Skullbase Lesions: Is SRS/SRT Better Than Surgery? Oystein TVEITEN (Neurosurgeon) (Speaker, Bergen, Norway)
08:30 - 08:50 Risk of Radiation-Associated Intracranial Malignancy after SRS for Benign Tumors. Matthias RADATZ (Director) (Speaker, Sheffield, United Kingdom)
Segovia Break Out

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C31
07:30 - 09:00

BREAKFAST SEMINAR
PROSTATE SBRT

Moderators: Sebastiao CORREA (RADIO-Oncologist) (São Paulo, Brazil), Ciro FRANZESE (MD) (Milano, Italy), Luis LARREA (Director) (Valencia, Spain)
07:50 - 08:10 Clinical Results. David PRYOR (Radiation Oncologist) (Speaker, Brisbane, Australia)
08:10 - 08:30 Quality of Life in prostate SBRT. Maris MEZECKIS (radiation oncologist) (Speaker, Sigulda, Latvia)
08:30 - 08:50 Quality Assurance. Fernando PAROIS JAPIASSU (Speaker, Brazil)
El Pardo I

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A31
07:30 - 09:00

BREAKFAST SEMINAR
PEDIATRIC BRAIN RADIOSURGERY

Moderators: Leonardo FRIGHETTO (Neurosurgeon) (Passo Fundo, Brazil), Paul SPERDUTO (Radiation Oncology) (Durham, USA), Amanda DE OLIVEIRA LÓPES (Pediatric Neurosurgery) (Recife, Brazil)
07:30 - 07:45 Craniopharyngioma Combined Approach - Surgery and Radiosurgery. Leonardo FRIGHETTO (Neurosurgeon) (Speaker, Passo Fundo, Brazil)
07:45 - 08:00 Efficacy, Outcomes, and new directions. Shannon FOGH (Radiation Oncologist) (Speaker, San Francisco, USA)
08:00 - 08:15 Long Term Outcomes: Brain Tumors. Erin MURPHY (Radiation Oncologoy) (Speaker, Cleveland, USA)
08:15 - 08:30 #17732 - a31-4 Radiosurgery for Paediatric AVM - A Single Centre Experience in 50 consecutive Patients.
a31-4 Radiosurgery for Paediatric AVM - A Single Centre Experience in 50 consecutive Patients.

BACKGROUND: Gamma Knife (GK) radio surgery for paediatric arteriovenous malformations (AVM) of the brain presents a non-invasive treatment option. Age has a potential influence on the characteristic presentation of these AVMs and their ultimate outcome. We report our institutional experience with GK for paediatric AVMs.

METHODS: We performed a retrospective review of 50 consecutive paediatric patients diagnosed with cerebral AVMs and treated with GK at our institution from January 2014 to and December 2016. Patient demographics, AVM characteristics, treatment parameters and AVM responses were recorded.

RESULTS: The commonest presentation was with headache in 70% of these patients , followed by bleed (24%) and 20% of these patients had seizures.AVMs were mostly located in the right-side seen in 18 patients. Mean nidus volume was around 3.6 cc with almost 44% of these patients had small AVMs corresponding to SM grading 1, 2 while remaining were SM grade 4,5.  Most of these patients were treated with primary GK (82%), while 9 patients received  secondary GK (6  post embolisation and 3 post surgery) for AVM. A minimum follow up period of two years showed almost 70% of patients had complete .elimination of the lesion. Rest of these patients had lesions reduced in volume. During the initial 6 months,  5 patients had weakness and focal neurological deficits but with close follow up and monitoring there was improvement.

 CONCLUSIONS: GK radio surgery for paediatric AVMs offers a safe and effective treatment option, with good obliteration rate.


Shweta KEDIA (New Delhi, India), Atmanranjan DASH, Deepak AGARWAL, Manmohan SINGH, Rajinder THAYLLING, Shashank KALE
08:30 - 08:45 #17544 - a31-5 Extracranial dose measurements in paediatric patients receiving radiosurgery and the risk of radiation-induced malignancy.
a31-5 Extracranial dose measurements in paediatric patients receiving radiosurgery and the risk of radiation-induced malignancy.

Background: Any medical procedure utilising ionising radiation carries a risk of developing a radiation-induced malignancy. The risk of developing extra-cranial malignancies is believed to be low in Gamma Knife Radiosurgery (GKRS) but few studies have been conducted which attempt to quantify this risk. Paediatric patients treated for Arteriovenous Malformations (AVMs) are of particular concern due to the non-malignant nature of their disease, increased risk of malignancy and their longer life expectancy.

Methods: Thermoluminescent dosimeter (TLD) measurements were conducted in 17 patients treated with GKRS for AVMs (9 Females and 8 Males, mean age at treatment = 12). Three sets of TLDs were positioned anteriorly on the skin of each patient at the levels of the thyroid, breast and pelvis. Each set was comprised of 10 TLDs, 5 Lithium Fluoride detectors and 5 Germanium-doped glass fibres. These were calibrated, annealed, handled and read-out in line with good practice procedures yielding a dose uncertainty of approximately 5%.  The average dose measured by each TLD set was used to approximate the doses delivered to individual organs in each patient’s body. Individual patient doses were then used in a radiation risk assessment tool (RadRAT) to calculate each patient’s Lifetime Excess Risk (LER) of developing malignancies due to the radiation exposure.

Results: The mean doses measured were 17.7 mGy, 7 mGy and 0.17 mGy for the neck, chest and pelvic areas respectively. The mean LER was calculated to be 0.18% on average and ranged from 0.04% to 0.41% between patients.

Conclusion: Considering the baseline cancer risk in this group of patients (»35%), the additional LER of body malignancy contributed by the GKRS exposure is acceptable when balanced against the possible risks from not treating the AVM.


Alexis DIMITRIADIS (London, Austria), Amjad ALYAHYAWI, Alison CAMERON, Neil KITCHEN, Gregory JAMES, Ian PADDICK
08:45 - 09:00 The risk of oncogenesis. Andrey GOLANOV (Chief of the Department) (Speaker, Moscow, Russia)
Segovia Plenary
09:00

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A32
09:00 - 10:15

PARALLEL SESSION
SPECIAL SYMPOSIUM: IMMUNOTHERAPY & SRS/SBRT

Moderators: Jing LI (Radiation Oncologist) (Houston, USA), Michael LIM (Professor of Neurosurgery) (Baltimore, USA), John SUH (Radiation Oncologist) (Cleveland, USA), Leonardo VIEIRA (Doctor) (Recife, Brazil)
09:00 - 09:15 Immunology for the Oncologist. James WELSH (Speaker, Chicago, USA)
09:15 - 09:30 Clinical Application in Brain: What we know. Michael LIM (Professor of Neurosurgery) (Speaker, Baltimore, USA)
09:30 - 09:45 Clinical Application in Lung: What we know. Clarissa BALDOTTO (Speaker, Brazil)
09:45 - 10:00 What We Don't Yet Know: Key Issues. Paul SPERDUTO (Radiation Oncology) (Speaker, Durham, USA)
10:00 - 10:15 Clinical Trials & Research Summary. Daniel M. TRIFILETTI (Professor) (Speaker, Jacksonville, USA)
Segovia Plenary

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B32
09:00 - 10:15

Oral Session
PHYSICS #2

Moderators: Fernando PAROIS JAPIASSU (Brazil), Anderson PASSARO (Medical Physicist) (São Paulo, Brazil), David SCHLESINGER (Medical Physics) (Charlottesville, VA, USA, USA)
09:00 - 09:10 #17753 - b32-1 A phase-space source model for Monte Carlo dosimetry calculations in Gamma Knife clinical applications.
b32-1 A phase-space source model for Monte Carlo dosimetry calculations in Gamma Knife clinical applications.

Purpose: To develop a phase space source model enabling Monte Carlo (MC) dosimetry calculations and verification of Gamma Knife treatments in inhomogeneous geometries.

Materials and methods: A previously validated Gamma Knife Perfexion (GKPFX) MC-based detailed source model was used to create single sector phase-space (PHSP) source models for the three available collimators.  These were validated in terms of single sector and single shot X-Y-Z dose profiles in a spherical water phantom with corresponding data obtained using the detailed model and experimental EBT-3 film measurements.

The PHSP-source model was subsequently used to validate GammaPlan (LGP) dose predictions using the convolution algorithm for a plan using a composite shot consisting of all collimator sizes delivered in a virtual phantom of 8 cm radius containing a 1.5 cm thick hemispherical bone inhomogeneity in the vicinity of the 50% isodose line.

Results: Single sector and single shot dosimetry results using PHSP simulations were found in excellent agreement with corresponding detailed MC model calculations and film measurements. Indicatively, gamma passing rates above 99.5% were achieved for local 1%/1mm criteria against detailed model simulation and 2%/1mm criteria against film measurements. Efficiency gain by a factor of up to 2500 for the smaller field size was attained compared with detailed model simulations. Convolution absolute dose distribution evaluation using the PHSP-source model simulations in the inhomogeneous phantom resulted in a gamma passing rate of 99.15%, applying 1%/1mm local gamma index criteria and 1% dose threshold.

Conclusion: An accurate and efficient GKPFX single sector PHSP source model was developed and validated. LGP calculations using the convolution algorithm were evaluated in an inhomogeneous geometry using this model and found to be in excellent agreement, indicating the accuracy of the convolution algorithm in water-bone inhomogeneities. Further work on convolution algorithm verification on more complex and clinical cases is in progress.


Andreas LOGOTHETIS, Evangelos PANTELIS, Emanouil ZOROS, Eleftherios PAPPAS, Georgios KOLLIAS, Alexis DIMITRIADIS, Ian PADDICK, Jonas GARDING, Jonas JOHANSSON, Pantelis KARAISKOS (Athens, Greece)
09:10 - 09:20 #17644 - b32-2 Evaluation of PTW microdiamond edge-on orientation for small field dosimetry.
b32-2 Evaluation of PTW microdiamond edge-on orientation for small field dosimetry.

The IAEA TRS-483 code of practice requires that solid state dosimeters used for quality assurance in small field radiotherapy be utilized in a “face-on” orientation [1]. However, this practice means that the high spatial resolution of the PTW microdiamond or uD in “edge-on” orientation is unrealized [2]. The aim of this study was to characterize the uD for small field applications in an edge-on orientation. To that end, the detector went through a rigorous characterization of its performance in both edge-on and face-on orientations for different field sizes and angular incidences

Output factor (OF), Percentage Depth Dose (PDD) curves and field profile measurements were performed with the uD in edge-on and face-on orientations and compared against the IBA RAZOR for 6MV photon field for both FF/FFF modalities in a IBA blue water phantom on a Varian True Beam linac for square field sizes between 0.5-10 cm. Angular dependence as a function of field size measurements (0.5x0.5-3x3cm2) were also performed in two different cylindrical PMMA phantoms to investigate the effect of orientation upon angular dependence.

The high spatial resolution of the uD in edge-on, allowed for precise profilometry of small FF/FFF square fields to be performed. The uD was shown to over-response in edge-on in comparison with face-on for fields ≤2x2cm2. Angular dependence measurements in the cylindrical edge2face phantom showed a 6-12% difference in response of the uD in the edge-on and face-on orientations for 0.5-3cm square fields, although larger variations (~31%) were observed. Additional angular dependence measurements in the cylindrical edge2edge phantom shows that the uD is almost angular independent over a range of 180° with differences of ±1%.

In edge-on orientation, the uD was shown to be suitable for profile reconstruction as well as exhibiting negligible angular dependence (±1%) making it an option for specific clinical applications. However, the orientation is deemed to be unsuitable for PDD and OF measurements, due to a less than ideal build-up behaviour and over-response. Full results including that of a dedicated Monte Carlo simulation study to optimise the detector packaging will be presented at the ISRS congress.

[1] H. Palmans, et al, Technical Report Series No. 483. International Atomic Energy Agency, Vienna; 2017

[2] V. De Coste, et al, Phys. Med. Biol. 62 (2017) 7036-7055


Jeremy DAVIS (Wollongong, Australia), Sultan ALHUJAI, Owen BRACE, Dean WILKINSON, Duncan BUTLER, Jason PAINO, Brad OBORN, Michael LERCH, Marco PETASECCA
09:20 - 09:30 #17682 - b32-3 Comparison of planning techniques for linac-based stereotactic radiosurgery in patients with 4 up to 10 brain metastases.
b32-3 Comparison of planning techniques for linac-based stereotactic radiosurgery in patients with 4 up to 10 brain metastases.

Purpose/Objective:Stereotactic radiosurgery (SRS) is a promising treatment option for patients with 4 to 10 brain metastases (BM). We studied whether automated planning can improve LINAC-based stereotactic radiosurgery plan quality for multiple BM. 

Materials/Methods:For 12 patients with 4 to 10 BM, five non-coplanar LINAC-based SRS plans were created for 6MV photons: a manually planned dynamic conformal arc (DCA) plan with a separate isocenter for each metastasis, a dynamic IMRT plan with one isocenter, a VMAT plan with one isocenter, two DCA plans with one isocenter for three and five couch rotations. The last three plans were automatically generated. The prescription dose was 21Gy or 18Gy single fraction or 25.5Gy in 3 fractions depending on the volume of the largest metastasis and prescribed to the 80% isodose line.The PTV coverage should be at least 98%.To assess SRS plan quality, the Paddick conformity index (CI), the Paddick gradient index (GI), the total V12Gy and V5Gy and the number of monitor units (MU) were studied. 

Results: The mean CI was the highest for dynamic IMRT and manual DCA plans. The lowest GI was for manual DCA plans with a separate isocenter for each metastasis and for automatically generated DCA plans with one isocenter, the highest GI was for VMAT plans. The V12Gy of automatically generated DCA plans with one isocenter and dynamic IMRT plans were comparable with the manual DCA plans. The number of MU was the smallest for VMAT plans, followed by IMRT and automatically generated DCA plans.

Conclusions: Automatically generated LINAC-based, single isocenter SRS plans for multiple BM result in fewer MUs, with a plan quality comparable to manual multiple-isocenter DCA plans. Based on all compared parameters, dynamic IMRT and DCA plans with one isocenter were the best and comparable with multiple-isocenter DCA plans. 


Ruud WIGGENRAAD (The Hague, The Netherlands), Anna PETOUKHOVA, Roland SNIJDER, Linda DE BOER-DE WIT, Ivonne MUDDE-VAN DER WOUDEN, Mireille FLORIJN, Jaap ZINDLER, Jan VAN SANTVOORT
09:30 - 09:40 #17810 - b32-4 Accuracy of frameless image guided stereotactic radio-surgery for brain metastases.
b32-4 Accuracy of frameless image guided stereotactic radio-surgery for brain metastases.

Objectives: To evaluate inter- and intra-fraction motion detected using frameless immobilization for Gamma Knife (GK) stereotactic radiosurgery (SRS).

Materials and Methods: Following consent to frameless GK-SRS, patients were immobilized with a thermoplastic mask followed by acquisition of a reference CBCT scan. Daily setup verification and intra-fraction motions were monitored using CBCT and an intra-fractional motion management (IFMM) system.  Patient setup and CBCT was repeated when IFMM thresholds were exceeded or when the patient needed a voluntary break. In-house Matlab scripts were developed to parse log files to determine patient inter- and intra-fraction setup variability.

Results: Thirty-eight plans were reviewed from 36 patients (2 patients treated twice). The average number of targets per plan was 1.3 [range: 1-4] and treatment time was 42 min [range: 8.3 - 145.9min]. The number of CBCT per fraction is 1.8 [range: 1-7]. Systematic setup error was found by the difference between reference and daily CBCTs as 0.93, 1.17, 1.17 mm and 0.8, 0.6, 2.2 degrees in x, y, and z direction respectively. Random error (intra fraction) was found 0.40, 0.33, 0.35mm and 0.3, 0.3, 0.6 degrees from successive CBCTs. IFMM measurement with marker motion larger than 0.2mm are  77 times/min during beam delivery and the average directional motion during beam on was 0.0, -0.1, 0.3mm (standard deviation of 0.4, 0.4, and 0.6mm) in x, y, and z direction. Systematic (random) motion of IFMM was 0.7mm, 0.5mm, 0.9mm (0.3, 0.2, and 0.5mm).

Conclusions: Preliminary analysis suggests good setup reproducibility with the largest discrepancy in the z-direction. After setup correction, random intra-fraction motion was found to be within 0.5mm with larger systematic motions triggered for pause or correction by the IFMM.


Young-Bin CHO (Toronto, Canada), Winnie LI, Normand LAPERRIERE, David SHULTZ, Caroline CHUNG, Barbara-Ann MILLAR, David JAFFRAY, Catherine COOLENS
09:40 - 09:50 #17882 - b32-5 Use of non-composite shots for robust planning in Gamma Knife Icon mask-based treatment.
b32-5 Use of non-composite shots for robust planning in Gamma Knife Icon mask-based treatment.

Purpose: Adapting manufacturer’s end-to-end test to the Gamma Knife Icon mask system, we were able to verify the accuracy of position correction in Gammaplan even for large angular and translational shifts. However, the test does not verify if isodose volume is preserved.

Methods and Materials: An anthropomorphic head phantom with a film insert in the mid-coronal plane is used. Lesion-E has an elliptical shape covered by one single composite shot. Lesion-S has a sausage shape covered by 4 composite shots. Close to either lesion are organs at risk (OAR1 and OAR2). For each lesion, a non-composite plan was also created to produce similar prescription isodose volume with comparable dose to OARs. The phantom was treated in the planning position (A), and in a position shifted 4 cm superiorly and rotated 95 degrees to right (D). For lesion-S, the phantom was irradiated in two additional positions: 14-degree chin-up (B), and 14-degree rotation to right with 7-degree chin-up (C). (Min, max, mean) dose reported under dose evaluation during treatment were analyzed. Gamma Index comparison of film dose at positions B, C, or D versus A was used. Prescription dose was 3 Gy per fraction.

Results: Non-composite-shot plans: All Gamma Index passing rates are > 97%, and all differences in (min, max mean) dose are <= 0.1 Gy. Composite-shot plans: Passing rate is 57% for position D for lesion-E, and 92%, 78%, and 44% for position B, C, and D, respectively for lesion-S. The difference in (min, max, mean) doses becomes larger as the phantom shifted from position B through D: from a maximum 0.4-Gy difference in position-B to a maximum difference of 0.8-Gy in position-D for lesion-S and as large as 1.4 Gy for lesion-E.

Conclusions: For robust planning, it is recommended to use only non-composite shots for mask-based treatments with Icon.


Dershan LUO (Houston, Texas, USA, USA), Eun HAN, Xin WANG, Tina BRIERE
09:50 - 10:00 #17785 - b32-6 End-to-End dosimetric and geometric accuracy of linac-based high-definition dynamic stereotactic treatments for multiple metastases: A multi-institutional study.
b32-6 End-to-End dosimetric and geometric accuracy of linac-based high-definition dynamic stereotactic treatments for multiple metastases: A multi-institutional study.

Objective:

Dosimetric and geometric accuracy are paramount in Stereotactic Radiosurgery (SRS) to achieve effective and safe implementation of the treatment. In this work, End-to-End accuracy was evaluated for single-isocenter multi-focal SRS treatments in six centers.   

Methods:

Eight identical 3D-printed head phantoms were constructed using the planning-CT dataset of a patient, simulating bone structures by a bone equivalent material. Six phantoms (one per clinic) were filled with 3D polymer gel, which simulates brain tissue and acts as a dosimeter in combination with an MR scanner, while the other two phantoms were filled with water and equipped with an ion chamber and a film insert, respectively. A single-isocenter plan using a 5-arc VMAT beam arrangement was created in Monaco Treatment Planning System (TPS). Six targets were adjusted to achieve a range of target sizes 6-25mm in diameter at various distances from the isocenter. Prescription dose was set to 8Gy and dose delivery was performed by the Elekta Versa HD-HDRS linear accelerator with HexaPOD system, following departments’ clinical SRS workflow. Point, 2D, and 3D dose values were obtained by ion chamber, film, and gel measurements, respectively. Geometric accuracy of all targets was evaluated by the comparison of 2D/3D relative dose distributions between measurements and TPS calculations. Dosimetric accuracy was verified by ion chamber measurements in one target.     

Results:

Excellent geometric agreement (<1mm) between TPS calculations and measurements was observed for the targets lying less than 4cm from the isocenter. For the targets with a distance from the isocenter greater than 4cm, the average difference from all sites was 0.8mm with a maximum discrepancy of 1.9 mm. Ion chamber measurements yielded an average difference of 1.2% ± 0.5% leading to a superb agreement within uncertainties.   

Conclusion:

The overall accuracy of single-isocenter multi-focal SRS treatments was found within acceptable limits for all clinics using a patient-specific End-to-End methodology.


Emmanouil ZOROS (Greece, Greece), Daniel SAENZ, Kyveli ZOURARI, Michael REINER, Lip Teck CHEW, Samuel HANCOCK, Alex NEVELSKY, Christopher F NJEH, Niko PAPANIKOLAOU, Evangelos PAPPAS
Segovia Break Out
10:15 COFFEE BREAK - POSTERS & EXHIBITION
10:45

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A34
10:45 - 11:15

PARALLEL SESSION
THE LEKSELL LECTURE

Moderators: Antonio DE SALLES (Professor - Chief) (SÃO PAULO, Brazil), Laura FARISELLI (director) (milan, Italy), Marc LEVIVIER (Chef de Service) (Lausanne, Switzerland), Ian PADDICK (Consultant Physicist) (London, United Kingdom), Jean REGIS (PROFESSEUR) (MARSEILLE, France)
10:45 - 11:15 Gamma Knife Radiosurgery from Leksell to the Present: An Insider’s View. Christer LINDQUIST (Medical co-director) (Speaker, LONDON, Sweden)
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C34
10:45 - 11:45

Oral Session
THORACIC & GASTRO-INTESTINAL

Moderators: David PRYOR (Radiation Oncologist) (Brisbane, Australia), Ben SLOTMAN (Professor) (AMSTERDAM, The Netherlands), Rosemarie STAHLSCHIMIDT (Brazil)
10:45 - 10:54 #17660 - c34-1 Dynamic tracking SBRT (DTSBRT) for the treatment of primary and/or metastatic lung cancer.
c34-1 Dynamic tracking SBRT (DTSBRT) for the treatment of primary and/or metastatic lung cancer.

Purpose/Objectives: There are several methods to reduce the effect of respiratory movement in SBRT for lung tumors. One of them is dynamic tumor tracking method, which has the merit over other methods to reduce the treatment time and the pressure of rigid fixation. We have been using this method (DTSBRT) for several years and analyzed the results.

Materials and Methods: Indications were tumors whose respiratory movement was larger than 10mm on planning CT, fit for SBRT, and normal organ dose constraints were met. DTTSBRT was performed using Vero-4DRT (Gimbal-based) and CyberKnife G4 (Robot arm-based). Prescription doses were 50 Gy/ 4 fr/1 wk at the PTV D95%.

Results: Between March 2013 and March 2017, 46 patients received DTT SBRT. Median age was 76.5 (range 41-90), Male to female ratio was 33:13, There were 26  primary tumors and 20 metastatic tumors. More than 90% tumors were located in the lower lobe (42/46). Median follow-up period was 23.7 months (4.6-59.3mos). 29 cases were treated with Vero-4DRT, whereas 17 cases were treated with CyberKnife. Two-year local control rates for primary and metastatic cancers were 95.0% and 94.7%, respectively (n.s). Two-year overall survival rates for primary and metastatic cancers were 84.6% and 75.0%, respectively (n.s.). There were no differences in local control or overall survival between the treatment machines. There was one Grade 3 pneumonitis. No serial organ toxicity has been observed.

Conclusions

DTSBRT for primary and/or metastatic lung cancer has been promising for good local control and overall survival despite that nearly all of the tumors were located in lower lobe, which has been known to be difficult to control.


Katsuyuki KARASAWA (Tokyo, Japan), Yumiko MACHITORI, Satoshi KITO, Sara HAYAKAWA, Kaiji NIHEI
10:54 - 11:03 #17713 - c34-2 DIBH implementation for lung SBRT treatment with low cost local solution in Argentina.
c34-2 DIBH implementation for lung SBRT treatment with low cost local solution in Argentina.

With improved outcomes, lung SBRT has begun for early-stage non-small cell lung cancer patients a routinely indication in the thoracic radiation oncology community. At Mevaterapia radiation therapy centre in Argentina we implemented lung SBRT using Deep Inspiration Breath-Hold (DIBH) technique by a local low cost (U$D 4000) spirometer customized for radiation therapy monitoring.

In DIBH treatment protocol, patients are instructed to breathe through a non-invasive naso-oral mask while theirs respiratory patterns are follow in real time using a hand spirometer connected to a portable computer. Normal respiratory (i.e. respiratory frequency, inspiration volume, espiration volume) and deep inspiration variables (i.e. deep inspiration volume, deep inspiration holding time, repeatability of deep inspiration volumes in time) are recorded during CT scans simulation.

CT scan for treatment planning in DIBH is obtained followed by several short DIBH CT scans at the lesion in order to evaluate absolute displacements within DIBH volumes treatment range.

Treatment planning is performed in Eclipse v13.6 using AAA algorithm and carried out through ARIA system in a Varian Trilogy LINAC with Exactrac and 6D couch technology. Time between CT simulation and treatment is around 5 days, prior to treatment a simulation session at LINAC is scheduled.

During simulation session patient is firstly localized using bone structures with Exactrac and positioning is verified by CBCT in DIBH. Treatment parameters are checked with the patient and treatment simulated in order to corroborate treatment applicability and to reduce patient’s anxiety and fears during actual treatment sessions.

Our protocol had been applied in 6 patients over the last 6 months with a total patient’s time in treatment room of 45±15 minutes. CTV localization in DIBH were regular and reproducible over treatment using spirometer monitoring with local technology low-cost solution. In our service this had become first choice protocol for SBRT lung treatment.


Ruben Oscar FARIAS, Leon ALDROVANDI, Florencia MAURI, Augusto ALVA, Federico Javier DIAZ, Maria Liliana MAIRAL, Mabel Edith SARDI, Mara Lia SCARABINO (Buenos Aires, Argentina)
11:03 - 11:12 #17747 - c34-3 Artificial Intelligence techniques improve SBRT treatment planning quality.
c34-3 Artificial Intelligence techniques improve SBRT treatment planning quality.

Purpose

Improve SBRT planning quality through application of AI techniques

 

Methods

Pancreas and liver SBRT planning is often challenging due to tolerance limits of the gastrointestinal (GI) structures.  The clinical treatment planning goal is to retain full PTV coverage at lower dose level and as much as ITV coverage at higher dose level after abiding by the GI constraints.  Since the overlap between targets and OARs vary from patient to patient, percentage of target volume covered at high dose levels has to be staged in order to avoid OARs.

We have developed AI techniques to navigate the optimal strategies to achieve high quality plans. The proposed system is based on a reinforcement learning (RL) framework which includes: (1) the planning states, which is designed in a similar fashion to how planners evaluate plans (e.g. constraint satisfaction, target coverage); (2) the planning objective adjustment actions that planners would take to address different planning needs; (3) a reward scheme based on physician’s prescriptions.  The RL strategy follows the state-action-reward-state-action (SARSA) algorithm with limited dimensionality which is designed to ensure coverage and performance.

The training process essentially simulates how the human planner interacts with the planning systems, evaluating planning objectives at different planning stages, taking different actions at different states, and after each action, the planning result is re-evaluated and a reward is assigned accordingly.

Results

16 clinical cases were used to demonstrate the feasibility of this approach: 10 for AI training and 6 for validation. All 6 validation plans satisfy OAR constraints, while maintaining comparable or better target coverage compared to clinical plans. Average AI planning takes 20 minutes vs. 30-60 minutes for manual planning.

 

Conclusions

The proposed AI approach can potentially improve clinical planning efficiency while achieving comparable planning quality.


Q. Jackie WU, Jiahang ZHANG, Chunhao WANG, Yang SHENG, Suradet JITPRAPAIKULSARN, Fang-Fang YIN (Durham, NC, USA), Yaorong GE
11:12 - 11:21 #17768 - C34-4 Clinical experience with calypso tracking in sbrt for pancreatic tumours.
C34-4 Clinical experience with calypso tracking in sbrt for pancreatic tumours.

Pancreatic adenocarcinoma is a deadly disease being the 4th in lethality despite being the 10th in incidence. Additionally, more then 80% of patients are not candidates for surgical resection, and their overall survival with only systemic therapy is around 6 months. SBRT treatments of locally advanced adenocarcinomas of pancreatic head and body are challenging due to difficulties in motion management and in proximity of radiosensitive organs at risk, primarily the duodenum. The Calypso extracranial tracking system uses implanted fiducials to track tumor movement in real time without any additional radiation dose.  At our clinic we percutaneously implant fiducials under CT navigation into a pancreatic tumor and perform a standard simulation two weeks after implantation. The Calypso extracranial tracking system allows us to significantly reduce contribution of target movement to the CTV PTV magin thus reducing tumor target volume compared to delineating contours on a average 4D CT or compared to using abdominal compression. Patients are simulated in a deep inspiration or expiration phase and contoured with the help of MRI. This reduced volume allows us to prescribe higher doses or to reduce the number of fractions while at the same time keeping the probability of toxicity low. Using the Calypso extracranial tracking system has also shown that the pancreas targets have significant movement contribution from peristaltic movement of the GI track, apart from the respiratory movement contribution. We used this technique for all our patients with pancreatic adenocarcenoma since June of 2017, totaling 30 with locally advanced disease (unresectable) with excellent local control rates and long overall survival, rivaling that of patients who underwent surgical resection.


Domagoj KOSMINA (Zagreb, Croatia), Hrvoje KAUCIC, Luka NOVOSEL, Adlan CEHOBASIC, Vanda LEIPOLD, Jelena HAJREDINI, Sanja GASPAR, Marica KESER, Ivo PEDISIC, Dragan SCHWARZ, Sasa SCHMIDT, Andreas MACK
11:21 - 11:30 #17821 - c34-5 Prospective duodenal sparing decreases GI toxicity in pancreatic SBRT.
c34-5 Prospective duodenal sparing decreases GI toxicity in pancreatic SBRT.

Purpose

The proximity of the pancreas to the small bowel presents a unique challenge for pancreatic cancer stereotactic body radiation therapy (SBRT). This study explores the safety and effectiveness of a novel approach optimizing pancreatic tumor coverage and duodenal sparing.

Materials/Methods

54 patients with locally advanced pancreatic cancer were treated with SBRT from 2011-2018. Treatment was delivered pre-operatively (N=23), definitively (N=18), adjuvantly (N=5), or for recurrence or palliation (N=7). All patients underwent endoscopic ultrasound-guided gold fiducial seed placement within and adjacent to the tumor. Planning involved a 4D CT scan with oral contrast, used in conjunction with EUS, PET, and diagnostic biphasic CT scans to identify the gross tumor volume (GTV). The planning target volume (PTV) was created by expanding the GTV by 2 mm. The gastrointestinal tract (GIT) included the duodenum, stomach and small bowel. The duodenum, from the pylorus to the 4th segment, surrounding the GTV was delineated. The small bowel was contoured as a bowel bag from the diaphragm to L1. Three 10 Gy fractions, normalized to the 85% isodose surface, were delivered to the PTV on consecutive weekdays using fiducial-based respiratory motion tracking. Dose-volume histogram (DVH) constraints included stomach and duodenal V7Gy <40%, V15Gy < 25%, and V20Gy <15%. D33% for the duodenal circumference was < 20Gy, and duodenal Dmax <27Gy. Additional dose constraints included liver D50%

Results

All patients tolerated and completed treatment and there were no Grade 3 or higher toxicities. There were 6 patients who did not meet the above mentioned GIT relative volume based dose constraints as per the treating physician’s clinical decision. GIT mean max point dose was 2379 cGy (range 383-3156 cGy). Mean dose to 5 cc and 10 cc of the GIT were 1665 cGy (94–2610 cGy) and 1443 cGy (82-2414 cGy), respectively.

Conclusion

We treated 54 patients with our prospective duodenal sparing protocol to improve the therapeutic index. We have shown that our unique way of delineating the bowel and using relative volume based constraints can be as effective as or better than using absolute volume based constraints which are used in most SBRT protocols. 


Prashant VEMPATI (Lake Success, USA), Raymond CHAN, Peter K TAYLOR, Huma CHAUDHRY, Emile GOGINENI, Sewit TECKIE, Rajiv SHARMA, Vincent VINCIGUERRA, Maged GHALY
11:30 - 11:39 #17904 - c34-6 Novel treatment planning technique to facilitate safe pancreatic SBRT dose escalation.
c34-6 Novel treatment planning technique to facilitate safe pancreatic SBRT dose escalation.

Pancreatic stereotactic body radiation therapy (SBRT) has emerged as a promising improvement to the radiation component of trimodality therapy for pancreatic adenocarcinoma. Recent data show dramatic clinical outcome improvements for patients treated with dose escalated SBRT. However, the sensitivity and proximity of organs-at-risk (OARs) such as duodenum, stomach, and small bowel pose a considerable challenge to escalation of prescription dose necessary for adequate tumo control. In our study, we identified patients treated on our institutional pancreatic SBRT protocol to 33Gy/5x, and replanned each case with non-coplanar arcs to maximal studied doses, and assessed OAR tolerance.

Methods and Materials:

12 patients were treated under institutional protocol with respiratory gated, triggered kV imaging, axial-arc VMAT plans (2-3 arcs) on a Varian Edge linac, with 10MV FFF beam. Plans were optimized in Eclipse TPS. Each patient’s treatment was re-planned with the addition of two non-coplanar arcs, at 10° and 350° couch kicks, to the axial arc. To isolate the impact of the non-coplanar beam arrangements on plan quality, the plans were optimized congruently with the clinical plans and utilized identical dose constraints. If PTV coverage of re-optimized plan was less than its clinical counterpart, the replan was normalized to identical PTV coverage percentage. Dosimetric quantities compared were: D[0.1cc] to duodenum, small bowel, and stomach; PTV and GTV prescription dose coverage and mean dose.

Each re-plan was exported to Mobius 3D which validated delivery of the plan with respect to gantry/patient/table clearance .

Results:

All non-coplanar arc replans met previously utilized clinical constraints. Mobius 3D verified each plan as deliverable with respect to patient/gantry/table clearance. The addition of non-coplanar arcs improved plan quality in every single re-planned case at no dosimetric expense. Median duodenum, stomach, and small bowel D0.1cc reductions were 203.1cGy, 166.2cGy, and 149.5cGy. PTV and GTV coverage was equivalent or improved in all of the non-coplanar arc plans as well.

Conclusion:

The incorporation of non-coplanar arcs is a simple and effective method to reduce OAR dose exposure in pancreatic SBRT planning. Such techniques become increasingly important as efforts to further dose escalate pancreatic SBRT treatments become more commonplace.


Evan THOMAS (BIRMINGHAM, USA), Christina BLALOCK, Rex CARDAN, Richard POPPLE, Rojymon JACOB
11:39 - 11:45 #17851 - c34-7 Stereotactic body radiation therapy in the management of oligometastatic colorectal cancer.
c34-7 Stereotactic body radiation therapy in the management of oligometastatic colorectal cancer.

Background: The prolongation of survival of metastatic colorectal cancer (CRC) patients with the introduction of new systemic treatments increased the relevance of local approaches in oligometastatic setting. Aim of the present study was to analyze pattern of care and recurrence of oligometastatic CRC patients, and to evaluate predictive factors of survival.

Materials and methods: We included patients with histologically confirmed colorectal adenocarcinoma and maximum of 5 metastases. Previous or concomitant systemic treatments were allowedEnd points of the present study were the outcome in terms of Local control of treated metastases (LC), progression free survival (PFS), and overall survival (OS).

Results: 270 patients were treated on 437 metastases. Characteristics are summarized in Table 1. Lung was site of metastases in 48.5% of cases, followed by liver (36.4%) and lymph nodes (12.4%). Systemic treatment was administered before SBRT in 199 patients (73.7%). Median follow-up time was 22.6 months (3- 98.7). Rates of LC at 1, 3 and 5 years were 95%, 73% and 73%, respectively. Time from diagnosis of metastases to SBRT was the only factor predictive of LC (HR 1.62, p=0.023). Median PFS was 8.6 months and both control of treated metastases (HR 1.86, p=0.000) and single line of systemic treatment before SBRT (HR 1.86, p=0.000) were positively correlated to PFS.  Rates of OS at 1, 3 and 5 years were 88.5%, 56.6%, and 37.2%, respectively. Lesion greater than 30 mm (HR 1.82, p=0.030), presence of metastases in organ different from lung ((HR 1.67, p=0.020), the use of systemic treatment before SBRT (HR 1.82, p=0.023), and progression of treated metastases (HR 1.80, p=0.007), were all predictive of worse OS (Figure 1).

Conclusions: Stereotactic body radiation therapy represents an effective approach in the management of oligometastatic CRC. Control of treated metastases was a strong positive predictive factor for both PFS and OS.


Ciro FRANZESE (Milano, Italy), Tiziana COMITO, Davide FRANCESCHINI, Elena CLERICI, Fiorenza DE ROSE, Angelo TOZZI, Pierina NAVARRIA, Pietro MANCOSU, Stefano TOMATIS, Marta SCORSETTI
El Pardo I
11:15

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A35
11:15 - 11:45

PARALLEL SESSION
EVOLUTION AND IMPACT OF RADIOSURGERY

Moderators: Laura FARISELLI (director) (milan, Italy), Christer LINDQUIST (Medical co-director) (LONDON, Sweden), Paul SPERDUTO (Radiation Oncology) (Durham, USA)
11:15 - 11:30 What I Know Now That I Wish I Knew Then. Antonio DE SALLES (Professor - Chief) (Speaker, SÃO PAULO, Brazil)
11:30 - 11:45 How Radiosurgery has Impacted Radiation Oncology. Scott SOLTYS (ISRS 2023) (Speaker, Stanford, CA, USA)
Segovia Plenary
11:45

"Tuesday 11 June"

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A36
11:45 - 12:30

PARALLEL SESSION
CONTEMPORARY MANAGEMENT OF BRAIN METASTASES

Moderators: Pablo CASTRO PENA (Radiation Oncologist) (Cordoba, Argentina), Marcos MALDAUN (Neurosurgical Oncology) (São Paulo - SP, Brazil), Scott SOLTYS (ISRS 2023) (Stanford, CA, USA)
11:45 - 12:00 #17647 - a36-1 Single versus multifraction stereotactic radiosurgery for large brain metastases: An international meta-analysis of 24 trials.
a36-1 Single versus multifraction stereotactic radiosurgery for large brain metastases: An international meta-analysis of 24 trials.

Purpose: Multifraction stereotactic radiosurgery (MF-SRS) purportedly reduces radionecrosis risk over single fraction SRS (SF-SRS) in the treatment of large brain metastases. The purpose of the current work is to compare local control (LC) and radionecrosis rates of SF-SRS and MF-SRS in the definitive (SF-SRSD and MF-SRSD) and postoperative (SF-SRSP and MF-SRSP) settings.

Methods/Materials: PICOS/PRISMA/MOOSE guidelines were used to select articles where patients: diagnosed with “large” brain metastases (Group A: 4-14 cm3, or about 2-3 cm; Group B:  >14 cm3, or > 3 cm); 1-year LC and/or rates of radionecrosis were reported; radiosurgery was administered definitively or postoperatively. Random effects meta-analyses using fractionation scheme and size as covariates were conducted. Meta-regression and Wald-type tests were used to determine the effect of increasing tumor size and fractionation on the summary estimate, where the null hypothesis was rejected for p<0.05.

Results: Twenty-four studies were included, published between 2008-2017 with 1,887 brain metastases. Local control at 1-year for Group A/SF-SRSD was 77.6% and for Group A/MF-SRSD was 92.9% (p=0.18). Local control at 1-year for Group B/SF-SRSD was 77.1% and for Group B/MF-SRSD was 79.2% (p=0.76). Local control at 1-year for Group B/SF-SRSP was 62.4% and for Group B/MF-SRSP was 85.7% (p=0.13). Radionecrosis incidence for Group A/SF-SRSD was 23.1% and for Group A/MF-SRSD was 7.3% (p=0.003). Radionecrosis incidence for Group B/SF-SRSD was 11.7% and for Group B/MF-SRSD was 6.5% (p=0.29). Radionecrosis incidence for Group B/SF-SRSP was 7.3% and for Group B/MF-SRSP was 7.5% (p=0.85). 

Conclusion: Treatment for large brain metastases with MF-SRS regimens may offer enhanced efficacy and safety when compared to SF-SRS, particularly for tumors 4-14 cm3 (2-3 cm in diameter) treated in the definitive setting. These findings are hypothesis-generating and require validation by ongoing and planned prospective randomized control trials.


Eric LEHRER, Jennifer PETERSON, Nicholas ZAORSKY, Paul BROWN, Arjun SAHGAL, Veronica CHIANG, Samuel CHAO, Jason SHEEHAN, Daniel TRIFILETTI (Jacksonville, USA)
12:00 - 12:15 Japanese Study Group Update: Evidence from “crazy treatment” to standard treatment. Yoshiaysu IWAI (Neurosurgery, Radiosurgery) (Speaker, Osaka, Japan)
12:15 - 12:30 Pre-operative SRS for Brain Metastases : A New Paradigm. Stuart BURRI (Chairman) (Speaker, Charlotte, USA)
11:45 - 12:30 Current status of pronostic models and grading systems. Paul SPERDUTO (Radiation Oncology) (Speaker, Durham, USA)
Segovia Plenary

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B36
11:45 - 12:45

Oral Session
FUNCTIONAL #2 - MOVEMENT DISORDERS

Moderators: Joao Gabriel GOMES (Neurosurgeon) (Recife, Brazil), Christer LINDQUIST (Medical co-director) (LONDON, Sweden), Alessandra MOURA LIMA (Sau Paulo, Brazil)
11:45 - 11:55 #17895 - b36-1 Probabilistic tractography for radiosurgical dosimetry of functional regions of the thalamus.
b36-1 Probabilistic tractography for radiosurgical dosimetry of functional regions of the thalamus.

RAD-1601 is a clinical trial to determine the efficacy of multileaf collimator based radiosurgical thalamotomy for essential tremor. Because the target location cannot be visualized using conventional MR sequences, it was determined using atlas-based stereotactic coordinates. The isocenter was adjusted to limit the maximum dose in the internal capsule to 26 Gy (20%). The stereotactic coordinates, isocenter, and creation of the treatment plan were automated using scripting of the treatment planning system. The prescription was 130 Gy maximum dose. Prior to treatment, diffusion MR imaging was obtained and used for single-subject thalamic segmentation based on probabilistic tractography (PT). Two relevant regions-of-interest (ROIs) were identified based on the PT results: the region most connected to primary motor cortex (M1), presumed to mirror the histologic ventral intermediate nucleus (VIM), and the region most connected to the supplementary motor area/premotor cortex (SMA/PMC), presumed to mirror the histologic ventral oral nucleus (VO). The corresponding ROIs were imported into the treatment planning system. Segmentation has been obtained for 4 patients. The volumes of M1 and SMA/PMC were 0.1-0.5 cm3 and 0.4-1.1 cm3, respectively. In all 4 cases, both the target based on stereotactic coordinates and the isocenter were located within the SMA/PMC rather than M1. The D0.03cc[Gy] was 81-91 Gy for SMA/PMC and 29.9-48.3 Gy for M1. The maximum dose was 130 Gy for SMA/PMC and 94.7-109.1 Gy for M1. Thalamic segmentation based on probabilistic tractography is a promising technique that may enhance traditional functional SRS targeting. In the future, prospective use of structural connectivity imaging data will result in more functionally relevant targeting for SRS thalamotomy. Correlation of outcome with radiation dosimetry to M1 and SMA/PMC are ongoing.


Richard A. POPPLE (Birmingham, USA), Erik H. MIDDLEBROOKS, Evan M. THOMAS, John B. FIVEASH, Rex A. CARDAN, Harrison C. WALKER, Barton L. GUTHRIE, Markus BREDEL
11:55 - 12:05 #17905 - b36-2 Preliminary results of phase II clinical trial for linac-based coneless and frameless SRS thalamotomy for essential tremor and tremor-dominant Parkinson's disease.
b36-2 Preliminary results of phase II clinical trial for linac-based coneless and frameless SRS thalamotomy for essential tremor and tremor-dominant Parkinson's disease.

Introduction:

Radiosurgery (SRS) has been used to manage tremor in patients with medically refractory tremor. Because of high doses, small target, and required precision, Gamma Knife has been the traditional platform. Our objective was to develop and evaluate a safe, effective, and precise alternative on the linear accelerator without frame or cone. We present here a pre-clinical evaluation of the technique, pilot treatment, and early results of recently-opened phase II evaluation trial of this technique for non-DBS candidate patients.

Methods

Patients’ pre-treatment tremor was evaluated with FTM score and PROMIS index. Patients were imaged on a Phillips 3T Magnetom Prisma MRI with additional optional Siemens 7T Magnetom MR imaging, to generate MPRAGE, diffusion-weighted tractographic, and resting-state fMRI sequences. VIM was identified via thalamic parcellation and compared to stereotactic reference location. Scan was fused to  thin-slice CT simulation obtained with patient immobilized in Qfix Encompass rigid mask. VIM was targeted to 130Gy dmax. SRS was delivered on Varian Edge linac with high-definition multi-leaf collimator (HDMLC) and intrafraction optical surface monitoring (OSMS) to ensure patient stationariness. Treatment was delivered in 13 flattening-filter free non-coplanar arcs with fixed-MLC position and pre-determined beam modulation (Virtual Cone), resulting in spherical dose equivalent to 4mm Gamma Knife shot. Post-treatment imaging and FTM/PROMIS scores were compared to pre-treatment baselines at scheduled intervals.

Results

In the study, 12 patients underwent VIM thalamotomy. QA revealed treatment accuracy to 0.3mm. Median follow-up was 4 months. All patients demonstrated T1-enhancing lesion at site of treatment. All patients had some degree of tremor improvement in limb contralateral to treatment site, ranging from near complete to modest tremor relief. No patient experienced grade 2 or greater treatment-related adverse effect. Additional follow-up continues.

Conclusion

Functional radiosurgery can now be delivered with equivalent dosimetry in comparison to Gamma Knife plans. Treatments on a coneless, frameless linac platform are fast and well tolerated, but as with all functional SRS, require collaborative expertise from an experience functional neurosurgeon, CNS radiation oncologist, and physicist comfortable with small target, high dose QA.


Evan THOMAS (BIRMINGHAM, USA), Richard POPPLE, John FIVEASH, Barton GUTHRIE, Markus BREDEL
12:05 - 12:15 #17661 - b36-3 Ventro-lateral motor thalamus abnormal functional connectivity before and after left Vim radiosurgery for drug-resistant essential tremor: a resting-state fMRI study.
b36-3 Ventro-lateral motor thalamus abnormal functional connectivity before and after left Vim radiosurgery for drug-resistant essential tremor: a resting-state fMRI study.

Background:Essential tremor (ET) is a common movement disorder. Resting state fMRI (rs-fMRI) is a non-invasive neuroimaging method acquired in absence of any task. 

Objective: The first aim of the present study was to correlate pretherapeutic ventro-lateral thalamus functional connectivity (FC) with clinical result 1 year after Vim radiosurgery (Vim RS) for drug-resistant ET. The second aim was to evaluate blood-oxygen level dependent (BOLD) changes between pre- and postherapeutic state. 

Methods: Resting-state was acquired for 17 consecutive (right handed) patients, before and after left unilateral Vim RS. Tremor network was investigated using region-of-interest (ROI), left ventro-lateral ventral (VLV, Morel’s nomenclature) cluster, obtained using automated segmentation from pretherapeutic diffusion MRI. Seed-based functional connectivity (FC) was assessed as correlations between the VLV’s time courses and the one of every voxel. One-year MR-signature volume was always located inside VLV and did not correlate with any reported seed-FC measures (p>0.05). 

Results: We report statistically significant correlations betweenpretherapeutic seed-FC with 1 year clinical outcome for: 1). right visual association area (Brodmann area, BA 19) predicting 1 year activities of daily living (ADL) drop (punc=0.02); 2). left fusiform gyrus (BA 37) predicting 1 year head tremor score improvement (punc=0.04); 3). posterior cingulate (left BA 23, puncor=0.009), lateral temporal cortex (right BA 21, punc=0.02) predicting time to tremor arrest . Longitudinal study displayed changes within right dorsal attention (frontal eye-fields and posterior parietal) and salience (anterior insula) networks, as well as areas involved in hand movement planning or language production. 

Conclusions: Our results suggest that pretherapeutic resting-state seed-FC of left VLV predicts tremor and time to tremor arrest after Vim RS for ET. Visual areas are identified as the main regions in this correlation. Longitudinal changes display reorganization of dorsal attention and salience networks after Vim RS. Beside attentional gateway, they are also known for their major role in facilitating a rapid access to the motor system.


Constantin TULEASCA (Lausanne, Switzerland), Jean RÉGIS, Elena NAJDENOVSKA, Tatiana WITJAS, Nadine GIRARD, Mohamed FAOUZI, Vincent MARION, Jean-Philippe THIRAN, Meritxell BACH CUADRA, Marc LEVIVIER, Dimitri VAN DE VILLE
12:15 - 12:25 #17868 - b36-4 Radiosurgical Pallidotomy for Generalised & Focal Dystonias: Is It The Last Part in The Ship of Theseus.
b36-4 Radiosurgical Pallidotomy for Generalised & Focal Dystonias: Is It The Last Part in The Ship of Theseus.

Objective 

To evaluate the role of radiosurgical pallidotomy in cases of medically refractory generalised and focal dystonias in current era.

Introduction

Gamma knife radiosurgery has been proved to be effective in the management of medically refractory dystonia. Technically, it is considered inferior to deep brain stimulation on the virtue of absence of real time monitoring, latency period for effective results, and irreversible nature of lesioning [1]. We present our experience with five cases of generalised dystonia managed with radiosurgery ablation of the globus pallidus interna. 

Material and Methods

5 patients were treated with Leksell Perfexion gamma knife radiosurgery. 3/5 patients were primary dystonia, while one was suffering from neuroacanthosis, and another developed post traumatic dystonia. Radiosurgical pallidotomy was performed. The target was localised on magnetic resonance imaging after fusion with anatomical atlas. A single shot of 4 mm collimator was used with 140 Gy marginal dose at prescription iso dose of 100% [1,2]. Peri procedure steroids were administered.

Results

The median time to improvement was 70 days. Complete abolition of movement was observed in 20% of patients, while excellent relief in 40%. New onset deficit was observed in 2/5 (40%) patients. One patient developed bilateral homonymous hemianopia within one week of GKRS. Another patient developed hemiparesis after 4 months of radiosurgery due to development of infarct in the posterior limb of internal capsule. One patient developed steroid resistant brain edema which needed Bevacizumab for the management. Follow up radiology at three months resulted in 4-5 mm well circumscribed lesion with peripheral contrast enhancement surrounding a low signal region. 

Conclusion

Radiosurgical pallidotomy is not a shot in the dark. It should still be considered a treatment modality for selected cases of dystonia. It remains an attractive option in patients with advanced age, significant medical comorbidities, that forbid open stereotactic procedures, or patients on anticoagulation therapy. In resource stricken countries such as India, where majority of the population remains noninsured, lesion intervention is a more feasible option. 


Manjul TRIPATHI (Chandigarh, India)
12:25 - 12:35 #17485 - b36-5 VIM Radiosurgery for tremor : results of a large prospective cohort of 626 consecutive patients.
b36-5 VIM Radiosurgery for tremor : results of a large prospective cohort of 626 consecutive patients.

Objective : Gamma Knife Radiosurgery (GKS) is one of the neurosurgical technics available for the management for severe drug resistant tremor. We are evaluating hereafter safety efficacy of GKS based on the prospective assessment of one of the larger cohort worldwide.

 Materiel & Method :  Between January 2004 & November 2018, 626 patients have been operated using GKS in Timone Marseille University by a single Neurosurgeon (JR). The tremor was an essential tremor (ET) in 432 patients, a parkinsonian one in 88, a mixt in 42, a multiple sclerosis in 8 and other in 11. GKS was performed on the left VIM in 81% of the patients who were males in 58,6% of the cases. The mean age was 73 years (min 31- max 93). Tremor, neuropsychological exam, speech, gait and balance were all assess before and 1 year after.

 Results : The mean follow up is 18 months. In 30 patients (4,7%) we were unable to achieve sufficient FU by ourselves and the FU was performed by the local neurologists of the patients or lost for FU. The mean delay of action of radiosurgery was 4,5 months. The mean disability was before GKS of 30,2/75 and at the last FU of 8,9/75 for a mean improvement of 70,5%. The amplitude of the hand tremor on the treated side was in mean before GKS of 18,7 and at the last FU of 6,6 for a mean improvement of 64,7%. The functional impact was in mean before GKS of 7,66/28 and at the last FU of 2,48/28 for a mean improvement of 67,6 %. An hyper-response to radiosurgery associated to clinical side effects (proprioceptive ataxia, dysarthria, hemiparesis) was observed in 77% of the patients and led to rehabilitation (+- Avastin or hyperbaric oxygen).

 Conclusion : It may be the largest series of GKS for tremor, with a strict prospective assessment. Results are demonstrating the high safety efficacy ratio of this approach in this population of aged and fragile patients. 


Jean REGIS, Giorgio SPATOLA, Axel CRETOL (MARSEILLE), Tatiana WITJAS
12:35 - 12:45 #17836 - b36-6 Gamma Forel's campotomy for dystonia with coarse tremor.
b36-6 Gamma Forel's campotomy for dystonia with coarse tremor.

Introduction: Multiple therapies exist for dystonia, however refractory forms are still challenging. In 1963, Spiegel reported stereotaxic radiofrequency Forel’s Campotomy (FC) to treat Parkinson's disease symptoms. The interruption of the fibers at this target improved dystonia and tremor. It also improved rigidity and tremor in patients with Parkinson’s disease.

Objective To show a Gamma Knife Radiosurgery (GKR) Forel's campotomy to treat dystonia levodopa-responsive with coarse tremor component using the GK Perfexion model (Elekta AB).

Methods: A 29-year-old-woman with a history of neuropsychomotor developmental delay presented generalized dystonia and bilateral proximal tremor of great amplitude since childhood. Magnetic resonance was unremarkable. The dystonia improved significantly with levodopa. She increased dosage over the years up to 1200mg/day and finally lost control of the movement disorder. The most limiting symptom was the coarse proximal tremor in the superior limbs. The patient is right handed. Bilateral deep brain stimulation was offered but declined by the family. GKR was indicated to improve control of the tremor and the dystonia. The left pallido-thalamic tract received 140Gy at the 100% point, using two 4mm collimators. Final targeting was defined using fiber tracking, with attention to the internal capsule dose constrains. Stereotactic coordinates in relation to AC-PC line for the first collimator were x=9mm to the left,  y= at MCP, z= 1mm above, while for the second collimator were x= 10mm left, y= 1mm posterior to MCP, z=1mm above. Treatment lasted 126 minutes. The patient was discharged on the same day. Progressive improvement was noticed at 2 months post-treatment with the patient initiating self-care tasks.

Conclusion: Gamma Knife Forel’s Campotomy for tremor associated with dystonia is feasible. The literature on ablative procedure at Forel’s field is very scarce. Larger number of cases and longer follow-up are needed to validate this approach. 


Juliete MELO DINIZ (SAO PAULO, Brazil), Antônio DE SALLES, Rafael COSTA LIMA MAIA, Aline Lariessy CAMPOS PAIVA, Crystian WILIAN CHAGAS SARAIVA, Alessandra GORGULHO
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C36
11:45 - 12:45

Oral Session
VASCULAR DISORDERS

Moderators: Marcello REIS DA SILVA (Neurosurgeon) (RIO DE JANEIRO, Brazil), Zhiyuan XU (Gamma Knife) (Charlottesville, USA), Vladimir ZACCARIOTTI (Neurosurgeon in Chief) (GOIÂNIA, Brazil)
11:45 - 11:55 #17638 - c36-1 Safety-efficacy of stereotactic radiosurgery in the treatment of ARUBA-eligible patients with unruptured brain AVM ⩽ 5 cc: a cohort of 247 patients.
c36-1 Safety-efficacy of stereotactic radiosurgery in the treatment of ARUBA-eligible patients with unruptured brain AVM ⩽ 5 cc: a cohort of 247 patients.

ObjectiveAccording to ARUBA’s trial conservative treatment seems to be superior to any intervention for unruptured brain arteriovenous malformations (AVM). The aim of this study is to evaluate if this cohort of ARUBA-eligible AVM with a volume ⩽5cc treated by SRS are in line with ARUBA trial. 

 

Materials and methods:A retrospective study was conducted to evaluate the middle and long-term outcomes of unruptured naive brain AVM with a volume ⩽5cc eligible to ARUBA study treated by Gamma-Knife (GKRS) and followed at least 3 years.

 

Results:

From 1992 to 2014, 1979 patients were treated by GKRS for AVM in the Timone University Hospital, among them 249 patients were included in this study. The median age was 36 years (range 18-78). The median treated volume of the nidus was 1.3 cc (range 0.4-5) and 63% of the AVM were in eloquent areas (n=157). In most of the AVM, the RBAS was 1-1.8 (76%) (n=190), the Spetzler-Martin grade was II-III (73%) (n=180), and the VBAS was ≤1point (75%) (n=187).

The overall AVM obliteration rate was 77.1% after at least 3 GKRS session. The obliteration rate was 67% and 73.5% after 1 or 2 GKRS session. The average dose at the margin was 24 Gy (range 15-25) and the median follow-up was 45.04 months (range 36–205.28). Eight patients (3.2%) experienced a hemorrhage after GKRS session, corresponding to a post-GKRS hemorrhage rate of 1.03% per year. The permanent symptomatic RIC rate was 2% (n=5), among them 4 patients (4.7%) increased seizure, 1 with neurological deficit (2.1%). No patient presented radionecrosis or cyst were at last follow-up. 

Conclusion: Our results are not confirming ARUBA conclusions for this AVM cohort ⩽5 cc. The very low toxicity rate with the high occlusion rate is preaching in favor of upfront GKRS for naive unruptured small AVM.


Jean REGIS (MARSEILLE), Jean-François HAK, Giorgio SPATOLA
11:55 - 12:05 #17886 - c36-2 IntuitivePlan inverse planning performance evaluation for arteriovenous malformations.
c36-2 IntuitivePlan inverse planning performance evaluation for arteriovenous malformations.

Forward dose planning for Gamma Knife radiosurgery (GKRS) can be a challenging task and typically requires substantial planning experience to produce optimal clinical plans. IntuitivePlan offers an inverse planning software solution based on convex optimization. It allows additional user interactivity for fine tuning, which has the potential to improve the treatment planning process in terms of quality and efficiency.

In this study we aim to prospectively compare the performance of this novel software solution against manual plans performed by an expert user. A total of 20 arteriovenous malformation (AVM) cases were included in this study, and competing inverse plans were compared using various plan parameters including: Coverage, selectivity, Gradient Index, Paddick Conformity Index, Efficiency Index, beam-on time, number of shots and total planning time

Initial results show that IntuitivePlan produces plans of comparable plan quality for a range of AVM shapes and volumes. Despite the use of substantially more shots that are not “classical”, IntuitivePlan produces dosimetric indices comparable to an expert planner in less than 8 minutes.


Ian PADDICK (London, United Kingdom), Alexis DIMITRIADIS
12:05 - 12:15 #17021 - c36-3 Intracranial Dural Arteriovenous Fistulas with Cortical Venous Drainage: Gamma Knife Radiosurgery as the Treatment of Choice.
c36-3 Intracranial Dural Arteriovenous Fistulas with Cortical Venous Drainage: Gamma Knife Radiosurgery as the Treatment of Choice.

Objective: To evaluate the clinical and radiological outcome of Gamma knife radiosurgery (GKS) in the treatment of intracranial dural arteriovenous fistula (DAVF) with cortical venous drainage (CVD) and compare it with the outcome of endovascular therapy.

Methods: This series includes patients who underwent GKS or endovascular therapy for intracranial DAVF with CVD over 10 years (Jan 2007 to Dec 2016) at the All India Institute of Medical Sciences, New Delhi. Their demographic profile, clinical presentation, imaging details, and follow up clinical status were reviewed retrospectively. Clinical follow up was done once in every 6 months. Radiological follow up using digital subtraction angiography (DSA) was performed at a mean duration of 24 months post intervention. Patients who had a clinical follow up of less than 1 year were excluded from the study.

Results: 35 patients (26 in embolization group and 9 in GKS group) who had intracranial DAVF with CVD were included the study. Clinical improvement was seen in 77.78% of the patients who received GKS and 57.7% in the patients who underwent embolization (p = 0.431). Complete obliteration of DAVF was seen in 55.56% of the patients in the GKS group and 57.7% of the patients in the embolization group (p = 1).

Conclusion: Our study shows that GKS is at least as effective as embolization in terms of clinical and radiological outcome in the treatment of intracranial DAVF with CVD. Contrary to popular perception, GKS should also be considered as the first line treatment of intracranial DAVF with CVD.


Hardik SARDANA (New Delhi, India), Deepak AGRAWAL
12:15 - 12:25 #16718 - c36-4 Dose Response in Volume Staged Radiosurgery for Large Arteriovenous Malformations: A Multi-Institutional Study.
c36-4 Dose Response in Volume Staged Radiosurgery for Large Arteriovenous Malformations: A Multi-Institutional Study.

Abstract

Background

Optimal treatment paradigm for large arteriovenous malformations (AVMs) is controversial. Volume-staged stereotactic radiosurgery (VS-SRS) provides an effective option for these high-risk lesions, but optimizing treatment for these recalcitrant and rare lesions has proven difficult.

 

Methods

This is a multi-centered retrospective review of patients treated with a planned prospective volume staging approach to stereotactically treat the entire nidus of an AVM with volume stages separated by intervals of 3-6 months. A total of 9 radiosurgical centers treated 257 patients with VS-SRS between 1991 and 2016. We evaluated near complete response (nCR), obliteration, cure, and overall survival.

 

Results

With a median age of 33 years old at the time of first SRS volume stage, patients received 2-4 total volume stages and a median follow up of 5.7 years after VS-SRS. The median total AVM nidus volume was 23.25 cc (range: 7.7-94.4 cc) with a median margin dose per stage of 17 Gy (range: 12-20 Gy). Total AVM volume, margin dose per stage, compact nidus, lack of prior embolization, and lack of thalamic location involvement were all associated with improved outcomes. Dose >/= 17.5 Gy was strongly associated with improved rates of nCR, obliteration, and cure. With dose >/= 17.5 Gy, 5- and 10- year cure rates were 33.7% and 76.8% in evaluable patients compared to 23.7% and 34.7% of patients with 17 Gy  and 6.4% and 20.6% with /= 17 Gy at 5 years (p = 0.007). For compact nidus architecture, the obliteration rates at 5 years were 10.7% vs 9.3% vs 26.6% for dose >17 Gy vs 17 Gy vs >/= 17.5 Gy (p = 0.952).

 

 

Conclusion

VS-SRS is an option for upfront treatment of large AVMs. Higher dose was associated with improved rates of nCR, obliteration, and cure suggesting that larger volumetric responses may facilitate salvage therapy and optimize the chance for cure.


Zachary SEYMOUR (Royal Oak, USA), Jason CHAN, Penny SNEED, Hideyuki KANO, Rachel JACOBS, Craig LEHOCKY, L. Dade LUNSFORD, Hong YE, Tomas CHYTKA, Roman LISCAK, Cheng-Chia LEE, Huai-Che YANG, Dale DING, Jason SHEEHAN, Caleb FELICIANO, Rafael RODRIGUEZ-MERCADO, Veronica CHIANG, Judith HESS, Samuel SOMMARUGA, Brendan MCSHANE, John LEE, Anthony KAUFMANN, Inga GRILLS, Micheal MCDERMOTT
12:25 - 12:35 #17861 - c36-5 Long-term results following repeat gamma knife surgery for incompletely obliterated arteriovenous malformations after the first gamma knife treatment.
c36-5 Long-term results following repeat gamma knife surgery for incompletely obliterated arteriovenous malformations after the first gamma knife treatment.

Objective: Gamma Knife Surgery (GKS) may be repeated for incompletely obliterated arteriovenous malformations (AVM) following initial GKS (iGKS). However, reports on the results are sparse. We reviewed our national series of patients.

 

Methods: Of 521 patients treated for AVM with GKS in Norway between 1988 and 2016, 55 (10.6%) (32 males, median age 39 y) received repeat-GKS including 26 (47.3%) unruptured and 7 AVMs (13%) with associated aneurysm. Two (3.6%) AVMs, one with prior hemorrhage and aneurysm, ruptured between treatments, at 5 and 29 months. The mean nidus volume was 1.67 cm³ (range 0.1-6.6) at iGKS and 0.49 cm³ (range 0.1-3.96) at repeat-GKS. The mean volume reduction and time between treatments was 62% (range 0-99.9%) and 44 months (range 5-110), respectively. Mean follow-up after repeat-GKS was 42 months (range 0-69). One patient (2%) refused follow-up.

 

Results: Complete obliteration was achieved in 28 out of 55 repeat-treated AVMs (51%) while 15 (27%) were reduced in size and 11 (20%) unchanged. The median time to obliteration was 57 months (95% CI: 40-74). Out-of-field failure was seen in 29 (52.7%) AVMs following iGKS (reapperance of compressed nidus by hemorrhage (n=2), inadequate angiography (n=5) and incomplete delineation of nidus (n=22)); and 3 (5.5%) following repeat-GKS (inadequate angiography). The risk of bleeding/year was reduced from 2.3% before treatment to 0.8% between treatments and 0% following repeat-GKS. The complication rate for iGKS and repeat-GKS was 9% (n=5); worsening of epilepsy (n=1), cyst formation (n=1) and temporary neurological deficits (n=3). One patient with an obliterated AVM died of an unrelated cause.

 

Conclusion: Our long-term results are encouraging compared to those predicted by the ARUBA trial. Following repeat-GKS the obliteration rate was increased from 0 to more than 50% with a low risk of complications. Of note, the risk of hemorrhage was reduced also for subtotally obliterated AVMs.


Bente Sandvei SKEIE (Bergen, Norway), Peter QUARCOO, Jan Ingemann HEGGDAL, Kjersti Gaustad KLETT, Elisabeth LARSEN, Paal-Henning PEDERSEN, Geir Olve SKEIE, Per Øyvind ENGER
12:35 - 12:45 #17875 - c36-6 Stereotactic Diffusion Tensor Tractography For Gamma Knife Stereotactic Treatment Of Brain Arteriovenous Malformations.
c36-6 Stereotactic Diffusion Tensor Tractography For Gamma Knife Stereotactic Treatment Of Brain Arteriovenous Malformations.

Objectives:

Advances in neuro-imaging have improved the safety of stereotactic radiosurgery. Nonetheless GammaKnife radiosurgery for AVM still has a risk of developing new neurological deficits which may be permanent. We report our experience with integrating stereotactic diffusion tensor imaging (DTI) tractography into treatment planning for Gamma Knife radio-surgery for Arteriovenous Malformations

Methods:

40 Day of treatment  Stereotactic DTI studies were performed in 37 patients who underwent GKRS for AVM. Marginal dose 18-25 Gy. 3 patients underwent staged SRS of large AVM & five patients were had previous GK for their AVM. DTI images were obtained at the time of standard GKRS protocol MRI (T1 and T2 weighted) for treatment, with the patient's head secured by a Leksell stereotactic frame. DTI was performed with diffusion gradients in 32 directions and coregistered with the volumetric T1-weighted study. DTI post-processing by means of commercially available software allowed tensor computation and the creation of directionally encoded color, apparent diffusion coefficient & fractional anisotropy mapped sequences. In addition, the software allowed visualized critical tracts to be exported as a structural volume and integrated into GammaPlan as an “organ at risk” during shot planning.Tracts at risk were subjected to dosimetry. Patient follow-up was 3 months to 3 1/2 years with 26 patients returning for post teatment DTI.

Results:

DTI allowed visualisation & dosimetry of eloquent white fibre tracts (optic radiation, corticospinal tract & arcuate fasiculus) during treatment planning.

Most patients had pathology in the vicinity of eloquent tracts and/or the cortex. One patient with mesial temporal AVM developed delayed worsening of a pre-existing hemianopia & another with AVM required steroids for cerebral swelling. no other neurological deficits due to radiation were recorded at follow-up.  

Conclusions:

Tractography has been reported to reduce the risk of motor complcations after SRS for AVM.iStereotactic Tractography represents a promising tool for preventing GK-SRS complications by reduction in radiation doses to functional organs at risk, including critical cortical areas and subcortical white matter tracts & further increase our knowledge of critical cerebral structure radiation tolerances to better improve the therapeutic potential and safety of SRS for AVMs


Cormac GAVIN (London, United Kingdom), H. Ian SABIN
El Pardo I
12:45 FREE TIME FOR LUNCH - VISIT OF THE EXHIBITION & POSTERS
14:00

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C37
14:00 - 15:30

Session Ibero-Latin-American Society of Radiosurgery
Part I

Moderators: Julio ANTICO (Argentina), Sergio MORENO-JIMENEZ (Chief) (Mexico city, Mexico), Kita SALLABANDA (Medical Direcor) (Madrid, Spain)
14:00 - 14:10 Advances in the Treatment of Giant Metastases: Surgery versus Staged Radiosurgery. Eduardo LOVO IGLESIAS (Brain and Spine Radiosurgery Program) (Speaker, San Salvador, El Salvador)
14:10 - 14:20 Radiosurgery as a Rescue Treatment for High Grade Glioma: Does it Work and Controversies. Pablo CASTRO PENA (Radiation Oncologist) (Speaker, Cordoba, Argentina)
14:20 - 14:30 Advances on the Treatment of Spine Metastases: Radiosurgery versus Conventional Radiotherapy. Lucas Ignacio CAUSSA (MD) (Speaker, Córdoba, Argentina)
14:30 - 14:40 Radiosurgery in the Treatment of Multiple Metastases: The Importance of Global Volume. Christian VARGAS (Speaker, Peru)
14:40 - 14:50 Radiosurgery and Epilepsy. Sergio MORENO-JIMENEZ (Chief) (Speaker, Mexico city, Mexico)
14:50 - 15:00 Radiosurgery in Giant AVMs: Which is the Best Option? Kita SALLABANDA (Medical Direcor) (Speaker, Madrid, Spain)
15:00 - 15:10 Treatment of Cranial Base Tumors: When Radiosurgery? Alessandra GORGULHO (Director) (Speaker, SÃO PAULO, Brazil)
15:10 - 15:30 Discussion.
El Pardo I
15:30 COFFEE BREAK - POSTERS & EXHIBITION
16:00

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C38
16:00 - 18:00

Session Ibero-Latin-American Society of Radiosurgery
Part II

Speakers: Miguel A. CELIS (DIRECTOR) (Speaker, MEXICO, Mexico), Sergio MORENO-JIMENEZ (Chief) (Speaker, Mexico city, Mexico), Kita SALLABANDA (Medical Direcor) (Speaker, Madrid, Spain)
16:00 - 16:10 Radiosurgery Concepts, Devices, Penumbra and Precision QA. Daniel VENENCIA (Speaker, Cordoba, Argentina)
16:10 - 16:20 Certification Program in Radiosurgery: Requirements. Kita SALLABANDA (Medical Direcor) (Speaker, Madrid, Spain)
16:20 - 16:30 Radiosurgery in Large Lesions: Hypofractionation, Advantages and Controversies. Ignacio SISAIMON (Speaker, Argentina)
16:30 - 16:40 Radiosurgery in Pediatric Patients: Specific Concepts. Carlos CHIRAOLA (Speaker, Argentina)
16:40 - 16:50 Combined Treatment in Large Schwannomas. Jose LORENZONI (Speaker, Chile)
16:50 - 17:00 Radiosurgery in Acoustic Schwannomas. Jorge MANDOLESI (Neurosurgeon) (Speaker, BUENOS AIRES, Argentina)
17:00 - 17:10 Long Term Follow up of SRS for Radiosurgery. Julio ANTICO (Speaker, Argentina)
17:10 - 17:20 SRS for Deep Cavernomas. Jessica CHAVEZ NOGUEDA (Radiation Oncologist) (Speaker, México, Mexico)
17:20 - 17:30 SRS for Glomus Tumors. Ascary VELAZQUEZ-PACHECO (Professor / Medical Staff) (Speaker, Monterrey, Mexico)
17:30 - 17:40 SRS for Choroidal Melanomas. Luis LARREA (Director) (Speaker, Valencia, Spain)
17:40 - 18:00 Discussion.
El Pardo I
Wednesday 12 June
07:30

"Wednesday 12 June"

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A41
07:30 - 09:00

BREAKFAST SEMINAR
QUALITY SRS/SRT: WHAT'S REQUIRED

Moderators: Guilherme BULGRAEN DOS SANTOS (Brazil), Alexis DIMITRIADIS (Physicist) (London, Austria), Anderson PASSARO (Medical Physicist) (São Paulo, Brazil)
07:30 - 07:50 Task Force Recommendations (AAPM/ASTRO). Steven GOETSCH (Medical Physicist) (Speaker, Solana Beach, USA)
07:50 - 08:10 The ISRS Accreditation Program. Ian PADDICK (Consultant Physicist) (Speaker, London, United Kingdom)
08:10 - 08:30 QA perspectives in the management of respiratory motion. Andrea GIRARDI (Medical Physicist) (Speaker, Brussels, Belgium)
08:30 - 08:50 Emerging QA techniques. Fang-Fang YIN (Medical Physicist/Professor) (Speaker, Durham, NC, USA)
Segovia Plenary

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B41
07:30 - 09:00

BREAKFAST SEMINAR
EMERGING SBRT INDICATIONS

Moderators: Sebastiao CORREA (RADIO-Oncologist) (São Paulo, Brazil), Richard POPPLE (Medical Physicist) (Birmingham, USA), Ben SLOTMAN (Professor) (AMSTERDAM, The Netherlands)
07:30 - 07:50 Cervical. Yoshiya Josh YAMADA (Speaker, New York, USA)
07:50 - 08:10 SBRT in the management of inoperable pancreatic cancer. Marta SCORSETTI (Director Department) (Speaker, Rozzano-Milan, Italy)
08:10 - 08:30 SBRT and liver. Lorenzo LIVI (Full Professor, Head of Radiation Oncology Unit) (Speaker, Florence, Italy)
08:30 - 08:50 Kidney. David PRYOR (Radiation Oncologist) (Speaker, Brisbane, Australia)
Segovia Break Out

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C41
07:30 - 09:00

BREAKFAST SEMINAR
VASCULAR DISORDERS

Moderators: Leonardo FRIGHETTO (Neurosurgeon) (Passo Fundo, Brazil), Bruce POLLOCK (Physician) (Rochester, USA), Bruno SANTOS (Neurosurgeon) (Aracaju, Brazil)
07:30 - 08:00 Management of Unruptured AVMs in the Post ARUBA Era. Steven CHANG (Member) (Speaker, Stanford, USA)
08:00 - 08:30 Large AVMs: Strategies and Outcomes. Isaac YANG (Associate Professor) (Speaker, Los Angeles, USA)
08:30 - 09:00 Endovascular Combination Therapy: Best Practices. Eduardo WAJNBERG (Speaker, Brazil)
El Pardo I
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A42
09:00 - 10:15

PLENARY SESSION
NOVEL TECHNOLOGIES & TECHNIQUES - PART I

Moderators: Matthew FOOTE (Deputy Director / Co-Director) (Brisbane, Australia), Marc LEVIVIER (Chef de Service) (Lausanne, Switzerland), Charles Ambroise. VALERY (directeur unité GK) (Paris, France)
09:00 - 09:15 Liquid Biopsy and Implications for SRS/SBRT. John SUH (Radiation Oncologist) (Speaker, Cleveland, USA)
09:15 - 09:30 DTI & SRS for Behavioral Disorders. Alessandra GORGULHO (Director) (Speaker, SÃO PAULO, Brazil)
09:30 - 09:45 Brain Radiosurgery Without a Bunker. John ADLER (neurosurgery) (Speaker, San Francisco, USA)
09:45 - 10:00 MR-LINAC Technology. David JAFFRAY (Reviewer) (Speaker, Houston, USA)
10:00 - 10:15 #17783 - When the machine is challenging the expert : Intuitive inverse planning.
When the machine is challenging the expert : Intuitive inverse planning.

Background : Inverse doseplanning are nowadays far to be competing with the quality of doseplanning elaborated by expert with an experience of thousands of planning for Gamma Knife radiosurgery (GKS). A new inverse planning (IP) method based on « efficient convex optimization algorithms » is supposed to provide high quality doseplans in real-time.

Material and Method : Have been recruited 86 patients treated by single dose GKS for vestibular schwannomas (VS). The planning elaborated by the first author with an experience of 27 years and more than 15000 doseplanning is serving as a reference. The constraints determined by the planner lead the IP for a first real-time planning. Interactive additional constraints are proposed by the planner in order to optimize the plan and a second optimized plan is calculated by the IP. The primary endpoint is the Paddick index. Coverage, selectivity and gradient indexes, dose at the organ at risk, 12 Gy isodose line volume are compared among the three plans (expert, IP run 1 and IP run 2). The statistical analyses is planned on a non-inferiority trial design.

Results: After a single run of the IP, the Paddick index of the IP is already demonstrating to be non-inferior to the one of the expert. For the expert and the IP respectively, the median conformity index was 0,99 and 0,98, the median selectivity index 0,92 and 0,90, the median gradient index was 2,95 and 2,84, the median dose at the modulus of the cochlea was 2,83 Gy and 2,86 Gy, the median number of shot 14,31 and 24,13, the median beam-on time was 46,20 min and 26,77 min.

Conclusion: These preliminary results are showing that the “Intuitive Plan” IP based on « efficient convex optimization algorithms » is providing, in real-time, high quality doseplans with excellent conformity, selectivity and gradient indexes with specially optimized beam-on time. If the new IP proposed here is truly able to compete in real -ime with the quality of the plans of an expert with long years of experience, this would allow customers with limited experience to provide immediately there patients with high quality GKS. Moreover, for more experienced users, it may also help to save both time spent planning and beam-on time, while being able to interact intuitively with the dosimetry.


Jean REGIS (MARSEILLE), Hamdi HUSSEIN, Louise MERLY, Castillo LAURA, Anne BALOSSIER, Giorgio SPATOLA
Segovia Plenary
10:15 COFFEE BREAK -POSTERS & EXHIBITION
10:45

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A44
10:45 - 11:15

PARALLEL SESSION
NOVEL TECHNOLOGIES & TECHNIQUES - PART II

Moderators: John ADLER (neurosurgery) (San Francisco, USA), Marc LEVIVIER (Chef de Service) (Lausanne, Switzerland), Sergio MORENO-JIMENEZ (Chief) (Mexico city, Mexico)
10:45 - 10:55 #17633 - a44-1 Procedural aspects of stereotactic radiosurgery for ablation of ventricular tachycardia.
a44-1 Procedural aspects of stereotactic radiosurgery for ablation of ventricular tachycardia.

Purpose

Authors present procedural aspects based on case report series of cardiac radiosurgery in a patient with malignant ventricular tachycardia.

Material and methods

Patients with stable chronic heart failure (NYHA II, III) with decreased left ventricular ejection fraction, recurrent therapies for VT from Implantable Cardioverter Defibrillator (ICD) and failure of catheter ablation were treated by radiosurgical ablation. Stereotactic radiosurgery system CyberKnife was used. The location of the critical part of the arrhythmogenic substrate was determined by electroanatomic mapping during catheter ablation procedure. The ICD lead was used as a surrogate for compensation of respiratory movements. No additional margin for Planning Target Volume (PTV) was added. We evaluated dosimetric aspects and and radiation-induced events.

 

Results

From January 2014 until March 2017, ten patients (9 males/1 female), mean age 66 years (range 64-80) received radiosurgical ablation 25Gy in one fraction. Mean PTV, treatment duration,  isodose line with prescribed dose, conformality index, and homogeneity index were 22.15 ccm (range 14.2-29.6), 68 min (range 45-80), 80% (range 66-84), 1.28 (range 1.15-1.78) and 1.24 (range 1.19-1.52), respectively. Nine correlation models have to be often created, median one per 12 minutes (range 2-15 min), to reach precision better than 3 mm (average correlation error 1,1 mm). Only one type of acute radiation-related toxicity was observed: nausea occurred in four patients with the target volume localized in the inferior wall of the left ventricle, close to the stomach. All four patients showed a good response to setron-based antiemetic drugs administered for three days. One patient (number 5 in apendix) with known mitral regurgitation presented with progression of regurgitation and changes in valvular morphology 17 month after radiosurgery (possible grade 3 late radiation related toxicity). No other late radiation-related toxicity events were observed and three patients suffered non-arrhythmic deaths during long follow up.

Conclusion

Stereotactic radiosurgery of recurrent ventricular tachycardia is feasible and seems a viable option as a bail-out procedure after failed catheter ablation of VT.


Jakub CVEK (OSTRAVA, Czech Republic), Radek NEUWIRTH, Lukas KNYBEL, Otakar JIRAVSKY, Lukas MOLENDA, Josef KAUTZNER, Marek SRAMKO, Petr PEICHL
11:05 - 11:15 #17738 - a44-3 Laser interstitial thermal therapy (LITT) in the diagnosis and treatment of suspected radiation-induced inflammation vs recurrence after SRS.
a44-3 Laser interstitial thermal therapy (LITT) in the diagnosis and treatment of suspected radiation-induced inflammation vs recurrence after SRS.

Brain metastases show very high rates of response to stereotactic radiosurgery (SRS.) However, a substantial fraction of treated lesions will enlarge and/or become more conspicuous, as early as 4 months or as late as 3 years or more, following SRS.  Management of these lesions is complicated by difficulty in definitively distinguishing radiation-induced inflammation (radionecrosis) from tumor recurrence / progression on imaging.  Surgical resection of a lesion can provide a histologic diagnosis and therapeutic benefit in such cases, but has dangers in patients who are poor surgical candidates. Conversely, stereotactic biopsy can provide a diagnosis with minimal risk, but does not provide needed therapeutic relief. Laser Interstitial Thermal Therapy (LITT), which combines minimally invasive laser thermal ablation with real time in vivo MRI-based temperature monitoring, has now emerged as a successful treatment approach for the management of radiographically progressive metastatic lesions post-SRS, which might otherwise have few remaining options. LITT proves effective against both radiation-induced inflammation and recurrent metastatic disease. Furthermore, ample evidence suggests LITT opens the blood-brain barrier (BBB) for a period of time after treatment, improving otherwise poor access for other modalities, including immune-based platforms. Therefore, LITT is well-suited to intracranial lesions, proffering a novel treatment platform on its own, while simultaneously potentiating therapies that otherwise provide limited efficacy in the brain. Unfortunately, LITT remains handicapped by a small radius of treatment (lesions larger than 3cm provide a challenge) and a lack of treatment specificity for tumor versus normal tissue. Despite these limits, LITT has reshaped our multi-disciplinary treatment algorithm for radiographic progression as applied in our Center for Brain Metastasis. We present our current clinical experience with LITT in more than 50 cases of radiographically progressing post-SRS metastatic lesions. We also highlight our research efforts to enhance the technology with a novel nanotechnology platform.


Peter FECCI (Durham, USA), Scott FLOYD, Jordan TOROK, John KIRKPATRICK
10:45 - 11:15 #17740 - A44-4 Molecular profiling of high dose irradiated tissues identifies differential gene expression profiles between conventional and high dose “flash” protons.
A44-4 Molecular profiling of high dose irradiated tissues identifies differential gene expression profiles between conventional and high dose “flash” protons.

Recent studies have highlighted an enhanced therapeutic index of ultra-high dose rate, or FLASH, irradiation compared to conventional radiation treatment modalities (Favaudon et al., 2014). However, the molecular correlates of response remain unknown and may aid to delineate the molecular underpinnings of efficacy and toxicity.  While previous studies have focused on experimental aspects of electron FLASH we sought to test proton FLASH in a preclinical setting. To this end, a clinical Varian ProBeam irradiated the entire thoracic region of sex and age matched mice to a dose range of 15-20 Gy at FLASH (40 Gy/sec), Conventional (1 Gy/s) and pulsed-FLASH (FLASH dose split into 10 doses at 1 second intervals) dose rates. Upon sacrifice after 24 hours, the lungs were harvested for histology and genetic expression profiling using Agilent mouse genome arrays. We observed 15 and 20-fold fewer differentially expressed genes in FLASH and pulsed-FLASH respectively when compared to the conventionally treated samples. To systematically assess the response pathways, we conducted Gene Set Enrichment Analysis (GSEA) on all expression profiles and observed down regulation of cell cycle and mitotic pathways in all treatment groups. Notably, split-flash induced immune and inflammatory signaling pathways such as JAK-STAT. We observed up to a 30% reduction in lung fibrosis, as well as reduced incidence of skin dermatitis and improved overall survival in FLASH- vs conventionally-treated mice. These findings highlight that flash modalities induce a unique subset of pathways which are not present in conventional proton therapy. Future work will seek to further validate our preliminary results of differential expression profiles and to provide insight into the mechanism of action of FLASH radiation and its impact on potential therapeutic opportunities.


Angel KU VILLANUEVA, Swati GIRDHANI, Eric ABEL, Isabel JACKSON, John ELEY, Zeljko VUJASKOVIC, Renate PARRY, Sengupta DEBANTI (Palo ALto, USA)
Segovia Plenary

"Wednesday 12 June"

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B44
10:45 - 11:45

PARALLEL SESSION
OVERVIEW OF CURRENT TREATMENT TECHNIQUES FOR GLIOMAS

Moderators: Jing LI (Radiation Oncologist) (Houston, USA), Marcos MALDAUN (Neurosurgical Oncology) (São Paulo - SP, Brazil), José Marcus ROTTA (Presidente) (Brazil)
10:45 - 10:55 Advancements of Immunotherapy for GBMs. Samuel CHAO (Radiation Oncologist) (Speaker, Cleveland, OH, USA)
10:55 - 11:05 What are the target and margin? John P. KIRKPATRICK (Professor - Radiation Oncology & Neurosurgey) (Speaker, Durham, NC, USA)
The rationale for radiosurgery the contrast-enhancing lesion alone in recurrent malignant gliomas
11:05 - 11:15 Radiosurgery and Stereotactic Radiotherapy for Gliomas. Luis LARREA (Director) (Speaker, Valencia, Spain)
11:15 - 11:25 Multimodality Approach for Glioma Management. Tony WANG (Professor of Radiation Oncology) (Speaker, New York, USA)
11:25 - 11:35 20 Years of Leading Edge GBM Radiosurgery: An Update. Christopher DUMA (Speaker) (Speaker, Newport Beach, USA)
Segovia Break Out

"Wednesday 12 June"

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C44
10:45 - 11:15

Oral Session
OCULAR DISORDERS

Moderators: Antonio DE SALLES (Professor - Chief) (SÃO PAULO, Brazil), Andrey GOLANOV (Chief of the Department) (Moscow, Russia), Bruno SANTOS (Neurosurgeon) (Aracaju, Brazil)
10:45 - 10:55 #16743 - c44-1 Relative survival rates and complications in uveal melanoma patients after C LINAC stereotactic radiosurgery.
c44-1 Relative survival rates and complications in uveal melanoma patients after C LINAC stereotactic radiosurgery.

Uveal melanoma (iris, ciliary body, choroid) is the most frequent intraocular malignant tumor in adults.

Long term analysis of 168 patients with intraocular uveal melanoma treated by stereotactic radio surgery (SRS) at linear accelerator in Slovakia by "One-day session" radiosurgery at C LINAC. The median tumor volume at baseline was 0.3cm3 with range from 0.05 to 2.6cm3. The therapeutic dose was 35.0Gy by 99% of DVH (dose volume histogram). Average overall survival after stereotactic irradiation was 1st year after SRS 96.4%, 2nd year 83%, in 5 years 82.7%. Survival rates at 5-year interval and the rates of secondary enucleating due to complications after one-day session linear accelerator irradiation were comparable to those achieved with other irradiation techniques used for treatment uveal melanoma. Radiation complications can lead to visual acuity reduction or secondary enucleation of the eye globe. Radiation-induced optic neuropathy (RION) is a severe ocular complication developing in high-risk patients with uveal melanoma after SRS. We analysed association between the secondary enucleation and the presence of secondary glaucoma or hemophtalmus as well as of the radiation-induced optic neuropathy after SRS. Secondary enucleation was necessary 16.7% patients due to secondary glaucoma. The presence of RION was significantly associated with a higher dose on the optic nerve (P=0.0123 in invariable and 0.0049 in multivariable analysis, respectively). Importantly, the overall survival of patients who underwent secondary enucleation was not different from the survival of patients without enucleation (P=0.7501).


Alena FURDOVA (Bratislava SLOVAKIA, Slovakia), Miron SRAMKA, Gabriel KRALIK, Martin CHORVATH
10:55 - 11:05 #17733 - c44-2 Gamma-Knife radiosurgery as an eye salvage treatment of intraocular retinoblastoma: three-year results of a pilot study.
c44-2 Gamma-Knife radiosurgery as an eye salvage treatment of intraocular retinoblastoma: three-year results of a pilot study.

Background: In some cases of chemoresistant or recurrent intraocular retinoblastoma (Rb) external beam radiotherapy (RT) is the only way to save the eye. Due to severe complications conventional RT currently has very limited use. To the best of our knowledge there is no information concerning Gamma-knife radiosurgery (GKRS) in the management of Rb.

Purpose: To present the three-year experience of single fraction GKRS of Rb as an alternative to enucleation.

Methods: Since June 2015 fifteen eyes of 14 patients aged from 12 to 114 months (mean 35) with Rb Group B (n=4), Group C (n=1) and Group D (n=10) were treated with GKRS. All patients previously were treated with all kinds of chemotherapy including systemic, intra-arterial, and intravitreal, different kinds of focal ophthalmological treatment. Due to different reasons there were no capabilities to preserve the eye using conventional approaches.

Three types of dosimetric plans were used and will be presented – single PTV for the whole vitreous cavity (3 eyes), PTV for single retinal or vitreous tumor (8 eyes), and double PTVs for double retinal tumors or retinal and vitreous lesions (4 eyes). In cases of massive vitreous Rb (4 patients) irradiation dose of 20-22 Gy at 50% isodose was prescribed along the inner MRI/CT contour of the eye globe and the lens. The retinal tumors were treated with 22-24 Gy at 50% isodose. Doses for critical structures of the eye and orbit have been also taken into consideration, and will be presented.

Results: Fourteen eyes were preserved. Complete tumor regression was achieved in 11 eyes. In 3 eyes more than 50% regression was seen. One eye was enucleated because of suspicion of tumor progression. Complications were analysed according to time after chemotherapy. Vitreous hemorrhage occurred in 4 patients and was successfully managed conservatively or surgically with intraocular Melphalan irrigation. In 5 eyes mild to moderate optic neuropathy and/or retinopathy developed. In 3 eyes retinal detachment occurred. One eye developed eccentric opacities of posterior lens capsule. No signs of iridocyclitis, keratopathy, and damage of orbital tissues, bones, or brain were seen. Follow-up was from 4 to 41 months (mean 12.5).          

Conclusions: The three-year experience of GKRS for Rb showed that it may be a reasonable treatment approach as an alternative to enucleation in selective cases. 


Andrey YAROVOY, Vera YAROVAYA (Moscow, Russia), Andrey GOLANOV, Valery KOSTJUCHENKO, Karina DZICCOEVA
11:05 - 11:15 #17781 - c44-3 Outcomes of gamma-knife radiosurgery of posterior uveal melanoma unsuitable for other eye-sparing treatment modalities.
c44-3 Outcomes of gamma-knife radiosurgery of posterior uveal melanoma unsuitable for other eye-sparing treatment modalities.

Currently a wide spectrum of eye-sparing treatment modalities for posterior uveal melanoma (PUM) are in use but they have limited indications.

Purpose: to present the results of gamma-knife radiosurgery (GKRS) of PUM unsuitable for other eye-sparing treatment modalities.

 Methods: Since 2012 sixteen consecutive patients aged from 15 to 78 years with PUM were included into the study and treated with GKRS. These tumors were not indicated to other eye-sparing modalities available in our clinic – ruthenium-106 brachytherapy, transretinal excision, transscleral excision, or laser treatment, because of the size or/and location. Majority of patients refused to remove the eye. Two patients had the only eye. Tumor thickness was from 5.5 to 9.6 mm, mean 7.7 mm, basal diameter from 9.4 to 21.4 mm, mean 15.0 mm. Four tumors were juxtapapillar. GKRS irradiation doses were 35-40 Gy on 50% isodose curve.

Results: Partial tumor regression was achieved in all cases. There were no cases of complete regression. Regression after GKRS was much slower than after brachytherapy. Two peripapillar tumors progressed and the eyes were enucleated.  Two patients underwent endoresection of irradiated tumors 2 years after GKRS because of very limited response. One eye was removed because of phthisis bulbi. Vision increased in 3 patients, decreased in 5. One patient developed liver metastasis and died in 2 years after treatment. Thirteen eyes (81%) were preserved. The follow up was from 12 to 82 months, mean 39 months.

Conclusion: GKRS is an effective treatment option for PUM not suitable for brachytherapy or surgical excision and can save the eye and vision in selective cases.


Andrey YAROVOY (Moscow, Russia), Andrey GOLANOV, Valery KOSTJUCHENKO, Vera YAROVAYA, Amina CHOCHAEVA
El Pardo I
11:15

"Wednesday 12 June"

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A45
11:15 - 11:45

PARALLEL SESSION
EXPANDING APPLICATION OF SBRT: HEAD AND NECK -- OLIGOMETASTASES

Moderators: Ana BOTERO (Radiation Oncologist) (Pembroke Pines, USA), Miguel A. CELIS (DIRECTOR) (MEXICO, Mexico), Sebastiao CORREA (RADIO-Oncologist) (São Paulo, Brazil)
11:15 - 11:25 #17814 - a45-1 Stereotactic Body Radiotherapy (SBRT) for head and neck cancers in previously unirradiated medically unfit patients.
a45-1 Stereotactic Body Radiotherapy (SBRT) for head and neck cancers in previously unirradiated medically unfit patients.

Background

SBRT has been established as an option for treatment of recurrent cancers of the head and neck (H&N) in previously irradiated patients. There has been limited data published on using SBRT palliatively for patients who have not undergone previous radiation therapy (RT).

Material and Methods

From August 2011 to August 2018, 66 patients with cancers of the H&N who had not received previous RT were treated with SBRT. Median age was 80 years (range, 25-98). 40 patients were men and 26 were women. 45 patients had newly diagnosed H&N cancers and 21 had recurrences previously treated by surgery. All were not considered to be candidates for curative treatment via surgery or conventionally fractionated chemoRT due to extent of primary of disease, presence of metastases or performance status. Median KPS was 70 (range, 50-90). Median SBRT dose was 40 Gy (range, 24-40). All but two patients underwent 5 fraction regimens. Median number of days between first and last fraction of SBRT was 15. Median PTV volume was 82 cubic centimeters. 32 patients received concurrent systemic therapy with SBRT (6 chemotherapy, 20 cetuximab, 4 chemotherapy and cetuximab, 2 nivolumab) and 34 patients received no systemic therapy.

Results

Median follow-up was 16 months (range, 1-89). Overall survival was 44% with a median survival of 10 months (range, 1-47). Local control was 68%, with 21 patients failing in-field at a median of 4.3 months. An additional 4 patients experienced marginal failure, with the majority of the recurrence occurring outside of the SBRT PTV.  Regional and distant control were 73% and 76%, respectively. No collected variables had a significant effect on control or survival using univariate and multivariate analysis, including age, gender, race, KPS, smoking, alcohol, stage, dose, time elapsed during SBRT, PTV volume or use of concurrent systemic therapy. Only two patients (3%) experienced grade 3+ toxicity, which included one grade 3 dysphagia and one grade 3 anorexia.  

Conclusion

SBRT is a viable option for control and palliation in previously unirradiated patients with H&N cancers who are not candidates for curative treatment. Rates of control, survival and toxicity are all similar to those reported in previously irradiated patients.


Emile GOGINENI (New York, USA), Zaker RANA, Prashant VEMPATI, Jessie KARTEN, Anurag SHARMA, Douglas FRANK, Doru PAUL, Nagashree SEETHARAMU, Maged GHALY
11:25 - 11:30 #17813 - a45-2 Safety and efficacy of repeat stereotactic body radiotherapy (SBRT) for local recurrence of head and neck cancer after initial SBRT.
a45-2 Safety and efficacy of repeat stereotactic body radiotherapy (SBRT) for local recurrence of head and neck cancer after initial SBRT.

Background

SBRT has been established as an option for treatment of recurrent cancers of the head and neck (H&N) in previously irradiated patients. There has been limited data published on effective means of salvaging patients who fail SBRT. Here we report on the safety and efficacy of repeat SBRT (RSBRT).

Material and Methods

From October 2012 to May 2018, 9 patients with local relapse of primary H&N cancer who failed first course of SBRT (FSBRT) were retreated with RSBRT. Median age at RSBRT was 67 years (range, 51-90). 7 patients were men and 2 were women. FSBRT doses were 25 Gy in 1 patient, 35 Gy in 3 patients and 40 Gy in 5 patients, all in 5 fractions. 3 patients received concurrent chemotherapy (CT) and 2 patients received concurrent cetuximab (CET) with first course of SBRT. Maximum toxicity grades were between 0 and 2 for FSBRT using CTCAE version 5.0. Local recurrences were diagnosed by CT and/or PET scans showing increasing size and/or avidity and confirmed pathologically via biopsy. Median interval between FSBRT and RSBRT was 9 months (range, 5-27). RSBRT doses were 35 Gy in 4 patients and 40 Gy in 5 patients, all in 5 fractions. Median PTV volume of RSBRT was 34.7 cubic centimeters (range, 8.6-90.2). The median percentage volume of overlap between the two SBRT courses was 64% (range, 26-100). 4 patients received concurrent CT, 4 patients received concurrent CET and 1 patient received concurrent nivolumab with RSBRT.

Results

 

Median follow-up (FU) from completion of RSBRT was 8 mo (range, 5-36). Overall survival rates were 78% at 6 mo and 57% at 12 mo. Local failure occurred in 4 patients, with one additional experiencing marginal failure, as the majority of recurrent tumor occurred outside of the PTV in this patient. Median time to recurrence was 4 mo (range, 2-13). 4 patients had not developed recurrence until their death or last FU at a median of 12 mo (range, 6-36). 9, 3 and 2 patients experienced grades 1, 2 and 3 toxicities, respectively. Grade 3 toxicities included fatigue in one patient and hearing loss in another, an expected side effect given that the cochlea fell within the PTV for both courses of SBRT.  No patient experienced grade 4 or 5 toxicities.

Conclusion

Repeat SBRT was well-tolerated, with rates of grade 3+ toxicity similar to those previously reported on H&N SBRT. Repeat SBRT is a viable option for those who fail initial SBRT.


Emile GOGINENI (New York, USA), Zaker RANA, Adam RIEGEL, Luis MADURO, Michael WOTMAN, Mihaela MARRERO, Edward GABALSKI, Lucio PEREIRA, Doru PAUL, Nagashree SEETHARAMU, Maged GHALY
11:30 - 11:35 #17815 - a45-3 Using the G8 screening tool to predict quality adjusted survival for elderly head and neck cancer patients treated with stereotactic body radiotherapy (SBRT).
a45-3 Using the G8 screening tool to predict quality adjusted survival for elderly head and neck cancer patients treated with stereotactic body radiotherapy (SBRT).

Background

The G8 has been a useful prognostic tool at baseline in order to predict elderly patients’ ability to tolerate surgery, chemotherapy and conventionally fractionated radiation. Studies have identified that patients with lower baseline scores, with the most common cutoff being 14, will be unable to complete curative treatment and should be considered instead for palliative measures. There has been limited data on how patients with lower baseline scores will respond to SBRT in terms of ability to tolerate treatment, local control (LC) and overall survival (OS). Additionally, while the G8 has been used as a predictor of prognosis at baseline, there has been little published on its use at follow-up (FU) after treatment.

Material and Methods

From December 2012 to November 2016, 171 patients with cancers of the H&N were treated with palliative SBRT. Median age and KPS were 75 years and 70 respectively. G8 scores were captured for all patients at baseline, 4-6 weeks FU after SBRT and 2-3 month FU. Factors influencing changes in baseline G8 score were compared through repeated measures ANOVA and the impact of change in score on OS and LC were calculated through Kaplan-Meier analysis.

Results

Median FU was 17.0 mo. Median baseline G8 was 10.5 (range, 4.5-16.0). OS was 40.4% with a median survival (MS) of 18.4 months. There were no significant differences in patients with baseline scores <=14 vs >14 in LC (71.0% vs 86.0%, p=0.104) or OS (38.3% vs 54.5%, p=0.171). Patients who saw a decrease in their G8 score at 2-3 month FU (n=69) had an OS of 8.7% with a MS of 8.6 months. This was significantly lower than patients who had a stable or increase in their G8 score at 2-3 month FU (n=102) with an OS of 61.8% and MS of 35.9 months (p<.001). Change in G8 score did not significantly affect local, regional or distant control, which were 74%, 67% and 60%, respectively. Grade 3 toxicity occurred in 9% of patients and there were no grade 4 or 5 toxicities.

Conclusion

Patients who are not candidates for curative treatment who have low baseline G8 scores still benefit from palliative SBRT, with high rates of LC.  Decline in G8 scores from baseline at 4-6 weeks and 2-3 months FU significantly predict worse OS compared to patients with stable or increasing G8 scores.  


Emile GOGINENI (New York, USA), Michael WOTMAN, Zaker RANA, Jessie KARTEN, Adam RIEGEL, Luis MADURO, Dev KAMDAR, Doru PAUL, Nagashree SEETHARAMU, Maged GHALY
11:35 - 11:45 Results of Oligometastases with SBRT. Daniel M. TRIFILETTI (Professor) (Speaker, Jacksonville, USA)
Segovia Plenary

"Wednesday 12 June"

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C45
11:15 - 13:00

Oral Session
MENINGIOMAS

Moderators: Gus BEUTE (Neurosurgeon) (Tilburg, The Netherlands), Waltter KRAVCIO (NEUROSURGEON) (PANAMA, Panama), Dennis SHRIEVE (Professor and Chair) (NY, USA)
11:15 - 11:25 #17630 - c45-1 Optic nerve sheath meningiomas multisession radiosurgery. Preliminary results from a prospective study.
c45-1 Optic nerve sheath meningiomas multisession radiosurgery. Preliminary results from a prospective study.

Objective. Optic nerve sheath meningiomas are rare benign neoplasms of the meninges surrounding the optic nerve. These can be a significant cause of visual impairment. Traditional treatment options for optic nerve sheath meningiomas (ONSM) include observation, surgery and radiotherapy, but to date none of these has become the clear treatment of choice.

The aim of this study is to evaluate the safety, especially in term of visual sparing, and the effectiveness of multisession radiosurgery for ONSM.

Materials and methods. This is a prospective single center. Patients suffering for ONSM which underwent a multisession radiosurgery have been considered.

Inclusions criteria are a ONSM diagnosis, visual impairment at presentation, progression of visual dysfunction during the observation period, disease progression. Adulthood and the informed consent signature are also required. Due to the histological diagnosis imply an invasive and hazardous procedure, no biopsies will be performed and the diagnosis will be exclusively radiological.

Results. According to the study protocol 50 patients underwent a mRS in the period between February 2011 and November 2018. All, had a 25 Gy treatment delivered in five fraction (five consecutive days), prescribed to the 77-91 % isodose line (median 82%). The mean age at the treatment time was 51 years old (range 18-82; median 51 yrs). The mean treatment volume was 2.5 cc (range 0.5-9.5; median 1.8 cc). The mean dose to the treated optic nerve ranged between 8.3 and 28.5 Gy (median 24.4 Gy); the maximum point dose ranged between 20.1 and 32.5 Gy (median 29.4 Gy). The mean dose to the optic chiasm ranged between 1.5 and 21.9 Gy (median 4.6 Gy).

After a mean follow-up period of 35 months (range 4-80: median 30 months) only one patients (2%) developed  a visual worsening. Eight patients (16 %) improved and 41 were stable along the follow-up period.

The toxicity rate was always very low and no patients required medication due to complication related to the treatment.

None of the treated meningioma showed a radiological progression

Conclusions. Multisession radiosurgery for ONSMs was found to be safe and effective. Twenty-five Gy delivered in 5 fractions is an effective treatment modality for these kind of tumors. The treatment schedule controlled the tumors while sparing visual function.


Marcello MARCHETTI (Milano, Italy), Valentina PINZI, Cecilia IEZZONI, Laura FARISELLI
11:25 - 11:35 #17642 - c45-2 Hypofractionated stereotactic radiosurgery for large-sized skull base meningiomas: a preliminary report on 31 patients.
c45-2 Hypofractionated stereotactic radiosurgery for large-sized skull base meningiomas: a preliminary report on 31 patients.

Purpose: Although stereotactic radiosurgery (SRS) has been proved to be effective and safe in the treatment of intracranial meningiomas, concerns are raised in the use of SRS for large-sized tumors with involvement of the skull base, which frequently encroach onto adjacent critical neurovascular structures. Here we investigated the role of hypofractionated SRS as a therapeutic option for large-sized skull base meningiomas.

Materials and Methods: Between November 2011 and December 2014, thirty-one consecutive patients (median age 55 years, 9 men and 22 women) had been treated with hypofractionated SRS using the CyberKnife for large-sized skull base meningiomas > 10 cm3 in volume (median volume 18.9 cm3, range 11.6-58.2 cm3). All patients harbored middle or posterior skull base tumors, most frequently of cavernous sinus (n=7, 22.6%), petroclival (n=6, 19.4%), or medial tentorial edge (n=6, 19.4%) locations. Most of them (n=27, 87.1%) did not receive any prior therapy and 4 patients received prior partial resection of the tumor. SRS was delivered in five daily fractions (range 3-5 fractions) with a median cumulative dose 27.8 Gy (range 22.6-27.8 Gy).

Results: With a median follow-up of 33 months (range 9-61 months), tumor control was achieved in 28 of 31 patients (90.3%). Treatment response on MRI included partial response (volume decrease > 20%) in 17 patients (54.8%), stable in 11 (35.5%), and progression (volume increase > 20%) in 3 (9.7%). Neurological symptoms improved in 10 patients (32.2%), unchanged in 20 (64.5%), and worsened in 1 (3.2%). Three patients underwent a craniotomy for their progressive tumors, which disclosed a histological diagnosis of atypical meningioma in all of them.

Conclusions: Our preliminary results suggest a promising role of hypofractionated SRS for large-sized skull base megningiomas in terms of both tumor control and functional outcomes, representing a reasonable therapeutic option in select patients.


Young Hyun CHO (SEOUL, Korea), Hyuk-Jin OH, Kyoungjun YOON, Eun Suk PARK, Do Hee LEE, Do Hoon KWON
11:35 - 11:45 #17675 - c45-3 Long-term outcome of low dose (≦12 Gy) gamma knife radiosurgery for skull base meningiomas.
c45-3 Long-term outcome of low dose (≦12 Gy) gamma knife radiosurgery for skull base meningiomas.

 Objective: The optimal doses of radiosurgery for skull base meningioma have been reported 13 - 15 Gy. We have been intended to perform low dose radiosurgery for treating close to critical structure of skull base. We evaluate long-term efficacy of low dose (≦12 Gy) gamma knife radiosurgery (GKS).

Methods:Between January 1994 and May 2013, the authors treated WHO grade  Ⅰmeningiomas in 295 patients using low dose radiosurgery. Median treatment volume was  6.9 cm3, median prescribed marginal dose was 12 Gy (range 8 -12 Gy) . 22 patients with large volume tumors were treated by two-staged radiosurgery (volume fractions).

Results:  The mead duration of follow-up was 8.7 years (range 0.5 - 21 years). Local tumor growth control was 85%, Actuarial local control rates at 5, 15, and 15 years were 92%, 82%, and 74%, respectively. 5% were aggressive change of tumors. Univariative analysis revealed without preGKS surgery and below 60 years old were positive factor and sex, tumor volume, treatment dose, staged surgery were not significant for tumor control. The clinical outcome was improved in 15% and unchanged in 69% of patients. The radiation induced neuropathy occurred 7.1% (21 patients). The trigeminal neuralgia considering most devastating symptoms was improved or disappeared in 40% (4/10patients), but new trigeminal neuralgia was occurred in 4.4%(13 patients).

Conclusion:The low dose GKS (≦12 Gy) for skull base meningiomas can achieve long-term tumor growth control with low morbidity with a long-term follow-up period of > 8.5 years.But the aggressive change was still difficult to control; this not related radiosurgery however this may be natural course. 


Yoshiyasu IWAI, Hiroshi UDA (Osaka, Japan), Kazuhiro YAMANAKA, Kenichi ISHIBASHI
11:45 - 11:55 #17684 - c45-4 Gamma knife radiosurgery as primary treatment for convexity meningiomas: clinical results at long-term follow-up in a series of 206 lesions.
c45-4 Gamma knife radiosurgery as primary treatment for convexity meningiomas: clinical results at long-term follow-up in a series of 206 lesions.

Object. Surgical resection has been for many years the treatment of choice for intracranial convexity meningiomas. To date Gamma Knife Radiosurgery (GKRS) has gained a clinical validation for the treatment of small, deep-seated tumors or in case of patients not eligible for surgery. Nevertheless, its role in the treatment of convexity meningiomas is still debated, due to the lack of clinical evidence. The present study aims to assess safety and efficacy of GKRS, as primary treatment for convexity meningiomas.

Methods. One-hundred-fifty-nine patients (107 females and 52 males; mean age: 59.7 years) harboring convexity meningiomas underwent GKRS as primary treatment, between January 2001 and December 2014. The total number of lesions was 206, with an average volume of 2.28 cm(median 1.35 cm3). Median margin dose was 15 Gy.

Results.The mean clinical and radiological follow-up (FU) were 65.1 and 56.1 months, respectively. At last FU 89.3% of lesions were stable or reduced in size. The actuarial 3-, 5- and 10-year progression-free survival were 94%, 92% and 76%, respectively. The actuarial 3-, 5- and 10-year local tumor control were 97%, 94% and 87%, respectively. Permanent complications after GKRS were reported in 6 cases (3.8%). Failure rate of GKRS was 10.7%. No treatment-related deaths were recorded.

Conclusion. GKRS demonstrated to be a safe and effective treatment for intracranial convexity meningioma providing high tumor control rates with low treatment-related morbidity. GKRS may represent a valuable alternative to surgery as primary treatment for patients harboring small lesions, or for whom are not eligible for surgery.


Filippo GAGLIARDI (MILAN, Italy), Michele BAILO, Giuseppe BARISANO, Nicola BOARI, Antonella DEL VECCHIO, Angelo BOLOGNESI, Pietro MORTINI
11:55 - 12:05 #17696 - c45-5 Optimized hypofractionated SRS regimens for perioptic lesions based on low alpha/beta ratio of the optic pathway.
c45-5 Optimized hypofractionated SRS regimens for perioptic lesions based on low alpha/beta ratio of the optic pathway.

Objectives:

Theoretically, hypofractionation can only be justified if there is a positive difference between alpha/beta ratio of the lesion and the alpha/beta ratio of the surrounding organs at risk. For the visual system 3 different alpha/beta ratios have been published so far, two of them negative, stressing the theoretical model. The knowledge of the alpha/beta ratio of the optic pathway is essential to calculate radiobiological dose parameters, such as the single fraction equivalent dose (SFED), from which optimized hypofractionated SRS (HF-SRS) regimens for perioptic lesions can be derived.

 

Material and methods

The alpha/beta ratio of the optic pathways was estimated from a meta-analysis of 429 studies published between 2000 and June 2018. We included 15 studies with fraction sizes between 1 and 31, considering the following inclusion criteria: frequency of radiation induced optical neuropathy, RION between >0% and <10%, follow up period of at least 24 months, no tumor progression, no prior radiation and detailed dosimetric analysis for the visual system. Additionally we included results from our center on 68 HF-SRS treatments and 161 single fraction treatments for perioptic lesions.

 

Results

The Fraction Equivalent (FE) plot method revealed an alpha/beta ratio of the optic pathway of 1.03 Gy, confidence interval [-0.38 – 1.60]. Based on this result and published alpha/beta ratios of brain tumors, optimized HF-SRS regimens were derived from SFED calculations. An increased SFED of up to 10% for perioptic meningiomas and of more than 25% for malignant tumors can be reached with optimized HF-SRS schedules, maintaining the same low risk of radiation induced optic neuropathy.

 

Conclusion

A significant benefit from HF-SRS can be achieved, because of the relatively low alpha/beta ratio of the optic system of 1.03 Gy. HF-SRS schedules can be optimized based on the knowledge of alpha/beta ratios and SFED calculations.


Herwin SPECKTER (Santo Domingo, Dominican Republic), Jairo SANTANA, Jose BIDO, Giancarlo HERNANDEZ, Diones RIVERA, Luis SUAZO, Santiago VALENZUELA, Peter STOETER
12:05 - 12:15 #17701 - c45-6 Atypical Meningiomas: pattern of post radiotherapy recurrences in relation to the irradiated area.
c45-6 Atypical Meningiomas: pattern of post radiotherapy recurrences in relation to the irradiated area.

Purpose:

In radiotherapy for macroscopic (residual) disease in atypical meningioma (AM), target volume definition and prescribed doses vary. Insight into the recurrence pattern of these tumors is needed for optimal target definition. The purpose of this study is to describe the patterns of recurrence after postoperative or salvage radiotherapy in our patients with AM.

 

Patients and methods:

Twenty-nine consecutive patients with AM referred to our department from 2005 through 2016 were retrospectively studied. Fractionated stereotactic radiotherapy (FSRT) was performed on a dedicated linac. The CTV was defined as the macroscopic tumor and included adjacent tissues that contained residual microscopic disease. CTV-PTV margin was 2mm. Prescribed doses were mostly 25-35Gy in 5 -7 fractions or 54-60Gy in 30 fractions, depending on the size of the PTV. The MRI scans that showed recurrent disease were registered with the planning CT and MRI scans to characterize the recurrences as in-field, marginal or distant. The relation of the recurrences with the dura was determined. 

 

Results

In total the included patients received 73 surgeries and 56 FSRT treatments. Median follow-up after FSRT was 11.2 years. In 72.4% of the patients a recurrence was diagnosed after FSRT. We found 26 in-field, 6 marginal and 7 distant recurrences; all were connected to the dura. First recurrence after first radiotherapy appeared after a median time of 3.3 years. Median survival after first radiotherapy was 8.7 years.

 

Conclusion

AM frequently recurs and multiple surgeries and radiation treatments may be needed. Most post radiotherapy recurrences of AM originate in or close to the irradiated dura and not in other adjacent tissues.  The high rate of in-field recurrence suggests high doses are needed. The high frequency of marginal recurrences suggests that radiation should be directed not only at the macroscopic tumor, but also at the adjacent dura.



Mônica Helena SCHURING-PEREIRA (Rotterdam, The Netherlands), Mirjam MAST, Jan VAN SANTVOORT, Rishi NANDOE TEWARIE, Rogier HAGENBEEK, Sjoerd VAN DUINEN, Ruud WIGGENRAAD
12:15 - 12:25 #17718 - c45-7 Hypofractionated SRS versus single session SRS for perioptic lesions. A single center study of 245 patients.
c45-7 Hypofractionated SRS versus single session SRS for perioptic lesions. A single center study of 245 patients.

Objectives:

Hypofractionated radiosurgery (HFSRS) of lesions in the sellar region is still controversially discussed as an alternative to single session SRS.

 

Material and methods

According to our protocol, HFSRS is performed when it is technically impossible to limit the maximum point dose to the anterior visual pathway (AVP) to 12 Gy. Between 2011 and 2018 a total of 72 patients with perioptic lesions (mean distance lesion-to-AVP=0.3mm, 69% in direct contact) were treated with HFSRS and 173 with single fraction (mean margin dose was 15.5 Gy, mean distance lesion-to-AVP=2.0mm, 30% in direct contact). In the HFSRS group, 7 treatments were performed with a 5 day course with a mean margin dose of 5x6.93 Gy, 56 treatments with 4x5.32 Gy, and 9 treatments with 3x6.31 Gy. Exact delineation of the optic pathways was performed on high resolution 3D T1 images and additionally since 2016 by applying FGATIR sequences.

  

Results

After a mean imaging follow-up period (FUP) of 23m [2-72m], local control was achieved in all lesions treated with HFSRS, except for 1 lesion (caused by pituitary apoplexy). An overall mean reduction in volume of 3.05%/m was observed. Mean FUP for ophthalmologic evaluation was 28m [2-79m]. Improved vision was observed in 10 cases; 1 case was confirmed for radiation induced optic neuropathy (RION) after delivery of 4x5.60 Gy as maximum optic point dose. All treatments were well tolerated and concluded satisfactorily. Spatial frame displacement during HFSRS course was measured <0.3mm using CT images. In the group of single session SRS, after a mean imaging FUP of 27m [4-78m], local control was achieved in all but 7 lesions, with an overall mean reduction of 1.52%/m. Mean FUP for ophthalmologic evaluation was 36m [7-81m]. 1 case was confirmed for RION, after delivery of 10.2 Gy as maximum optic point dose. For all patients dose volume histograms were analyzed for both nerves, both tracts and chiasm.

 

Conclusion

According to our preliminary results, HFSRS can be considered as an efficient and relatively safe alternative to treat lesions even contacting the AVP, benefiting from a low alpha/beta ratio of 1.03 Gy (study submitted to ISRS 2019) of the visual pathway.


Herwin SPECKTER (Santo Domingo, Dominican Republic), Jairo SANTANA, Jose BIDO, Giancarlo HERNANDEZ, Diones RIVERA, Luis SUAZO, Santiago VALENZUELA, Peter STOETER
12:25 - 12:35 #17728 - c45-8 Radiosurgical decompression for skull base meningiomas causing compressive ophthalmic neuropathy.
Radiosurgical decompression for skull base meningiomas causing compressive ophthalmic neuropathy.

Background & Purpose: Skull base meningiomas frequently need complex and technically demanding surgery risking morbidities. Radiosurgery is a strong alternative but considered as a controversial option especially for tumors causing compressive ophthalmic neuropathy. To reduce the risk of radiation toxicity, we applied hypofractionated stereotactic radiosurgery (hSRS) in treating these tumors and reviewed our outcomes.

 Methods and Materials: Nineteen patients with compressive ophthalmic neuropathy (CN II = 9; CN III/IV/VI = 12) caused by meningiomas received hSRS between 2011 and 2014. All tumors were located at the skull base (cavernous sinus = 8; petroclival = 3; clinoidal = 8). hSRS was delivered in five daily fractions with a median marginal dose of 27.1 Gy (≈14 Gy in a single fraction, assuming an α/β of three) to a tumor volume of 13.1 ± 12.2 cm3. The mean follow-up periods was 27 months.

 Results: All tumors except one shrank after treatment, with a mean volume decrease of 26.1 % (range 4-48 %). In nine patients with compressive optic neuropathy, vision improved in 66.7 % (n = 6), was unchanged in 33.3 % (n = 3). Ophthalmoplegia improved in 66.6 % of eyes (n = 8), was unchanged in 25 % (n = 3), and worsened in 8.3 % (n = 1). One patient with histologically proven atypical meningioma experienced tumor progression and aggravation in neurological symptom.

 Conclusion: Our results suggest a promising role of hSRS for skull base meningiomas causing compressive ophthalmic neuropathy in terms of both tumor control and functional outcomes.


Eun Suk PARK, Hyuk-Jin OH, Eun Jung LEE, Kyoung Jun YOON, Young Hyun CHO (SEOUL, Korea)
12:45 - 12:55 #17799 - c45-10 Risk of carotid artery stenosis or occlusion after radiosurgery of cavernous sinus meningiomas.
c45-10 Risk of carotid artery stenosis or occlusion after radiosurgery of cavernous sinus meningiomas.

Introduction: Stereotactic radiosurgery (SRS) is an accepted treatment option for patients with cavernous sinus meningiomas (CSM).  The risk of stenosis or occlusion of the internal carotid artery (ICA) after SRS of CSM has never been reported.

Methods: Retrospective review of 154 patients (41 men/113 women) having single-fraction SRS from 1990-2015.  Inclusion criteria included no prior history of radiation and a minimum of 12 months of MRI follow-up after SRS.  Pre-SRS grading of ICA involvement was based on the method of Hirsch et al (1993): Grade I (n=62), tumor touches or partially encircles ICA; Grade II (n=57), tumor encircles but does not narrow lumen of ICA; Grade III (n=35), tumor encircles and narrows the ICA.  The median treatment volume was 8.3 cm3 (range, 0.7-42.2).  The median tumor margin dose was 15 Gy (range, 12-20).

Results: The median MRI follow-up after SRS was 8.1 years (range, 1-24.9).  No Grade I patient developed ICA narrowing.  Three Grade II patients (5.3%) had asymptomatic ICA stenosis.  Five Grade III patients (14.3%) progressed to ICA occlusion (4 asymptomatic, 1 symptomatic).  The median time after SRS to stenosis or occlusion was 4.9 years (range, 2.8-7.6).  The 5-year and 10-year risk of ICA stenosis was 4.3% and 7.1% for Grade II patients.  The 5-year and 10-year risk of ICA occlusion was 10.3% and 18.1% for Grade III patients.  The 5-year and 10-year risk of symptomatic ICA occlusion was 0.7% for the entire group, and 3.3% for Grade III patients.  Multivariate analysis found younger patient age (RR 0.92, 95% CI 0.86-0.99, p=0.03) and higher carotid grade (RR 5.4, 95% CI 1.7-17.1, p=0.004) to be associated with ICA stenosis or occlusion.   

Conclusion: ICA stenosis or occlusion was not uncommon after SRS for CSM if the tumor encircles the artery at the time of procedure, although it was typically not symptomatic. 


Bruce POLLOCK (Rochester, USA), Michael LINK, Scott STAFFORD, Ian PARNEY, Robert FOOTE
El Pardo I
11:45

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A46
11:45 - 13:00

PARALLEL SESSION
FUNCTIONAL RADIOSURGERY UPDATE

Moderators: Daniel BENZECRY ALMEIDA (Brazil), Antonio DE SALLES (Professor - Chief) (SÃO PAULO, Brazil), David MATHIEU (Professor) (Sherbrooke, Canada)
11:45 - 12:00 Imaging of Mind Function & Resting State fMRI. Constantin TULEASCA (Staff neurosurgeon, senior lecturer) (Speaker, Lausanne, Switzerland)
12:00 - 12:15 Facial Pain Syndromes. K Singh SAHNI (Chief, Department Of Neuroscience.) (Speaker, RICHMOND, VA.USA., USA)
12:15 - 12:30 Movement Disorders. Jean REGIS (PROFESSEUR) (Speaker, MARSEILLE, France)
12:30 - 12:45 Evolution of Gamma Knife Capsulotomy for Intractable Obsessive-Compulsive Disorder. Miguel EURIPEDES (Chairman of the Department of Psychiatry and Full Professor) (Speaker, São Paulo - SP, Brazil)
12:45 - 13:00 History in the Context of Behavioral Disorder Surgery. Michael SCHULDER (Vice Chair, Neurosurgery) (Speaker, Lake Success, NY, USA)
Segovia Plenary

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B46
11:45 - 13:00

Oral Session
METASTASES #3

Moderators: Lilyana ANGELOV (Staff Neurosurgeon) (Cleveland, USA), Kita SALLABANDA (Medical Direcor) (Madrid, Spain), Leonardo VIEIRA (Doctor) (Recife, Brazil)
11:45 - 11:55 #17636 - b46-1 Cranial radiosurgery using ELEKTA Unity MR-LINAC. Preliminary results on patient-specific End-to-End QA for a multiple brain metastases case.
b46-1 Cranial radiosurgery using ELEKTA Unity MR-LINAC. Preliminary results on patient-specific End-to-End QA for a multiple brain metastases case.

The ELEKTA Unity MR-linac combines a 1.5T magnet with a linac. The added value for cranial radiosurgery by such a system that combines diagnostic quality MR images taken before and during radiosurgery, is expected to be high. The aim of this work is to present preliminary results regarding patient-specific End-to-End QA for a multiple brain metastasis case treated with Unity. Spatial and dosimetric accuracy are evaluated in 3D, following a full clinical patient treatment workflow.

An RTsafe polymer gel filled phantom was created using anonymized planning CT scans of a real patient. Three arbitrary brain metastases (size ~ 10 mm) were delineated on the real patient planning CT scans A Monaco treatment plan was then created. The RTsafe polymer gel filled phantom was then irradiated as if it is the real patient following the clinical workflow: set up on a head frame and a thermoplastic mask, image guidance using the Unity MR scanning capabilities and treatment delivery with Unity. Immediately after the termination of the treatment delivery, without changing the set-up, the irradiated phantom was MR-scanned using a MR pulse sequence that derived 3D T2-maps of the phantom (spatial resolution of 1x1x2 mm^3). The high-dose areas within the patient-specific phantom exhibit low T2-values and therefore apear dark in the MR scans. A co-registration was followed between: a) the real patient planning CT scans were the RStructure file is superimposed and b) the 3D T2-maps of the irradiated patient-specific phantom. A bone-to-bone registration process was used. 

After the corregistration process and by blending the registered images, a direct inspection of the spatial coincidence between: a) the three PTVs structures and b) the corresponding  high dose areas (low T2 - dark areas), revealed a superb spatial accuracy of dose delivery. For a quantitative spatial and dosimetric analysis, the 3D T2-maps were converted to 3D relative dose maps. 1D, 2D and 3D intercomparison between the TPS calculations and the corresponding polymer gel measurements, revealed a truly satisfying 3D dosimetric precission. The spatial accuracy of dose delivery was also quantitatively verifyied. 

By the use of the proposed End to End QA methodology, it was demonstrated that the ELEKTA Unity MR-linac is capable for multiple brain metastases treatments with superb geometric and dosimetric performance


Evangelos PAPPAS (ATHENS, Greece), Georgios KALAITZAKIS, Thomas MARIS, Dimitris MAKRIS, Efstathios EFSTATHOPOULOS, Ioannis SEIMENIS
11:55 - 12:05 #17669 - b46-2 Rapid Rescue Radiosurgery (RRR) in the acute management of critically located brain metastases: a two-center short-term outcome analysis.
b46-2 Rapid Rescue Radiosurgery (RRR) in the acute management of critically located brain metastases: a two-center short-term outcome analysis.

Background: The management of metastatic lesions in the eloquent brain remains a major challenge. Adaptive hypofractionated gamma knife radiosurgery may be applied in next-to emergency situations to treat life- and function-threatening intracranial metastases deemed not indicated for microsurgery or other treatment; debulking or even ablative effects might be achieved within days to weeks post therapy. The application of this treatment modality in defined acute settings has been termed Rapid Rescue Radiosurgery (RRR). We report the expeditious effects of RRR during treatment and 4 weeks after treatment completion with focus on tumour ablation, salvage/rescue of organs at risk and toxicity.

Methods: 39 patients with 50 brain metastases, treated over 7 days in three separate Gamma Knife radiosurgery sessions (GKRS 1 - 3) between November 2013 and December 2018, were retrospectively analyzed in terms of tumour volume reduction, salvage of organs at risk and radiation induced toxicity under the period of treatment (GKRS 1 to GKRS 3) and at first follow up MRI (4 weeks after GKRS 3). The Leksell® Coordinate Frame G was mounted prior each GKRS. All patients were treated using the Leksell Gamma Knife® Perfexion™ (Karolinska University Hospital, Stockholm, Sweden) and Leksell Gamma Knife® Model C (Bezmialem Vakif University Medical School, Istanbul, Turkey).

Results:  Frame mounting prior each GKRS was well tolerated. Mean peripheral doses at GKRS 1, GKRS 2 and GKRS 3 were 7.7, 8.0, and 8.3 Gy, respectively (range 6.0-9.5 Gy) at the 35-50% isodose lines. In the surviving group at first follow-up (n=38), mean tumor volume reduction was -6% at 1 week (GKRS 1- GKRS 3) and -53% % 4 weeks after GKRS 3. Six patients died prior to first follow-up due to extracranial disease; however, further neurologic deterioration post RRR was not reported in this subgroup of patients.

Conclusions: In this study, RRR proved effective in terms of debulking, rapid tumour volume reduction and preservation/rescue of neurological function. Radiation induced toxicity was not reported in this short term follow-up. RRR should be considered when microsurgery and other therapies are not feasible, yet an acute intervention remains necessary.  However, the true potential of this procedure lies on a set of synergic radiation-modulated immune responses aiming to achieve long-lasting systemic effect.


Georges SINCLAIR, Georges SINCLAIR (Reading, UK, United Kingdom), Georges SINCLAIR, Hamza BENMAKHLOUF, Kerime AKDUR, Mustafa Aziz HATIBOGLU
12:05 - 12:15 #17705 - b46-3 Stereotactic radiosurgery for brain metastases from renal-cell carcinoma.
b46-3 Stereotactic radiosurgery for brain metastases from renal-cell carcinoma.

BACKGROUND: Brain metastases (BM) is a significant problem in patients with metastatic renal-cell carcinoma (RCC). Local and systemic therapies including stereotactic radiosurgery (SRS) are rapidly evolving, necessitating reassessments of outcomes for modern patient management.

PURPOSE: The study purpose was to evaluate the impact of gamma knife radiosurgery (GKRS) alone on the overall survival and intracranial recurrence rates in brain metastasis patients from RCC.

PATIENTS AND METHODS: The RCC patients with BM treated with SRS were reviewed. 74 patients were identified with BM treated between 2010 and 2015.  A total of 309 BM were treated with SRS with 1 to 24 BMs treated per session (median, 2 BMs). The median (range) of volume was 4,47 cc (0,3-19,8). The median (range) SRS treatment dose was 20 (15-24) Gy.

RESULTS: The median overall survival was 10 months (95% CI 6,5-13,3). Survival after 1-year was 43,2% for all patients. Survival was not statistically different between patients with < 5 BM versus ≥ 5 BM (P = 0,4583). Local control after 12 months was achieved in 87,1% patients. Progression-free survival after 12 months was 48,4%. Аccording to multivariate analysis, favorable prognostic factors were  KPS >70 and total target volume BMs <5 cm3.

CONCLUSION: SRS is effective in controlling BM in patients with RCC. Over half of treated patients survive  one  year, and no differences in survival were noted in patients with ≥ 5 BM metastases in comparison with those, who had < 5 BM. Factors predicting better survival were high functional status and low total target volume BMs


Andrey GOLANOV (Moscow, Russia), Sergey BANOV, Elena VETLOVA, Alexandra DALECHINA, Valery KOSTJUCHENKO, Natalia ANTIPINA, Ivan OSINOV, Amayak DURGARYAN
12:15 - 12:25 #17744 - b46-4 Hypofractionated Stereotactic Radiosurgery and Radiotherapy to Large Resection Cavity of Metastatic Brain Tumors.
b46-4 Hypofractionated Stereotactic Radiosurgery and Radiotherapy to Large Resection Cavity of Metastatic Brain Tumors.

- OBJECTIVE: To evaluate the efficacy of postoperative fractionated stereotactic radiosurgery (FSRS) and hypo-fractionated stereotactic radiotherapy (SRT) to large surgical cavities after gross total resection of brain metastases.

- METHODS: A retrospective analysis of 41 patients who had received tumor-bed FSRS (5 fractions) or SRT (10 fractions) after resection of brain metastasis between 2005 and 2015 was performed. All resection cavities were treated with a frameless linear accelerator-based system. Patients who underwent subtotal resection, single-dose SRS to the resection cavity, or were treated with a fractionation schedule other than 5 or 10 fractions, were excluded.

- RESULTS: Twenty-six patients were treated with 5 fractions and 15 patients with 10 fractions. The median planning target volume was 19.78 cm3 (12.3 - 28 cm3) to the 5-fraction group and 29.79 cm3 (26.3 - 47.6 cm3) to the 10-fraction group (P [ 0.020). The 1-year and 2-year local control rates for all patients were 89.4% and 77.1%, respectively, and 89.6% and 78.6% were free from distant intracranial progression, respectively. No difference was observed in local control or freedom from distant intracranial progression between the 5-fraction or 10-fraction groups. The median overall survival was 28.27 months (95% confidence interval, 19.42 - 37.12) for all patients. No patient developed necrosis at the resection cavity.

- CONCLUSIONS: Fractionation offers the potential to exploit the different biological responses between neoplastic and normal tissues to ionizing radiation. The use of 5 daily doses of 5-6 Gy or 10 daily doses of 3 Gy is a good strategy to have a reasonable local control and avoid neurotoxicity.


Leonardo CONRADO (Salvador, Brazil), Tania KAPREALIAN, Alisson R. TELES, Stephen TENN, Nader POURATIAN
12:25 - 12:35 #17838 - b46-5 Immune checkpoint inhibitors and stereotactic radiosurgery in melanoma brain metastases.
b46-5 Immune checkpoint inhibitors and stereotactic radiosurgery in melanoma brain metastases.

Background: “On demand” Stereotactic Radiosurgery (SRS) is increasingly used in combination with immune checkpoint therapy (ICT) to control melanoma brain metastases (MBM). However, little is known about potential interactions between ICT and RS in terms of toxicity and efficacy.

Goal: The goal of this retrospective study was to analyze results of a cohort of patients treated for MBM from January 2014 to December 2016 in our institution.

Methods: From an institutional database, we identified consecutive patients with MBM, treated with GK and receiving concurrent ICT with anti-CTLA4 or anti-PD1 within the 12 weeks of SRS procedure.

Results:  Sixty-two patients presenting 296 lesions were included, and 52 patients (84%) had ongoing ICT at the time of irradiation. Median follow-up time was 18 months (13-22). Minimal median dose delivered was 18 Gy. Median volume per lesion and total tumor volume were 0.219 cm3 and 2.1 cm3 respectively. The 1-year control rate per irradiated lesion was 89%. Thirty-one patients (44.3%) developed distant brain metastases after a median time of 6 months after GK. At the time of analysis, 34 patients had died. Median overall survival (OS) was 14 months. Median OS in subgroups treated with Ipilimumab, Nivolumab, multiples immunotherapy were respectively: 11 months, 15 months and 13.5 months and was not reached for Pembrolizumab subgroup. In multivariate analysis, positive predictive factors for local control were: delay since the initiation of immunotherapy more than 1 month (p=0.009) and previous brain irradiation (p=0.009). Total tumor volume <2.1 cm3 was a positive predictive factor for both OS (p=0.003) and intracranial disease control (p=0.038).  Predictive factors of toxicity were: female gender (p=0.001) and previous treatment with MAPK (p=0.05).

Conclusion: Combination of GK and ICT in MBM is safe and shows favorable outcomes.  A long duration of ICT before SRS seems to improve local control.

 


Charles VALERY (Paris), Charlotte FENIOUX, Aymeric AMELOT, Pierre-Yves BORIUS, Idriss TROUSSIER, Iannis LAMPROGLOU, Philippe SAIAG, Philippe MAINGON, Jean-Jacques MAZERON, Philippe CORNU
12:35 - 12:45 #17859 - b46-6 Hypofractionated stereotactic radiosurgery for resected brain metastases.
b46-6 Hypofractionated stereotactic radiosurgery for resected brain metastases.

Background: After resection of brain metastases, stereotactic radiosurgery (SRS) to the surgical cavity reduces local recurrence with minimal cognitive impairment. For large surgical cavities, reduced single-fraction doses required to minimize toxicity can compromise local control. Hypofractionated stereotactic radiosurgery (HF-SRS) may better balance tumor control with toxicity.

Materials/Methods: Patients treated with adjuvant HF-SRS following resection for brain metastases at Duke University Medical Center between 2012 and 2016 were included. The gross target volume was contoured per consensus guidelines with 2mm margin to obtain the planning target volume.  All patients were treated with image-guided SRS using a linear accelerator with high-resolution collimation. Patient demographics, primary disease characteristics and treatment details were recorded. Rates of local control (LC), distant brain failure (DBF), radionecrosis (RN) and overall survival (OS) were calculated.  

Results: 86 patients with a total of 91 lesions that were resected and treated with HF-SRS were identified. The median age and KPS were 61 and 80, respectively. The majority of patients were female (n=49, 57%), had extracranial metastases at the time of HF-SRS (n=53, 62%) and a single brain metastases (n=55, 64%). The most common histology was NSCLC (n=36, 42%) followed by breast (n=18, 21%) and melanoma (n=10, 12%). The median pre-operative maximum tumor dimension was 3.3 cm (range 0.8-6.2). All patients were treated in five fractions, the majority with a fraction size of 5 Gy (n=81, 89%). Median follow up was 10.7 months. The 2-yr LC and DBF rates were 69% and 63%, respectively. Subsequent brain irradiation was utilized in 38 patients. Median OS was 13.8 months and 2-yr OS was 38%. One case of symptomatic RN was observed.

Conclusions: Post-operative HF-SRS delivered in five fractions has an excellent safety profile and reasonable probability of local control. Close surveillance is warranted given the high risk of DBF in this setting.


Jordan TOROK (Durham, NC, USA), Andrew FAIRCHILD, Justus ADAMSON, Zhanerke ABISHEVA, Scott FLOYD, Michael MORAVAN, Peter FECCI, Fang-Fang YIN, John KIRKPATRICK
Segovia Break Out
13:00 LUNCH (exhibition area), VISIT OF THE EXHIBITION & POSTERS
13:15

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13:15 - 14:15

BRAINLAB SPONSORED SESSION
Novalis Circle Symposium: Clinical and Technical Innovations in Spine SRS Treatments

13:15 - 13:30 Value of SRS over Conventional Fractionation for Bone Metastases. Yoshiya Josh YAMADA (Partenaire: GOLD PARTNERS, New York, USA)
13:30 - 13:45 Commissioning and Clinical Implementation of Elements Spine SRS. Niko PAPANIKOLAOU (Professor and chief) (Partenaire: GOLD PARTNERS, San antonio, USA)
13:45 - 14:00 Clinical Experience Utilizing Elements Spine SRS. Pablo CASTRO PENA (Radiation Oncologist) (Partenaire: GOLD PARTNERS, Cordoba, Argentina)
14:00 - 14:15 Review of 6D Setup and Monitoring for Spine SRS Treatment. Amol GHIA (Associate Professor) (Partenaire: GOLD PARTNERS, Houston, USA)
Segovia Break Out

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C47
13:15 - 14:15

ACCURAY SPONSORED SESSION
Cyberknife Radiosurgery for Intramedullary Arteriovenous Malformations

13:15 - 14:15 Cyberknife Radiosurgery for Intramedullary Arteriovenous Malformations. Iris GIBBS (Professor) (Partenaire: GOLD PARTNERS, Stanford, USA)
El Pardo I
14:30

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A48
14:30 - 15:00

PANEL 1
PITUITARY TUMORS POINT - COUNTERPOINT

Moderator: Manoel PAIVA (NEUROSURGEON/CHIEF DEPARTMENT) (SAO PAULO, Brazil)
14:30 - 14:37 The Case for SRS. Bruce POLLOCK (Physician) (Speaker, Rochester, USA)
14:37 - 14:44 The Case for SRT. Daniel M. TRIFILETTI (Professor) (Speaker, Jacksonville, USA)
14:44 - 15:00 Panelist. Yoshiaysu IWAI (Neurosurgery, Radiosurgery) (Speaker, Osaka, Japan), Alessandra GORGULHO (Director) (Speaker, SÃO PAULO, Brazil)
Segovia Plenary

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B48
14:30 - 15:00

PANEL 2
SPINE POINT - COUNTERPOINT

14:30 - 14:37 The Case for SRS. Amol GHIA (Associate Professor) (Speaker, Houston, USA)
14:37 - 14:44 The Case for SRT. Yoshiya Josh YAMADA (Speaker, New York, USA)
14:44 - 14:55 Panelist: Stereotactic radiosurgery for patients with asymptomatic spine metastasis: observation versus early intervention. Lilyana ANGELOV (Staff Neurosurgeon) (Speaker, Cleveland, USA), Moon-Jun SOHN (Stererotactic radiosurgery using Dedicated LINAC plateform) (Speaker, Goyang, Korea)
14:55 - 15:00 Panelist: Stereotactic radiotherapy for intramedullary spinal lesions. Yoshimasa MORI (Director) (Speaker, Kawasaki, Japan), Samuel RYU (Professor) (Speaker, Stony Brook, NY, USA)
Segovia Break Out

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C48
14:30 - 15:30

Oral Session
PHYSICS #3

Moderators: Batista DELANO (Brazil), Steven GOETSCH (Medical Physicist) (Solana Beach, USA), Uriel NOVICK (Chief Medical Physicist) (CABA, Argentina)
14:30 - 14:39 #17885 - c48-1 C48-1 Commissioning tests on a Gamma Knife Icon using an RTSafe humanoid phantom.
C48-1 Commissioning tests on a Gamma Knife Icon using an RTSafe humanoid phantom.

The RTsafe avatar phantom is a novel water based humanoid phantom, modelled on a patient’s CT scan, with a highly detailed skull anatomy created by virtue of its 3D printed construction. During the commissioning of three Gamma Knife Icon units, a variety of tests were devised using these phantoms:

Point dose measurements with ionisation chambers (PTW Semiflex 31010 and Pinpoint 3D 31014) were performed for single (16mm) shot plans and compared with the Leksell GammaPlan (LGP) calculated dose using the TMR10 algorithm. 2D measurements using EBT3 film and 3D measurements using gel dosimetry allowed End-to-End testing for complex multi-isocentric plans.
It was possible to mount the Leksell G frame on the rigid outer surface of the phantom. This allowed measurement of the degradation of stereotactic accuracy due to frame distortion. The four mounting pins were torqued to values between 20 and 90cNm in 10cNm steps. For each torque setting, separate CT and CBCT scans were acquired. Correction of the location of a reference isocentre was investigated when a treatment plan based on the stereotactic (fiducialised) CT was co-registered with a pre-treatment CBCT.

Results
Point dose measurements for the single shot plans demonstrated a mean error of -8.0% and -6.1% for Semiflex and Pinpoint respectively when compared to the TMR10 algorithm, but reduced to -3.4% when planned in the heterogenous phantom with Convolution. Local gamma pass rates for 5%/1mm were >95% for 2D film studies. 3D gel dosimetry yielded acceptable correlation between LGP and measured dose when assessed via DVH comparison and gamma index analysis.
Comparison between targeting using conventional stereotactic CT and CBCT showed a mean agreement of 0.25mm over a wide range of torque settings.

Conclusion
The RTsafe phantom has demonstrated its versatility for use in commissioning the Gamma Knife Icon


Ian PADDICK (London, United Kingdom), Ben EARNER, Thomas BURROWS, Alexis DIMITRIADIS
14:39 - 14:48 #16789 - c48-2 A high-precision, registration accuracy and full-system test for adaptive SRS.
c48-2 A high-precision, registration accuracy and full-system test for adaptive SRS.

A novel full-system test (FST) phantom and method have been developed to demonstrate and quality assure the geometric accuracy of image co-registration and overall shot delivery in the context of SRS using Gamma Knife® Icon™.  The method uses eight Vernier scale bars to achieve sub-voxel precision co-registration accuracy measurements and pin-located radiochromic films to determine overall shot delivery precision.  A Procrustes superimposition analysis method was used to assess residual registration errors and decouple these from focal precision errors which also contribute to the observed shot position full-system test error.

 

Validation tests demonstrated that artificially applied randomly generated synthetic registration errors of < 0.15 mm could be accurately detected and quantified.  Cross-validation of full-system test results with the manufacturer standard focal precision test demonstrated that both approaches measure similar focal precision errors, to within < 0.1 mm, and that registration and focal precision components of the full-system geometric error can be successfully decoupled using our Vernier registration analysis approach. 

 

CBCT co-registration errors were shown to be of comparable magnitude to the focal precision errors, demonstrating that CBCT registration based in-mask treatments can achieve sub-voxel inter-fraction geometric accuracy, rivalling traditional frame-based immobilisation.  Whilst real patient treatments also exhibit intra-fraction motion, the use of IFMM monitoring has been shown to restrict this error to the same order as the inter-fraction motion errors reported here. This novel full-system geometric test method and phantom design concept is in principle applicable in principle to any SRS technique involving high (sub-voxel) image co-registration performance, enhancing confidence in rigid registration based positional correction for these critical applications.


Michael NIX, Gavin WRIGHT (Leeds, United Kingdom), Peter BOWNES, Peter FALLOWS, Wayne SYKES
14:48 - 14:56 #16886 - c48-3 Interfractional Patient Motion and Adaptive Planning in Fractionated Gamma Knife Radiotherapy.
c48-3 Interfractional Patient Motion and Adaptive Planning in Fractionated Gamma Knife Radiotherapy.

Introduction:

The Gamma Knife Icon allows adaptive, fractionated radiotherapy (a-gkFSRT) of cerebral lesions in a stereotactic environment using cone-beam computer tomography (CBCT) (re)positioning and thermoplastic mask fixation. Interfractional patient motion is countered with translational table movement and rotation of the treatment plan/shots, resulting in an updated dose calculation. Here, we analyzed interfractional patient motions and the corresponding plan adaptions.

Material and Methods:

We recorded a total of 439 fractions for 36 patients (15 male and 21 female) that underwent a-gkFSRT for intracranial lesions (meningioma, brain metastasis resection cavities, primary metastases, vestibular schwannoma and pituitary adenoma). For each fraction, we analyzed the mean interfractional patient motion and compared the resulting deviation after adaptive planinng. Furthermore, a subset of 198 fractions were analyzed in terms of plan quality of the daily plan adaption. Finally we analyzed the largest patient motions and the resulting deviations after plan adaption.

Results:

For all 439 fractions, the interfractional translation shifts were 0.05±0.55mm, -0.39±0.59mm and -0.08±1.37 mm in x-, y- and z-direction, respectively. The interfractional rotational differences were -0.15±0.98°, -0.09±0.62° and -0.15±0.93° around the x-, y- and z-axis. When analyzing 198 selected fractions, we found a deviation between planned and delivered fraction doses of -0.05±0.15% for the Dmin to the target, 0.08±0.40% for Dmax to the target, 0.00±0.06% for target volume coverage, 0.00±0.00% for PCI and 0.24±0.37% for gradient. Of note, even the largest interfractional patient shift (>2mm or >2°) did not result in clinically relevant deviations of dose distribution after plan adaption with only minimal deviations in gradient (<0.72%) and Dmin to an organ-at-risk (‑11.55%). 

Conclusion:

Interfractional patient shifts in a-gkFSRT are in submillimeter ranges and do not require patient repositioning. Daily plan adaption results in plans that are almost identical to the reference treatment plan, even in case of major interfractional positioning shifts.


Florian STIELER (Mannheim, Germany), Beate SCHWEIZER, Frederik WENZ, Frank Anton GIORDANO, Sabine MAI
14:56 - 15:04 #17708 - c48-4 Pre-treatment CBCT image verification for frame-based SRS on Gamma Knife Icon.
c48-4 Pre-treatment CBCT image verification for frame-based SRS on Gamma Knife Icon.

The Icon-model Gamma Knife (GK) introduced on-board CBCT for GK SRS.  Intended to facilitate mask-based SRS, Icon also provides an opportunity for QA of conventional frame-based patients via pre-treatment image verification.

Stereotactic definition of planning MR images for our frame patients is based upon conventional fiducial marker localisation.  Pre-treatment CBCT is performed routinely for these cases.  Within Leksell GammaPlan (LGP) pre-treatment CBCT is co-registered to planning MRI.  Since both should share a common stereotactic space, LGP-reported co-registration translations and rotations are ideally zero.  In practice non-zero values result from definition and co-registration uncertainties, but excessive non-zero values could indicate frame slippage or fiducial box displacement.

Analysis of 501 co-registrations from 470 patients fitted with one of four frames (n = 126, 121, 126 and 128, respectively) between Dec-15 and Jan-19 is presented.  CBCT was co-registered against a 120-slice 0.8x0.8x1.5mm voxel MPRAGE (n=465) or a 52-slice 0.4x0.4x1.0mm voxel CISS (n=33) acquired on a Siemens Avanto (n=483) or Aera (n=18).

Overall mean(S.D.) X/Y/Z translations and rotations were 0.16(0.39)/0.11(0.26)/0.67(0.34)mm and 0.15(0.31)/-0.05(0.22)/0.26(0.16)deg, respectively.  Mean differences of 0.00/0.21/0.38mm and 0.42/0.01/0.19deg MPRAGE-vs-CISS were significant (p<0.01) for Y,Z rotations and X,Z translations, as were Avanto-vs-Aera mean differences of -0.10/0.00/0.06mm and -0.20/0.03/0.38deg for X,Z rotations.   Single factor ANOVA indicated significant (p<0.01) mean differences in translations and Z rotation between frames.  No correlation to LGP-reported definition errors was found.

Pre-treatment CBCT offers valuable verification of MR fiducial-based stereotactic definition integrity beyond the LGP-reported definition errors.  Three cases of frame slippage were identified by this process, all characterised by excessive (>2 S.D.) values for at least two of the translation/rotation values as compared to the overall data.  More detailed analysis of our data has indicated dependence upon sequence, scanner and frame and these factors should be considered when interpreting pre-treatment CBCT verifications on Icon.


Gavin WRIGHT (Leeds, United Kingdom), Peter FALLOW, Paul HATFIELD, Nick PHILLIPS, Peter BOWNES
15:04 - 15:12 #17754 - c48-5 Comparison of initial setup accuracy of the ExacTrac system using the mask-base fusion method or the localizer and target positioner method for intracranial frameless stereotactic radiosurgery.
c48-5 Comparison of initial setup accuracy of the ExacTrac system using the mask-base fusion method or the localizer and target positioner method for intracranial frameless stereotactic radiosurgery.

Aim

The recent upgrade of the BrainLab Exactrac system (v6.2) removes the need for the use of a Frameless Localizer and Target Positioner (TarPo) at CT, allowing for treatment prepositioning based on a fusion of an internally stored CT of the frameless SRS mask base. The redundancy of the TarPo gives way for the use of the Frameless Radiosurgery Positioning Array at CT, allowing it to be contoured and its attenuation accounted for in iPlan dosimetry. We report on the initial setup accuracy of the mask base fusion (MBF) feature compared to the TarPo localisation (TL) method using ExacTrac <v.6.2 for patients receiving stereotactic radiosurgery (SRS) or fractionated SRS (fSRS) for intracranial tumours.

Methods

94 SRS (39 TL, 55 MBF) and 72 fSRS (40 TL, 34 MBF) patients were retrospectively analysed. The median initial image corrections in 6-degrees of freedom (DOF) were compared between TL (n=79) and MBF (n=79) for both SRS and fSRS (first fraction only) patients with a Wilcoxon-Rank test (p<0.05). Systematic and random error was calculated for all 6DOF using the daily initial corrections of all fractions of the fSRS patients.

Results

The median initial corrections for the TL method and MBF method respectively were: lateral shift -0.52mm vs -0.97mm (p=0.06), longitudinal shift 0.18mm vs 1.11mm (p=0.001), vertical shift 0.80mm vs -1.56mm (p <0.001), lateral angle -0.03deg vs -0.21deg (p=0.18), longitudinal angle 0.43deg vs 0.05deg (p=0.03) and vertical angle -0.15deg vs 0.07deg (p=0.37). The systematic error for positioning accuracy of fSRS was 1.5mm or less for all directions regardless of setup method, except the vertical shift (6.1mm using TL and 2.2mm using MBF). The random error for both methods was 0.9mm or less for all directions.

Conclusion

The initial setup accuracy is comparable between the TL and MBF methods. The longitudinal shift, vertical shift and longitudinal angle corrections are greater with the MBF method, but are less than 2mm or 0.5deg making them clinically inconsequential to the image verification process. An advantage of the MBF method is the redundancy of the TarPo allows for the Frameless Radiosurgery Positioning Array to be placed at CT and contoured, with attenuation then accounted for in the planning dosimetry, reducing the dose variation produced by the array during SRS delivery.


Katrina WOODFORD (Melbourne, Australia), Gishan RATNAYAKE, Sashendra SENTHI, Jeremy D RUBEN, Vanessa PANETTIERI
15:12 - 15:20 #17766 - c48-6 Using Cone Beam Computer Tomography for stereotactic space verification within frame-based Leksell Gamma Knife Icon radiosurgery.
c48-6 Using Cone Beam Computer Tomography for stereotactic space verification within frame-based Leksell Gamma Knife Icon radiosurgery.

Leksell Gamma Knife Icon (Elekta AB) includes a cone-beam CT (CBCT) to define the stereotactic space without the need for an invasive frame. The aim of this study was to analyze the differences between the stereotactic frame - based coordinates and the CBCT - determined coordinates.

We performed CBCT before frame-based stereotactic Gamma Knife radiosurgery for 212 patients as an additional quality assurance (QA) procedure within radiosurgery treatment. The rotational and translational shifts, maximum shot displacement,delivered maximum doses for critical structures and coverage of the tumors were recorded. The factors investigated were z-coordinates of the right and left posterior pins, tumor localization, Leksell stereotactic coordinates of the tumor, tumor volume,  mean and maximum definition errors for the MR study. The statistical analysis was performed by the R statistical package.

The maximum shot displacement in anatomy was more than 1 mm for 32 patients. Planned tumor coverage was no less than 99% but the delivered one was less 95% in 12 cases. The z-coordinate of the tumor (p=0.036), volume of the tumor (p=0.045) were associated with differences of  the coverage. The x-coordinate of the tumor (p=0.029) and the mean definition error (p=0.024) on MR images were associated with maximum shot displacement.

The understanding of the differences between the stereotactic frame - based and the CBCT 3D stereotactic space is an important aspect of Gamma Knife Icon radiosurgery.

The differences between radiological and mechanical isocenters in case of frame-based radiosurgery are often assumed to be 0.2 - 0.5 mm. But the uncertainty of target and the structure localization could lead to more than 5% reduction of the prescribed dose coverage of the tumor.  The method of stereotactic space definition (frame or CBCT) that obtains more accurate results should be determined as well as the clinical significance of the demonstrated shifts are supposed to be defined


Valery KOSTJUCHENKO (Moscow, Russia), Irina BANNIKOVA, Alexandra DALECHINA, Andrey GOLANOV, Sergey BANOV, Angelika ARTEMENKOVA, Ivan OSINOV
15:20 - 15:28 #17796 - c48-7 Preliminary report of stereotactic radiotherapy using mask system of Leksell Gamma Knife Icon.
c48-7 Preliminary report of stereotactic radiotherapy using mask system of Leksell Gamma Knife Icon.

Object: Leksell Gamma Knife Icon enables us to apply new methods of immobilization using mask fixation and the option of fractionated treatment. This provides exceptional accuracy and precision of radiosurgery, making it a possibility for many more disease types and many more patients to be treated. We have consistently selected mask fixation, except 3 AVM patients, who needed digital angiography after frame fixation for dose planning.

Methods: We retrospectively analyzed 566 patients (702 times) who underwent Gamma Knife Icon using mask fixation between September 25th, 2017 and December 31th, 2018 at Rakusai Shimizu Hospital. The most common disease was brain metastases (384 patients), followed by meningioma (78), vestibular schwannoma (24), AVM (17), trigeminal neuralgia (15) and others (48). Patients with small, few, newly diagnosed, and non-eloquent area tumors were treated in a single session. If the tumor volume was larger than 5.0 ml, recurrence, or the location was in an eloquent area, we applied a fractionated schedule. If the tumor number was large, we selected a multisession schedule. Therefore, 209 patients were treated in a   single session, 377 with fractionation, and 116 with multiple sessions. For higher accuracy, we changed the upper limit of the HDMM system from 1.5mm to 1.0mm for malignant tumors and 0.5mm for benign tumors.

Results: We selected fractionated schedules as follows; 7.0 Gy x 5Fr (5-10 ml), 4.2Gy x 10Fr (10-20ml), 3.7Gy x 10Fr (20-30ml), 3.2Gy x 10Fr (30ml-) for malignant tumors, and 2.7Gy x 10Fr for benign tumors. Compared with frame fixation, almost all of patients (97%) who had previously experienced the frame fixation felt more comfortable.

Conclusions: Although these results are limited to short periods, survival rated, local control rates and qualitative survival rated in patients unsuitable for SRS, such as those with large, recurrent, and eloquent site lesions, were within the acceptable ranges. Further examination is needed for comparison with staged Gamma Knife radiotherapy, Cyber-Knife and Novalis radiotherapies


Takuya KAWABE (Kyoto, Japan), Manabu SATO
El Pardo I
15:00

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A49
15:00 - 15:30

PANEL 3
VESTIBULAR SCHWANNOMA POINT-COUNTERPOINT

15:00 - 15:10 Earlier is Better. Marc LEVIVIER (Chef de Service) (Speaker, Lausanne, Switzerland)
15:10 - 15:20 Watch and Wait. Oystein TVEITEN (Neurosurgeon) (Speaker, Bergen, Norway)
15:20 - 15:30 Panelist. Gus BEUTE (Neurosurgeon) (Speaker, Tilburg, The Netherlands), Manoel PAIVA (NEUROSURGEON/CHIEF DEPARTMENT) (Speaker, SAO PAULO, Brazil), Isaac YANG (Associate Professor) (Speaker, Los Angeles, USA)
Segovia Plenary

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B49
15:00 - 15:30

PARALLEL
STANDARDISATION IN RADIOSURGERY

Moderators: Felipe ERLICH (Radiation Oncologist) (Rio de Janeiro, Brazil), Patrick HANSSENS (Radiation Oncologist) (Tilburg, The Netherlands), Crystian SARAIVA (Medical Physicist) (São Paulo, Brazil)
15:00 - 15:10 Contouring: How do we improve what we see? Caroline CHUNG (Associate Professor, Radiation Oncology) (Speaker, Houston, USA)
15:10 - 15:20 #17857 - b49-2 The impact of the variability of target delineation on the resulting treatment planning and dose distributions in GK radiosurgery – a multicentre analysis.
b49-2 The impact of the variability of target delineation on the resulting treatment planning and dose distributions in GK radiosurgery – a multicentre analysis.

Objective

The aim of this study was to quantify the multiobserver variability in treatment planning for six common radiosurgery targets in relation to the variability in target contouring.

Material and methods

Twelve experienced Gamma Knife® centers participated in the study providing contours of targets and organs-at-risk together with the treatment plan for six common targets in radiosurgery.

The agreement volume index (AVI), defined as the ratio of the common to the encompassing volume for each target, was calculated. This metric was calculated for each volume within the X Gy isodose  (VXGy).  The correlation between the variability in the dosimetric and contouring parameters was assessed by plotting the AVI's of contours and volumes within the prescription isodose as well as for a broad range of VXGy. Variability in contouring and resulting dose distributions were also estimated by calculating the conformity of the plans to the average target.

Results and discussion

Analysis of prescription isodoses showed lower variability in treatment plan dosimetry for the cavernous sinus meningioma, pituitary adenoma and medium metastasis (AVI's of 0.28, 0.40 and 0.28, respectably) than in the contouring.  Variability between the plans and contours were similar for small metastasis (AVI = 0.37)  and the vestibular schwannoma (AVI = 0.48) but larger for the large metastasis (AVI = 0.52) . Absolute differences in dose at the voxel level also showed high variability for all cases, in the order of 5-15 Gy. Clinically, the coverage pass-rate to the average target ranged between 50% (cavernous sinus meningioma) and 83% (Vestibular schwannoma) across all the treatment plans.

Conclusions

The treatment plan dosimetry variability was as large as the contouring variability for this highly conformal treatment with enough range in dose coverage to have potential implications on tumor control.


Helena SANDSTRÖM (Stockholm, Sweden), Caroline CHUNG, Hidefumi JOKURA, Iuliana TOMA-DASU
15:20 - 15:30 Variations in dose According to Planning Philosophy. Ian PADDICK (Consultant Physicist) (Speaker, London, United Kingdom)
Segovia Break Out
15:30

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A491
15:30 - 16:20

Oral Session
GLIOMAS

Moderators: Samuel CHAO (Radiation Oncologist) (Cleveland, OH, USA), Christopher DUMA (Speaker) (Newport Beach, USA), Rodrigo GUIMARAES (Brazil)
15:30 - 15:40 #17650 - a491-2 Interplay of focal radiation therapy with targeted cellular therapy in glioblastoma.
a491-2 Interplay of focal radiation therapy with targeted cellular therapy in glioblastoma.

INTRODUCTION: Glioblastoma (GBM) is the most common primary adult brain tumor and carries a devastating prognosis. We have shown that mesenchymal stem cell (MSC) therapies offer a new treatment paradigm for therapy delivery; however, it is unknown if radiosurgery can promote or inhibit MSC activity.

AIMS: Study the modulatory effect of single-dose, focused ionizing radiation (IR) on MSC migratory patterns.

METHODS AND RESULTS: To confirm IR-induced cytotoxicity, MTT assay of the radiated patient-derived glioblastoma brain tumor initiating cells (BTICS) showed decreased viability after 2 Gy, 8 Gy and 20 Gy IR at 48 hours and further (p=0.006). MSCs were transduced with an iRFP lentiviral vector, and ex vivo implantation of MSCs was carried out on organotypic slices of normal mouse brain to evaluate engraftment and migration in the setting of IR delivery, groups of 0 Gy, 2 Gy, 5 Gy and 10 Gy were compared via confocal microscopy using 3D time lapse, daily qualitative evaluation of migratory patterns showed a trend to longer migratory distances with increasing dose of IR compared to control.

Additionally, to assess IR effects on MSC migration, transwell assays were performed, in quadruplicate, using conditioned media from radiated patient-derived glioblastoma BTICs; after 12 hours incubation, migration was assessed by directly counting DAPI-labeled nuclei via fluorescence microscopy. Reduced MSC transwell migration was found after 10 Gy IR compared to the control, 2 Gy IR and 5 Gy IR groups (p=0.008, p=0.002, and p=0.010, respectively). Finally, in an in vivo murine model, IR to orthotopic glioblastoma tumor, followed by intracardiac injection of MSC, resulted in MSC homing in irradiated and non-irradiated tumor.

CONCLUSION: MSC migration to BTIC-conditioned media decreases when BTICs are exposed to high dose IR in vitro, and migration of MSCs seems to likewise follow a positive relationship with the delivery of IR on an ex vivo, and in vivo mouse model. This suggests that radiosurgery could ‘prime’ the tumor microenvironment if delivered prior to MSC delivery. Further efforts to synergize IR with the MSC payload are underway.


Daniel TRIFILETTI (Jacksonville, USA), Henry RUIZ-GARCIA, Rachel SARABIA ESTRADA, Hugo GUERRERO-CAZARES, Anna HARRELL, Sujan MONDAL, Keila ALVARADO-ESTRADA, Alfredo QUINONES-HINOJOSA
15:40 - 15:50 #17678 - a491-3 Bioengineering TRAIL for synergy with focal irradiation in glioblastoma.
a491-3 Bioengineering TRAIL for synergy with focal irradiation in glioblastoma.

INTRODUCTION: Glioblastoma (GBM) is the most common primary adult brain tumor. We have shown that mesenchymal stem cell (MSC) therapies offer a new treatment paradigm for therapy delivery; however, the ideal payload has not been identified. We believe that TRAIL (tumor necrosis factor-related apoptosis inducing ligand), a cancer cell-death triggering protein, could synergize with current existing therapies, including focal irradiation.

AIMS: Design and produce a regulable expression vector for exploring the boosting effect of glioblastoma focal radiation priming on TRAIL-secreting MSC therapy.

METHODS AND RESULTS: To study the synergy of focal radiation and TRAIL therapy, 8 Gy of ionizing radiation was delivery to an in vitro patient-derived GBM model. TRAIL receptors levels (DR4 & DR5) increased at 48 hours after irradiation when compared to non-irradiated GBM using RT-qPCR (p<0.01). Thereafter, we designed a secretable version of TRAIL aiming to enable MSCs TRAIL secretion.  The original gene was modified by adding a novel tag to assure its secretion to the extracellular compartment. We also included a tetracycline-inducible TRAIL expression system to allow for on-demand TRAIL release, increasing the safety of the protein secretion. Structural and functional validation was carried, and TRAIL protein was proven on the conditioned media. To generate stable MSCs able to secrete TRAIL, a lentiviral vector was produced and successfully tested on three different primary adipose MSC cell lines. Further work is being carried out to test the final synergism of radiation, MSC and TRAIL therapies. 

CONCLUSION: We have showed that GBM TRAIL receptors increase after 48 hours of focal radiation and that TRAIL-secreting MSCs can be bioengineered for possible synergy with radiation. Consequently, appropriate use of modern radiation delivery techniques such as SRS could possess a boosting effect on targeted cellular therapies. Our novel TRAIL-secreting adipose MSCs will help allow us to further study this system.


Henry RUIZ-GARCIA, Natanael ZARCO, Virginea DE ARAUJO-FARIAS, Anna HARRELL, Hugo GUERRERO-CAZARES, Rachel SARABIA ESTRADA, Alfredo QUINONES-HINOJOSA, Daniel TRIFILETTI (Jacksonville, USA)
15:50 - 16:00 #17657 - a491-4 Stereotactic radiosurgery in combination with high-dose methotrexate as a first-line treatment for primary central nervous system lymphoma: a single institution experience.
a491-4 Stereotactic radiosurgery in combination with high-dose methotrexate as a first-line treatment for primary central nervous system lymphoma: a single institution experience.

Objective: Primary central nervous system lymphoma (PCNSL) is a rare cancer accounting for less than 4% of primary brain and central nervous system tumors. High-dose methotrexate (HD-MTX) is the gold standard for newly diagnosed PCNSL. However, stereotactic radiosurgery (SRS) may be efficacious as a co-adjuvant treatment. The purpose of this study is to determine the effectiveness of HD-MTX in combination with SRS in the treatment of PCNSL.

Methods: This is a prospective, observational cohort study evaluating the treatment of histologically confirmed PCNSL with HD-MTX in a dose of 3.5 g/m2 and treatment with HD-MTX, plus SRS. Strict inclusion and exclusion criteria were employed. Primary outcomes were measured by survival rate. Secondary outcomes were assessed by the tumor's responsiveness to treatment and reduction in size as noted on imaging, the Karnofsky Performance Status (KPS), the activities of daily living (ADL) and mini-mental state examination (MMSE).

Results: Between January 2010 and January 2018, 82 cases were evaluated. Included in this evaluation were 44 chemotherapy and 38 chemotherapy, plus SRS, patients. The follow-up period was 12 to 96 months (mean: 54.8 months). Patients were treated with SRS prescription doses ranging from 12 Gy to 16 Gy (median: 14 Gy). The median survival rate from initial diagnosis was 38.4 months in the chemotherapy group and 52.6 in the chemotherapy, plus SRS, group (p-value: 0.005). All lesions showed a complete response after SRS when evaluated using magnetic resonance imaging after one to three weeks (mean range: 2.2 weeks). No significant side effects related to SRS were observed. During follow-up period, the good ADL preservation was achieved for 22.4 months from SRS. Patients with KPS >90 at SRS demonstrated longer ADL preservation (36 months from SRS). No significant difference in MMSE between two groups was found.

Conclusions: SRS in combination with HD-MTX as a first-line treatment provided better prognosis and not worse neurocognition state. This noninvasive treatment modality should be considered as an option for patients with PCNSL. A newly registered study (SRS-PCNSL*) is underway.

*SRS-PCNSL: Upfront Stereotactic Radiosurgery in Combination with Methotrexate Based Chemotherapy in the Treatment of Newly Diagnosed Primary Central Nervous System Lymphoma 


Hao LONG (Guangzhou, China)
16:00 - 16:10 #18092 - a491-6 Fractionated Radiosurgery plus Check Point Blockade is a Novel Paradigm for Treating Glioblastoma Multiforme.
a491-6 Fractionated Radiosurgery plus Check Point Blockade is a Novel Paradigm for Treating Glioblastoma Multiforme.

Purpose: We have shown that fractionated radiosurgery (fSRS) with simultaneous differential dosing of 32 Gy (to enhancing tumor) and 24 Gy (to flair abnormality) in 4 fractions improved the local control of recurrent glioblastoma (GBM).  Although immunotherapy improved outcome in many tumor types, CHECKMATE 143 showed no benefit of adding checkpoint inhibitors to the standard GBM treatment. We carried out experiments to develop a new strategy of in-situ vaccination effect against the local tumor by fSRS combined with immune checkpoint inhibitor. 

Materials and Method: Orthotopic GL261 glioma cells implanted to the forebrain in immunocompetent B57 mice. The tumor diameter becomes 2-3 mm on day 10 post-implantation. Total of 46 tumor-bearing mice were randomized to treatment groups of 1) untreated control, 2) anti-PD-1 (aPD1) mouse nivolumab 10 mg/kg i.p. on days 10, 12, and 14 post-implantation, 3) RS 10 Gy on day 10 post-implantation, and 4) combination of RS and aPD1. Survival time was measured. The brains at time points of 11, 15, 30 days, and death. The whole brain samples were prepared for multiplex IHC, flow cytometry, and western blot and gene expression assay by RNA extraction to examine the dynamics in immune effector cells and the signatures. The mice were imaged with 9.4 Tesla MRI scan to measure the tumor size and to identify the predictive imaging markers.

Results: Median survival time was 22.5 days in untreated control, 30 days by aPD1 monotherapy, and 36 days RS 10 Gy alone. After RS and aPD-1 together, the median survival was not reached up to 60 days with 75% of mice being alive with a complete pathological response at the end of the study duration. IHC and gene expression arrays showed that tumor growth by itself induced a dramatic increase in both the CD8+ T-cells and tumor-infiltrating phagocytic cells, associated with increased INF-γ level in the tumor tissue and serum, and elevated expression of CD86 (a marker of dendritic cells/macrophages). Therapy with aPD1 alone did not cause any significant change.  All these increases were completely abrogated by 10 Gy radiation. However, CD8+ cells and CD86 were increased again by the combined RS and aPD1. The expression of IFN-γ was sustained in the mice that were cured of the tumor. MRI scan showed increased permeability and T2 kurtosis parameter in the responders.

Conclusion: Combined RS and aPD1 significantly improved GBM tumor control and survival. CD8+ and CD86+ cells play a major role with increased INF-γ level. The findings indicate that the local anti-tumor immune response against GBM may be a unique mechanism, distinct from the abscopal (distant) effects.


Samuel RYU (Stony Brook, NY, USA), Alex STESSIN, Mariano CLAUSI, Timothy DUONG, Stella TSIRKA
Segovia Plenary

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B491
15:30 - 16:20

Oral Session
PITUITARY TUMORS

Moderators: Gustavo ADOLPHO (Brazil), Benjamin JONKER (Neurosurgeon) (Sydney, Australia), Manoel PAIVA (NEUROSURGEON/CHIEF DEPARTMENT) (SAO PAULO, Brazil)
15:30 - 15:40 #17659 - a491-1 Follow-up studies of Gamma Knife radiosurgery for non-functioning pituitary adenomas.
a491-1 Follow-up studies of Gamma Knife radiosurgery for non-functioning pituitary adenomas.

OBJECTIVE

  The aim of this study was to evaluate the long term clinical outcomes of Gamma Knife surgery(GKS) for non-functioning pituitary adenomas (NFPAs) and the role of GKS in the management of NFPAs. 

 METHODS  

Between January 2000 and December 2010,204 patients with residual or recurrent NFPAs after surgery undergoing GKS were enrolled in this study.The median age of the patients was 48 years old (mean 48 years,range 14 to 79 years).The median tumor volume was 3.3 ml (mean 5.2 ml, range 0.326.4 ml).The median margin dose was 14Gy (mean 14 Gy,918Gy).The median maximum dose was 31Gy (mean 30Gy,2040Gy).The median duration of follow up was 86 months (mean 88 months,range 12-213 months).

Duaring the same period,52 patients with NFPAs without prior surgery undergoing GKS were enrolled in this study.The mean age of the patients was 55 years old.The mean tumor volume was 5.0 ml.The mean margin dose was 14Gy.The mean maximum dose was 31Gy.The mean duration of follow up was 41 months.

 RESULTS

Of these 204 patients with adjuvant GKS,the latest follow-up MR imaging studies demonstrated tumor regression in 102 patients(50%),tumor stable in 81 patients(40%),and tumor enlargement in 21 patients(10%).The tumor control rate of this cohort was 90%.37 patients(18%) developed new onset hypopituitarism.5 patients(2.5%) presented new or worsening visual dysfunction without tumor growth.

Of these 52 patients with primary GKS,the latest follow-up MR imaging studies demonstrated that the tumor control rate of this cohort was 88%.5 patients(10%) developed new onset hypopituitarism.6 patients(12%) presented worsening visual dysfunction all due to tumor growth.

CONCLUSION  

GKS provided a high tumor control and low complication rate for NFPAs.We recommended that early GKS should be considered the routine adjuvant treatment for residual NFPAs after subtotal surgical resection.


Shibin SUN (Beijing, China)
15:40 - 15:50 #17665 - a491-2 Long-term outcome of gamma knife radiosurgery for patients with nonfunctioning pituitary adenomas.
a491-2 Long-term outcome of gamma knife radiosurgery for patients with nonfunctioning pituitary adenomas.

Purpose: We evaluated the treatment results of gamma knife radiosurgery for nonfunctioning pituitary adenomas.

Material and methods: Between January 1994 and December 2014, we treated and followed up 134 patients with nonfunctioning pituitary adenomas. All the tumors were treated by neurosurgery prior to radiosurgery, 3 patients (2.2%) received conventional radiation therapy before radiosurgery. Tumor volume ranged from 0.27 to 15.1 ml (median: 2.17 ml). Radiosurgical dose ranged from 8 to 16 Gy (median: 12 Gy) for the tumor margin. The median follow-up was 9 years (1 to 22 years).

Results: Tumor growth control rate was 95% at 5-years, 94% at 10-years and 91% at 15 years. 3 patients (2.2%) suffered out-of filed recurrences. The actuarial endocriopathy needed hormonal replacement therapy was 4% at 5-years, 7% at 10-years and 15% at 15 years. 3 patients (2.2%) suffered the permanent cranial neuropathy. The suprasellar extension was significant factors of poor tumor control (p=0.049) and high incidence of endocrinopathy (p=0.014). Cystic enlargement was occurred in 8%, but all lesions were decreased or unchanged in size during follow-up periods. New cranial neuropthy was occurred 2.2% during 42 to 144 months after radiosurgery.

Conclusion: Gamma knife radiosurgery is very useful for nonfunctioning pituitary adenomas in the standpoint of long-term tumor growth control. We recommend early adjuvant radiosurgery for the residual tumor after enough tumor debulking or regrowth after surgery.


Yoshiaysu IWAI (Osaka, Japan), Kenichi ISHIBASHI, Kazuhiro YAMANAKA
15:50 - 16:00 #17697 - a491-3 Plasticity of the visual cortex to visual pathway injuries before and after SRS of suprasellar tumors.
a491-3 Plasticity of the visual cortex to visual pathway injuries before and after SRS of suprasellar tumors.

Objectives:

To demonstrate that lesions of the visual pathways due to suprasellar tumors are accompanied by alterations of the visual cortex and to see if these alterations are reversible after treatment of tumors by Gamma Knife radiosurgery.

Methods:

In 36 patients with perioptic tumors and defects of their visual fields and in an age-matched control group, magnetic resonance imaging was performed before and after Gamma Knife radiosurgery. T1 weighted images were evaluated by voxel-based morphometry and correlated to the degree of visual field defects.

Results:

In patients, grey matter density and cortical thickness were reduced in all parts of the occipital cortex, reaching significance (p<0.05) in the left superior and middle occipital gyri, with correlation to visual field defects. Follow-up scans showed further reduction in all occipital areas.

Conclusions:

As in other peripheral lesions of the optic system, damage of the optic nerves, chiasm and tracts due to compression by suprasellar tumors affects the visual cortex and induces a reduction of grey matter density which - in contrast to some clinical recuperation - does not recuperate after successful Gamma Knife radiosurgery. However, a follow-up study in a prospective design including only patients without previous operations, which might have injured these structures in an irreversible way, is needed to confirm this conclusion or show under which conditions exceptional recuperations of the visual cortex are possible. In addition, the unexpected finding of a more general affection of cortical thickness in patients with pituitary tumors could be looked into more closely in order to identify and possibly prevent any predisposing factors.


Herwin SPECKTER (Santo Domingo, Dominican Republic), Jairo SANTANA, Jose BIDO, Giancarlo HERNANDEZ, Diones RIVERA, Luis SUAZO, Santiago VALENZUELA, Peter STOETER
16:00 - 16:10 #17888 - a491-4 Gamma knife radiosurgery in patients with Crooke’s cell adenoma.
a491-4 Gamma knife radiosurgery in patients with Crooke’s cell adenoma.

Background: Crooke’s cell adenoma, which is known to be clinically aggressive, is a very rare subtype of pituitary neoplasm. They could secreting adreno-corticotropic hormone or endocrinologically silent. Gamma knife radiosurgery (GKRS) for this subtype of adenoma is extremely rare. We aim to evaluate the effect of GKRS on endocrine remission and tumor control.

Patients and methods: A total of seven patients (3M/4F, median age at GKRS, 54 years, range, 21 to 65 years) with a pathology-confirmed Crooke’s cell adenoma treated with GKRS at University of Virginia Gamma Knife Center constituted this study. The median time interval between TSR and GKRS was 3 months. The median margin dose was 25Gy (range, 18Gy to 25Gy). Median treated adenoma volume was 3.12cc. The median follow-up was 74 months (range, 54 to 120 months).

Results: The tumor control was achieved in all patients. All but one achieved endocrine remission. The median time interval to cortisol normalization off of anti-hormone secreting medication was 9 months (range, 0 to 24 months). Newly developed or worsening endocrinopathy occurred in 3 patients at the time interval of 6, 15, and 18 months, respectively. The CN III neuropathy developed in 1 patient. Two patients required bilateral adrenalectomy at 44 months and 50 months following GKRS, respectively.

Conclusion: This study suggests that Crooke’s cell adenoma is truly an aggressive entity. GKRS represents a safe and effective treatment option. Large number of patients from a multicenter study is warranted to further elucidate the effectiveness of GKRS. A multimodality treatment in this patient cohort is necessary.


Zhiyuan XU (Charlottesville, USA), David SCHLESINGER, Sheehan JASON
Segovia Break Out

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C491
15:30 - 16:20

Oral Session
VESTIBULAR SCHWANNOMA #2

Moderators: Yuri ANDRADE SOUZA (Brazil), Laura FARISELLI (director) (milan, Italy), Randy JENSEN (Professor) (Salt Lake City, USA)
15:30 - 15:40 #17545 - c491-1 Efficiency Index comparison of linac-based and Gamma Knife-based radiosurgery of vestibular schwannoma treatment plans.
c491-1 Efficiency Index comparison of linac-based and Gamma Knife-based radiosurgery of vestibular schwannoma treatment plans.

Background: The Efficiency Index (EI) was recently proposed as a plan quality descriptor for stereotactic radiosurgery (SRS) plans, combining conformity, gradient and mean dose to the target in a single value (EI=Intergal DoseTV / Integral Dose50%PIV) 1. It has theoretical limits between 0-100%, and the values achieved clinically have been quantified to range from 37.7% to 58.0 (mean: 49.0%) for a group of 100 Gamma Knife (GK) plans.

Methods: This study aims to compare the achieved EIs between two similar groups of linac-based and GK-based SRS plans with a scope of assessing the utility of this index in linac-based SRS. A group of 20 consecutive vestibular schwannoma treatments with useful hearing were collected from each platform database making a total of 40 plans. The average target volumes were 2.77 and 2.18cc for linac and GK respectively. The linac plans included a 1mm treatment margin in the target volume whereas the GK plans did not. Linac cases were treated with a Varian TrueBeam, micro-MLC collimator single isocentre VMAT technique. GK cases were treated with an Elekta Perfexion using multiple isocentres.

Results: The average EIs achieved were 39.8% (range: 23.5-52.8%) and 51.3% (range: 36.4-56.7%) for linac and GK plans respectively. In both groups a higher score was seen with improvements in conformity and gradient. The differences in EIs seen between the two groups are attributed to differences in conformity (Mean Conformity Index: 0.87 vs 0.88), differences in gradient (Mean Gradient Index: 3.69 vs 2.71) and differences in mean dose to the target (15.5 vs 17.3 Gy). A trend for lower EIs was observed in smaller target volumes, mainly due to the poor gradients achieved in these plans.

Conclusion: The EI is a useful metric for both linac and GK plan quality assessment, and its score increases with improvements to qualities that are considered clinically relevant.

1.         Dimitriadis A, Paddick I: A novel index for assessing treatment plan quality in stereotactic radiosurgery. J Neurosurg 129:118–124, 2018


Alexis DIMITRIADIS (London, Austria), Hany ATTALLAH, Ronald BEANEY, Ian PADDICK
15:40 - 15:50 #17691 - c491-2 Radiomic: prediction of acoustic neuroma response to the cyberknife treatment.
c491-2 Radiomic: prediction of acoustic neuroma response to the cyberknife treatment.

Aim: The aim of the study was to use a radiomic approach to evaluate the possibility to predict the response of an acoustic neuroma to Cyberknife® radiotherapy analyzing pre-treatment MR images. Materials:  38 patients presenting an acoustic neuroma treated with Cyberknife® at our institute were selected. Comparing the pre and post-radiotherapy images , acquired after at least 2 years, the radiotherapist divided the patients according to the volumetric treatment outcome (stability, reduction, increasement). This classification was used by the machine learning algorithm as a reference value. All images were acquired on two 1.5T machines with contrast enhanced T1-weighted sequences in axial plane. Semi-automatic tumor segmentation was carried out by a radiotherapist  on MR images using the level tracing effect of the 3DSlicer image analysis software.  After the segmentation a resampling step was done to harmonize the images acquired on the scanners. Sequentially, 1135 shape-based, intensity-based and texture-based features were extracted using IBEX, an open software infrastructure platform. An evolutionary machine learning algorithm (a TWIST system based on KNN algorithm) was used to subdivide the dataset into training and test set and select features yielding the maximal amount of information. After the features extraction, a predictive model based on a training-testing crossover procedure was developed. The best neural network obtained was a 2-layers feed forward back propagation algorithm with 37 input variables containing the maximal amount of information.
Results: The neural network was used twice inverting the training/testing set. In the first analysis the sensitivity was 71.43%, while the specificity was 100%, with a global accuracy of 85.71%. In the second analysis the sensitivity was 83.33% and the specificity 88.24%, with a global accuracy of 85.78%. The mean value of the global accuracy was 85.75%.
Conclusions: The obtained results show that Machine Learning coupled with Radiomics has a great potential in distinguishing, before radiosurgery,  patients with volume reduction from patients without.


Isa BOSSI ZANETTI (Milano, Italy), Natascha Claudia D'AMICO, Enzo GROSSI, Giovanni VALBUSA, Deborah FAZZINI, Achille BERGANTIN, Irene REDAELLI, Anna Stefania MARTINOTTI, Cecilia IEZZONI, Giuseppe SCOTTI, Laura FARISELLI, Sergio PAPA, Giancarlo BELTRAMO
15:50 - 16:00 #17854 - c491-3 Short-term volumetric tumor response as predictor for long-term tumor control after Gamma Knife radiosurgery of vestibular schwannoma.
c491-3 Short-term volumetric tumor response as predictor for long-term tumor control after Gamma Knife radiosurgery of vestibular schwannoma.

Introduction

Gamma Knife radiosurgery (GKRS) is an effective treatment strategy for vestibular schwannomas (VSs), obtaining long-term tumor control rates of 90%. Currently, predicting long-term tumor control is not possible, making lifelong follow-up mandatory and prospective studies on tumor control difficult to conduct. Therefore, predicting tumor control at earlier stages would be beneficial. We explored the predictability of long-term tumor control employing short-term volumetric tumor responses.

Methods

All VS patients with minimum follow-up of 3 years were included. Tumor volumes were obtained from follow-up MRIs. Tumor volume reduction (TVR) was calculated at 6, 12, 24 and 36 months following GKRS. Correlations between TVRs and long-term tumor control were evaluated.

Results

We included 795 patients, of which 96 showed loss of tumor control. The median follow-up time was 61 months. TVRs at 6, 12, 24, and 36 months were based on MRIs from 186, 693, 541 and 399 patients, respectively. Cox regression analyses indicate that TVRs at 6, 24 and 36 months are significantly related to tumor control, indicating a proportional correlation. Kaplan-Meier analyses, when stratifying the cohort in 4 groups based on the TVRs, confirmed this relation: tumors with pronounced TVRs in the first years following GKRS had significantly lower risks of treatment failure, as compared to increasing tumors. For example, if tumor volumes were stable or decreasing between 6 and 24 months after GKRS, loss of long-term tumor control was observed rarely compared to tumors with increasing volumes in this follow-up period: 5-year tumor control probabilities are 97.5% and 67.1%, and the 10-year probabilities are 92.0% and 67.1%, respectively.

Conclusions

Results from this research clearly indicate that TVRs at 6, 24 and 36 months following treatment are predictive for long-term tumor control in GKRS-treated VS. These findings can help in determining an individual follow-up schedule for VS patients and make prospective studies on long-term tumor control more feasible.


Patrick LANGENHUIZEN (Tilburg, The Netherlands), Svetlana ZINGER, Sieger LEENSTRA, Patrick HANSSENS, Peter DE WITH, Jeroen VERHEUL
16:00 - 16:10 #17864 - c491-4 Role Of Bevacizumab As A Prophylactic And Rehabilitative Treatment Modality In Cases Of Sporadic And Syndromic Vestibular Schwannoma: Fifty Shades Of Grey.
c491-4 Role Of Bevacizumab As A Prophylactic And Rehabilitative Treatment Modality In Cases Of Sporadic And Syndromic Vestibular Schwannoma: Fifty Shades Of Grey.

Objectives:

Detection of vestibular schwannoma (VS) in young patient demands specific attention considering it’s relatively aggressive course and natural

history of the disease. Patients with syndromic variants such as neurofirbromatosis type 2 (NF2) suffer from multiple tumors including bilateral VS,

meningioma, ependymomas, and peripheral nerve sheath tumors. Such patients may suffer from unprecedented complications following radio

surgical treatment such as poor tumor control and functional outcome.

Methods:

Authors describe their own experience with Bevacizumab as a preventive and rehabilitative treatment option in two such patients who suffered from

complications of radiosurgery in the immediate post-procedure period. Literature is reviewed for the indications, dosage, safety profile, and

complications profile on short and long-term of Bevacizumab in vestibular schwannomas.

Results:

One middle-aged patient of sporadic vestibular schwannoma suffered rapid onset facial paresis within one month of GKRS. After a failed attempt

with steroids, the patient regained partial improvement following Bevacizumab treatment. Another young female of phenotypic NF2 syndrome

suffered rapid onset hearing deficit within two weeks of GKRS, which improved to pre GKRS level with the early introduction of Bevacizumab.

Bevacizumab has shown its efficacy both as a prophylactic and rehabilitative treatment modality for syndromic patients of VS.

Conclusions:

Though not a wonder drug, Bevacizumab is a valuable adjunct in crossroad situations. It has a proven role as a prophylactic treatment option to

retard the growth of VS and spinal ependymomas with no role on meningiomas. As a rehabilitative treatment option, Bevacizumab may be used in

steroid-resistant cases to prevent radiosurgery-induced complications. Long-term studies are warranted to confirm the dosing schedules, regimens,

and complication profile.


Manjul TRIPATHI (Chandigarh, India)
16:10 - 16:20 #17646 - c491-5 Observation or stereotactic radiosurgery for newly diagnosed vestibular schwannomas: A systematic review and meta-analysis.
c491-5 Observation or stereotactic radiosurgery for newly diagnosed vestibular schwannomas: A systematic review and meta-analysis.

Introduction: Vestibular schwannomas are benign tumors with a slow growth rate. There exists controversy regarding whether patients should receive upfront observation, radiotherapy including SRS or FSRT, or surgery at the time of diagnosis. For patients declining resection, this systematic review evaluates the risks and benefits between observation and SRS upon diagnosis of VS.

Methods: Published studies on VS were systematically reviewed for clinical series including patients with newly/recently diagnosed unilateral VS. Studies that included patients with previous treatment for the VS or focused on patients with neurofibromatosis were excluded. Review articles and systematic reviews were excluded but reviewed for relevant references that would otherwise meet search criteria.

Results: Most patients electing observation underwent their first surveillance scan 6 months after initial      diagnosis. Follow up was similar for patients receiving radiosurgery. Observation alone conferred a radiographic tumor control rate of 65% and serviceable hearing in 71.3% by the end of the follow up period in the reviewed studies, and 34% of patients initially opting for observation ultimately opted for treatment. The follow up period varied between studies. Initial radiosurgery resulted in a tumor control rate of 97% and serviceable hearing rate of 73.8% at by the end of the follow up period. Radiosurgery resulted in improved tumor control at the end of the follow up period (p < 0.0001), and serviceable hearing did not statistically differ (p = 0.69).

Conclusion: Based on the available published data, observation after initial diagnosis is appropriate for many patients with VS without symptomatic brainstem compression. However, initial observation does risk early progressive hearing dysfunction if the tumor grows and patients with serviceable hearing at diagnosis may benefit from early therapy. Long term follow up is critical, and an algorithm to better risk-stratify patients with newly diagnosed VS is underway.


Janet LEON, Eric LEHRER, Jennifer PETERSON, Laura VALLOW, Henry RUIZ-GARCIA, Austin HADLEY, Steven HERCHKO, Larry LUNDY, Kaisorn CHAICHANA, Prasanna VIBHUTE, Jason SHEEHAN, Daniel TRIFILETTI (Jacksonville, USA)
El Pardo I
16:20 COFFEE BREAK - POSTERS & EXHIBITION
17:00

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A493
17:00 - 17:45

ISRS GENERAL ASSEMBLY

Segovia Plenary

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C493
17:00 - 18:00

REDE D'OR SPONSORED SESSION

17:00 - 18:00 Moderator. Karina MOUTINHO (neurosurgery) (Partenaire: SILVER PARTNERS, Santa Paula, Brazil)
17:00 - 17:20 The Challenges of Radiosurgery in Brain Metastases. Felipe ERLICH (Radiation Oncologist) (Partenaire: SILVER PARTNERS, Rio de Janeiro, Brazil)
17:20 - 17:40 The Challenges of Radiosurgery in treatment of oligometastatic disease. Allisson Barcelos BORGES (Radiation Oncologist) (Partenaire: SILVER PARTNERS, Brasilia-DF, Brazil)
17:40 - 18:00 The Oncologia D’Or Changing the Radiotherapy and Radiosurgery Scenario. Karina MOUTINHO (neurosurgery) (Partenaire: SILVER PARTNERS, Santa Paula, Brazil)
El Pardo I
20:00 CONGRESS DINNER - Casa Das Canoas, Tijuca Forest - (Upon Registration)
Thursday 13 June
07:30

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A51
07:30 - 09:00

BREAKFAST SEMINAR
EVERYTHING YOU NEED TO KNOW ABOUT IMAGING

Moderators: Xiao FUREN (Neurosurgeon) (Taipei, Taiwan), Paulo OPPITZ (Neurosurgeon) (Porto Alegre, Brazil), Georges SINCLAIR (Consultant Clinical Oncologist) (Reading, UK, United Kingdom)
07:30 - 07:50 Novel MRI Sequences for SRS. Herwin SPECKTER (Mr.) (Speaker, Santo Domingo, Dominican Republic)
07:50 - 08:10 Functional images for behavior disorders. Ricardo DE OLIVEIRA (Speaker, Brazil)
08:10 - 08:30 #17884 - a51-3 Integrated Stereotactic Diffusion Tensor Tractography for Gamma Knife Stereotactic Radiosurgery.
a51-3 Integrated Stereotactic Diffusion Tensor Tractography for Gamma Knife Stereotactic Radiosurgery.

Objectives:

Integration of modern neuroimaging techniques into treatment planning has increased the therapeutic potential and safety of stereotactic radiosurgery. We report our experience over the past three years with integrating Stereotactically acquired Diffusion Tensor Tractography (DTI) into treatment planning for Gamma Knife Radiosurgery in patients with a variety of pathology in eloquent intracranial locations.

Methods:

Our study cohort comprised of 115 patients who underwent 122 Gamma Knife radiosurgical treatments at our centre.
32 Channel DTI at 1.5 T & 3T was performed at the time of standard treatment GK Protocol MR T1 & T2) imaging. DTI images were post processed with commercial software using a deterministic protocol. Generated Tracts were imported into Gamma plan to aid shot planning & perform dosimetry on vulnerable white matter tracts. Tailored & 3T sequences wer alos evaluated.

Results:

Stereotactic diffusion tensor tractography was successful in generating the appropriate ADC, FA & DEC sequences. Tractography provided additional useful clinical information for treatment planning. In patients with cerebral oligo-metastatic disease requiring multiple treatments, clinical & radiological response correlated well with preservation or improvement in adjacent tract volumes. One patient with a mesial temporal AVM developed delayed worsening of a pre-existing hemianopia & another with AVM required steroids for cerebral swelling. no other neurological deficits due to radiation were recorded at follow-up

Conclusions:

 Tractographyi is a useful technique for preventing complications in stereotactic radiosurgery by reducing radiation doses to functional organs at risk, including critical cortical areas and subcortical white matter tracts. Tractography use in SRS can further increase our knowledge of critical cerebral structure radiation tolerances. Stereotactic Tractography is a useful technique to improve the therapeutic potential and safety of stereotactic radiosurgery. 


Cormac GAVIN (London, United Kingdom), H. Ian SABIN
08:30 - 08:50 Review of MR Pulse Sequences for SRS/SBRT: What Does Each Provide. Stephen HOLMES (Imaging Consultant and Conference Organizer) (Speaker, honolulu, USA)
Segovia Plenary

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B51
07:30 - 09:00

BREAKFAST SEMINAR
ATYPICAL MENINGIOMAS

Moderators: Andrey GOLANOV (Chief of the Department) (Moscow, Russia), Carlos MATTOZO (NEUROSURGEON, MD.) (CURITIBA, Brazil), Gelareh ZADEH (Radiosurgery) (Toronto, Canada)
07:30 - 07:45 #17896 - b51-1 A tentative strategy to management of atypical or WHO I meningiomas with high grade MIB-Ki67.
b51-1 A tentative strategy to management of atypical or WHO I meningiomas with high grade MIB-Ki67.

The efficacy of radiosurgery in the control of WHO I meningioma growth has been demonstrated both as up-front strategy and as the primary salvage therapy following surgical incomplete removal. (Santacroce et al. 2012)
Some lesions however are failing radiosurgery in a pattern closely resembling Atypical meningioma. Historically atypical meningiomas undergo conventional radiotherapy following on or multiple attempts at surgical removal. The long-term efficacy of radiotherapy in controlling the growth of meningiomas above grade I has historically been poor.
We have analyzed the meningiomas in our series of radiosurgically treated meningiomas who had failed surgery or radiosurgery or both and as a rule recognized (as also Mukhopadhyay et al. (2017) a Ki-67 labeling index equal or above 3%. In other words: some WHO I meningiomas behaved, in regard to recurrence, in a very similar way to the more aggressive atypical variants albeit missing the invasive, necrotic features of the higher grades.
We have then tried in both groups a strategy of re-operation (whenever feasible in order to reduce the target tissue volume) followed by:
•in 60 patients (2004-2018) a course of conventional radiotherapy (25 Fractions of 180cGy, Tot. 45Gy) followed after 12-15 days by a radiosurgical boost (10-14Gy). Results: 26 controlled at 3yrs F-U and 14 failed (at any time in the course of F-U)
•in 60 small size WHO I lesions (1995-2018) only radiosurgery at a higher dose than customary (21-16Gy). Results: 19 controlled at 3yrs F-U and 18 failed (at any time in the course of F-U)
Evaluation of this complex subpopulations of meningioma patients requires longer F-U times and careful analysis of the local and distant recurrence events.


Enrico MOTTI (LUGO, Italy), Enrico GIUGNI, Laura VENTRELLA, Federico RAMPA, Floranna MAURO
07:45 - 08:15 Prognostic Tools. Isaac YANG (Associate Professor) (Speaker, Los Angeles, USA)
08:15 - 08:30 Clinical Results. Randy JENSEN (Professor) (Speaker, Salt Lake City, USA)
08:30 - 09:00 Improving the Treatment Paradigm of Atypical Meningiomas. Carlos MATTOZO (NEUROSURGEON, MD.) (Speaker, CURITIBA, Brazil)
Segovia Break Out

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C51
07:30 - 09:00

BREAKFAST SEMINAR
HOT TOPICS

Moderators: Yuri ANDRADE SOUZA (Brazil), David JAFFRAY (Reviewer) (Houston, USA), Christian VARGAS (Peru)
07:30 - 07:50 The Prescription Dose Debate. Gennady NEYMAN (Medical Physicist) (Speaker, Cleveland, USA)
07:50 - 08:10 The Case for Margins. Andrea GIRARDI (Medical Physicist) (Speaker, Brussels, Belgium)
08:10 - 08:30 The Case against Margins. David SCHLESINGER (Medical Physics) (Speaker, Charlottesville, VA, USA, USA)
08:30 - 08:50 Dose fall-off characterization of isocentric and non-isocentric brain radiosurgery. David SCHLESINGER (Medical Physics) (Speaker, Charlottesville, VA, USA, USA)
El Pardo I
09:00

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A52
09:00 - 09:40

PLENARY SESSION
SPECIAL GUESTS LECTURE

Moderators: Antonio DE SALLES (Professor - Chief) (SÃO PAULO, Brazil), Ian PADDICK (Consultant Physicist) (London, United Kingdom)
09:00 - 09:20 What does the market has to teach us? The experience of a MD, PhD who lead R&D at multibillion dollar company. Luiz Eugenio MELLO
09:20 - 09:40 Challenges of Big Data and the Promises of Artificial Intelligence. David JAFFRAY (Reviewer) (Speaker, Houston, USA)
Segovia Plenary
09:40

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A53
09:40 - 10:00

SPECIAL LECTURE
FABRIKANT LECTURE

Moderators: Antonio DE SALLES (Professor - Chief) (SÃO PAULO, Brazil), Ian PADDICK (Consultant Physicist) (London, United Kingdom)
09:40 - 10:00 Fabrikant lecture. John ADLER (neurosurgery) (Speaker, San Francisco, USA)
Segovia Plenary

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B53
09:40 - 10:00

Flash Oral Session
PHYSICS: HOT TOPICS

Moderators: Guilherme BULGRAEN DOS SANTOS (Brazil), Alexis DIMITRIADIS (Physicist) (London, Austria), Thiago SCHMELING (Master Student) (RECIFE, Brazil)
09:40 - 09:50 #17801 - B53-1 Comparison of planning techniques for single-isocenter multiple-target stereotactic radiosurgery.
Comparison of planning techniques for single-isocenter multiple-target stereotactic radiosurgery.

The purpose of this project is to compare treatment planning techniques that use a single isocenter to treat multiple brain metastases. We want to determine if volumetric modulated arc therapy (VMAT) or dynamic conformal arc (DCA) therapy is the better method to treat multiple mets patients using a single isocenter. We also want to know if using U-frame or frameless masks provide better plan quality. DCA plans were created for each of the 40 single-isocenter patients who received VMAT at Duke Hospital from 2016-2018. These patients were randomly selected based only on the number of metastases, from 2 to 14. We created the DCA plans using 5 couch positions, 2 collimator angles, and 100-degree arcs on BrainLab Elements. We modeled U-frame and frameless masks using 100-degree and 180-degree arcs, respectively. The clinical VMAT plans delivered to the 40 patients had an average conformity index of 1.47 and average gradient index of 8.57. Average whole-brain V3Gy and V5Gy were 14.07% and 5.80%, respectively. In comparison, using DCA the conformity index was 1.75 and the gradient index was 6.87. Whole-brain V3Gy and V5Gy were 11.25% and 5.59%, respectively. The frameless mask plans had conformity and gradient indexes of 1.68 and 6.39 and V3Gy and V5Gy of 11.39% and 5.09%, respectively. Overall, VMAT plans had higher conformity index with lower gradient index at the cost of healthy brain protection compared to DCA. Frameless masks also increased the conformity index and decreased the gradient index with minimal impact on low doses to the brain.


Andrew BALLESIO (Durham, USA), Zhiheng WANG
09:46 - 09:52 #17807 - B53-2 MRI only radiotherapy planning for brain metastases with Varian’s HyperArc SRS system.
B53-2 MRI only radiotherapy planning for brain metastases with Varian’s HyperArc SRS system.

Purpose or Objective: To evaluate the feasibility of MRI only non-coplanar radiotherapy planning with Varian’s HyperArc SRS treatment by comparison with CT planning.

Materials and methods: Radiotherapy plans for ten patients, previously treated with HyperArc, for cranial metastases in a single fraction were recalculated on diagnostic MRI scans. Target volumes varied in size from 1cc to 11.4cc, with a mean size of 4.4cc. The MRI scans were registered, by rigid registration, to the treatment planning CT. Brain, body, bones and PTV were outlined in the MRI scans and assigned representative bulk HU values based on the sample of patients. Brain was assigned 37HU and Bone to 787HU, all other tissue is assigned 0 HU.  Treatment plans were recalculated using the Eclipse Treatment Planning System v15.1 [Varian Medical Systems, Palo Alto, CA, USA] and the superposition/convolution Anisotropic Analytical Algorithm v15.05.07.

Comparisons were made between the original CT plan, CT_Bulk with; bone, brain and water bulk assigned, MRI_Bulk with; bone, brain and water bulk assigned and MRI_Water with the entire MRI scan assigned to 0 HU, irrespective of anatomy. Water Equivalent Depth (WED) to the geometric centre of PTV was also measured to determine the significance of bulk assigning densities.

Treatment plans were compared by D99%, Dmax, Gradient Index (V40/V80), V100%, dose to OARs and V12Gy to brain.

Results: Fitting a line to WED values for CT and MRI_Bulk gives a goodness of fit R-squared value of 0.9259, indicating strong correlation. The gradient of this line, 0.89, indicates that MRI_Bulk is displaying reduced HU to the original CT.

Average change in D99% is 0.1%, 0.9% and 2.4% and average change in DMax is 0.1%, 1.1% and 3.1% for CT_Bulk, MRI_Bulk and MRI_Water respectively. There is no significant change in Gradient Index, V100% or V12Gy to brain.

Conclusion: Bulk assigment of HU to voxels in MRI scans results in relatively shorter WEDs in comparison to CT but does not have a significantly detrimental effect on plan quality. MRI only planning with HyperArc, using bulk assignment of HU, is possible and calculated doses to PTV and OARs and plan quality metrics are similar to those on an uncorrected CT. Further work may incorporate monte-carlo style dose calculation algorithms to characterise CT-MRI planning discrepancies when modelling material properties.


Peter HOUSTON, Westley INGRAM, Suzy CURRIE (Glasgow, United Kingdom)
09:52 - 09:58 #17873 - B53-3 Radiosurgery of brain metastases using a linear accelerator (SRS-Cones vs. VMAT).
B53-3 Radiosurgery of brain metastases using a linear accelerator (SRS-Cones vs. VMAT).

Stereotactic treatment of brain metastases with high single exposures (~20 Gy) lead to high local tumour control. At the Institute for Radiation Oncology in Klagenfurt a Versa HD accelerator (Elekta) with Agility-MLC and stereotactic cones (SRS-Cones) is used for single fraction irradiation of small volumes in the brain. The Agility-MLC has the ability to create 5x5 mm2 fields at the isocentre. SRS-Cones are mounted onto the accelerator head. The collimation of the beam is closer to the patient. This leads to a smaller penumbra compared to MLC-only collimation. The objective of this research was to see if and at which target volume the Agility-MLC will reach similar results compared to SRS-Cones. Retrospectively for 20 patients 4 spherical target volumes for the cone diameter (5, 10, 15 and 20) mm were created (TV5, TV10, TV15, und TV20). For each target volume treatment plans using SRS-cones and VMAT were calculated with the TPS Monaco 5.11 using 6 MeV FFF photons. 4 arcs were used for each plan, which considered size and position of the target volumes by adapting table- and arc angle. Attention was paid to make sure that no beam was irradiating through the eyes. The beam setups were kept the same for Cone- and VMAT-plans. For the Cone-plans maximum dose was set to 25 Gy. VMAT-plans were scaled to D99% = 20 Gy. All plans were analysed by their dose distribution and comparison of their dose-volume-histograms. Special attention was paid to the 12 and 10 Gy isodose volumes, as they are an important basis for medical decision if single fraction radiation is feasible. Also RTOG and Paddick conformity index (CIRTOG und CIP) and Paddick gradient index (GIP) were calculated for each plan. Analyses of the 160 plans showed that all plans calculated with the SRS-Cones outclass the VMAT-plans. Due to the smaller penumbra of the Cones the low dose volume was clearly reduced. All plans (VMAT and Cone) were within the given criteria for Paddick conformity (0.9 to 1) and gradient index, although GIP for VMATs was higher than for Cones. While all Cone-plans met the criteria for coverage and low dose volumes, 50 % of VMAT-plans for the TV20 failed the requirement for V10Gy (< 14 cm3) and 85 % failed the V12Gy criteria (< 10 cm3). The study showed that the difference between Cones and VMAT decreases while target size increases. Still for 20 mm targets, Cones outclass VMAT.


Andrea SCHMOELZER (Klagenfurt, Austria), Andreas GMOSER, Christine ORASCH, Wolfgang RAUNIK
Segovia Break Out
10:00 COFFEE BREAK - POSTERS & EXHIBITION
10:30

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10:30 - 11:00

PLENARY SESSION
CONGRESS SUMMARY I

Moderators: Gilberto FONSECA (Brazil), Randy JENSEN (Professor) (Salt Lake City, USA), Isaac YANG (Associate Professor) (Los Angeles, USA)
10:30 - 10:40 ISRS 2019 Review: Malignant Tumors. Samuel CHAO (Radiation Oncologist) (Speaker, Cleveland, OH, USA)
10:40 - 10:50 ISRS 2019 Review: Vascular Disorders. Gus BEUTE (Neurosurgeon) (Speaker, Tilburg, The Netherlands)
10:50 - 11:00 ISRS 2019 Review: Benign Tumors. Michael SCHULDER (Vice Chair, Neurosurgery) (Speaker, Lake Success, NY, USA)
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PLENARY SESSION
CONGRESS SUMMARY II

Moderators: Laura FARISELLI (director) (milan, Italy), Alessandra GORGULHO (Director) (SÃO PAULO, Brazil), Jean SABATIER (MD, PhD) (Toulouse, France)
11:00 - 11:10 ISRS 2019 Review: FUNCTIONAL RADIOSURGERY. Jean REGIS (PROFESSEUR) (Speaker, MARSEILLE, France)
11:10 - 11:20 ISRS 2019 Review: Immunotherapy + SRS. Jonathan KNISELY (Faculty) (Speaker, New York, USA)
11:20 - 11:30 ISRS 2019 Review: Extracranial SRS/SRT. Rupesh KOTECHA (Radiation Oncologist and Chief of Radiosurgery) (Speaker, Miami, USA)
11:30 - 11:40 ISRS 2019 Review: Physics. Steven GOETSCH (Medical Physicist) (Speaker, Solana Beach, USA)
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11:40 - 12:00

PLENARY SESSION
SRS/SBRT CLINICAL TRIALS OVERVIEW

Moderator: Dennis SHRIEVE (Professor and Chair) (NY, USA)
11:40 - 11:50 International Radiosurgery Research Foundation (IRRF). Gene BARNETT (neurosurgery) (Speaker, Cleveland, USA)
11:50 - 12:00 Clinical Trials for Oligometastatic Disease: A Scientific Path Forward. Rupesh KOTECHA (Radiation Oncologist and Chief of Radiosurgery) (Speaker, Miami, USA)
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A58
12:00 - 13:05

CLOSING SESSION & AWARDS CEREMONY

Moderators: Antonio DE SALLES (Professor - Chief) (SÃO PAULO, Brazil), Laura FARISELLI (director) (milan, Italy), Ian PADDICK (Consultant Physicist) (London, United Kingdom)
12:00 - 12:10 ISRS Educational Courses. Mikhail CHERNOV (Assistant Professor) (Speaker, Tokyo, Japan)
12:10 - 12:20 ISRS: Past, Present and Future. Ian PADDICK (Consultant Physicist) (Speaker, London, United Kingdom)
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12:40 - 12:50 Best Poster Award. Marc LEVIVIER (Chef de Service) (Speaker, Lausanne, Switzerland)
12:50 - 12:55 2021 Congress Introduction. Matthew FOOTE (Deputy Director / Co-Director) (Speaker, Brisbane, Australia)
12:55 - 13:05 Final Remarks. Antonio DE SALLES (Professor - Chief) (Speaker, SÃO PAULO, Brazil)
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P01
09:00 - 18:00

EPOSTER - 01 Acoustics
Electronic Poster displayed from June 9 to June 13

09:00 - 18:00 #17883 - Combined approach for large vestibular schwannomas: long-term follow-up in a series of 46 consecutive cases.
Combined approach for large vestibular schwannomas: long-term follow-up in a series of 46 consecutive cases.

Background: Microsurgical management of large vestibular schwannomas (VS) yields a high risk for the facial and cochlear nerve functions. Gamma Knife radiosurgery (GKRS) allows optimal functional results in small- and medium-size VS, but cannot be used upfront in large VS because of the high rate of volume-related side effects. 

Methods: In this context, we developed a new treatment paradigm of combined approach with planned subtotal microsurgical excision and GKRS, aiming at optimal functional outcome for the facial and cochlear nerves in patients with large VS (i.e. Koos grade IV). We report our long-term follow-up using this approach. 

Results: A consecutive a series of 46 patients was treated between 2010 and October 2018. The mean presurgical tumor volume was 11.3 cm3(1.47-34.9). The mean follow-up after surgery was 36.9 months (range 6-96). All cases had normal facial nerve function (HB I) before surgery, except for one who was in HB IV. Postoperative status showed normal facial nerve function (House-Brackmann grade I) in all patients. In a subgroup of 26 patients in which cochlear nerve preservation was attempted at surgery (patients with residual hearing before surgery), 24 of them (92.3%) retained residual hearing. Among them, 17 patients had normal hearing (Gardner-Robertson class 1) before surgery, and 14 (82.3%) retained normal hearing after surgery. The mean duration between surgery and GKRS was 6.2 months (4-13.9, median 6 months). The mean tumor volume at the time of GKRS was 3.2 cm3(0.5-9.9), which corresponds to a mean residual volume of 31.7% (range 3.6-50.2) of the pre-operative volume. There was a tendency towards larger postoperative residual volume in patients with attempt to cochlear nerve preservation. The mean marginal prescription dose for GKS was 11.9 Gy (median 12 Gy). Four patients were considered a failure and benefitted from a second combined approach in 3 cases and GKRS only, in one case. Three patients had a shunt. 

Conclusion: The current data suggests that the combined management of large VS with planned subtotal resection followed by GKRS may yield an excellent clinical outcome with respect to retaining facial and cochlear nerve functions. Our results with this approach are comparable to those obtained with upfront GKRS alone in small- and medium-size VS. 

 


Marc LEVIVIER (Lausanne, Switzerland), Constantin TULEASCA, Michaela DEDECIUSOVA, Mercy GEORGE, Luis SCHIAPPACASSE, David PATIN, Raphael MAIRE, Roy Thomas DANIEL
09:00 - 18:00 #17839 - Fate of cystic enlargement of vestibular schwannoma after gamma knife radiosurgery : insight into pseudoprogression based on 2 cases reports with long-term follow-up.
Fate of cystic enlargement of vestibular schwannoma after gamma knife radiosurgery : insight into pseudoprogression based on 2 cases reports with long-term follow-up.

Background: Gamma kniferadiosurgery (GKRS) has been accepted as a safe and effective treatment in patients harboring a vestibular schwannoma (VS). However, during follow-up, tumor expansion induced by irradiation can occur and diagnosis of failure in radiosurgery of VS is still controversial. Tumor expansion with cystic enlargement causes some confusion regarding whether further treatment should be performed.

Materials and Methods: We investigate the change of cystic enlargement in VS after GKRS during the long-term follow-up period and propose the possibility of pseudoprogression to prevent unnecessary and inappropriate surgery.

Results: A 57-year-old male with hearing loss was treated with GKRS (12Gy, isodose 50%) for the left VS and thepreoperative tumor size was 0.8cc.This tumor started to increasein size with cystic change from the third year after radiosurgery and increased to 10.8cc at 5 years after radiosurgery.At 7 years after GKRS, the size of the tumor began to decrease on follow-up, and the volume of tumor was degenerated to 1cc in the 11 years follow-up.A 66-year-old female with dizziness and gait disturbance was treated with GKRS for the left VS (13Gy, isodose 50%). Thepreoperative tumor size was 6.3cc and the tumors started to increase in size with cystic enlargement from the first year after radiosurgery and increased to 18cc at 5 years after radiosurgery. The tumor maintained a cystic pattern with a slight change in size but no other neurologic symptomsduring the follow-up period.The regression of tumor was observed at 11 years after GKRS and the volume of tumor was decreasedto 3.2 cc in the 13 years follow-up.In both cases,continuous enlargement of the tumor cyst had observed over 5 yearsafter GKRS, and then tumor became stable afterwards. Over 10 years after GKRS, the cystic portion of the tumor has declined significantly.

Conclusions: Enlargement with cystic formation in the first3 to 5 years after GKRS has been considered as treatment failure.Based on our cases, however, additional treatment for cystic enlargement of VSshould be delayed until at least 10 years, especially in patient without neurological deterioration.


Shin JUNG (Jeollanam-do, Korea), Gwang-Jun LEE, Kyung-Sub MOON, Woo-Youl JANG, In-Young KIM, Tae-Young JUNG, Sa-Hoe LIM
09:00 - 18:00 #17793 - Fractionated stereotactic radiation therapy for large vestibular schwanomas.
Fractionated stereotactic radiation therapy for large vestibular schwanomas.

Background : Managements for vestibular schwanoma include observation, radiation and microsurgical resection. If the tumor shows signs of growth, or causes neurological deterioration, treatmqent with microsurgery or radiation therapy is considered. Stereotactic radiosurgery have established effective treatment for small- to medium-sized vestibular schwannomas. In large tumors with radiological or neurological signs of brainstem compression, microsurgery is applied because radiosurgery cannot be used safely due to the high risk for radiation-induced complications associated with large volume of the tumors. However radical surgery might yields unacceptable complication. Our institute applies fractionated stereotactic radiation therapy (FSRT) for the treatment of vestibular schwanomas when the volume of them are large. In this study we evaluated the efficacy and the role of FSRT considering control of large vestibular schwanomas.
Materials and Methods : Between July 2006 and December 2018, we treated 7 patients with large vestibular schwanomas by FSRT using Novalis. The mean age of the patients at FSRT was 45.7 (range, 29 to 61) years. The mean planning target volume of all tumor was 26.6 (range, 12.8 to 46.2) ml and the mean prescription dose at the tumor margin was 40.4 Gy (range, 35 to 42.5 Gy / 10-17 fraction) .
Results : The median follow-up time was 40.3 months (range 9 to 86 months). All patients were alive at the last follow-up visit without receiving additional surgery or irradiation. Four patients out of 7 presented tumor shrinkage and the other 3 patients showed no change in size. No patients demonstrated neurological deterioration compared with the condition at FSRT. 
Conclusion : FSRT is thought to be an effective management option for patients with large vestibular schwanomas.


Takahiko TSUGAWA (Nagoya, Japan), Chisa HASHIZUME, Sachko KATO, Yoshimasa MORI
09:00 - 18:00 #16943 - Gamma Knife radiosurgery as first intention treatment for intravestibular and intracochlear schwannomas.
Gamma Knife radiosurgery as first intention treatment for intravestibular and intracochlear schwannomas.

Background

Schwannomas of the VIII-th cranial nerve are benign tumours, with vast majority occurring in vestibular division. Rarely, can also arise from distal branches of cochlear, superior or inferior vestibular. We review our experience with Gamma Knife radiosurgery (GKR), as first intention treatment for intracochlear (ICS) and intravestibular (IVS) schwannomas.

Methods

A total number of 5 patients were analysed, treated over 8 years, between June 2010 and September 2018, with Leksell Gamma Knife Perfexion or Icon (Elekta Instruments, AB, Sweden). The marginal dose prescribed was 12 Gy at a mean prescription isodose line of 61.4% (range 50-70). Clinical evaluation included auditory and facial function. 

Results

The mean age was 49.9 (range 34-63). The mean follow-up period was 52.8 months (range 12-84). The mean target volume (TV) was 0.087 ml (range 0.014-0.281). The mean maximal dose received by the cochlea was 11.2 Gy (range 2.6-20.3). The mean marginal dose received by the vestibule (e.g. utricula) was 14.2 Gy (range 3.8-17.5). No patient experienced an acute or subacute clinical adverse radiation effect after GKR. Four cases had overall symptom stability. In one patient (1/5), the vertigo, which was the main clinical complain, disappeared one year after GKR. However, it reappeared 3 years latter, with same pretherapeutic characteristics and is currently fluctuating. One patient experienced hearing decrease after GKR, during the first 12 months. This case received 11.2 Gy to the cochlea. Follow-up MRI course showed a decrease in size in four patients, and stability in one.

Conclusions

Gamma Knife radiosurgery is a valuable first intention treatment for ICS or IVS, in selected cases. Special attention should be paid for the dose delivered to the cochlea and the vestibular apparatus. Acute and subacute clinical effects are exceptional, while tumour control was achieved in all cases in our small series. 


Constantin TULEASCA (Lausanne, Switzerland), Mercy GEORGE, Luis SCHIAPPACASSE, David PATIN, Raphael MAIRE, Marc LEVIVIER
09:00 - 18:00 #17680 - Gamma knife radiosurgery for large vestibular schwannoma more than 10cc: An Indian outlook.
Gamma knife radiosurgery for large vestibular schwannoma more than 10cc: An Indian outlook.

OBJECTIVE :

Stereotactic radiosurgery (SRS) is an important alternative management option for patients with small- and medium-sized vestibular schwannomas (VSs). Its use in the treatment of large tumors, however, is still being debated. We reviewed our recent experience to assess the potential role of SRS in larger-sized VSs who refused surgery or had co-morbidity.

METHODS Between 2006 and 2016, 34 patients with large VSs, defined as having a volume > 10 cm3, underwent Gamma Knife radiosurgery (GKRS) were analyzed. Clinical, radiological and radiosurgical parameters were studied. Post op tumor control, patients requiring surgery, factors predicting tumor failure were analysed.

RESULTS The median follow-up duration was 36 months (range 12-72 months). 7 patients (29.7) had previously undergone resection. The median total volume covered in this group of patients was 10.8 cm3 (range 10.0-13.5 cm3). The median tumor margin dose was 11.75 Gy (range 11-12 Gy). Mean size of tumor was 3.0cm (2.8-3.5)

All 34 patients had regular MRI follow-up examinations. Five had a volume reduction of greater than 50%, 12 had a volume reduction of 15%-50%, 14 were stable in size (volume change < 15%), and 3  had larger volumes. All patients had severe to profund hearing loss. Five patients has new onset deficits.  Four patients (11.76%) underwent surgery due to various reasons in one year duration after GKRS. Tumor control was achieved in 30 patients (88.24%).Patients having multiple cranial nerve involvement with cerebellar signs are the factor which predicts GKRS failure (p<0.0001). All other factors like age, sex, marginal dose, single cranial nerve involvement are not significant


CONCLUSIONS Although microsurgical resection remains the primary management choice in patients with VSs, most VSs that are defined as having both a single dimension > 3 cm and a volume > 10 cm3 and tolerable mass effect can be managed satisfactorily with GKRS.

 


Prabu Raj ANDIPERUMAL RAJ (BANGALORE, INDIA, India), Arivazhagan ARIMA, Dhananjaya BHAT, Dwarakanath SRINIVAS, Sampath SOMANNA
09:00 - 18:00 #17731 - Long term (>10 year) outcomes of gamma knife radiosurgery for vestibular schwannomas: Single Center Study.
Long term (>10 year) outcomes of gamma knife radiosurgery for vestibular schwannomas: Single Center Study.

Introduction: Gamma knife (RS) has now been accepted as a treatment option for Vestibular Schwannoma (VS), either in combination with surgery or alone since last past two decades. The ultimate aim has therefore been to achieve maximum tumor control along with preserved neurological functioning. There have been only few reports evaluating the long term treatment outcome of RS for VS; all but two limited to 5 years follow up.

Objective: To present the 10 years follow up data on patients treated with RS for VS. Also we wanted to assess the factors responsible for failure of RS and worsening neurology.

Results: A total of 77 patients treated with Gamma Knife from the year 1997 to 2007 and available for follow up were ambispectively reviewed. Majority of them were treated with primary GK (73%) and most of them were Koo’s grade 3 (12%) and 4 (56%). Ten-year tumour control rates with Gamma Knife radiosurgery (RS) were at 81-100%. The tumour marginal dose was 12 Gy and revealed 10-year tumour control rates of 89%, hearing preservation rates of 50%, facial nerve preservation rates of 96% and trigeminal preservation rates of 93%. The tumor control rate was affected by the nature of the tumor , solid vs cystic. The neurology of patient’s post RS largely depended on the Koos grading of the tumor. No secondary malignancy or long term radiation adverse effects were observed in these patients.

Conclusion: RS remains a viable option for treatment of VS, with a good tumor control rate even on long term follow up. It may be used as a primary modality of treatment for small to medium sized lesions. However, for larger Koos grade tumor, a careful patient selection is required because of the chances of worsening cranial nerve functioning.


Ambuj KUMAR, Rajinder THAYLLING (New Delhi, India), Shweta KEDIA, Hardik SARDANA, Deepak AGARWAL, Manmohan SINGH
09:00 - 18:00 #17700 - Radiosurgery for facial nerve schwannomas: a case report.
Radiosurgery for facial nerve schwannomas: a case report.

Background: Facial nerve schwannomas are benign, rare tumors which constitute less than 2% of intracranial schwannomas and less than 1% of intrapetrous mass lesions. Due to the very low incidence of this condition and its occurrence anywhere along the facial nerve tract, its treatment is controversial.

Objective: To describe the case report of one patient with facial nerve schwannoma treated with radiosurgery and to evaluate the follow-up of tumor control and functional evolution.

Materials and Methods: A 55-year-old female patient with facial palsy and vertigo was referred to the Radiosurgery Department at the Hospital Español, Mexico City. The patient was examined with CT and MRI scans, audiometry, logoaudiometry and electroneuronography of the facial nerve. Once the diagnosis of facial schwannoma was confirmed the patient was treated with cone-based radiosurgery using a Novalis 600N 6 MV (BrainLab) linear accelerator using 7 circular arcs. A total dose of 13.2 Gy was delivered to 100% of the tumor volume of 0.032cc; the dose to the cochlea and vestibule was 6 Gy. The patient has received to date a three years and six months follow-up.

Results: The tumor was located in the right mastoid tympanic junction (intrapetrous, second knee of the facial nerve) with MRI. Initially the patient was classified as grade V in the House-Brackmann scale; two years after treatment the patient showed a minor improvement and was classified as grade IV. The audiometry and logoaudiometry report have been normal to date but the patient has an abnormal right facial electroneuronography. Tumor control is 100%. After the radiosurgery the patient received rehabilitation therapies.

Conclusions: Radiosurgery is a safe technique for the treatment of facial nerve schwannomas, sparing the organs at risk and preserving organ functions. Radiosurgery is a good alternative for the treatment of small and medium-sized facial schwannomas.


Claudia Katiuska GONZÁLEZ-VALDEZ (Mexico City, Mexico), Lourdes Olivia VALES HIDALGO, César DÍAZ-PÉREZ, Ana CANO-AGUILAR, Javier Emiliano SÁNCHEZ GUERRERO, Eric HERNÁNDEZ-FERREIRA, Raúl FLORENTINO GONZÁLEZ, Rebeca GIL-GARCÍA
09:00 - 18:00 #17558 - Stereotactic radiosurgery is associated with significantly decreased hearing preservation for vestibular schwannomas versus fractionated stereotactic radiotherapy.
Stereotactic radiosurgery is associated with significantly decreased hearing preservation for vestibular schwannomas versus fractionated stereotactic radiotherapy.

Isaac Yang, MD1-7 , Methma Udawatta, BS1,7, Isabelle Kwan1, Komal Preet, BS1,7, Thien Nguyen, BS1,7, Vera Ong1, John P. Sheppard, MS1,7, Courtney Duong, BS1, Prasanth Romiyo, BS1, Percy Lee, MD2, Stephen Tenn, PhD2, Tania Kaprealian, MD1,2,4, Quinton Gopen, MD3

 

Departments of 1Neurosurgery, 2Radiation Oncology, 3Head and Neck Surgery, 4Jonsson Comprehensive Cancer Center, 5Los Angeles Biomedical Research Institute, 6Harbor-UCLA Medical Center, 7David Geffen School of Medicine of the University of California, Los Angeles (UCLA), Los Angeles, CA, United States

 

ABSTRACT

Background: Vestibular schwannomas (VS) are benign intracranial neoplasms arising from the eighth cranial nerve for which targeted radiation therapy (RT) has proved increasingly successful. Long-term hearing and related cranial nerve outcomes, however, have been disputed for the three current RT modalities.

Objective: To determine differences in hearing preservation for patients treated with stereotactic radiosurgery (SRS), fractionated stereotactic radiotherapy (FSRT), or hypofractionated stereotactic radiotherapy (hypoFSRT) for VS.

Methods: A retrospective electronic chart review was conducted for all patients with unilateral VS treated with primary RT at a single academic medical center. Primary outcome measure was preservation of serviceable hearing status in the affected ear at last follow-up. Secondary outcomes included tinnitus, vertigo, and imbalance.

Results: 33 FSRT cases, 21 SRS cases, and 6 hypoFSRT cases were identified. Post-operative deterioration in serviceable hearing and tinnitus demonstrated significant differences across cohorts. Hearing retention rates were 69.2% in FSRT patients, 37.5% in SRS patients, and 100% in hypoFSRT patients, which represented the 64.9% of total patients with post-operative serviceable hearing. Five-year tumor control rate was 95.2%, 93.9%, and 100% with SRS, FSRT, and hypoFSRT respectively.

Conclusion: Our series indicated an excellent tumor control rate in all the modalities. FSRT and hypoFSRT cohorts exhibited comparable overall outcomes. Our SRS cohort exhibited increased incidence and shorter time to hearing deterioration compared to FSRT and hypoFSRT cohort. Single fraction SRS was associated with significantly decreased hearing preservation compared to 28 or 5 fraction radiation for vestibular schwannomas


Isaac YANG (Los Angeles, USA)
09:00 - 18:00 #17681 - Stereotactic radiotherapy for large vestibular schwannomas: volume change following radiosurgery versus hypofractionated stereotactic radiotherapy.
Stereotactic radiotherapy for large vestibular schwannomas: volume change following radiosurgery versus hypofractionated stereotactic radiotherapy.

Introduction:

Stereotactic radiosurgery (SRS) is an established treatment option for vestibular schwannomas.[1] Hypofractionated stereotactic radiotherapy (HF-SRT) has demonstrated comparable local control rates, albeit with less long-term follow up.[2, 3] HF-SRT may be an option for larger lesions, potentially increasing the therapeutic ratio. While fractionated SRT can produce more rapid tumor shrinkage compared to SRS [4], there is no published data comparing SRS with HF-SRT with respect to tumor volume reduction over time.

Methods:

A single-institution retrospective review of large (>3.5cc) vestibular schwannomas treated with SRS or HF-SRT was conducted. Patients received either Gamma Knife SRS (GK-SRS) to a dose of 12-13.5 Gy or linac-based HF-SRT to 25Gy in 5 fractions, between 2013 and 2018. Follow-up MRIs were uploaded onto planning software, and individual tumors were contoured to determine volume. These volumes were then calculated as a percentage of original tumor size.

Results:

A total of 33 patients had vestibular schwannomas greater than 3.5cc. Of these, 19 received GK-SRS and 14 received HF-SRT. Median follow-up duration was 16 months for GK-SRS, and 21.5 months for HF-SRT. Mean tumor volume for patients treated with GK-SRS was 4.48cc, and 7.24cc for HF-SRT. At 3-6 months post-treatment, mean tumor size was 100.4% for GK-SRS compared to 97.7% for HF-SRT (p=0.30). At 7-12 months, mean tumor size was 81.6% compared to 77.0% respectively (p=0.34). At 13-18 months, mean tumor size was 88.6% versus 76.8% (p=0.28). There was a significant difference in mean tumor volume between solid lesions (106.5%) and cystic lesions (57.8%) at 13-18 months (p=0.0015). Two patients in the GK-SRS arm required shunt insertion for hydrocephalus. One patient in each arm experienced local failure.

Conclusions:

There was a greater tumor volume reduction within our study period with HF-SRT, though this was not statistically significant. Cystic tumors reduced in volume significantly more than solid lesions.


Michael HUO (Brisbane, Australia), Michael HUO, Heath FOLEY, Mark PINKHAM, Catherine JONES, Michael JENKINS, Emma THOMPSON, Sarah OLSON, Bruce HALL, Trevor WATKINS, Matthew FOOTE
09:00 - 18:00 #17525 - “Facial nerve outcomes of Gamma Knife Radiosurgery treating vestibular Schwannomas; Kingdom’s first experience”.
“Facial nerve outcomes of Gamma Knife Radiosurgery treating vestibular Schwannomas; Kingdom’s first experience”.

Objective: Facial nerve weakness is a known surgical complication of treating Vestibular Schwannomas. The study is reported in order to describe facial nerve outcomes with standard dose GK radiosurgery as the first ever experience from the Kingdom.

Methods: The “Perfexion” unit was installed at PSMMC in Sep. 2013. A total of 110 patients have been treated including 26 Vestibular Schwannomas. Patient’s treatment details and course of follow up were collected and updated on Departmental Radiosurgery Database. All the patients were reviewed first in combined Neuro-Oncology meeting to plan course of GK radiosurgery. Baseline Audiometry of all (100%) and Brainstem Auditory Evoked responses (BAER) in selected cases were performed. Patients were assessed and documented for hearing, vestibular and facial nerves (House Brackmann grading) functions during their follow up. SPSS version 24 was used to analyze outcomes.

Results: A total of 26 patients were treated with median age of 48 years (range: 23-78). Female to male ratio; 1.6:1. ZM (Zini Magnan) classification; Stage 1: 19%, Stage 2: 19%, Stage 3: 38.5%, Stage 4: 23.5%. Median marginal dose: 12.5 Gy at 50% isodose line. After a median 26 months follow up (excluding 2 patients who lost to follow up), three-dimensional volume reduction was 20.5% (base line median volume: 1.95cc and at last FU: 1.55 cc). 9/26(34%) had their volumes remained stable. 1 patient had an asymptomatic progression of 3 mm with cystic transformation present. 2 patients had mild asymptomatic hydrocephalus. And all the patients available for follow up did not express Facial nerve weakness beyond G2 HB grading(G1:22/24, G2: 2/24 pts).

Conclusion: Standard GK radiosurgery treatment is considered preferred over surgical approach for saving facial nerve functions.


Bilal MUHAMMAD, Maarouf MAHMOUD ADILI (Riyadh, Saudi Arabia), Ali Matar ALZAHRANI, Abdulaziz ALHAMAD, Saleh BAMAJBOUR
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P02
09:00 - 18:00

EPOSTER - 02 AVMs
Electronic Poster displayed from June 9 to June 13

09:00 - 18:00 #17715 - Assessing the volume of large cerebral arteriovenous malformations: Can the ABC/2 formula reliably predict true volume?
Assessing the volume of large cerebral arteriovenous malformations: Can the ABC/2 formula reliably predict true volume?

Background: Stereotactic radiosurgery (SRS) is an important treatment option for preventing intracranial hemorrhage with cerebral arteriovenous malformations (AVMs). Treatment outcome with SRS is volume-dependent, with smaller AVMs having greater rates of obliteration than larger AVMs. The ability to estimate AVM volume has significant value in guiding AVM management and prior studies have focused on relatively small AVMs.

Objective: To determine whether AVM volume measurement calculated from the ABC/2 formula is accurate compared to volume calculated by the computer-assisted planimetric method for large AVMs.

Methods: Retrospective review of 37 patients with 42 intracranial AVMs >3cm in diameter that underwent treatment with dose-hypofractionated stereotactic radiotherapy (HSRT) from 2001 to 2018. Two raters independently measured pre- and post-HSRT volumes by ABC/2 formula and computer-assisted planimetry in a blinded fashion. Inter-rater reliability was assessed by calculation of intra-class correlation coefficient (ICC). Volumes were compared using paired t-tests, Pearson correlation, linear regression, and Bland-Altman plot analyses.

Results: The ICC between the 2 raters for planimetric and ABC/2 volumes was .859 and .799, respectively. ABC/2 volumes (mean = 28.6 cm3) were significantly smaller than planimetric volumes (mean = 26.1 cm3) (P = 0.008). Strong correlation was seen between the two methods using both linear regression (R2 = 0.904) and Pearson correlation (r = 0.951, p <0.001) analyses. The percent volume change following HSRT was significantly different between the two methods (P = 0.009). 

Conclusion: The ABC/2 and planimetric methods are reproducible for measuring cerebral AVM volumes. Volume estimation using the ABC/2 formula underestimates planimetric AVM volume, and has limited clinical utility.


Alon KASHANIAN (Los Angeles, USA), Hiro SPARKS, Tania KAPREALIAN, Nader POURATIAN
09:00 - 18:00 #17526 - AVM’s radiosurgery outcomes from the first Gamma Knife experience in KSA.
AVM’s radiosurgery outcomes from the first Gamma Knife experience in KSA.

Objective: To review outcomes of radiosurgery in previously embolized AVMs as a first experience in the kingdom.

Methods: Gamma Knife Perfexion system was installed at PSMMC in September 2013. A total of 110 patients including 24 Arteriovenous Malformations have been treated. The data has been documented in a prospective radiosurgery database. All the AVMs were treated by a team of professional Interventionists, Radiation oncologists, Neurosurgeons and Physicists. All treated cases remain on follow up with interval reassessment through MRI and yearly Angiograms. SPSS version 24 was used to analyze outcomes.

Results: A total of 24 patients underwent radiosurgery with same day MRI and Angiogram co- registration. Males: 15, Females: 9. Mean age was 36 years. Mean number of past embolizations: 1.33.

Brain site involvement: Temporal lobe: 7(29%), Frontal and occipital lobes: 5(21%)each, Parietal lobe: 4(17%), and 1 case(4%) each for cerebellar, midbrain and thalamic AVMs.

Spetzler-Martin grading; G2: 3(12.5%), G3: 12(50%), G4: 8(33.3%), G5: 1(4.2%). Response; CR: 8/17 evaluable patients (47%), PR: 7/17(41%), No response: 2/17(11%). Objective response rate: 88%. Median Follow up: 23 months.

7 patients did not complete their one year follow up yet. Non-responding patients underwent combination of surgery and further embolizations. 2 patients underwent partial volume treatment due to large size of AVM. Volume based Radiosurgery median dose: 18 Gy. Post radiosurgery bleed: none.

Conclusion: Gamma knife Radiosurgery is an effective treatment modality for medium to large AVMs. Radiosurgery reduces risk of bleeding without causing major complications.


Bilal MUHAMMAD, Abdulaziz ALHAMAD, Maarouf MAHMOUD ADILI (Riyadh, Saudi Arabia), Saleh BAMAJBOUR, Riyadh OKAILI, Maher HIJJI
09:00 - 18:00 #17848 - Excellent outcomes with frameless linear accelerator radiosurgery for arteriovenous malformations with 3D catheter angiographic planning and conservative patient selection.
Excellent outcomes with frameless linear accelerator radiosurgery for arteriovenous malformations with 3D catheter angiographic planning and conservative patient selection.

Introduction

 

Patients with brain arteriovenous malformations (AVMs) can be treated with observation, surgery, embolization or radiosurgery. Since the publication of the ARUBA trial there has been increased concern that the risks of interventional treatment such as surgery or radiosurgery may exceed the benefits for unruptured AVMs. Our series shows that radiosurgery remains safe and highly effective for carefully selected and planned small AVMs.

 

Methods

 

During the period 2010-2018, radiosurgery treatment for 31 AVMs in 30 patients was administered at our centre. All patients underwent frameless radiosurgery with a Novalis Tx radiosurgery system incorporating a 6D robotic couch and the BrainLab Exactrac system for frameless positioning and a Varian linear accelereator with a micro multi-leaf collimator. In all cases catheter based angiography was performed prior to the treatment and the 3D rotational non-subtracted images were incorporated into the planning.

 

Results

 

The average age was 40 at time of radiosurgery. 17/31 patients (55%) had a history of haemorrhage. Average AVM volume was 1.27cc (range: 0.131 – 3.499 cc). Median prescription isodose was 20Gy (range 15-22Gy) prescribed to the 70% isodose in the vast majority of patients. The mean modified Pollock-Flickinger score was 1.116 (range 0.46-1.96). 16/31 (52%) were Spetzler-Martin Grade 3.

 

Two patients were lost to follow up. Of patients who are 2 years or more post radiosurgery the AVM obliteration rate was 100% (21/21) confirmed by DSA or MRA.

No patient experienced a post SRS haemorrhage during 93 patient years of follow-up.

One patient (3%) experienced a worsening of neurological deficit with mild lower limb paresis after SRS for an internal capsule AVM that had presented with haemorrhage.

 

Discussion and Conclusions

 

In small carefully selected and planned AVMs treated with frameless radiosurgery 97% of patients with minimum 2 years follow up have achieved AVM obliteration without new neurological deficit.


Benjamin JONKER (Sydney, Australia), Nitya PATANJALI
09:00 - 18:00 #17022 - Gamma Knife Radiosurgery: The Gold Standard Treatment for Intracranial Dural Arteriovenous Fistulas without Cortical Venous Drainage.
Gamma Knife Radiosurgery: The Gold Standard Treatment for Intracranial Dural Arteriovenous Fistulas without Cortical Venous Drainage.

Context: Endovascular therapy is currently the most common treatment approach for intracranial dural arteriovenous fistula (DAVF), followed by microsurgery. Gamma Knife radiosurgery (GKS) is usually reserved as the last modality of treatment of intracranial DAVF.

 

Aim: To evaluate the clinical and radiological outcome of GKS in the treatment of DAVF without CVD.

 

Methods and Material: This series includes patients who underwent GKS for intracranial DAVF without CVD over 10 years (Jan 2007 to Dec 2016) in All India Institute of Medical Sciences, New Delhi. Their demographic profile, clinical presentation, imaging details, GKS details and follow up clinical status was obtained retrospectively. Clinical follow up, along with radiological assessment using MRI every 6 months was done after GKS. DSA was performed once MRI strongly suggested obliteration of DAVF. Patients who had a clinical follow up of less than 1 year were excluded from the study.

 

Results: 5 patients (4 males and 1 female) who had DAVF without CVD were included the study. The mean age was 44.8 years. All patients had complete obliteration of fistula on digital subtraction angiography (DSA) at a mean duration of 24 months post GKS. All patients had complete resolution of symptoms at the last follow up.

 

Conclusions: Gamma Knife surgery is the most effective and the safest treatment modality for dealing with DAVFs without CVD. Instead of reserving it as the last resort for patients with DAVF without CVD, it should be considered as the gold standard treatment for DAVFs without CVD.


Hardik SARDANA (New Delhi, India), Deepak AGRAWAL
09:00 - 18:00 #17775 - Impact of high dose GammaKnife radiosurgery on control of AVM; review of single center in Saudi Arabia.
Impact of high dose GammaKnife radiosurgery on control of AVM; review of single center in Saudi Arabia.

Introduction: AVM is uncommon problem however it’s management usually including either surgery, embolization or radiotherapy. Radiosurgery is an efficient method of treatment even though there’s a lot of variation in the literature about it’s outcome.

 

Method: we conduct a chart review for 21 patients diagnosed with AVM been treated at Prince Sultan Military Medical City (PSMMC)using gammaKnife radiosurgery (GK-RSR) regardless if they received any previous treatments.  We used high dose (18-22 Gy/1 fx depends on the initial size of the lesion).  We assessed the response of the treatment by systemic review, clinical examination and imaging.

 

Results: among of 21 patients unfortunately 2 of them no available records  follow/up after KG-RSR. The  rang of follow/up  was (62-2134 days) with average of  839.4 days. 9 patients (47%) developed 100% response clinically & radiologically. 8 patients (42.10%) were clinically stable with >75% radiologically response. 2 patients (10.5%) unfortunately had <75% response radiologically with partial clinical response.

 

Conclusion: Gk-RSR is very efficient especially for those who didn’t respond very well for other modalities of treatment.


Bilal MOHAMMED, Ma'aroof ADILLI, Abdulaziz ALHAMAD (Riyadh, Saudi Arabia)
09:00 - 18:00 #17776 - Predictors of Adverse Radiation Effect with a Volume Staged Radiosurgical Approach: A Multi-Institutional Study.
Predictors of Adverse Radiation Effect with a Volume Staged Radiosurgical Approach: A Multi-Institutional Study.

Abstract

Background

Volume-staged stereotactic radiosurgery (VS-SRS) provides an effective option for large arteriovenous malformations, but optimizing treatment for these recalcitrant and rare lesions has proven difficult and there are no reports of predictors of adverse radiation effect with a volume-staged approach in the literature.

 

Methods

This is a multi-centered retrospective review of patients treated with a planned prospective volume staging approach to stereotactically treat the entire nidus of an AVM with volume stages separated by intervals of 3-6 months. A total of 9 radiosurgical centers treated 257 patients with VS-SRS between 1991 and 2016. We evaluated transient and permanant symptomatic adverse radiation effects (ARE). Neurologic status was graded as improved, declined, or stable.

Results

With a median age of 33 years old at the time of first SRS volume stage, patients received 2-4 total volume stages and a median follow up of 5.7 years after VS-SRS. The median total AVM nidus volume was 23.25 cc (range: 7.7-94.4 cc) with a median margin dose per stage of 17 Gy (range: 12-20 Gy). The volume per stage ranged from 1.9-62.9 cc (median 11.5 cc) in the initial stage and 0.8-47.2 cc in the second volume stage (median 9.7 cc). A total of 74 patients experienced at least one event of ARE. Transient ARE events occured in 66 cases and permanant ARE deficits occured in 31 events. The most common event was headache occuring in 21 patients. Deep draining venous structure, larger total AVM volume, larger V12 per stage, larger summated V12 Gy, larger volume per stage, and increasing the number of isocenters per stage were all associated with increased risk of ARE. Of available AVM scores, only modified RBAS was associated with ARE (Hazard Ratio 1.526, 95% Confidence Interval 1.279-1.820).

 

Conclusion

VS-SRS is an option for upfront treatment of large AVMs. Higher dose per stage reported here was not associated with increased rates of ARE. However, larger volumes per stage, larger lesions, and higher volumes of V12 Gy were associated with risk of ARE suggesting a continued dissociation between treatment volume and dose with a volume-staged approach. Smaller volumes per stage with higher gradient indexes may be associated with reduced risk of ARE.  


Zachary SEYMOUR, Jason CHAN (San Francisco, USA), Penny SNEED, Hideyuki KANO, Rachel JACOBS, Judith HESS, Craig LEHOCKY, Veronica CHIANG, Jason SHEEHAN, Tomas CHYTKA, Dale DING, Anthony KAUFMANN, Caleb FELICIANO, Cheng-Chia LEE, John LEE, Roman LISCAK, Brendan MCSHANE, Hong YE, Huai-Che YANG, Samuel SOMMARUGA, Rafael RODRIGUEZ-MERCADO, Inga GRILLS, Micheal MCDERMOTT
09:00 - 18:00 #17699 - Radiation induced change after Gamma knife radiosurgery for cerebral arteriovenous malformation.
Radiation induced change after Gamma knife radiosurgery for cerebral arteriovenous malformation.

Object

Radiation induced change (RIC) on magnetic resonance image after Gamma knife radiosurgery (GKRS) for cerebral arteriovenous malformation (AVM) is not rare. We reviewed the patients who underwent GKRS for AVM and analyzed the results and factors associated with RIC.

Material and method

We reviewed 251 patients who underwent GKRS for AVM from October 2010 to August 2016. All the patients were followed up at least 3 years. Males were 140 and females were 111. Pediatric patients were 44 and adults were 207. Mean age of the patients was 33.91(range: 4.21-72.00). Six patients had undergone pre-GKRS embolization. One hundred and twenty three patients had ruptured AVMs and 128 had unruptured ones. We analyzed the obliteration rate and RIC occurrence rate. The factors such as sex, age, diameter of lesion, lesion volume, treatment volume, ruptured or not, isodose, marginal dose, maximal dose, and pre-GKRS embolization or not were analyzed to figure out the influence of obliteration and RIC occurrence.

Results

Overall obliteration rate was 64.94% (163/251) at final follow-up. Actuarial obliteration rate at 36 months after GKRS was 69.2%. Overall RIC occurrence rate was 42.63% (107/251) and actuarial RIC occurrence rate was 21.2% at 24 months after GKRS. There were no statistical differences between pediatric patients and adult ones. Obliteration rate showed statistically significant difference according to marginal dose (p=0.01) and maximal dose (p<0.01). RIC occurrence rate was statistically related to large lesion volume (p<0.01, r=0.37), large treatment volume (p<0.01, r=0.40), low marginal dose (p=0.04, r=0.32), and unruptured AVM (p<0.01, r=0.39). All other factors were not statistically significant.

Conclusions

Obliteration rate after GKRS for AVMs were comparable with the results from other reports. RIC was not rare findings after GKRS for AVMs. However most of the patients showed no significant clinical symptoms. In this study, there could be higher RIC occurrence in large AVMs, and unruptured ones.


Hae Yu KIM (Busan, Korea), Sun-Il LEE
09:00 - 18:00 #17676 - Radiosurgery as a salvage therapy for refractory or difficult to treat intracranial dural arteriovenous malformations.
Radiosurgery as a salvage therapy for refractory or difficult to treat intracranial dural arteriovenous malformations.

Introduction:Dural arteriovenous fistulas (dAVFs) are primarily treated with endovascular therapy. However, stereotactic radiosurgery (SRS) is a viable alternative strategy when endovascular therapy is not possible or when it fails to achieve either angiographic occlusion or symptomatic relief. We examined our single-institution experience treating refractory dAVF with SRS.

Methods:An institutional database was searched for patients treated with linear accelerator based SRS for dAVF after failed endovascular therapy with more than one-year follow up. We specifically examined patient and treatment characteristics and outcomes (angiographic and symptomatic) with an emphasis on determining how radiosurgery can be used as a salvage after failed endovascular therapy.

Results:Ten patients, 6 men and 4 women, average age 48.2 (range 4-57), were treated with 13 SRS sessions. All patients had undergone one or more attempts at endovascular occlusion. Average follow up was 67.9 months. One patient suffered from recurrent fistulas in different regions of the posterior fossa and required 3 treatments. Another patient’s fistula was large enough that we treated her in two separate sessions. The remaining patients were treated in a single session. Treatment volumes ranged from 0.6 cc to 28.1 cc, average 5.38 cc. Median SRS dose was 1953 Gy (range 1600-2400 Gy) delivered by dynamic conformal arcs in 8 patients and by intensity modulated therapy in two patients. There was  one serious complication, the patient requiring three treatments developed radiation necrosis requiring surgery for diagnosis and treatment. One other patient with presenting symptoms of seizure and headache continued to require ongoing treatment for both symptoms despite angiographic occlusion of her fistula. Six patients have angiographic confirmed occlusion of their fistula. The remaining 4 have decreased fistula size on computed tomographic angiography but not occlusion. 

Conclusions:SRS is a reasonable treatment modality for refractory or difficult to treat dAVF with an acceptable complication rate and good treatment success.


Randy L. JENSEN (Salt Lake City, USA), Phillip TAUSSKY, Dennis C. SHRIEVE
09:00 - 18:00 #17695 - Radiosurgery in Giant AVMs, wich is the best option?
Radiosurgery in Giant AVMs, wich is the best option?

The tretament of big AVMs still remaind a challenge for the neurosurgeon and radiosurgeon. Surgery is difficult and the embolization is recomendet as an preeliminary treatment to help the surgery and radiosurgery.The old experience in the treatment of big AVMs is based in stage dose Radiosurgery, low dose and after one or two years another low dose, latter we beagn to use the consept of stage volume radiosurgery. Stage volumen SRS means to separete in two volumen the AVM and to treated in to times with high therapeutic dose. The introduction of Cyberknife make posible to use onother concept of tretament ,Hypofractionation. There is a big discusion about which is the best option and if we have to use surgery or embolization.

We treat in our department 1010 patient, 20% of tham big AVMs, we use all the method we plan and in pur opinion the more eficient way are stage volumen and Hypofractination ( 2x10 Gy) The previous embolization did not use us in the early AVM oclusion, we strongly belive that we don-t need previous embolization. We can use it only in high flow AVMs. Syrgery was needed in some special cases


Kita SALLABANADA DIAZ (Madrid, Spain), Rafel GARCIA, Iciar SANTAOLALIA
09:00 - 18:00 #17734 - Stereotatic radiosurgery for arteriovenous malformations after endovascular embolization.
Stereotatic radiosurgery for arteriovenous malformations after endovascular embolization.

Microsurgery, embolization or stereotactic radiosurgery (SRS) can be used, both individually or in combination with each other for AVM treatment. Nidus volume is one of the factors that is crucial for predicting the control of AVM. Combined treatment approach with endovascular embolization followed by SRS can help to reduce the SRS target volume.

 The aim of the work is evaluation safety and feasibility of this aproach.

Methods and Materials: 8 patients with AVM after previous endovascular treatment underwent SRS on the CyberKnife M6 from 2016 till 2018 at the Sigulda Hospital, Stereotactic radiosurgery Centre. The mean age of patients was 32.5 [95% CI [23.5-37.8]. 6 patients had history of previous hemorrhage from AVM. All 8 patients had incomplete endovascular AVM Onyx embolization prior to radiosurgery. Patients were divided into 2 groups depending of the volume of AVM: small AVM 10 cm3 - 6 patients.

Single-fraction CyberKnife SRS was performed in 2 patients at a dose of 20 Gy, 6 patients had hypofractinated SRS (2 fractions, a total dose of 24 Gy).

Results: Patients undergo a radiological examination (MRI and MRI angiography) after the treatment. Patients had no signs of repeated bleeding from AVM after SRS. Digital subtraction angiography (DSA) was performed for 2 patients, who were 18 and 24 months after CyberKnife SRS. Both patients had signs of complete obliteration of AVM. No one patient had signs of postradiation toxicity grade 2-3. 4 patients had brain edema in the follow-up MRI, that after medication resolved later.

 Conclusions: The combined endovascular/SRS approach is safe, in terms of post-SRS hemorrhage, or post-radiation toxicity. However, the assessment of statistically reliable levels of obliteration requires further observation and research.


Vladyslav BURYK (Sigulda, Latvia), Maris MEZECKIS, Mirza KHINIKADZE, Dace SAUKUMA, Jelena NIKOLAJEVA, Maris SKROMANIS
09:00 - 18:00 #17712 - Treatment of large arteriovenous malformations with dose hypofractionated stereotactic radiation therapy: an institutional experience.
Treatment of large arteriovenous malformations with dose hypofractionated stereotactic radiation therapy: an institutional experience.

Background: Brain arteriovenous malformations (AVMs) are pathologic tangles of intracerebral vessels. Treatment of AVMs aims to reduce the risk of devastating intracranial hemorrhage (ICH). Dose hypofractionated stereotactic radiation therapy (HSRT), can be used to treat large lesions while reducing the risk of radiation toxicity to surrounding structures. We describe a study of our institutional experience over the last fifteen years in treating large AVM’s with both five- and six-fraction HSRT and evaluate pre-treatment characteristics that are most predictive of radiographic response.

Methods: 37 patients and 42 treatments for intracranial AVMs measuring >3cm in their largest dimension were included.  Data was collected retrospectively using review of electronic health records. AVM volume was measured prior to HSRT with LINAC and at the patient’s most recent follow-up appointment. Symptomatic outcomes, including treatment-related inflammation, were measured and defined categorically.

Results: Complete obliteration was achieved in 11.9% of patients. Mean AVM volume reduced significantly after HSRT (P=8.7e-8). Percent volume reduction differed significantly between patients receiving 30Gy fractions, (∂V=-48.7%), and 25Gy fractions (∂V=-29.1%), (P=0.035).  Patients with partial or complete obliteration were more likely to receive a total dose of 30Gy rather than 25Gy (P=0.056), and trended toward being treatment naïve (P=0.053).

Conclusion:  HSRT may be used as a means to manage large AVMs, with obliteration in some cases and sufficient volume reduction in most others for adjuvant treatment with other modalities.  30Gy total dose was generally superior to 25Gy in achieving significant complete or partial obliteration. Further studies focused on longer follow-up periods are warranted.


Hiro SPARKS, Arev HOVSEPIAN, Bayard WILSON, Antonio DESALLES, Michael SELCH, Alon KASHANIAN (Los Angeles, USA), Tania KAPREALIAN, Nader POURATIAN
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EPOSTER - 03 Functional
Electronic Poster displayed from June 9 to June 13

09:00 - 18:00 #17741 - Clinical Outcomes Following Linac-Based Radiosurgery for Trigeminal Neuralgia.
Clinical Outcomes Following Linac-Based Radiosurgery for Trigeminal Neuralgia.

Objective: Radiosurgery is a reliable and safetreatment option for trigeminal neuralgia. Nevertheless, precise and accurate targeting is critical to optimize outcome after radiosurgery for trigeminal neuralgia (TN). We reviewed clinical outcomes and complications following frame-based versus frameless stereotactic radiosurgery using a linear accelerator (linac) based treatment device, with radiation collimated using 4mm versus 5mm diameter cones in patients with medically refractory, intractable TN. 

Methods: We performed a retrospective review of all patients who underwent stereotactic radiosurgery for TN at our institution between 1996 and 2018. The Barrow Neurological Institute (BNI) pain score was used to evaluate pain relief.

Results: A total of 282 patients were identified. Their mean age at the time of radiosurgery was 68.1 years (range, 24.3 – 95.5 years). A total of 119 (42.2%) patients underwent radiation collimated by 4mm cones, whereas 5mm cones were used in the remaining 163 (57.8%) patients. Overall, frameless stereotaxy was used in 112 (39.7%) patients. Statistically significant differences in demographic parameters amongst groups were observed for preoperative BNI pain scores and age (p<0.005). Following radiosurgery, 67.5% of patients in the 5mm group experienced complete pain relief (BNI I), compared to 40.3% in the 4mm group (p<0.005). A complete pain relief was achieved in 42.0% of cases in the frameless group, and in 65.3% in the frame-based group (p<0.005). Overall, mean latency to initial pain relief was 1.1 months. Pain recurrence occurred overall in 15.6% of cases. A higher frequency of pain recurrence was present in the 4mm and the frameless group (28.6%) (p<0.005). Side effects of SRS treatment included permanent facial hypoesthesia in 5% (n=14), hyperesthesia/paresthesia in 2.5% (n=7), dry eye syndrome in 1.8% (n=5) and deafferentiation pain in 5.7% (n=16). 

Conclusion: Frameless radiosurgery with a 5mm collimator, is a feasible treatment option for patients with TN, avoiding the complications and hindrances associated with rigid head frame fixation without compromising clinical safety or outcomes. Despite the risk of spillage-related brainstem adverse effects of larger collimator size, confirmed our results, that a 5mm collimator is superior to 4mm collimator size in terms of pain relief, with no increase in long-term side effects. 


Jenny KIENZLER, Nader POURATIAN (Los Angeles, USA), Won KIM, Kaprealian TANIA
09:00 - 18:00 #17774 - Cyberknife treatment of medically intractable Trigeminal Neuralgia: A comparison of the outcomes between isocentric and non-isocentric treatment planning techniques.
Cyberknife treatment of medically intractable Trigeminal Neuralgia: A comparison of the outcomes between isocentric and non-isocentric treatment planning techniques.

Introduction: The efficacy of using SRS to treat medically intractable trigeminal neuralgia is well established.  When treating with CyberKnife®, some practitioners like to use an isocentric strategy and others advocate irradiating a portion of the cisternal segment of the nerve in a non-isocentric manner. Both strategies aim to optimize the success of the treatment and mitigate facial numbness as the potential side effect.

 

Objective: This abstract compares the treatment outcome of these two strategies.

 

Method: We retrospectively reviewed 81 patients from 2009-2017 in our treatment data base.  The non-isocentric technique was used for treating 40 patients, while the isocentric technique was used to treat 41 patients.  The efficacy in pain control and the occurrence of facial numbness were analyzed.

 

Results: The median follow up was 68 months. For the non-isocentric treatments the median prescription dose was 60 Gy (80% isodose line) and median target volume was and 0.069 cc.   For isocentric treatments the median prescription dose was 85 Gy (100% isodose) and median volume of nerve receiving 60 Gy was 0.033 cc. Of the 81 patients, 69 (85%) patients responded to the treatment (Barrow Neurological Institute BNI pain score equal to or below 3). There is no difference when comparing the two strategies (80.0% and 90.2% in isocentric and non-isocentric respectively, p=0.2). The number of patients with symptomatic facial numbness in both groups was 13 (16%), 8 (20%) in the non-isocentric group and 5 (12%) in the isocentric respectively.

 

Conclusion: We found no significant difference in the outcome in treating TN with isocentric and non-isocentric paradigm.   


Victor TSE (Redwood City, USA), Christopher MCGUINNESS, Ming TENG, Amy GILLIS, Laura MILLENDER, Minn YURI, Anand KRISHNAMURTHY, William SHERIDAN, Adler JOHN
09:00 - 18:00 #17903 - Gamma knife thalamotomy (GKT) for essential tremor (ET).
Gamma knife thalamotomy (GKT) for essential tremor (ET).

Abstract  07 SRS 

Gamma knife thalamotomy (GKT)  for essential tremor (ET)

E.Larrachea,  J.Lorenzoni, F.Bova, M.Henriquez, P.Navarrete, C.Luhr, G. Zomosa

Gamma knife Chile, Santiago de Chile.

Intruduction : There are several ET patients specially older yhat are medically refractory, fot those we propose to perform GK thalamotomy.                                                                                                    Objectives : To relieve ET in medically refractory patients.                                                                                                                                                                                                                            Material and Methods : We presen our experience using GKT for the treatment of medically refractory ET .Nine ET patient underwent GKT. High resolution magnetic resonance imaging guidance was used for Ventral Intermedius nucleus (Vim) targeting. A single  4 mm isocenterwas used to  target a maximum dose of 130 Gray to the Vim. Pre and post treatment clinical evaluation was performed using Global (A+B+C)  Fahn Tolosa Marin tremor rating scale (FTM) .                                                                                                                                                                                                                              Results :The mean patient age was  68,2 years (57-80) with a mean  follow-up of 36 months (12-60). In seven  patients (78%) an important clinical improvement was observed ( mean pre-treatment FTM= 35.5 and mean post  treatment FTM=16.5) . In one patientno significant effect was observed and a second GKT was performed achieving a FTM score improvement from 28.9 to 11.5. One patient present edema in the Vim target  and remitted with corticosteroids.                                                                                                                                                                                                                                      Discussion and Conclusion : GKT could be considered as an effective and safe  neurosurgical  treatment for medically refractory  ET  and also  is elegible  for older patients over  seventy years.

Keywords . Essential tremor, thalamothomy, gamma knife radiosurgery.


Eduardo LARRACHEA, Jose LORENZONI, Marcos HENRIQUEZ, Francisco BOVA, Claudio LUHR, Gustavo ZOMOSA (santiago de Chile, Chile)
09:00 - 18:00 #17784 - High single dose of Radiotherapy using Gamma-Knife is efficient treatment for Trigeminal Neuralgia either mono or combined with other modality . single institute retrospective review.
High single dose of Radiotherapy using Gamma-Knife is efficient treatment for Trigeminal Neuralgia either mono or combined with other modality . single institute retrospective review.

Introduction: Trigeminal Neuralgia (TN) is serious problem with poor response to RSR  ≤75Gy, Fractionated radiotherapy, local nerve anesthesia or medicine.  Some literature showed that high dose single fraction radiotherapy maybe a effective choice.

 

Method: we conduct a retrospective review for 13 patients of TN been treated at Prince Sultan Military Medical City (PSMMC) by single fraction of Gamma-Knife radiosurgery (GK-RSR)80Gy/100% or above, between (11/4/2013 till end of December 2017). These patients had been followed up by history, physical examination & phone call assessment going over symptoms of pain control, need further methods for control of TN and using pain killers or no.

 

Results: among all 13 patients one received 75Gy/100%, another one received 85Gy/100% while the rest received 80Gy/100%. The average of follow/up was 1058 days after receiving the GK-RSR. 8 patients (61.5%) achieved 100% response, 3 patients (23.10%) achieved ≥75% response & 2 patients (15.4%) achieved 25-75% response. Regarding the pain score within 3-6 months post therapy was as following 0 patients (0%) had a score of >7, 8 patients (61.5%) had a score of ≥4-≤7 and 5 patients (38.5%) had a score of <4. Regarding continuity of using pain killers; 9 patients (69.20%) are still using pain killers regularly in contrast to 4 patients (30.80%) stop using pain killers. 4 patients (30.80%) needed further therapy including (radiotherapy & nerve block).

 

Conclusion: high dose ≥ 80Gy/100% is very effective treatment for TN. With minority of them would need to go for further therapy. With good patient satisfaction


Abdulaziz ALHAMAD (Riyadh, Saudi Arabia), Ma'aroof ADILLI, Abdullah ALRUSHOUD, Bilal MOHAMMED, Maher AL HEJJI, Jamal ABDULLAH
09:00 - 18:00 #17825 - Sphenopalatine Ganglion Landmarks for treatment of Facial Dysautonomia.
Sphenopalatine Ganglion Landmarks for treatment of Facial Dysautonomia.

Introduction:Cluster headache (CH) is the most common trigeminal autonomic headache. It remains a medical management challenge. Gamma Knife Radiosurgery (GKR) has been described as a non-invasive alternative treatment. Landmarks for the targeting of the sphenopalatine ganglion still remain obscure, mostly in the Magnetic Resonance Imaging. 

Objective and Methodology:To describe the anatomical characteristics of the sphenopalatine ganglion target using the Gamma Knife, Perfexion model (Elekta AB). 

Case report:A 55-year-old female patient from Angola had been diagnosed with CH for over 10 years, with severe pain on the right hemicranium, progressive worsening, reaching three monthly crises, causing important limitation of her daily routine. MRI showed no abnormalities. Extensive drug regimens and botulin toxin failed to relieve her symptoms. Initially, an anesthetic block of the sphenopalatine ganglion was performed, providing temporary relief. Next, radiofrequency ablation of the ganglion was performed with the sphenopalatine fossa being targeted by fluoroscopy. She returned to Angola obtaining relief for one year, when pain recurred. Therefore we offered the option GKR. The procedure was performed using MRI and CT for targeting. The entire sphenopalatine fossa had a volume of 3.44 cm³ being covered with a single isocenter of 4 mm collimator. Uneventful GKR with dose of 90 Gy to 100% of isodoseline was accomplished. Treatment duration was 50 minutes. The patient was discharged on the same day. She has reported since control of her pain with rare episodes of pain controlled with common analgesics.  

Conclusion:Radiosurgery represents a therapeutic option for patients with CH refractory to medical therapy. It is attractive as a minimally invasive approach without hospitalization and low morbidity for patients who have already failed a multitude of treatments. Bone landmarks seen on CT offer a corridor limiting soft tissue assuring, together with the MRI, safe targeting of the sphenopalatine ganglion.


Aline Lariessy CAMPOS PAIVA (Sao Paulo, Brazil), Alessandra GORGULHO, Bruno Henrique DALLO GALLO, Rafael COSTA LIMA MAIA, Juliete MELO DINIZ, Crystian Willian CHAGAS SARAIVA, Antonio DE SALLES
09:00 - 18:00 #17655 - Stereotactic linac radiosurgery in the treatment of trigeminal neuralgia: dosimetric evaluation and long-term follow-up.
Stereotactic linac radiosurgery in the treatment of trigeminal neuralgia: dosimetric evaluation and long-term follow-up.

Objective: To evaluate long-term outcomes and report dosimetric parameters for patients with trigeminal neuralgia treated with linear accelerator (LINAC)-based cone radiosurgery over a 15-year period from a single institution.

 Methods: We conducted a retrospective single-institution review of 68 trigeminal neuralgia (TN) patients treated between 2003 and 2018. All patients were planned with a 5 mm diameter cone using SRS on a LINAC delivered with 4-6 non-coplanar arcs. A dose of 40 Gy was prescribed to the 50% isodose line with the goal of 80 Gy to the isocentre within the trigeminal nerve root and limiting the abutting brainstem dose to 40 Gy. Dosimetric information extracted from the plans was examined for: (i) maximum brainstem dose (ii) mean volume of hippocampus receiving 10 Gy (iii) cranial nerve VII-VIII (CNVII-VIII) maximum dose. Maximum dose was defined as the dose received by a volume of 0.05 cc. The primary outcomes were treatment response and treatment success was defined by the Barrow Neurological Institute (BNI) pain scores ranging I-IIb and I-IIIa, respectively. A Kaplan-Meier (KP) analysis was also conducted.

 Results: Based on the most recent follow-up data, overall treatment response and success rates were 84% (57/68) and 69% (47/68), with approximately 30% no longer requiring medication (22/68).  From the KP analysis, the actuarial probabilities of maintaining pain relief at 1, 5 and 10 years were 89.1%, 54.6% and 47.8 %. The maximum dose to the nerve was 79.5 ±1.7 Gy. A strong consistency in the plan dosimetry was observed for all 68 patients with a maximum brainstem dose of 32.7 ±4.0 Gy, the volume of hippocampus receiving 10 Gy was 0.04 ±0.08 cm3, and the maximum dose to the CNVII-VIII was 7.0 ±4.5 Gy.No patients suffered symptomatic brainstem or other late radiation injuries.  

 Conclusion: Doses to the nerve, brainstem, hippocampus and CNVII-VIII are shown to be consistent; however, further analysis will explore if there are subtle differences in dosimetry between responders and non-responders. Therefore, LINAC SRS is a safe and effective treatment for long-term TN pain control with results similar to those reported using other SRS techniques, such as Gamma Knife. It should be considered a favorable treatment option for both untreated cases and for recurrent pain following other treatment modalities. 


Nicolas P PLOQUIN (Calgary, Canada), Scott AGNEW, Alana HUDSON, Robert NORDAL, Shaun LOEWEN, Zelma Ht KISS
09:00 - 18:00 #17823 - Treatment of Glossopharyngeal Neuralgia with Gamma Knife.
Treatment of Glossopharyngeal Neuralgia with Gamma Knife.

Introduction: Glossopharyngeal neuralgia is a rare condition of difficult diagnosis and medical management. Gamma Knife Radiosurgery (GKR) may represent an excellent minimally invasive treatment with similar to microsurgery results. 

Objective and Methodology:To discuss the GKR treatment of glossopharyngeal neuralgia. 

Results: A 59-year-old male presented in 2012 with change in voice tone and severe pain in the left hemi-face. It had worsened over five-years with painful sudden irradiation to the left ear, cough and difficulty swallowing.   Magnetic Resonance (MRI) showed the vagus-glossopharynngeal complex on FIESTA/CISS sequencing, as well as an artery at bulbar nerves exit, dividing the complex. Glossopharyngeal neuralgia with failed medical therapy was established after side effects of high doses of Carbamazepine and 12-sessions of trans cranial magnetic stimulation. Pain continued worsening, interfering in his daily routine. GKR was performed targeting the medial cisternae segment of the glossopharyngeal nerve (volume of 3.44 cm³) with a prescription dose of 90 Gy, 100% isodose site. The patient was discharged on the same day, now 5 months after the procedure he reported pain improvement. 

Conclusion: Gamma Knife Radiosurgery becomes an excellent alternative for the treatment of glossopharyngeal neuralgia. The targeting has varied in the small literature series, although the mid-cistern portion of the nerve is considered the safest and well contrasted from the CSF using MRI FIESTA/CISS sequencing.


Aline Lariessy CAMPOS PAIVA (Sao Paulo, Brazil), Antonio DE SALLES, Juliete MELO DINIZ, Bruno Henrique DALLO GALLO, Anderson MARTINS PÁSSARO, Alessandra GORGULHO
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P04
09:00 - 18:00

EPOSTER - 04 Gliomas
Electronic Poster displayed from June 9 to June 13

09:00 - 18:00 #17748 - 11C-methionine positron emission tomography for target delineation of newly diagnosed and recurrent glioblastoma in radiation therapy planning.
11C-methionine positron emission tomography for target delineation of newly diagnosed and recurrent glioblastoma in radiation therapy planning.

PURPOSE: The purpose of this work was to define the optimal margins for gadolinium-enhanced T(1)-weighted magnetic resonance imaging (Gd-MRI) and T(2)-weighted MRI (T(2)-MRI) for delineating target volumes in planning radiation therapy for both newly diagnosed and recurrent glioblastoma multiforme (GBM) by comparison to carbon-11-labeled methionine positron emission tomography (MET-PET) findings.

Materials and Methods: Computed tomography (CT), MRI, and MET-PET were separately performed for radiation therapy planning for 32 newly diagnosed and 25 recurrent patients with GBM over the course of 2 weeks. Among the MRI scans, we used the contrast-enhanced T1-weighted images (Gd-MRI) and T2-weighted images (T2-MRI). The Gd-MRI-based clinical target volume (CTV) (CTV-Gd) and the T2-MRI-based CTV (CTV-T2) were defined as the contrast-enhanced area on Gd-MRI and the high intensity area on T2-MRI, respectively. We defined CTV x mm (x = 5, 10, 15, 20) as x mm outside the CTV. MET-PET-based CTV (CTV-MPET) was defined as the area of accumulation of MET-PET. We calculated the sensitivity and specificity of CTV-Gd and CTV-T2 following comparison with CTV-MPET, which served as the gold standard in this study.

Results: In newly diagnosed patients, the sensitivity of CTV-Gd (20 mm) (86.4%) was significantly higher than that of the other CTV-Gd. The sensitivity of CTV-T(2) (20 mm) (96.4%) was significantly higher than that of the other CTV-T(2) (x = 0, 2, 5, 10 mm). The highest sensitivity and lowest specificity was found with CTV-T(2) (x = 20 mm). In recurrent patients, the sensitivity of CTV-T2 5 mm (98%) was significantly higher than CTV-T2 (87%), and there was no significant difference in the sensitivity between CTV-T2 5 mm and CTV T2 10, 15, or 20 mm. The sensitivity of CTV-Gd 20 mm (97%) was lower than that of CTV-T2 5 mm (98%).

Conclusions: It is necessary to use a margin of at least 2 cm around the high intensity area on T2-MRI for the initial target planning of GBM, and 5 mm around the high intensity area on T2-MRI for the recurrent target planning of GBM in the coverage of MET-PET findings.


Masayuki MATSUO (Gifu, Japan), Hidekazu TANAKA, Fuminori HYODO, Kazuhiro MIWA, Jun SHINODA
09:00 - 18:00 #17687 - Clinical outcomes from stereotactic radiosurgery of recurrent glioblastoma in relation to subventricular zone invasion.
Clinical outcomes from stereotactic radiosurgery of recurrent glioblastoma in relation to subventricular zone invasion.

Purpose: The benefit of radiosurgery (SRS) in recurrent glioblastoma (GBM) remains unclear, partly due to disease heterogeneity. Subventricular zone (SVZ) invasion is a prognostic factor for primary GBM, but whether SVZ involvement is also prognostic in recurrent GBM and whether SRS is useful in this setting is unknown. Here we compared outcomes from SRS and non-SRS treatment of GBM recurrence and determined whether SVZ involvement by recurrent GBM has an impact on outcomes after salvage radiosurgery.

Methods: Consecutive patients with first recurrence who were treated with SRS were retrospectively reviewed and compared with patients not treated with SRS. Propensity score matching was used to match patients. Magnetic resonance images were reviewed according to SVZ invasion by the primary tumor and at time of recurrence. Outcomes were evaluated using univariable and multivariable analyses.

Results: The median OS was 31 months in the SRS group and 15.5 months in the non-SRS group (p=0.01). The median survival after first recurrence was 18 months in the SRS group vs. 6.5 months in the non-SRS group (p=0.02). Individuals treated with SRS without SVZ involvement had the best overall survival (OS, 33months p=0.01). The median survival after first recurrence in SRS group was shorter when recurrences were localized to the SVZ ( SVZ+ vs SVZ-, 11 months vs 23 months,p=0.01), however patients with SVZ involvement treated with SRS had better overall outcomes then SVZ-negative patients not treated with SRS (OS, 28 months vs 15 months).

Conclusions: SRS appears to be an effective salvage modality for small recurrent GBMs. Although SVZ-positive tumors have a worse prognosis, these tumors may benefit from SRS. 


Maciej HARAT (Bydgoszcz, Poland), Sebastian DZIERZECKI, Katarzyna DYTTUS-CYBULOK, Mirosław ZABEK
09:00 - 18:00 #17797 - Fractionated radiotherapy for malignant brain tumors using mask system of Leksell Gamma Knife Icon.
Fractionated radiotherapy for malignant brain tumors using mask system of Leksell Gamma Knife Icon.

Object: Leksell Gamma Knife Icon enables us to apply new methods of immobilization using mask fixation and the option of fractionated treatment. This provides exceptional accuracy and precision of radiosurgery, making it a possibility for many more disease types and many more patients to be treated. If the tumor volume was larger than 5.0 ml, recurrence, or the location was in an eloquent area, we applied a fractionated schedule.

Methods: We retrospectively analyzed 230 patients (275 times) with malignant brain tumors who underwent fractionated radiotherapy using mask system of Gamma Knife Icon between September 25th, 2017 and December 31th, 2018 at Rakusai Shimizu Hospital. The most common disease was brain metastases (221 patients), followed by glioblastoma (3), malignant lymphoma (2), anaplastic meningioma (2) and nasopharyngeal carcinoma (2). For higher accuracy, we changed the upper limit of the HDMM system from 1.5mm to 1.0mm for malignant tumors.

Results: We selected fractionated schedules as follows; 7.0 Gy x 5Fr (5-10 ml), 4.2Gy x 10Fr (10-20ml), 3.7Gy x 10Fr (20-30ml), 3.2Gy x 10Fr (30ml-) for malignant tumors. Concerning about 221 patients with brain metastases, survival rates were 79% at 6 months and 65% at 12 months, local control rates were 83% at 6 months and 63% at 12 months, and qualitative survival rates were 93% at 6 months and 89% at 12 months after Icon treatment.

Conclusions: Although these results are limited to short periods, survival rated, local control rates and qualitative survival rated in patients unsuitable for SRS, such as those with large, recurrent, and eloquent site lesions, were within the acceptable ranges. Further examination is needed for comparison with staged Gamma Knife radiotherapy, Cyber-Knife and Novalis radiotherapies


Takuya KAWABE (Kyoto, Japan), Manabu SATO
09:00 - 18:00 #17686 - Infiltration of glioma based on hybrid PET/MRI using 18F-FET for stereotacic radiotherapy.
Infiltration of glioma based on hybrid PET/MRI using 18F-FET for stereotacic radiotherapy.

Introduction: 

Extent of glioma infiltration using MRI imaging in not well defined and is a major factor limiting efficacy of stereotactic radiotherapy (SRT). Nevertheless in many studies results of SRT in time of recurrence was encouraging.  Up to date there is a lack of data regarding exact threshold in PET/MRI imaging, sufficient for accurate differential diagnosis between non-tumoral and tumoral changes in areas without contrast enhancement (CE) in T1-CE sequence. The aim of the study was to find the threshold between tumor infiltration and non tumoral brain tissue to improve the precison of SRT in dual-time point FET-PET/MR.

Our hypothesis was that by improving understanding of precise target definition, the role of SRT in gliomas may be redefined.

 

Methods and Results:

 

21 target points from tumor border were biopsied using hybrid PET/MRI in dual-time point aquisition (early and late examination after 18F-FET injection).  SUV values in voxels related to target points, ROI surrounding biopsy site and in contralateral brain were defined. In 7 cases non tumoral tissue, in 5 cases glioma WHO II , in 6 cases  WHO III and in 3 WHOIV tumors were diagnosed. Increased FET uptake in the area of non-CE locations on MRI correlated well with high grade gliomas localized as far as 3 cm from T1-CE foci. Selecting a target in the motor cortex based on FET kinetics defined by dual time-point PET resulted in a grade IV diagnosis after previous negative biopsies based on MRI. An additional grade III diagnosis was obtained from an area of glioma infiltration with moderate FET uptake (between 1-1.25 SUV).

Detailed correlation of all PET parameters (SUVmax, SUVmean, TBRmax, TBRmean within voxel and ROI) with histopathological  results will be presented during conference.

 

Conclusion

Stereotactic biopsy of malignant tumor infiltration not visible on T1-CE sequence based on hybrid PET/MRI imaging can be distinguished from non tumoral brain tissue and confirmed histopatologically. Finally, by using exact uptake value, measured in dual-time point aquisition of 18F-FET-PET precise target volume for stereotactic radiosurgery may be defined.


Maciej HARAT (Bydgoszcz, Poland), Józefina RAKOWSKA, Maciej BLOK, Jacek FURTAK, Bogdan MALKOWSKI
09:00 - 18:00 #17819 - Inhomogeneous dose distribution in high-dose irradiation of brain metastases and high-grade gliomas.
Inhomogeneous dose distribution in high-dose irradiation of brain metastases and high-grade gliomas.

Objectives

This study presents a biologically-based dose distribution approach to high-dose irradiation of malignant brain tumors in order to improve treatment efficiency and safety.

Methods

Patients treated with stereotactic high-dose irradiation for large brain metastases or high-grade glioma recurrences revealing structural or metabolic heterogeneity on MRI or 11C-methionine PET/CT were included in the study. Radiation treatment was performed with Cyber Knife and linear accelerator TrueBeam STX. Delineation of tumors and their parts was performed on the basis of all available imaging studies (CT, MRI, PET). Dose distribution was optimized to achieve at least 98% coverage of the target with the prescription dose set at 70-80% isodose, high conformality, steep gradients and maximal sparing of critical structures. Distribution of higher doses inside the target took account of structural and metabolic heterogeneity. After treatment, patients underwent regular follow-up examinations (MRI or PET).

Results

The differential approach to dose distribution involves redistributing large amounts of radiation between tumor parts within prescribed general dosimetry. It has become possible thanks to cutting-edge radiation equipment, which guarantees precise dose delivery, and improvements in visualization techniques, which make visible tumor heterogeneity. Using this approach allowed us to achieve significant differences in mean doses delivered to distinct tumor parts, with higher doses targeted at solid and more metabolically active areas. At the first follow-up, the approach resulted in noticeable tumor shrinkage without MRI-detectable changes in surrounding tissues both for large metastases and glioma recurrences. Over a median follow-up period of 10 months, local control was consistently achieved for both tumor types, and no clinically relevant treatment-related complications were registered.

Conclusions

The dose redistribution approach shows promise in the targeting of large metastases and glioma recurrences with optimal effectiveness and safety.


Irina ZUBATKINA (Saint-Petersburg, Russia), Pavel IVANOV, Alexandr KUZMIN, Dmitriy NIKITIN, Vladimir KRASNYUK, Darya BUTOVSKAYA, Fedor SHCHEPINOV, Yuliia MERKULOVA, Georgij ANDREEV
09:00 - 18:00 #17769 - Multisession radiosurgery re-irradiation for glioblastoma recurrence: a retrospective single center analysis.
Multisession radiosurgery re-irradiation for glioblastoma recurrence: a retrospective single center analysis.

Introduction. Despite being various treatment strategies available, recurrent multiforme glioblastomas (rGBM) are difficult to manage. Limited evidence exists to suggest the superiority of any treatment modality for rGBM. The aim of this study is to evaluate the effectiveness of multisession radiosurgery (mRS) reirradiation as salvage treatment in terms of overall survival (OS) and progression free survival (PFS).

Material and Methods. Patients previously treated with surgery and chemo-radiotherapy and re-irradiated with radiosurgery for rGBM from January 2014 to December 2016 were considered eligible. Global OS (gOS) was defined as the time between first surgery and death, OS as the time between the end of re-irradiation and death, PFS as the time between re-irradiation and disease progression. The statistical analysis was conducted using the Kaplan-Meier method.

Results. Forty-six patients were included in the analysis. Median time from primary treatment to recurrence was 14 months (range 1–79 months). Median follow-up was 4 months (range 2 days–32 months). All patients were treated with robotic radiosurgery (CyberKnife®). At the time of the analysis six of the 46 patients were alive. The median survival from initial diagnosis was 26 months (range 12–107 months). The 1-, 2-, and 3-years actuarial survival rates from diagnosis were 100, 70, and 50% respectively. Median survival following mRS was 7 months (range 1–24 months). The 1-, and 2-years actuarial survival rate following mRS were 29, and 11% respectively. The acute toxicity rate was 17%.

Conclusions. Our data suggest that mRS is a safe and effective treatment option for patients with rGBM. Further research and prospective studies are needed to better define the parameters of re-irradiation in this subset of patients.


Valentina PINZI (Milan, Italy), Anna VIOLA, Marcello MARCHETTI, Laura FARISELLI
09:00 - 18:00 #17746 - Outcomes of patients with primary central nervous system (CNS) melanoma.
Outcomes of patients with primary central nervous system (CNS) melanoma.

Background: Primary melanocytic tumors (PMT) of the central nervous system (CNS) are exceedingly rare.  As a result, optimal management strategies are uncertain. We sought to evaluate patient outcomes in this rare tumor type.

Methods: We reviewed the records of 10 patients with PMT of the CNS treated at our institution between 2010 and 2018. 

Results: Median follow-up time was 22.1 months (range: 4.1-87.6). The median age at initial PMT diagnosis was 52.4 years (range, 27.9-83.8), with equal male: female distribution (1:1). All patients presented with neurological symptoms. Eight patients presented with solitary lesions (C-spine= 4, T-spine= 1, brain=3) whereas 2 had leptomeningeal disease (LMD). All but one PMT expressed a GNAQ mutation (n=9).  

Surgical resection was the most common initial intervention (n=9), with several patients receiving adjuvant radiation therapy (RT) (n=3) or immunotherapy (n=2) [intrathecal (IT) and intravenous (IV)]. Two patients presented with LMD and received whole brain RT (WBRT) with concurrent temozolomide (TMZ) and immunotherapy. Median survival time from initial diagnosis was 54.8 months (95% CI: 21.1- Not reached).  

Tumor control was achieved in 7 patients with the other 3 lost to follow up or rapidly progressed despite treatment, respectively. In the 7 patients in which tumor control was achieved, all relapsed (local only, n=2; LMD, n=5).  The median time to recurrence was 24.9 months (95% CI: 17.7-Not reached). Salvage therapy varied: RT alone (n=2), RT + immunotherapy (IT +/- IV) +/- TMZ (n=1), surgery + immunotherapy (IV/IT) (n=1), and immunotherapy (IV) alone (n=1). Two patients died rapidly from LMD without additional treatment. The median overall survival from the date of relapse was 19.7 months (95% CI: 19.7-Not reached).

Conclusion: Despite new advances in the treatment of cutaneous melanoma, outcomes for PMT of the CNS are poor.  Multi-institutional collaborations are needed to obtain more data for this rare CNS tumor subtype. 


Isabella Claudia GLITZA (Houston, USA), Andrew J BISHOP, Junsheng MA, Jing LI, Ian MCCUTCHEON, Claudio TATSUI, Guadagnolo ASHLEIGH
09:00 - 18:00 #17831 - Radiosurgery for Central Nervous System Lymphoma with Medical Management Failure.
Radiosurgery for Central Nervous System Lymphoma with Medical Management Failure.

Introduction: Gamma Knife Radiosurgery (GKR) for relapsed/refractory secondary CNS-lymphoma is seldom performed, while whole brain radiotherapy (WBRT) is frequently considered when medical management fails.

Objective: Evaluate GKR for secondary CNS lymphoma treated with GK-Perfexion avoiding WBRT.

Methods: A 60-year-old-man since 2016 with B-cell diffuse-lymphoma underwent treatment with R-CHOP, 6-cycles. Complete response lasted until May-2017, when he received salvage chemotherapy and autologous hematopoietic stem-cell transplant (HSCT). In October-2017, appeared diplopia and left arm paresthesias. MRI showed periventricular lesions and edema bilaterally. Stereotactic biopsy confirmed secondary CNS-lymphoma with expression of BCL-2, BCL-6 and c-MYC, triple hit. Rescue chemotherapy was repeated followed by allogenic HSCT. Complete response ensued with symptoms resolution. Generalized weakness, mood changes, attention and short-term memory impairment appeared in June-2018. Disease progression was observed in the hypothalamic and periventricular region. Patient and family refused WBRT. GKR with 13Gy at the 50% isodose was given to each lesion. Two-weeks post-GKR MRI showed remarkable response. Associated chemotherapy led to complete regression of the lesions within one month. Six-months after GKR, new diplopia occurred and MRI disclosed a midbrain tumor. He received LINAC-radiosurgery, 8 Gy in another facility. One month later he presented complete radiological response. The patient's clinical condition improved substantially after both treatments. He continues in close treatment with hematologist. To date, radiosurgery allowed avoidance of WBRT maintaining the patient with good quality of life.

Conclusion: GKR is a safe and effective alternative in the treatment of recurrent CNS-lymphomas, avoiding WBRT side effects for disease-debilitated patients. Larger series should allow better understanding of its impacts in quality of life and disease palliation. Radiosurgery dose and duration of local control must be better defined.


Rafael COSTA LIMA MAIA (São Paulo, Brazil), Alessandra GORGULHO, Daniel ALVES NEIVA BARBOSA, Bruno FERNANDES DE OLIVEIRA SANTOS, Crystian WILIAN CHAGAS SARAIVA, Anderson MARTINS PASSARO, Antonio DE SALLES
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P05
09:00 - 18:00

EPOSTER - 05 Liver/Pancreas
Electronic Poster displayed from June 9 to June 13

09:00 - 18:00 #17847 - Australian experience of stereotactic radiation therapy in early and advanced stage hepatocellular carcinoma.
Australian experience of stereotactic radiation therapy in early and advanced stage hepatocellular carcinoma.

Purpose

Intra-hepatic progression remains the predominant mode of death in hepatocellular carcinoma (HCC). Stereotactic radiotherapy (SBRT) is an emerging non-invasive locoregional therapy for early to advanced HCC. We report our early experience at an Australian tertiary liver centre.

Methods and Materials

Retrospective study of patients treated between October 2013 and June 2018. Efficacy of SBRT was determined by in-field local control (LC) with CT or MRI, utilizing Response Evaluation Criteria in Solid Tumours (RECIST). Kaplan-Meier methodology was used to determine one year LC, progression free survival (PFS) and overall survival (OS) from date of SBRT. Toxicity was assessed by CTCAE V4.

Results

Ninety-five lesions in 79 patients were treated. Median age was 65 years (range 35-88), 89% male, baseline liver function Child-Turcotte-Pugh (CTP) A (72%), CTP-B (14%), non-cirrhotic (14%). Barcelona Clinic Liver Cancer (BCLC) stage was 0/A (61%), B (9%) and C (30%), with 50% receiving prior liver-directed therapies (median 2 courses, range 1-5). Median tumour diameter was 4.8cm (range 1.5-17cm), Macrovascular invasion was present in 18 (25%), IVC invasion in 5 (7%). Median follow-up was 8 months (range, 1-54). One year LC for BCLC 0/A and B/C cohorts was 95% and 73% with median covering isodoses of 40Gy and 35Gy in 5 fractions respectively. One year LC was 100% if both CTP-A and BCLC 0/A. Local recurrence type was in-field (n=2) and edge-of-field (n=3). Intra-hepatic relapse occurred in 20 (28%) and extrahepatic relapse in 11 (15%). One year PFS and OS was 74% and 89% for BCLC 0/A, 34% and 52% for BCLC B/C disease. Two of 48 patients who were progression free had an increase in CTP score >1, both with intercurrent illness (pneumonia, endocarditis). There were no other non-liver, grade ≥3 gastrointestinal toxicity events. The commonest grade 2 clinical toxicities included fatigue (18%) and pain (3%).

Conclusion

SBRT provides high rates of local control in early to advanced stage HCC and is well tolerated, even in a heavily pre-treated cohort. Out of field relapse is common in advanced stage HCC supporting a rationale to investigate SBRT in combination with other locoregional and emerging systemic therapies.


David PRYOR, David PRYOR (Brisbane, Australia), Howard LIU, Dominique LEE, Peter HODGKINSON, Katherine STUART
09:00 - 18:00 #17786 - Liver stereotactic radiotherapy in heavily pre-treated elderly patients – single institution retrospective experience.
Liver stereotactic radiotherapy in heavily pre-treated elderly patients – single institution retrospective experience.

Background: Liver SABR is increasingly being integrated into multimodality treatment pathways due to advances in treatment delivery, image guidance, and promising outcome data. Tolerability and toxicity, especially among pre-treated elderly patients with multiple comorbidities, is still a matter of concern in clinical practice.

Methods: We undertook a single institution retrospective analysis of patients treated with linac-based liver SABR between January 2016 and January 2019 at Guy’s Cancer Centre, London.

Results: There were 30 tumours from 27 patients of which 13 were Colorectal metastases (CRCm), 11 Hepatocellular carcinoma (HCC) and 3 Cholangiocarcinoma (CHC). Median age was 72 (36-91); 19 patients were ≥70 years old; median ECOG performance status was 1 (range 0-2). Many patients were heavily pre-treated and not suitable for other therapies due to comorbidities or lack of treatment options. All HCC patients were Child-Pugh A and 63% of these were non-viral aetiology; 2 patients were treated as a bridge to transplant. Median tumour size was 4 cm (1.3-9.5). Median prescription dose was 50Gy (40-60) delivered in 3-10 fractions, with median GTV and liver volumes of 67.5cc (27-188) and 1496.1cc (1060-2651) respectively. Median dose to 700cc Liver-GTV was 10.5Gy (7-27.8). 9 treatments (36%) were performed in end expiratory breath hold (EEBH). Six weeks post-radiotherapy, fatigue G1 was the only treatment-related toxicity reported by 31% of patients; 27% were asymptomatic and 1 developed a duodenal ulcer. Median liver function test results were bilirubin 11 umol/L(5-32), AST/ALT 37 IU/L (16-136), albumin 38.5 g/L (30-45) and ALP 162 IU/L (60-649). At 6 months, 3 patients died from out-of-field progression (2CRCm; 1HCC); 85% of patients reported no toxicities. One death from radiation-induced hepatic decompensation and extrahepatic disease progression was reported after 8 months. 1-year actuarial survival was 71%; 6 patients remained asymptomatic. There was an asymptomatic duodenal perforation managed conservatively and one SABR-induced liver dysfunction with no active disease that recovered completely.

Conclusion: Liver SABR is safe, effective, and well tolerated in heavily pre-treated elderly patients with multiple comorbidities.


Pollyanna D AVILA LEITE (London, United Kingdom), Asad QURESHI, Kasia OWCZARCZYK, Benjamin TAYLOR, Clare HARTILL, James BARBER, Mark MCGOVERN, Vicky GOH, Andrew GAYA
09:00 - 18:00 #17852 - Phase II trial of high dose stereotactic body radiation therapy for abdomen and pelvis lymph node metastases.
Phase II trial of high dose stereotactic body radiation therapy for abdomen and pelvis lymph node metastases.

Background: Stereotactic body radiotherapy (SBRT) is nowadays considered an effective approach for the management of oligometastatic patients. We analyzed clinical results of oligometastatic patients treated with high dose SBRT for lymph node metastases in abdomen and pelvis.

Materials and Methods: This is a prospective, phase II study. Primary end-point was the assessment of acute and late toxicity; secondary end-points were local control (LC), progression free survival (PFS) and overall survival (OS) The schedule of SBRT was 48 Gy delivered in 4 fractions of 12 Gy each. Inclusion criteria were: Histologically-proven carcinoma of gastro-intestinal, genito-urinary of gynecological primary districts, maximum 3 lymph node sites of disease, maximum diameter ≤ 5 cm

Results: From 2015 to May 2018, 43 patients with 54 lymph nodes were enrolled. Genito-urinary (69.7%) and in particular prostate adenocarcinoma (61.1%) was the most common site of primary tumour, followed by gastro-intestinal (25.6%) and gynecological (4.6%). One single lymph node was treated 34 patients, while 2 and 3 lymph nodes in 7 and 2 patients, respectively. With a median follow-up of 16.7 months, only 3 patients reported grade 1 acute toxicity, in the form of pain, dysuria and fatigue. In the late setting, chronic pain was observed in 1 patient. In-field progression was observed in 5 patients with a 1- and 2- years rate of 96.6% and 80.6%.  Systemic therapy during SBRT was associated with a worse LC (HR 10.3, p=0.012). Rates of PFS at 1- and 2-years were 82.8%% and 57.1%. Median PFS was 26.1 months. One and 2-years were OS of 100% and 95.6%.

Conclusion: Treatment of lymph node metastases with high dose SBRT can be considered a safe option in a multidisciplinary approach, with high rates of local control. One year median delay of new system therapy has been demonstrated in this phase II trial. 


Ciro FRANZESE (Milano, Italy), Davide FRANCESCHINI, Tiziana COMITO, Angelo TOZZI, Fiorenza DE ROSE, Pierina NAVARRIA, Giuseppe Roberto D'AGOSTINO, Giacomo REGGIORI, Stefano TOMATIS, Marta SCORSETTI
09:00 - 18:00 #17853 - Role of Stereotactic body radiation therapy in the management of oligometastatic pancreatic cancer: single institution experience.
Role of Stereotactic body radiation therapy in the management of oligometastatic pancreatic cancer: single institution experience.

Introduction: Despite recent advancement in systemic and local treatments, prognosis of patients with pancreatic cancer (PC) still remains poor, with 5 year survival less than 10%. According to literature, a percentage of cancer patients will develop a limited number of metastases, defined as oligometastatic disease. Aim of our study was to evaluate efficacy of Stereotactic body radiation therapy (SBRT) in selected oligometastatic PC.

 Materials and methods: We included patients with a with a maximum of 5 metastases in up to 2 sites. Tumor response was graded according to EORTC-RECIST criteria. Endpoints  were local control (LC), progression free survival (PFS) and overall survival (OS).

 Results: From 2013 to 2017, a total of 41 patients was treated on 64 metastases. Seven (17.1%) patients were naive to systemic therapy at time of SBRT and 25 (61%) patients were treated on one single lesion. Most common sites of disease were lung (29.3%) and liver (56.1%). Median Biologic effective dose (BED) was 105.6 Gy (57.6 – 262.5). Rates of LC  at 1 and 2 years were 88.9% and 73.9%.  Median LC was 39.9 months. Rates of PFS at 1 and 2 years were 21.9% and 10.9%. Median PFS was  5.4 months. At multivariable analysis sex (HR  4.59; p=0.001), time to metastases (HR 0.96; p=0.031) and extra-target disease (HR 7.36; p=0.001) were significant for PFS. Rates of OS at 1 and 2 years were 79.9% and 46.7%. Median OS was 23 months.  At univariate analysis time to metastases (HR 0.95; p=0.036), and BED (HR 1.00; p=0.017) were significant for OS.     

 Conclusion: Our study shows that SBRT on oligometastases from pancreatic cancer is a feasible and effective approach in terms of local disease control. Prospective trials are necessary to improve patient’s selection and to better define the integration of local treatment with more effective systemic therapy.  


Ciro FRANZESE (Milano, Italy), Tiziana COMITO, Davide FRANCESCHINI, Ilaria RENNA, Angelo TOZZI, Fiorenza DE ROSE, Pierina NAVARRIA, Giacomo REGGIORI, Stefano TOMATIS, Marta SCORSETTI
09:00 - 18:00 #17601 - Stereotactic body radiation therapy as management of functional neuroendocrine neoplasms.
Stereotactic body radiation therapy as management of functional neuroendocrine neoplasms.

Neuroendocrine neoplasms (NEN) are heterogeneous malignancies that commonly arise in the lungs, GI tract and pancreas. One unique characteristic of these tumors can be the dysregulated secretion of hormones.  Due to unique indolent biology patients can be managed for many years with prolonged survival; the challenge in managing this patient population is to obtain both tumor and hormonal control. 

Patients with NEN require multidisciplinary assessment and care. For localized disease, surgical resection may be performed with curative intent.  Even in the scenario of metastatic disease, aggressive surgical debulking may improve quality of life by decreasing tumor burden and lessening hormonal production. Non-surgical options for metastatic disease include liver-directed therapy such as ablation or liver embolization, as well as systemic therapy, including somatostatin analogues (SSA), peptide receptor radionuclide therapy (PRRT), targeted agents or traditional cytotoxic chemotherapy.

External beam radiation has been sparingly used for NEN, due to modest responses seen with conventionally delivered treatment. The development of stereotactic body radiation therapy (SBRT) has been made possible by technical advances within the radiation planning and delivery process. SBRT is characterized by high ablative doses delivered over a few treatments and is increasingly utilized technique for both primary and metastatic solid tumors. Despite the rapid uptake of SBRT within other cancers, there are limited data evaluating its impact within NENs, and specifically on hormonal control in this patient population. We submit a series of 4 patients (2 insulinoma, 1 glucagonoma and 1 bronchial) in which SBRT has been utilized as part of multidisciplinary management of primary or metastatic neuroendocrine disease. Each patient was treated with SBRT to either the primary/dominalnt metastatic site of disease or the end organ of hormonal release. No significant toxicity was noted during or after treatment. Each patient had biochemical, clinical and radiographic response to therapy. These cases represent proof of concept that SBRT is an effective therapeutic strategy for functional neuroendocrine neoplasms.


Sten MYREHAUG (Toronto, Canada), Julie HALLET, William CHU, Elaine YONG, Calvin LAW, Angela ASSAL, Alexander LOUIE, Simron SINGH
09:00 - 18:00 #17616 - Stereotactic body radiation therapy for oligometastatic gastric cancer.
Stereotactic body radiation therapy for oligometastatic gastric cancer.

Purpose : To evaluate the efficacy of stereotactic body radiotherapy (SBRT) for oligometastatic gastric cancer

Methods and materials : Between January 2005 and November 2017, 30 patients with 35 oligometastatic lesions from gastric cancer were treated with SBRT. All patients had metastatic lesions of 3 or less with controlled primary tumor. We divided the 33 lesions into three groups : Group A (n=18), abdominal lymph nodes; Group B (n=11), liver; Group C (n=6), others. The median follow-up period was 34 months (range; 3-85). The median tumor volume was 5.8 ml (range, 0.4-204 ml). The prescribed dose ranged from 30 to 60 Gy in 3-5 fractions. 

Results : Involved field failure occurred in 5 lesions (14.3%), regional recurrence occurred in 14 lesions (40.0%) and the distant metastases occurred in 9 lesions (25.7%). The 5-year overall survival rate of group A, B and C were 38.8%, 56.0% and 20.0%, respectively. The 5-year involved field control rate of group A, B and C were 92.3%, 87.59% and 40.0%, respectively. The 5-year progression-free survival rate of group A, B, and C were 33.3%, 56.0%, and 0.0%, respectively. Only two patients experienced grade 2 toxicity, gastrointestinal bleeding in one and radiation pneumonitis in the other. There was no grade 3 or higher acute or late toxicity.

Conclusion : The survival of patients with oligometastases of gastric cancer differed according to the site of recurrence. SBRT could be a safe and effective treatment option to treat oligometastatic lesions from gastric cancer, especially for liver metastases. The selected abdominal lymph node also could be treated effectively with SBRT.


Won Il JANG (SEOUL, Korea), Mi-Sook KIM, Chul Koo CHO, Kwang Mo YANG, Hyung Jun YOO, Eun Kyung PAIK, Eunji KIM, Hee Kyung JEONG, Dong Han LEE, Kyubo KIM
09:00 - 18:00 #17562 - Stereotactic body radiotherapy as a part of combine treatment or single modality for patients with oligometastatic liver disease: own experience.
Stereotactic body radiotherapy as a part of combine treatment or single modality for patients with oligometastatic liver disease: own experience.

Purpose: To determine the importance of maintaining treated metastases control for progression-free survival in patients with oligometastatic liver disease. To conduct if stereotactic body radiotherapy might be more effective alone or combined with systemic therapy.

Methods and Materials: Since 2012 until 2018, 45 patients with 69 lesions were treated. There were 35 patients who had been treated with chemotherapy before stereotactic body radiotherapy. Average lesion volume was 35,2 cc. Histological types were represented mostly by colorectal cancer(72,5%). Respiratory tracking motion systems were used in all cases, with fiducial tracking motion system for patients treated with Cyberknife, and daily ConeBeamCT for patients treated with Truebeam.

Results: Median follow-up was 9 months. Treated metastases control was achieved in all cases with median of 6 months, and it had strong correlation with progression-free survival (p<0,05; 0,73). Patients who received stereotactic body radiotherapy after a few courses of chemotherapy with partial response had longer progression-free survival than patients with stabilization or progression after chemotherapy(median of 25 mo feat 4 mo; p=0,005) or without chemotherapy at all(median of 3,5 mo; p=0,005). The same pattern persisted for treated metastases control. There was no significant correlation between BED10 or target volume and TMC (0,15 and 0,17; p<0,05).

Conclusion: Achievement of local control is an important part of treatment for patients with oligometastatic disease. According to literature, pre-SBRT chemotherapy was related to favorable overall survival, but also the response of chemotherapy can be seen as a prognostic factor of progression-free survival and treated metastases control for patients with oligometastatic liver disease. A significant impact of BED10 on local control couldn’t be seen, possibly because of too narrow dosage range.


Natalia MARTYNOVA (Saint-Petersburg, Russia), Nikolay VOROBYOV, Darya KUPLEVATSKAYA, Alina SMIRNOVA, Julia GUTSALO, Aleksey MIKHAYLOV, Denis ANTIPIN, Georgy ANDREEV, Anton KUBASOV
09:00 - 18:00 #17649 - Stereotactic body radiotherapy for unresectable pancreatic cancer protocol and first implementation.
Stereotactic body radiotherapy for unresectable pancreatic cancer protocol and first implementation.

Introduction

Unresectable pancreatic cancer remains a challenging disease to treat. The role of radiation therapy in the management of such cases is still controversial. The aim of this work is to describe the protocol adopted in Hygeia Hospital, Athens, Greece for the implementation of SBRT to patients with unresectable pancreatic cancer.

Materials and Methods

The inclusion criteria are: age≥18years, histologically proven unresectable primary adenocarcinoma, neo-adjuvant chemotherapy, lesion diameter<5cm, Karnofsky Performance score³70. Patients are immobilized in supine position using Deep Inspiration Breath Hold technique. Patients are given a barium meal 15min prior to imaging for visualization of the stomach and duodenum. Clinical Target Volume (CTV) is delineated on the arterial phase of the planning CT scan (1mm slice thickness) using registered MR images. Additional margins of 5mm in the left-right direction, 5mm in the anterior-posterior direction and 10mm in the cranial-caudal direction are used to form the Planning Target Volume (PTV). Dose prescription is 40Gy in 5 fractions delivered over a two weeks period. Patient plans are created with Elekta Monaco TPS and are treated on an Elekta VersaHD Linac using a 10 MV Flattening Filter Free (FFF) beam. Patients should fast 3hrs prior to treatment and be given a barium meal 15min before being treated. Accurate patient positioning is verified with CBCT image guidance.Five male patients (median age 55yrs) were treated with the SBRT departmental protocol for unresectable pancreatic cancer.

 

Results

All patients treated showed well tolerated gastrointestinal grade I-II toxicity, confirming that the departmental SBRT protocol is well within international guidelines and could be used for treatment of patients with unresectable pancreatic cancer.

 

Conclusion

Patients with locally advanced, inoperable pancreatic cancer can be safely treated with SBRT, in short duration fractionation scheme with minimum disruption of chemotherapy treatment, resulting in less toxicity and better quality of life.


Georgios KRITSELIS (ATHENS, Greece), Chryssa PARASKEVOPOULOU, Nikolaos GIAKOUMAKIS, Efi KOUTSOUVELI, Pantelis KARAISKOS, Georgios KOLLIAS
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P06
09:00 - 18:00

EPOSTER - 06 Lung
Electronic Poster displayed from June 9 to June 13

09:00 - 18:00 #17629 - Comparing phase- and amplitude-gated volumetric modulated arc therapy for stereotactic body radiation therapy using 3D printed lung phantom.
Comparing phase- and amplitude-gated volumetric modulated arc therapy for stereotactic body radiation therapy using 3D printed lung phantom.

Purpose: To compare the dosimetric impact and treatment delivery efficacy of phase-gated volumetric modulated arc therapy (VMAT) versus amplitude-gated VMAT for stereotactic body radiation therapy (SBRT) for lung cancer by using realistic 3D-printed phantoms

Methods: Four patient-specific moving lung phantoms that closely simulate the heterogeneity of lung tissue and breathing patterns were fabricated with four planning computed tomography (CT) images for lung SBRT cases. The phantoms were designed to be bisected for the measurement of 2D dose distributions by using EBT3 dosimetry film. The dosimetric accuracy of treatment under respiratory motion was analyzed with the gamma index (2%/1 mm) between the plan dose and film dose measured under phase- and amplitude-gated VMAT. For the validation of the direct usage of the real-time position management (RPM) data for respiratory motion, the relationship between the RPM signal and the diaphragm position was measured by 4D CT. By using data recorded during the beam delivery of both phase- and amplitude-gated VMAT, the total time intervals were compared for each treatment mode.

Results: Film dosimetry showed a 5.2 ± 4.2% difference of gamma passing rate (2%/1 mm) on average between the phase- versus amplitude-gated VMAT (77.7% [72.7%–85.9%] for the phase mode and 82.9% [81.4%–86.2%] for the amplitude mode). For delivery efficiency, frequent interruptions were observed during the phase-gated VMAT, which stopped the beam delivery and required a certain amount of time before resuming the beam. This abnormality in phase-gated VMAT caused a prolonged treatment delivery time of 366 s compared with 183 s for amplitude-gated VMAT.

Conclusions: Considering the dosimetric accuracy and delivery efficacy between the gating methods, amplitude mode is superior to phase mode for gated VMAT treatment.


Kyoungjun YOON (Korea, Korea), Minsik LEE, Byungchul CHO, Su Ssan KIM, Si Yeol SONG, Eun Kyung CHOI, Seungdo AHN, Sang-Wook LEE, Jungwon KWAK
09:00 - 18:00 #17664 - Estimating the probability of local control, depending on fractionation for tongue cancer.
Estimating the probability of local control, depending on fractionation for tongue cancer.

Malignant neoplasms of the head and neck are characterized by a high proliferation rate during radiation treatment. Modern equipment for radiotherapy (RT) allows to increase the dose per fraction (i.e., implement hypofractionation) without complications of organ at risk and reduce the total time of the entire RT course. Hypofractionated RT for head and neck cancer could increase the treatment effectiveness in terms of tumor control probability (TCP).

The aim of the work is to investigate the dependence of the TCP for head and neck tumors on the total course dose and dose per fraction values, and to analyze hypofractionated VMAT dosimetric plans from the radiobiological point of view in order to maximize TCP value. This investigation was carried out using data of the patients with tongue cancer.

The data of four patients with tongue cancer of second and third stages (T2N0M0-T3N2M0) was used during this investigation. All VMAT treatment plans were created using Elekta MONACO planning system and delivered at Elekta Synergy linac.  Simultaneously integrated boost (SIB-VMAT) technic was used.
TCP values were calculated using at-home developed code in Wolfram Mathematica based on Niemierko model using the parameters of  and  for head neck tumors (Maciejewski and et al, 1989). Since head and neck tumors are characterized by high proliferation rate with a doubling time of 3 days, starting, according to different estimates after 14-30 days of treatment,  were taken for different treatment durations (5, 6, or 7 weeks) .

TCP calculation results show that increase of treatment duration for the stages (T2N0M0-T3N2M0) significantly reduces TCP. Thus, for RT with standard fractionation of 35 fractions and 2 Gy per fraction, the TCP values for the stages T2N0M0-T3N1-2Mis equal to 77%, and for T3N3M0 – 68%. In order to obtain TCP values more than 95% for the second and third stages using standard fractionation of 2 Gy / fraction, one needs to increase total dose to 78 Gy, resulting in TCP values more than 95%. A more rational alternative is the use of hypofractionation, i.e. increase fractional dose. Indeed, the dose of 70 Gy delivered over 30 fractions allows to obtain TCP values for the stages T2N1-3M0-T3N1-2M0 equal to 98.7%, and for the stage T3N3M0 – 98.0%. Reduction of the duration of treatment to 25 fractions will allow obtaining TCP values more than 99.8%.


Sukhikh EVGENYA (Tomsk, Russia), Sukhikh LEONID
09:00 - 18:00 #16999 - First Report of Pulmonary Large Cell Neuroendocrine Carcinoma Treated with Stereotactic Body Radiation Therapy.
First Report of Pulmonary Large Cell Neuroendocrine Carcinoma Treated with Stereotactic Body Radiation Therapy.

INTRODUCTION: Pulmonary large-cell neuroendocrine carcinoma (LCNEC) is a very rare disease, comprising approximately 3% of lung cancers.  Even for Stage I disease, recurrence after resection is common, with a poor five-year overall survival. We present the first report of stereotactic body radiotherapy (SBRT) for pulmonary LCNEC.

METHODS: A 54-year-old woman with a left upper lobe pulmonary nodule underwent a wedge resection with thoracoscopic mediastinal lymph node dissection, revealing a 2.3 cm pT1b N0 LCNEC. Approximately one year later, surveillance imaging demonstrated a new left upper lobe PET-avid nodule, resulting in completion left upper lobectomy revealing LCNEC, with 0/6 involved lymph nodes and negative staging studies. The patient subsequently chose surveillance over adjuvant chemotherapy; unfortunately 23 months later imaging revealed an enlarging 0.7 cm nodule adjacent to the previous resection site, despite the patient remaining in good health (KPS=90).  Subsequent restaging demonstrated no evidence of metastatic disease.  Due to the morbidity of a third operation in this region, and based on the safety of SBRT for Stage I non small-cell lung cancer, the consensus decision from our thoracic oncology team was to proceed with SBRT as preferred management for presumptive second recurrence of LCNEC. The patient shortly thereafter underwent SBRT (50 Gy in 10 Gy/fraction) to this new nodule, 41 months following initial LCNEC diagnosis.

RESULTS: Four months following SBRT, the patient remains in excellent clinical condition (KPS 90), with no evidence of disease spread on surveillance studies.  The nodule itself demonstrated no evidence of growth following SBRT.

CONCLUSIONS: This first report of SBRT for pulmonary LCNEC demonstrates that SBRT is a feasible modality for this rare disease.  A multidisciplinary thoracic oncology approach involving medical oncology, thoracic surgery, radiation oncology and pulmonology is strongly recommended to ensure proper patient selection for receipt of SBRT.


Shearwood MCCLELLAND III (Cleveland, USA), Gregory DURM, Thomas J BIRDAS, Paul M MUSTO, Tim LAUTENSCHLAEGER
09:00 - 18:00 #17716 - ITV calculation for lung SBRT treatment with CBCT during free breathing cycles. Case Report.
ITV calculation for lung SBRT treatment with CBCT during free breathing cycles. Case Report.

SBRT refers to the precise irradiation of an image define extracranial target using a small number of high dose fractions.  SBRT it is a useful treatment option for lung cancer in carefully selected patients.

The variation in clinical target volume (CTV) position and size due to respiratory motion is generally accounted by adding an internal margin to the CTV, resulting in the internal target volume (ITV).

Cone beam (CBCT) is increasingly being used for localization of lung tumours. CBCT scans can have an acquisition time 60s or more, an therefore have the advantage of capturing the average tumour position over 15 or more breathing cycles, which may correspond well to the planning internal target volume as obtained from 4D CT.

In the absence of 4DCT as a simulation image set, this work aims to show the possibility of calculating the ITV of lung lesions greater than 2 cm using multiple CBCT as complementary images to those of free breathing tomography simulation using a respiration correlated approach (flux med).


We analysed the inter-observer differences in blurring delimitation of the lesion with the objective of validate the use of CBCT as an image set to estimate ITV of lung lesions during free breathing cycle as well as the reproducibility of this target verification using CBCT after exactrac positioning using surrogate isocenter in proximal vertebral body in Varian Trilogy LINAC with Exactrac and 6D couch technology. 


Ruben Oscar FARIAS, Florencia MAURI, Leon ALDROVANDI, Augusto ALVA, Maria Liliana MAIRAL, Mabel Edith SARDI, Federico Javier DIAZ, Mara Lia SCARABINO (Buenos Aires, Argentina)
09:00 - 18:00 #17658 - Lung cancer stereotactic radiotherapy at genesiscare victoria australia: 3D conformal radiotherapy vs dynamic conformal arc therapy.
Lung cancer stereotactic radiotherapy at genesiscare victoria australia: 3D conformal radiotherapy vs dynamic conformal arc therapy.

This retrospective study aims to show a dosimetric comparison between three-dimensional conformal radiotherapy (3DCRT) and dynamic conformal radiotherapy (DCAT) for Lung cancer patients being treated with stereotactic body radiotherapy (SBRT). The study compares 3DCRT and DCAT plans for twenty clinical lung cancer patients that were treated at GenesisCare Victoria in 2018. The aim of this planning study is to help planners identify early in the planning process which technique will give optimal results for the patient. Each of the twenty patients met an eligibility criteria and were all planned for TrueBeam™ machine delivery using Pinnacle3 ™ radiation therapy treatment planning system.

 

Following guidelines outlined in RTOG 0915 for Planning treatment volume (PTV) reporting and Organs at Risk (OAR) tolerances, the tumour coverage was maintained between both techniques (D95%>100%, minor variation D99%>90%). Preliminary findings indicate higher R50 (50% isodose) and D2 (Max dose at 2cm from PTV) values in the 3DCRT plans.  Full cohort of patient’s results will be outlined at the congress. Ultimately both techniques are viable and safe treatment options for delivery of SBRT, however factors such as of lesion position, arm placement and OAR proximity need to be considered when deciding between 3DCRT and DCAT for optimal planning outcomes.


Stephanie BARNAO (Melbourne, Australia), Michael NG, Tam NGUYEN
09:00 - 18:00 #17878 - Preliminar results of cyberknife stereotactic radiotherapy for oligometastatic non small cell lung cancer.
Preliminar results of cyberknife stereotactic radiotherapy for oligometastatic non small cell lung cancer.

Aims: Stereotactic radiotherapy (SRT) is a therapeutic possibility for selected oligo-metastatic/oligo-progressive (OM/OP) non-small cell lung cancer (NSCLC), that  is one of the tumour most frequently treated with SRT. We retrospective analyzed clinical outcomes and treatment related toxicities of a cohort of  patients (pts) treated with Cyberknife - SRT for OM/OP NSCLC at Cyberknife Unit, Centro Diagnostico Italiano (CDI), Milan, italy.Patients and methods: We retrospective analyzed 39 OM/OP NSCLC pts treated in our Center  from January 2016 to January 2017. OM/OP disease was defined as one to five metastatic lesions. 30 pts (77%) had adenocarcinoma histology (6 and 2 pts with EGFR and ALK mutation respectively). The median age at the treatment was 69 years, and most of the pts with a high performance status (74% with a Karnofsky Index  90 or more). Most of patients have been already treated (with 1 and 2 systemic therapy lines, surgery or radiotherapy) for metastatic disease before Cyberknife. 16 pts continued systemic therapy during SRT. At the time of radiotherapy, 72% of pts were oligometastatic, while 28 % had oligoprogressive disease. Of the 55 treated lesions, 29 were brain metastasis (53%), 13 lung metastases (24%), 4 bone metastases (7%) and respectively 7 (13 %) 1 (2%) and 2 (4%) lesions were lymph nodes, adrenal and other sites.Results:  After a median follow-up of 17 months, overall survival was 94.65% (range 87.43 -100) and 82.43% (range 67.77 – 97.09) at 1 and 2 years, respectively; one year local progression free survival (LPFS) and progression free survival (PFS) were 91.47% (82.17-100) and 38.46% (23.19-53.75) respectively. The pattern of progression was analyzed for 73 pts showing no progression for 27 pts (37%), oligo-progression in 30 pts (41%) and poli-progressive disease in 16 cases (22%). The majority of pts did not reported any acute toxicities (only one patient has experienced a G2 neurotoxicity). Regarding late toxicity 3 pts reported G2 neurotoxicity while 1 patient died for radionecrosis after a treatment for brain metastases. Conclusions: in our preliminar data SRT-Cyberknife appears to be safe and effective in OM/OP NSCLC, with promising results according to the literature.


Isa BOSSI ZANETTI (Milano, Italy), Livia Corinna BIANCHI, Achille BERGANTIN, Anna Stefania MARTINOTTI, Irene REDAELLI, Paolo BONFANTI, Chiara SPADAVECCHIA, Giancarlo BELTRAMO
09:00 - 18:00 #17561 - Primary and metastatic lung tumors treated with stereotactic body radiation therapy: own experience.
Primary and metastatic lung tumors treated with stereotactic body radiation therapy: own experience.

Purpose: Assessing stereotactic body radiotherapy efficiency and toxicity for primary lung cancer and lung metastases.
Methods and Materials: In a period from December 2011 to February 2017, 71 patients with primary and metastatic lung tumors were treated. Stereotactic body radiotherapy was applied to 103 tumors: 33 primary tumors, 70 metastases of different tumor sites. Two linear accelerators with different respiratory motion tracking systems were used: CyberKnife with Synchrony respiratory motion tracking system and TrueBeam STx with Gating.
Results: Clinical observation group include 52 patients with 81 lung tumors. Average tumor volume was 44.7 cc (0.2-496.5 cc). Observation median was 7 months. Local control was achieved in all cases, median of local control was 6 months. For 19(23.5%) tumors complete response was achieved, median was 5 months. There was a local relapse in 17(21%) cases, 15 of which were squamous cell relapse. There was a negative linear dependence of local relapse probability from BED10 for squamous cell tumors. Disease progression was observed among 29 patients, 93% of them had a local control preserved during the whole observation period. Early toxicity was grade 1-2 for most patients; 5 patients with large tumor volume (more than 300 cc) had grade 3 early toxicity. None of the patients had grade 4 early toxicity. Late toxicity did not exceed grade 2 for all the patients.
Conclusion: Stereotactic body radiotherapy appears to be safe and effective treatment option for patients with lung lesions, including huge and central tumors. It allows to use higher radiation doses even in palliative care.  Potentially, higher radiation doses are needed to achieve better local control for squamous cell tumors. 


Natalia MARTYNOVA (Saint-Petersburg, Russia), Nikolay VOROBYOV, Aleksey MIKHAYLOV, Julia GUTSALO, Georgy ANDREEV, Anton KUBASOV
09:00 - 18:00 #17757 - SBRT: 1, 3 or 5 fractions in the treatment of lung tumors in elderly patients.
SBRT: 1, 3 or 5 fractions in the treatment of lung tumors in elderly patients.

BACKGROUND/PURPOSE/OBJECTIVES

The aim of this study is to describe the impact of fractionation scheme on results with SBRT for lung tumors in elderly patients.

MATERIALS/METHODS

Our institutional lung SBRT experience for patients aged 75 years or older, extracting details of patient factors, treatment specifics, toxicity and clinical outcomes.

Local control and survival rates were calculated and compared between subsets of patients.     All events were calculated from the end of radiation therapy.  Toxicity and radiologic response were assessed using standardized criteria. Cause-specific survival and overall survival were calculated using the Kaplan-Meier method.  Outcomes were compared for those with single 30 Gy fraction and other schemas. 

 

RESULTS

Between 2002 and 2017, 104 patients had 121 SBRT procedures; 67 were for primary lung tumors (T1-2N0M0) and 44 oligometastases. Median patient age was 79.6 years (75-88).  All cases had ECOG PS 0-1.

Treatments schema:  30 Gy single fraction (n=12), 45-48 Gy in 3 fractions (n=81)  and 50 Gy in 5 fractions- (n=26)

In a comparison of single and multiple fractions cohort, patient and tumor characteristics were balanced and median follow-up was 16 months (2-70).

For the 30 Gy and other schedules rates of 1-year local control, overall survival and cancer specific survival were 100% vs 98 %; 84 % vs 78 % and 92 % vs 90 %, respectively (p differences were not significant).

Median ITV was 11.6 cm3 (0.9-143) BED>100Gy. Transient grade 1-2 acute toxicities in 11 %.  No grade > 3 acute or any chronic toxicities.

OS was significantly influenced by pretreatment performance status, primary tumor histology and ptv size in metastases.  For LC pretreatment performance status was the only prognostic factor.  No factor significantly influenced toxicity.

 

CONCLUSIONS

Excellent OS and LC is achievable in elderly patients.  In our cohort there were no differences in results comparing single vs multifraction lung SBRT.


Luis LARREA (Valencia, Spain), Enrique LOPEZ-MUNOZ, Paola ANTONINI, Veronica GONZALEZ, Jose BEA-GILABERT, Maria BANOS-CAPILLA
09:00 - 18:00 #17714 - Timing of PET for diagnosis of local recurrence of NSCLC after SBRT using SULmax.
Timing of PET for diagnosis of local recurrence of NSCLC after SBRT using SULmax.

Maximum standardised uptake value (SUVmax) is measured with 18F-Fludeoxyglucose (FDG) positron emission tomography (PET) and has previously been investigated as a marker for local recurrence of non-small cell lung cancer (NSCLC) with mixed results, possibly due to the acute radiation inflammatory response in the first 3-9 months. The authors assessed the accuracy of semi-quantitative PET measurements to detect local recurrence at different time points after SBRT.

Method

A retrospective review was performed of patients with stage1 NSCLC treated with stereotactic body radiation (SBRT) who underwent follow-up PET scan/s at a single centre. Maximum standardised uptake value normalised for lean body mass (SULmax) was calculated for the primary tumour including surrounding CT changes. Outcomes of local recurrence, locoregional recurrence and distant metastasis were diagnosed based on histopathology where available, and clinical follow-up.

Results

52 lesions underwent a total of 107 follow-up PET scans after treatment with SBRT. Prescribed doses were between 48-60Gy in 4-8fractions.The median time to first PET scan was 9.3 months, and the median follow-up period was 22.4months (range 6.5-54 months). 

Local recurrence was diagnosed in 10 patients (19%), of which 5 were histopathology confirmed, at a median period of 16 months. Locoregional recurrence and distant metastasis were diagnosed in 9 and 11 patients respectively. The median SULmax was significantly higher for local recurrences compared to non-recurrences (5.97 vs 2.27) and a threshold of SULmax>5 yielded a sensitivity of 90% and specificity of 88%.

33 PET scans were performed within 9 months of SBRT, which found that SULmax was not specific with 3 false positives.  Beyond 9 months, SULmax>5 has a sensitivity of 90% and specificity of 94%.

Conclusion

Beyond 9 months after SBRT, SULmax can reliably identify local recurrence.

Further studies are required to investigate the utility of SULmax earlier than 9 months after SABR.


Daren TAN (Perth, Australia), Suki GILL, Nelson LOH
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P07
09:00 - 18:00

EPOSTER - 07 Meningioma
Electronic Poster displayed from June 9 to June 13

09:00 - 18:00 #17628 - Dosimetric comparison between CyberKnife and GammaKnife hypofractionated radiosurgery for benign perioptic tumors: a retrospective multi-institutional study.
Dosimetric comparison between CyberKnife and GammaKnife hypofractionated radiosurgery for benign perioptic tumors: a retrospective multi-institutional study.

Purpose: We conducted a retrospective multi-institutional study to compared the dosimetric differences between CyberKnife (CK) and GammaKnife (GK) in treatment planning of hypofractionated stereotactic radiosurgery (hSRS) for benign perioptic tumors.

 

Methods: We selected 18 perioptic tumors (contact to optic nerve = 9; contact between optic nerve and optic track = 8; wrapped around optic nerve = 1) previously treated using CK between 2011 and 2015. The CK plan was generated using 4 or 5 dose-limiting auto-shells, one at prescription dose level, another at intermediate dose level for steeper dose fall-off, and the others at low-dose levels, with an optimized shell-dilation size based on our experience. The GK plans were also produced using the original contour set in two institutions (GK1 and GK2). Thus, three data sets of dosimetric parameters were generated and compared. hSRS was delivered in five fractions with a median marginal dose of 27.8 Gy (≈14 Gy in a single fraction, assuming an α/β of 3) to a median tumor volume of 3.1 cm3. All treatment planning goals was maximizing the minimum dose (Dmin) to tumor, while satisfying the dose-volume constraints criteria (Dmax < 25 Gy and V20Gy < 0.2 cc) of the optic apparatus (OA) as closely as possible.

Results: All treatment plans achieved a high level of CI (1.24 for CK, 1.27 and 1.25 for GK1 and GK2 plan, respectively; P=0.742), although the OA doses were well within the tolerated dose-volume limits in all plans. However, statistically significant differences in plan qualities were observed between the CK, GK1, and GK2 plans [Dmin, 22.87 for CK vs. 19.09 and 17.95 for GK1 and GK2 (p < 0.014); tumor coverage (CO), 94.39% for CK vs. 88.51% and 94.83% for GK1 and GK2 (p < 0.001), and gradient index (GI50), 3.39 for CK vs. 2.89 and 2.65 for GK1 and GK2 (p = 0.007)].

 

Conclusions: These results indicate that CK plans produced significantly high quality values of Dmin and CO than those produced by both GK plans (P<0.001). In particular, the wrapped around optic nerve case showed the largest difference, maintained dose-volume limit of the OA. However, the both GK plans achieved a level of GI50 (2.89 for GK1 and 2.65 for GK2) higher than the CK (3.39, p = 0.007). The GK plans achieved more rapid dose fall-off around the tumor than the CK plan and therefore saved more critical normal tissue.


Kyoungjun YOON (Korea, Korea), Byungchul CHO, Jungwon KWAK, Doheui LEE, Weon Seop SEO, Do Hoon KWON, Seungdo AHN, Sang-Wook LEE, Chang Jin KIM, Sung Woo ROH, Young Hyun CHO
09:00 - 18:00 #17706 - Gamma knife surgery for Atypical and Anaplastic meningiomas: determination of irradiation dose based on MIB-1 index in addition to devise irradiation field.
Gamma knife surgery for Atypical and Anaplastic meningiomas: determination of irradiation dose based on MIB-1 index in addition to devise irradiation field.

Gamma knife surgery for benign meningioma can be said to have established its effectiveness, but the results of gamma knife surgery for atypical and anaplastic meningioma are not favorable . It seems that this is related not only to the tissue type of the tumor but also to the proliferation ability of the tumor cells which are very extensive. In 2009, Nakaya et.al. reported that Gamma knife surgery  for  meningioma increases the risk for recurrence when MIB-1 index exceeds 3%. Based on this report, we made a protocol to raise the dose according to the value of MIB-1 index with the minimum irradiation dose 15 Gy for atypical meningioma. and  in residual tumor after surgery, we made a strategy that the irradiation field was devised so as to cover the attachment area of the tumor before surgery to prevent marginal recurrence.We report the results and problems of the protocal and strategy.

13 patients with atypical and anaplastic meningioma who underwent gamma knife surgery at our institute  from January 1, 2012 to February 10 2017 

Male :8  Female :5  Median age: 69 y.o  (21 to 80 )  Median follow up period 28 month (5 to 57 )  Median tumor volume :2.93 ml (0.1 to 8.4 ml)  Median MIB-1 index :9.7% (3.4 to 29.1%)  Median irradiation dose :17GyRecurrence was observed in one case, but in other 12 cases local tumor control  was obtained. 

There are so many cases with high MIB-1 index, it is desirable to treat with high dose from the viewpoint of risk for recurrence.

Because the number of cases is small and the follow up period is short, it is necessary to accumulate more cases and long observation period.

 


Kawai HIDEYA (Akita-City, Japan)
09:00 - 18:00 #17739 - Long term results of stereotactic radiosurgery treatment for cavernous sinus meningiomas on multiple devices.
Long term results of stereotactic radiosurgery treatment for cavernous sinus meningiomas on multiple devices.

Introduction. Stereotactic radiosurgery (SRS) is an important treatment option for patients with cavernous sinus meningiomas and can be performed using various radiosurgical techniques. The purpose of clinical study was retrospective analysis of the efficiency of SRS and long-term results for cavernous sinus meningiomas.
Materials and methods. Linear accelerator «Trilogy + BrainLab» stereotactic radiosurgery was performed in 30 patients (8 males and 22 females; mean age - 52 years) with cavernous sinus meningiomas. Tumor volume ranged from 2.8 cc to 20.9 cc (median, 9.1 cc). 23 patients in LINAC group (76.7%) received SRS alone, and 7 patients (23.3%) had undergone surgery before SRS. CyberKnife(CK) SRS was performed in 12 patients (5 males and 7 females; mean age - 47 years, median tumor volume 13,6 cc). In CK SRS group only 3(25%) patients had surgery before. The marginal doses for the tumors were  for LINAC SRS 11 Gy to 12.5 Gy (median, 12.1 Gy), for CK SRS 18-25 Gy in 3-5 fractions. Median follow-up of patients was 42 months (range, 30-60 months).
Results Follow-up images showed a reduction in tumor size in 14 patients (46.7%), no further growth in 16 (53.3%) cases in LINAC group and decrease of the tumor size in 5 (41,6%) patients and stable tumor size in 7 (58,4%) patients in CK group. In both group 16 (38,1%) patients demonstrated improvement in their neurological condition. Other 61,9 % patients also had no worsening of their neurological status. None of the patients in both groups experienced post-radiation toxicity grade 2-3. patients.  

Conclusions. SRS − is an effective method of treatment for сavernous sinus meningiomas, that can be performed using various radiosurgical techniques providing tumor control without significant difference and with same quality of life outcome.


Vladyslav BURYK, Olga CHUVASHOVA (Kyiv, Ukraine), Maris MEZECKIS, Igors AKSIKS, Dace SAUKUMA, Maris SKROMANIS, Jelena NIKOLAJEVA, Iryna KRUCHOK
09:00 - 18:00 #17822 - Outcomes after gamma knife radiosurgery for intracranial meningiomas.
Outcomes after gamma knife radiosurgery for intracranial meningiomas.

Intro: Gamma Knife Radiosurgery (GKRS) is both an important primary and adjuvant management strategy for patients with meningiomas. We analyzed outcomes in patients treated with GKRS and attempted to determine risk factors related to treatment failure and overall survival.

Methods: Between March 2014 and June 2018, 96 consecutive patients with a total of 143 meningiomas were treated with GKRS utilizing doses between 10-20 Gy. The series consisted of 74 women and 26 men. Median age was 63 years-old (Range, 29-87) and 48 patients had previous resection. There were 12 patients with 23 radiation induced meningiomas along with an additional 15 patients who were receiving reirradiation. In total, there were 32 posterior fossa, 22 middle fossa, 8 anterior fossa, 4 torcular, 4 intraorbital, 3 sylvian fissure, 40 convexity, 23 parasaggital, and 11 falcine meningiomas.

Results: At a median follow-up of 24 months (Range, 2-55) the overall local control (LC) rate was 88% with a mean time to progression of 46 months. When compared to patients with WHO Grade 2 or Grade 3 meningiomas, patients with Grade 1 meningiomas had significantly improved progression free survival (95% Grade 1 vs. 50% Grade 2 vs. 0% Grade 3, p < .001), disease free survival (100% Grade 1 vs. 75% Grade 2 vs. 33% Grade 3), and overall survival rate (97% Grade 1 vs. 70% Grade 2 vs. 33.3% Grade 3). Twelve patients had radiation induced meningiomas and were found to have significantly worse control compared to patients without radiation induced meningiomas (50% vs 90.5%, p<.001) and decreased mean time to progression at 27.4 months. Skull base location, dose, age, race, gender, previous surgery, or previous radiation treatment, did not affect LC, PFS, OS, or DFS on multivariate analysis.  

Conclusion: GKRS is an effective treatment modality for benign meningiomas. Survival and local control decreases with increasing tumor grade and radiation induced etiology.


Zaker RANA (New Hyde Park, USA), Troy DAWLEY, Michael SCHULDER, Anuj GOENKA
09:00 - 18:00 #17892 - PRELIMINARY RESULTS AFTER HYPOFRACTIONATED RADIOSURGERY WITH GAMMA KNIFE ICON FOR CAVERNOUS SINUS MENINGIOMAS.
PRELIMINARY RESULTS AFTER HYPOFRACTIONATED RADIOSURGERY WITH GAMMA KNIFE ICON FOR CAVERNOUS SINUS MENINGIOMAS.

Hypofractionated stereotactic radio-surgery allows physicians to treat larger volumes or lesions in the proximity of critical structures, in particular optical nerves and chiasma.

Using Gamma Knife Icon is possible to deliver treatments in frameless modality thanks to a Cone-Beam CT integrated with the machine, which assigns stereotactic coordinates coregistering MR-CT treatment plans to a reference CBCT acquired at the beginning of each treatment.

Between November 2017 and November 2018, 64 patiest with a meningioma underwent Gamma Knife radiosurgery in Fondanzione Poliambulanza in a frameless modality; of them 17 patients had a cavernous sinus meningiomas very close to optic pathways. The aim of the study is to validate the accuracy of hypocractionated treatments with Gamma Knife Icon analyzing the possible side effects.

Gamma Knife radiosurgery was delivered in frameless modality in 5 sessions with a mean prescription dose of 5 Gy per session and a total prescription dose of 25 Gy. Mean tumor volume was 7,910 ml (0,917 - 16,473 ml). Mean maximum dose to the optic apparatus was always below 5 Gy for each session. 

With a minimum follow-up of three months no patient presented a worsening of the visual function or the appearance of deficit of other cranial nerves. The first MRIs of follow up did not show edema. 

Very  preliminary experience suggests that hypo-fractioned radiosurgery with Gamma Knife Icon can be asafe treatment for tumors immediately close to segments of the optic apparatus.


Alberto FRANZIN (Brescia, Italy), Lodoviga GIUDICE, Cesare GIORGI, Chiara BASSETTI, Ivan VILLA, Oscar VIVALDI, Mario BIGNARDI
09:00 - 18:00 #17794 - Rotating Gamma System (RGS) treatment of petroclival meningioma. Was that helpful for patients?
Rotating Gamma System (RGS) treatment of petroclival meningioma. Was that helpful for patients?

Purpose: Radiosurgery is widely accepted in management of benign intracranial tumors such as meningioma. Petroclival meningioma(PC) arise in the area surrounding the spheno-occipital synchondrosis. Because of its location, it can displace the brainstem and encase the surrounding critical neurovascular structures. Despite the advances in neurosurgical operative technique, the surgical resection still remains a substantial challenge. In the last decades, radiosurgery gave new hope for meningioma patients.The aim of the study was to retrospectively investigate and report our experience with RGS treatment of PC meningioma and compare our results to other radiosurgery systems as well.

Method:From 2007 to 2017, 75 treatments for PC meningioma was performed as primary indication or next to surgery. Single session treatment was carried out with RGS (GammaART 6000ND, San Diego, CA) device. Mean total volume was 6.23ccm (0.81-39.01ccm). Mean marginal dose was 12.25Gy (10-16Gy). After treatment, the patients were regularly examined. Mean follow up time was 63months (9-118months). Clinical symptoms and MRI findings were assessed. 

Results:Good clinical and radiological outcome was observed in majority of cases. After irradiation, we found that in 94% of patients, tumor volume decreased (19.7%) or controlled(74.3%). In 6% further action (repeat of irradiation or surgery) was necessary. One patient was passed away in complications caused by the tumor growth. In other cases, survival time was not affected by tumor itself. Good, acceptable life quality was found in 82% of patients. Symptoms were improved (12%) or were in stable, tolerable condition (70%). In 18% of cases symptom progression or new symptom was detected even the tumor volume was unchanged. Most of the clinical exacerbation were due to increasing pain of trigeminal neuralgia. These patients were reirradiated with a higher radiation dose or underwent open surgical procedure.

Conclusion:Our results suggest that in case of small- to medium-sized PC meningioma, single session radiosurgery is an acceptable alternative to surgery. Tumor volume and symptoms are highly controlled with this procedure. Reviewed our series and compared to previously published results we can conclude that RGS treatment is practically as effective as other radiosurgical system treatments. 


József Gábor DOBAI (Debrecen, Hungary), Bernadett SZŰCS, Gulyás LÁSZLÓ, Tamás HOLLÓ, Imre FEDORCSÁK, László BOGNÁR
09:00 - 18:00 #17806 - Visual outcomes after radiotherapy and radiosurgery for optic nerve sheath meningioma.
Visual outcomes after radiotherapy and radiosurgery for optic nerve sheath meningioma.

Introduction: Optic Nerve Sheath Meningiomas (ONSMs) are rare, benign neoplasms of the anterior visual pathway, accounting for 2% of orbital tumours. Left untreated, they may blind and disfigure patients. Currently, radiotherapy is preferred over surgery or observation, however the optimal modality of radiotherapy has not been established. The use of stereotactic radiosurgery in treating ONSMs has been limited due to the high radiation doses delivered to the optic nerve.

 

Methods: We performed a retrospective analysis of visual outcomes and side effects in ONSM patients treated with radiosurgery at three centres in Sydney, Australia, between 2000 and 2016 (n = 15). We also performed pooled data analysis of available studies, comparing visual outcomes between fractionated radiotherapy and hypofractionated radiosurgery (hfSRS, up to 5 fractions).

 

Results: In our cohort, a significant majority experienced improved visual field outcomes (p = 0.046), and stable or improved visual acuity (p = 0.0017) and colour vision (p = 0.015) after fractionated radiotherapy with an average follow up time of 46.5 months. When patients who had previous surgical procedures were excluded, no patient experienced worse visual acuity, visual fields or colour vision. Pooled data analysis with strict inclusion criteria revealed a significantly poorer visual acuity for patients receiving 3D conformal radiotherapy (3D-CRT) compared to those receiving fractionated stereotactic radiotherapy (FSRT). When all published studies were included, there was no significant difference between hfSRS and fractionated methods (3D-CRT, FSRT, intensity-modulated radiotherapy) for visual acuity, visual fields or tumour response. Rates of long term side effects were lowest in the hfSRS group.

 

Conclusion: These results support the use of stereotactic radiotherapy delivery, and suggest hfSRS is a viable treatment option for ONSM patients despite the higher radiation doses associated with each fraction. 


Christopher OVENS, Benjamin DEAN, Cecelia GZELL (SYDNEY, Australia), Nitya PANATJALI, Benkamin JONKER, Michael O'CONNOR, Patrick ESTOESTA, Tatiana DE MARTIN, Clare FRASER
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EPOSTER - 09 Metastases
Electronic Poster displayed from June 9 to June 13

09:00 - 18:00 #16793 - A standardised method for use of the leksell gammaplan inverse planning module for metastases.
A standardised method for use of the leksell gammaplan inverse planning module for metastases.

Leksell GammaPlan version 10 and higher contains an inverse planning module, consisting of functions to automatically fill a target volume with shots and subsequently optimise their resulting dosimetry. A standardised method for using the inverse planning module was developed for metastases, using the following optimisation parameter weightings: {coverage 0.9, selectivity 0.1, gradient index (GI) 0.2, beam on time (BOT) 0.0} and nineteen plans produced using this method were compared to manually produced clinical plans.

The average parameters for plans produced using the optimisation module were; coverage 98.8%; Paddick conformity index (PCI) 0.85; GI 2.68, compared to coverage 99.4%; PCI 0.84; GI 2.69 for manual plans. Decay corrected BOT for plans produced using the optimisation module was on average 17% shorter than manual plans.

The standardised method for using the optimisation module has potential for shortening treatment times and planning times.  


Peter FALLOWS, Gavin WRIGHT (Leeds, United Kingdom), Peter BOWNES
09:00 - 18:00 #17862 - Brain metastases from renal cancer are sensitive to gamma knife treatment.
Brain metastases from renal cancer are sensitive to gamma knife treatment.

Objective:

Gamma knife surgery (GKS) is increasingly used in the treatment of brain metastasis (BM) from renal cell carcinoma (RCC) due to their resistance towards whole brain radiotherapy (WBRT). In lack of prospective studies, retrospective reviews are valuable.

 

Methods:

Between 2005 and 2015, 66 patients with 140 RCC BM from RCC were treated with GKS at Haukeland University hospital, Norway. The mean age was 62 y (range 26-83) and 41 (62.1%) patients were males. Total tumor volume was 5.30 cm3 (range 0.03 – 26.2) and mean prescription dose 21.3 Gy.

Results:

Local control was achieved in 117 (91.4%) and radiation induced edema occurred in 19 (14.8%) of the 128 BM with follow-up images. Median OS was 9.8 months (95 % CI 6.3 -13.4). Patients with 1 BM had the longest OS, 17.4 months (95% CI 6.8–28.0) compared to 16.6 (95% CI 5.2–27.9) and 4.8 (2.9–6.7) months for patients with 2 and 3 BM, respectively (p < 0.001). OS was longer for patients with KPS ≥ 70 vs. patients with KPS < 70 (p=0.048) and those treated with nephrectomy vs. not for their primary cancer (p=0.006). Intratumoral BM hemorrhage before GKS observed in 7 (10.6 %) patients was associated with poor OS, 4.6 months (95 % CI 3.0-6.1) vs. 10.9 months (95 % CI 5.2-16.6), p < 0.001. The number of BM, presence of intratumoral hemorrhage and prior nephrectomy remained significant factors for survival after multivariate analyses.

Conclusion:

GKS is a safe and effective treatment option in patients with BM from RCC. GKS seems to overcome the radioresistance observed towards WBRT. A reason may be the high vascularity of RCC-BM, similar to melanoma BM. The prognostic factors in the present study are in line with prior studies. A new finding is the poor survival associated with BM hemorrhage.


Bente Sandvei SKEIE (Bergen, Norway), Veronika LABUSOVA, Geir Olve SKEIE, Jan Ingemann HEGGDAL, Elisabeth LARSEN, Paal-Henning PEDERSEN, Per Øyvind ENGER
09:00 - 18:00 #17737 - Brain metastases radiosurgery: comparison of two irradiation tehniques.
Brain metastases radiosurgery: comparison of two irradiation tehniques.

Stereotactic radiosurgery (SRS) treatments can be performed on various devices: cyber-knife, linear accelerators (linacs), tomotherapy, gamma knife, particle accelerators. Every device has advantages over other. Linacs still remain one of the most common devices for SRS. Main advantage of linacs is multi leaf collimator (MLC). MLC can shape irregular fields, and form the best possible blocks for sparring organs at risk. Linacs can have, as add-on, another collimator for SRS treatments: cone collimator. Although it is not completely new feature of linacs, it is still not widely used. Cone collimator provides steep dose gradient, and because of it, dose to the brain is reduced. In theory, cone collimator should provide better sparring of brain tissue. In this work, in depth comparison of MLC and cone collimator have been performed in order to provide answer to questions: will cone collimator give statistical significant difference in dose to the brain in the case of single and multiple metastasis for small, medium and large lesion volumes, how accurate is cone algorithm, does simplified cone algorithm reduces optimization and calculation time and is there a difference for patient treatment time. 

27 patients with total of 120 metastasis have been selected into three groups and plan for micro MLC and cones have been calculated. Both plan types have same couch rotations, number of fields, start and stop gantry angles and linac (Varian EDGE). The first group consists of 30 comparison plans for lesions volume less than 1.0 ccm, second group consists of 30 comparison plans for lesions whose volume is between 1.0 and 2.5 ccm. Third group consists of 11 comparison plans for lesions whose volume is over 2.5 ccm.  Out of field dose measurement has been performed to test algorithm accuracy. All plans were planned on Varian Eclipse 13.7. MLC calculation algorithm is AcurosXB, cone algorithm is Eclipse Cone Dose Calculator (ECDC).


Adlan CEHOBASIC (Zagreb, Croatia), Domagoj KOSMINA, Vanda LEIPOLD, Hrvoje KAUCIC, Andreas MACK
09:00 - 18:00 #17632 - CyberKnife dosimetric planning using a dose-limiting shell method for brain metastases.
CyberKnife dosimetric planning using a dose-limiting shell method for brain metastases.

Purpose: We investigated the effect of optimization in dose-limiting shell method on the dosimetric quality of CyberKnife (CK) plans in treating brain metastases (BMs).

Methods: We selected 19 BMs previously treated using CK between 2014 and 2015. The original CK plans (CKoriginal) had been produced using one to 3 dose-limiting shells: one at the prescription isodose level (PIDL) for dose conformity and the others at low-isodose levels (10%–30% of prescription dose) for dose spillage. In each case, a modified CK plan (CKmodified) was generated using five dose-limiting shells: one at the PIDL, another at the intermediate isodose level (50% of prescription dose) for steeper dose fall-off, and the others at low-isodose levels, with an optimized shell-dilation size based on our experience. A Gamma Knife (GK) plan was also produced using the original contour set. Thus, three data sets of dosimetric parameters were generated and compared.

Results: There were no differences in the conformity indices among the CKoriginal, CKmodified, and GK plans (mean 1.22, 1.18, and 1.24, respectively; P = 0.079) and tumor coverage (mean 99.5%, 99.5%, and 99.4%, respectively; P = 0.177), whereas the CKmodified plans produced significantly smaller normal tissue volumes receiving 50% of prescription dose than those produced by the CKoriginal plans (P < 0.001), with no statistical differences in those volumes compared with GK plans (P = 0.345).

Conclusions: These results indicate that significantly steeper dose fall-off is able to be achieved in the CK system by optimizing the shell function while maintaining high conformity of dose to tumor.


Kyoungjun YOON (Korea, Korea), Byungchul CHO, Jungwon KWAK, Doheui LEE, Do Hoon KWON, Seungdo AHN, Sang-Wook LEE, Chang Jin KIM, Sung Woo ROH, Young Hyun CHO
09:00 - 18:00 #17707 - Efficacy of pre-operative stereotactic radiosurgery of brain metastases.
Efficacy of pre-operative stereotactic radiosurgery of brain metastases.

Preoperative stereotactic radiosurgery (pre-SRS) is a new strategy of  management for  brain metastases (BM). The goal of this analysis is to evaluate 6/12-month local control, overall survival and toxicity utilizing pre-operative SRS followed by surgical resection for patients with brain metastases.

Materials and methods. 35 patients with 83 BM (22 female and 13 male) have been treated using SRS & pre-SRS. 47 symptomatic metastatic lesions were pre-SRS in the series. 8 patients had NSCLC, 9 - BC, 7 - melanoma, 5 - renal carcinoma and 6 - other. Median target volume for combined treatment was 12,26 cc (4,074 - 57,098). Median of target dose was 18,94 Gy (12 and 24,36). Radiation dose was increased by approximately 20% compared to standard dosing as per RTOG 90-05 and was determined by tolerance of intact brain tissues. Pre-SRS followed by delivered surgical resection within 48 hours (Me=24 hours).

Results. All patients tolerated pre-SRS well, without any neurological deterioration, and surgical treatment was performed as scheduled. Median follow-up period was 11.3 months. Local recurrences were found in 3 cases. Local control was noted in 95.7% and 89.3% at 6 and 12 m respectively during follow-up. The median overall survival (OS) and 6 / 12 months OS rate were 17,1 months and 77,8/62,5 %, respectively.  Radionecrosis was present in 3 pts.

Conclusion: Pre-SRS confers excellent cavity local control with very low risk of RN. Pre-SRS confers excellent cavity local control with very low risk of RN.  Optimal dose, technique and  timing  for presurgical irradiation has not been established yet.


Andrey GOLANOV (Moscow, Russia), Elena VETLOVA, Sergey BANOV, Natalia ANTIPINA, Valery KOSTJUCHENKO, Amayak DURGARYAN, Alexandra DALECHINA, Ivan OSINOV
09:00 - 18:00 #17887 - Fractionated stereotactic radiosurgery for brain metastases using Gamma Knife Icon.
Fractionated stereotactic radiosurgery for brain metastases using Gamma Knife Icon.

Treatment of large brain metastases in patients with poor prognosis or declining clinical conditions and treatment of metastases close to critical areas are still a challenge. Fractionated stereotactic radiosurgery (SRS) is one of the options. Gamma Knife treatments are usually delivered in single fractions, however few articles in literature report its use in fractional mode for these conditions.

Between November 2017 and October 2018 11 patients with brain metastases underwent fractionated Gamma Knife radiosurgery in Fondazione Poliambulanza: for seven patients the treatments were fractionated in three or five consecutive days (hypo-fractionated SRS), for four patients in two fractions (staged SRS) separated by and interval of about four/five weeks.

Median volume for large metastases prior to radiosurgery was 11,539 ml (range 7,334 – 26,777 ml), whereas for metastases close to critical areas was 4,549 ml  (range 0,815 – 5,548 ml). Median total margin dose for hypo-fractionated Gamma Knife treatments was 25 Gy (range 21 -.32,5 Gy), median dose per fraction was 7,5 Gy (range 5 – 9 Gy).  Median marginal dose for staged Gamma Knife treatments was 12 Gy (range 12 – 15 Gy) for both first and second fraction.

Results: in the staged SRS group all lesions decreased in volume at the second fraction, no complication or radionecrosis occurred between the two treatments. In the hypo-fractionated SRS group the survival rate is 71%, 57% and 35% at three, sex and nine months, respectively. One patient developed a seizure during recovery, instead in two cases there was an improvement in the clinical conditions at first follow up (3 months).

Conclusions: fractionated Gamma Knife SRS (hypo-fractionated or staged) is a valid and safe option for the treatment of metastases localized in critical sites or for large metastases in which surgery is less indicated.


Alberto FRANZIN (Brescia, Italy), Lodoviga GIUDICE, Cesare GIORGI, Chiara BASSETTI, Oscar VIVALDI, Mario BIGNARDI
09:00 - 18:00 #17828 - HyperArc for stereotactic radiosurgery: comparison of delivery modalities.
HyperArc for stereotactic radiosurgery: comparison of delivery modalities.

Plan quality metrics for four different HyperArc modalities were investigated; two different energy modes 6FFFand 10FFF and different multi-leaf collimators systems, standard 120 leaves and high definition (HD-MLC) 120 leaves.  Twenty metastatic cranial patients treated with HyperArc were retrospectively planned using the Eclipse Treatment Planning System v15.5.

The cohort of patients included a range of patients with two to ten lesions (2.9cc to 26.0cc). Plans included four non-coplanar single isocentre arcs. Plans were optimised using standard objectives to meet clinical constraints based on SRS guidelines. All plans were normalized such that 80% of the highest prescription target volume received the prescribed dose.

Plan quality was evaluated by: volume of the brain receiving 20%,40% and 60% of the maximum PTV prescription for that patient; and median brain dose

All plans met local constraints and were suitable for treatment.

The brain dose was reduced in all plans using 6FFF together with HD MLC.  When compared with 10FFF HD-MLC selection, this was significant statistically at both the 20% and 40% values (p<0.05).  There was no significant variation in brain when comparing the 10FFF HD-MLC plan and 6FFF standard MLC plan, the median dose was reduced with the 10FFF plan.

10FFF plan with the standard MLC was least conformal. The median dose was also higher than the other plan situations, however this was not statistically significant. The number of PTVs did not influence optimal plan selection and plan quality metrics

The use of 6FFF and a HD-MLC provided the optimal solution to provide the sharpest dose gradient and to minimise brain dose.  The disadvantage of 6FFF to 10FFF is that delivery time is reduced from 24Gy to 14Gy per minute which may impact on PTV margins.  Current practice is being reviewed to produce two HD MLC plans at both energies to help determine plan selection.


Suzanne CURRIE (Glasgow, United Kingdom)
09:00 - 18:00 #17802 - Influence of the rotational patient setup errors on the quality of single isocenter SRS-VMAT brain metastases treatments.
Influence of the rotational patient setup errors on the quality of single isocenter SRS-VMAT brain metastases treatments.

Purpose

Stereotactic radiosurgery with VMAT (SRS-VMAT), using a single isocenter, is widely used nowadays for multitarget treatments providing highly conformal dose distributions and rapid dose fall-off outside the target volume. The purpose of this study is to determine the dosimetric effects of rotational errors on target coverage and organs at risk (OARs) in brain metastases cases.

Methods

Anonymized CT datasets of five patients with different number and size of multiple metastases were used. Single isocenter VMAT plans were generated for each patient using four noncoplanar arcs with 6MV FFF x-ray beams and Versa HD linear accelerator in Monaco (Elekta) TPS. Rotational errors of ±0.5°, ±1° and ±2° were simulated by rotating the plan dose distribution around the isocenter. Indices clinically used for plan evaluation were determined for the different degrees of rotational errors and compared with the reference values which correspond to zero rotation/error.

Results

For targets positioned away from the isocenter, rotational errors >1° produce geometric uncertainties greater than 1mm which may influence significantly plan evaluation indices leading to target coverage and conformity index deterioration (>10%).  Dose limits violations and differences >10% occur for Dmax, and D20mm3 for OARs in close proximity to targets. The degree of indices deterioration depends on the degree and direction of the rotational error as well as on target volume and target's distance from the isocenter.

Conclusions

For targets within a short distance from the isocenter, rotational errors of the order of 0.5° are negligible and high quality plans are achieved. In any other case, rotational errors may significant affect plan quality indices.

Acknowledgements

The research work was supported by the Hellenic Foundation for Research and Innovation (HFRI) and the General Secretariat for Research and Technology (GSRT), under the HFRI PhD Fellowship grant (GA. no.74112/2017 ).


Georgia PRENTOU, Andreas LOGOTHETIS, Eleftherios PAPPAS, Efi KOUTSOUVELI, Evangelos PANTELIS, Panagiotis PAPAGIANNIS, Pantelis KARAISKOS (Athens, Greece)
09:00 - 18:00 #17652 - Integrating salvage hypofractionated radiosurgery with low-dose adjuvant bevacizumab for locally recurrent brain metastasis with high dose irradiation previously.
Integrating salvage hypofractionated radiosurgery with low-dose adjuvant bevacizumab for locally recurrent brain metastasis with high dose irradiation previously.

Background

Selection of the appropriate treatment for recurrent brain metastasis (BM) remains uncertain. Recent studies have demonstrated a significant response rate of fractionated stereotactic radiosurgery (FSRS) in locally recurrent glioma. However, radiation necrosis (RN) is a severe complication associated with salvage re-irradiation which may be treated with bevacizumab. The purpose of this research was to evaluate the efficacy and toxicity of FSRS combined with early use of low-dose bevacizumab as a new salvage treatment for locally recurrent BM with high dose irradiation.

Materials and methods

Patients with locally recurrent intracranial metastasis previously treated with SRS or WBRT with SRS were enrolled in this prospective study. The salvage FSRS dose ranged from 9.5 to 29 Gy in two to five sessions with 62–75% isodose line by CyberKnife according to the tumor volume, site, and previous irradiation dose. Bevacizumab was prescribed to all patients within 24 hours after completion of the treatment for four cycles (5 mg/kg, 3-week intervals). Magnetic resonance imaging (MRI), Karnofsky Performance Scale (KPS), adverse events and associated clinical outcomes were recorded. The primary objective of this study was to identify the overall survival after salvage treatment. Secondary objectives included clinical response (KPS), imaging response (MRI)and treatment-related adverse events.

Results

From December 2009 to October 2016, 24 patients were enrolled. Nine received WBRT followed by SRS, and 15 underwent SRS before diagnosed with recurrent BM. The median 1-year overall survival (OS) after salvage SRS was 87.5%. Twenty-three (96%) patients had a positive imaging response within a range of 6 to 22 cm3(median 14 cm3, p= 0.032, paired t-test). Significant clinical improvement was achieved (p<0.05, best KPS paired t-test). Grade 1/2 fatigue was observed in 8 (33%) patients followed by headache, hypertension, and nausea. Grade 3 fatigue and headache occurred in 1 patient. No grade 4 toxicity was observed.

Conclusions

Salvage FSRS with early use of low dose adjuvant bevacizumab treatment showed favorable clinical and radiologic control with manageable toxicity for locally recurrent brain metastasis patients who underwent high dose irradiation previously. The diagnosis of RN and LR after salvage FSRS merit further study.


Xin WANG, Huaguang ZHU (Shanghai, China), Chaozhuang WANG, Jing LI, Wenqian XU, Lei SUN, Li PAN, Jiazhong DAI, Yang WANG, Yun GUAN, Enmin WANG
09:00 - 18:00 #17808 - Machine learning binary classification task for overall survival prediction in patients with brain metastases.
Machine learning binary classification task for overall survival prediction in patients with brain metastases.

The aim of this study was to predict overall survival in patients with brain metastases  after stereotactic radiosurgery and identify the prognostic factors using machine learning (ML) approach.

1023 patients treated with SRS between January 2005 and December 2017 were analyzed. 26 features (clinical, biological and morphological) were selected to develop a prognostic model  to predict overall survival for these patients. The target variable was time from the date of oncological diagnosis to the date of death. The data were divided into two sets: a training dataset and a test dataset. The training dataset consisted of 577 patients with different features, for which the target variable was known. The overall survival classes were: less than 8 months (292 patients), more than 10 months (285 patients). The second class ( OS > 10 months) included 92 patients that were alive at the day of the analysis. Splitting the group of patients on those classes supports class balancing and minimizes overfitting probability. The machine learning technique “Gradient boosting” was used to identify the favorable prognostic factors associated with long term overall survival.  The 5 - folds cross validation technique was performed to estimate the accuracy of the predictive model.

The most significant features were: age at the time of diagnosis, total volume of brain metastases, maximum metastasis volume, time from primary  diagnosis to brain metastases, time from brain metastases to the first radiosurgery. The accuracy of the classification model was 0.81. The accuracy computed from the confusion matrix was 0.80. The predictor had an average area under the curve (AUC) of 0.87.

To classify patients  into risk classes is the important step in making therapeutic decisions. The predictive model demonstrates accuracy of the brain metastases patients classification. Machine learning techniques seem to be a very promising tool for clinical decision making. But the principal challenge and the key ingredient of successful application of ML in radiation oncology  is data collection from the multimodal data sources. ML techniques will be fully integrated in clinic routine only if it combines with modern databases provided routine data collection.


Gleb VAZHENIN, Alexandra DALECHINA (Moscow, Russia), Sergey BANOV, Pavel RYABOV, Valery KOSTJUCHENKO
09:00 - 18:00 #17643 - Mask-based, fractionated radiosurgery for brain metastases using gamma knife icon.
Mask-based, fractionated radiosurgery for brain metastases using gamma knife icon.

Gamma Knife Icon allows mask-based, fractionated brain radiosurgery, as well as standard, frame-based treatment. Leeds was one of the first centres in the world to start using it in December 2015. Between then and December 2017, 58 patients with brain metastases were treated in this way (median age 67, range 27-89). Standardised fractionation was used (either 27Gy in 3 in 64% or 30Gy in 5 in 33%, largely depending on volume). Two patients (3%) had single fractions using a mask to avoid having a frame. Unlike some centres that “stage” fractions with 1-2 week gaps, treatment was given on consecutive working days using a single treatment plan (planning MRI within 72 hours of first fraction).

 

Lung (41%), breast (24%) and gastrointestinal (22%) were the commonest primary tumour sites. The main indication for mask-based treatment was size (in 74%) - median 16cm3, IQR 12.3 - 19.7cm3, maximum 30.4cm3 in this group. Others included re-treatment (14%), eloquent location such as brainstem (9%) or patient choice (3%). Median KPS - 90 (range 70-100). Solitary metastasis in 53% of cases, multiple (range 2-5) in the remainder.

 

Detailed follow up was available for 43 patients. 94% of those on steroids reduced them after treatment. 85% stopped them completely. None had a permanent neurological deficit caused by treatment. 9% developed leptomeningeal disease during follow up. 26% had local failure at a median of 300 days. 40% had changes felt to represent treatment effects but this was only symptomatic in 9%. Only 2% required admission for these (one of which was re-treatment in an eloquent location).

 

Median overall survival was 12.2 months. Survival was not significantly different between the 3 or 5 fraction groups (p=0.74), target volumes greater or less than a 3cm diameter sphere (p=0.32), or total treated volumes greater or less than 20cm3 (p=0.51).


Paul HATFIELD (Leeds, United Kingdom), Gavin WRIGHT, Finbar SLEVIN
09:00 - 18:00 #17907 - Multiple Brain Metastases Radiosurgery with Gantry-Based Linac.
Multiple Brain Metastases Radiosurgery with Gantry-Based Linac.

Purpose 

Evaluate tolerance, toxicity and survival in patients with multiple brain metastases.

Material and Methods

Between Nov'16&Dec'17,24patients were treated with SRS.Frameless Brainlab System was utilized. Treatment planning was performed using Elements TPSv1.5(BrainLab). Patients were positioned on a6D couch. Radiosurgery was given by Novalis Tx accelerator HDMLC-IGRT with ExacTracV6 using 6 MV photons. Early and late toxicities as well as survival were evaluated. Patients with up to 5metastases were compared with te ones with6 or more, and  the ones with a tumor volume<10cc were compared with the rest with>10cc tumor volume. OS from SRS until last follow up or death, and progression-free survival(PFS) from SRS until first brain progression or last follow up, were estimated by the Kaplan-Meyer method.

Results

Mean age:54.2years[10.3-73.9]and mean follow-up8.16 months[3.2-16.6].The mean number of lesions per patient was 7[2-23] while the average volume of irradiated metastases was 1.34 cc[0.02-20.8].The prescribed dose was 22.2Gy[20.0-35.0] in1-5 fractions.5 patients were re-irradiated because of tumor regrowth(22 lesions)or new lesions(12 lesions); Of the24 patients,19 showed no symptoms of early toxicity whereas the remaining 5 presentedG1-2 toxicity .Late toxicity was evaluated in19 patients who survived for more than3 months. Of the 19patients,12did not show any toxicity while the remaining group presented G1-2 toxicity .No differences were found in patients with5 or more metastases regarding the presence or absence of toxicities, or related to fractioning.The overall survival(OS) for the24 patients at6 months was71%, and at one year59%. No differences were found in the OS of patients with five or moremetastases when compared with patients with less than five lesions(Cox-Mantel test, p = 0.806); There were no differences when comparing patients with a total volume of metastases<10cc and ≥10cc(p=0.865). The progression-free survival at6 months was89% and at one year62%. No differences were found in PFS related to the number of metastases(p=0.982) or to the total volume of metastases(Cox-Mantel test, p = 0.296).

Conclusion

Results suggest that irradiation to multiple metastases is safe,showing acceptable toxicity and survival.
If well in literature a detrimental inOS is described with a total tumor volume>10cc, we didn't find these difference.


Pablo CASTRO PENA (Cordoba, Argentina), Daniel VENENCIA, Oscar MURIANO, Lourdes SUAREZ VILLASMIL, Silvia ZUNINO
09:00 - 18:00 #17762 - Neoadjuvant stereotactic radiosurgery for brain metastases; a novel sequencing approach.
Neoadjuvant stereotactic radiosurgery for brain metastases; a novel sequencing approach.

In modern oncology, therapeutic advances have been made in the management of brain metastases. Local therapies such as surgery and stereotactic radiosurgery (SRS), are currently standard of care for patients with oligo-metastatic or symptomatic brain disease. Whilst randomised evidence supports postoperative SRS for optimising local control, this treatment method has known challenges such as accuracy of radiotherapy target delineation, relatively high rate of leptomeningeal disease (LMD) and radiation necrosis (RN). Neoadjuvant radiosurgery (NaSRS) is an emerging sequencing approach with promising results for local control and toxicity. We performed a retrospective review of clinical records of thirteen patients who were treated with NaSRS followed by surgery from May 2017- October 2018. The median follow up was 7.8 months (range 0.4-16.1). The median age was 58.5 (range 45-72). Majority had primary Non-Small Cell Lung Cancer (62%) followed by Melanoma (31%) and Colorectal Cancer (7%).  One patient died of unrelated cause the day after SRS and never had surgery. Two patients (15%) had received whole brain radiotherapy prior to NaSRS. Of the remaining 12 patients, the interval between NaSRS and surgery was 1-20 days (mean 6.5). The most common dose fractionation schedule was 20Gy in 1 fraction and 24Gy in 3 fractions to the covering 80-90% isodose using Linac based SRS technology. Majority of targets were in the supra-tentorial space (80%), with only two patients with cerebellar lesions. At time of last follow up all treated patients (100%) had local control along the surgical cavity on imaging. Five patients (38%) had distant failure within the brain. At date of last follow up 9 patients (70%) were still alive. There was no reported incidence of LMD or RN related to the treated site. One patient developed a cerebral abscess 12 weeks after surgery. No other grade 3 or 4 toxicities were recorded.

Conclusion: Whilst the numbers in this cohort is relatively low and longer follow up is required, the results are promising and supportive of emerging data which suggest that NaSRS is an effective and safe sequencing strategy for select group of patients with brain metastases. The advantages of this approach appear to relate to local toxicity and reduction in leptomeningeal spread when compared with surgery and postoperative SRS. 


Neda HAGHIGHI (Melbourne, Australia), Damien TANGE, Cristian UDOVICICH
09:00 - 18:00 #17767 - Personalized treatment options for patients with large cerebellar metastases by Gamma Knife radiosurgery.
Personalized treatment options for patients with large cerebellar metastases by Gamma Knife radiosurgery.

OBJECTIVE: To report our experience in patients with large cerebellar metastases for single-session, multiple-session or staged Gamma Knife radiosurgery (GKRS); and the evaluation of its efficacy and toxicity.

 

METHODS: From January 2017 to October 2018,826 patients with brain metastases underwent GKRS at our hospital. Among them, 25 patients with cerebellar metastases(maximal diameter≥2cm) were treated with single-session, multiple-session or staged GKRS. Individualized treatment strategy was chosen according to prior treatment history,size and location of tumor, or tumor harboring gene mutation. Dose selection was based on various factors including tumor size, previous history of radiation, or proximity to critical structure nearby. Overall survival (OS) and intracranial progression-free survival (PFS) were measured from the date of brain metastases treated by GKRS.

 

RESULTS: The median age was 64 years (range 42-78 years), and the median Karnofsky performance status (KPS) scoce was 70. Thirteen patients (52%) had non-small cell lung cancer. Fourteen patients (56%) underwent treatment with hypofractionated GKRS or staged GKRS, whereas 11 patients (44%) underwent single session GKRS. The median OS was 10.9 months (95% CI: 6.4-17.7). For staged treatment, median tumor volumes at the first and second GKRS were 11.9 cm3(range 3.1- 30.2 cm3) and 9.3 cm3 (range 1.7-26.1 cm3). Twenty patients died, and five patients were still alive at the time of the last follow-up. Sixteen patients (80.0%) died from systemic causes, two (10.0%) from neurologic causes, and two (10.0%) of unknown causes. Radiation necrosis developed in two cases 8.0%) during the follow-up period, one case with CTCAE grade 2 and one case with CTCAE grade 3.

 

 

CONCLUSIONS: Fractionated and staged GKRS are safe and effective options for large, unresectable cerebellar metastases. Prospective studies are necessary to validate the findings in this study. 


Ying TONG, Ping LAN (Hangzhou, China)
09:00 - 18:00 #17902 - Plan Quality Comparison of HyperArc and Elements Platforms for Single Isocenter Multiple Metastasis Single Isocenter Radiosurgery.
Plan Quality Comparison of HyperArc and Elements Platforms for Single Isocenter Multiple Metastasis Single Isocenter Radiosurgery.

Background: Radiosurgery to multiple intracranial metastases is a rapidly increasingly employed treatment modality in an era of increasing survival for patients with stage IV cancer.  Several single-isocenter treatment planning solutions have been developed for planning efficient radiosurgery to multiple metastases. Two of the most advanced are the HyperArc (Varian Medical Systems) VMAT-based and Elements (BrainLab) DCA-based platforms. Each is designed to streamline and optimize complex radiosurgical treatment planning.

Methods: Fifteen multiple metastases (n = 4 - 10) radiosurgery cases were planned in HyperArc (HA) and Elements (MME) at institutions with leading expertise in each’s respective treatment planning and delivery (UAB and Thomas Jefferson University). All plans had a single isocenter and used a Varian linac equipped with high definition MLC. HA plans were generated with either both two and four non-coplanar VMAT arcs with 10MV flattening filter free (FFF) beam.  MME plans used four to nine non-coplanar dynamic conformal arcs and a 6MV FFF beam.  Prescription doses ranged from 14 to 24 Gy in a single fraction. Each target was planned to receive the prescription dose to at least 99% of target volume. Plans were evaluated according to standard radiosurgery metrics including conformity index (RTOG and Paddick) for each target, surrogate radionecrosis risk (V12Gy & V8Gy), and low dose spill (V5Gy and mean brain dose). Plan modulation and delivery times were also compared.

Results:  Conformity, V12Gy, V8Gy, V5Gy, and mean brain dose were favorable for HA plans (either 2 arc or 4 arc) for all cases (p<0.001 for all comparisons). 4-arc HA plans were overall superior to 2-arc HA plans for all metrics except for mean dose, where they were similar, and in delivery time, where they required an additional sixty seconds of delivery.

Conclusion: Both HA and MME were able to create clinically acceptable intracranial radiosurgery treatment plans. However, for single-isocenter linac-based multiple metastasis intracranial radiosurgery, VMAT-based HA facilitated favorable conformity, V12Gy, V8Gy, V5Gy, and mean brain dose compared to DCA-based MME plan.  


Rodney SULLIVAN, Evan THOMAS (BIRMINGHAM, USA), Richard POPPLE, Haisong LIU, James MARKERT, David ANDREWS, Wenyin SHI, Yan YU, John FIVEASH
09:00 - 18:00 #17817 - Post metastasis srs delayed radiation change mimicking recurrent disease: the ghost lesion.
Post metastasis srs delayed radiation change mimicking recurrent disease: the ghost lesion.

Post gamma knife SRS for metastatic disease can result in localized delayed recurrent gadolineum enhancement, many months to years after the initially treated lesion had completely resolved. If not recognized as delayed radiation change at the primary treatment site, this can easily be mistaken for recurrent malignancy and therefore initiate recurrent un-necessary treatement, including SRS.


Stephen HOLMES (honolulu, USA)
09:00 - 18:00 #17871 - Preoperative Gamma Knife radiosurgery for recurrent brain metastases.
Preoperative Gamma Knife radiosurgery for recurrent brain metastases.

Introduction:

Whole brain radiation (WBRT) impairs neurocognition. Resection of brain metastases (BM) without additional radiation therapy yields a high local failure rate. Postoperative stereotactic radiosurgery (SRS) maximizes local control while minimizing the risk of neurocognitive deterioration. Drawbacks of postoperative SRS include uncertainty in target delineation, potential delay in the administration of SRS and intraoperative risk of tumor spillage. Preoperative SRS might address these potential drawbacks. We present our experience with preoperative Gamma Knife radiosurgery (GKRS) for recurrent BM.

Material and Methods:

Between June 2016 and January 2019, 16 patients (male 5, female 11; mean age 62 years (range 21-79 years) underwent preoperative GKRS. Previous treatments were GKRS (9 patients), SRS (4 patients), WBRT (2 patients), resection and postoperative SRS (1 patients). Primary tumors were NSCLC (9 patients), SCLC (2 patients), melanoma (2 patients), breast cancer (2 patients), oesophageal cancer (1 patients). A dose of 18-20 Gy, was prescribed to the isodoseline (mean 44,7%; range 40-53%) covering 99-100% of the target. All patients had follow-up in our center with MRI scan as long as clinical meaningful.

Results:

Mean follow-up was 9,8 months (range 0,5-31 months). In all patients, the resection was performed as scheduled on the next day following preoperative GKRS. There were 2 surgical complications: seizures immediately postoperatively and 1 patient needed admission to intensive care because of extensive edema around the resection cavity. Two patient developed leptomeningeal disease after 3 and 4 months respectively. Six patients developed a local / marginal recurrence after median 6,8 months (range 2,0-14 months). Six patients died after median 4,3 months (range 0,5-24 months) due to leptomeningeal disease (2 patients), local recurrence (1 patients), systemic disease (1 patient), pneumonia (1 patient). Cause of death was unknown in 1 patient. 

Conclusion:

Preoperative GKRS for recurrent brain metastases is well tolerated. A randomized trial comparing preoperative GKRS versus postoperative SRS is warranted.


Patrick HANSSENS (Tilburg, The Netherlands), Guus BEUTE, Suan Te LIE, Liselotte LAMERS, Jeroen VERHEUL, Bram VAN DER POL, Diana GROOTENBOERS, Hilko ARDON, Hazem AL-KHAWAJA, Wouter VERFAILLIE, Wim DE JONG, Jannie SCHASFOORT - VAN DEN TILLAART
09:00 - 18:00 #17889 - Prescription Estimation of Postoperative Brain Metastasis Stereotactic Radiosurgery (SRS) with Dose Energy Density Distribution Index (DEDDI).
Prescription Estimation of Postoperative Brain Metastasis Stereotactic Radiosurgery (SRS) with Dose Energy Density Distribution Index (DEDDI).

Introduction: There were three options of clinical approach for brain metastasis patient. The first is the execution target resection by neurosurgeon, the second is the application of radiosurgery only, and the third is the combination of first and second procedures, which could be at different temporal sequence selection by alternating the order of resection surgery and stereotactic radiosurgery. However, the difference between these two sequences could require different dose prescriptions. In this study, the prescription dose distribution effect was analyzed by a dose energy density distribution index. Method and Materials: The selected patient was underwent the resection of the brain metastatic tumor from prostate cancer. The original target size showed in MRI with contrast was about 2cm in diameter.  It is assumed that the margin between 1 cm radius and 2cm radius around the target before resection was considered to be irradiation region for postoperative SRS. The prescription of residual region after resection was treated as isotropic shrink from the original tumor target, which is at the level of 2cm in diameter. And the geometric comparison was done by registration of image sets at different temporal point. The dose energy density distribution index (DEDDI) was computed to reach the prescription requirement at the scenario of treating without target resection. And DEDDI was defined to be dose rate with energy spectrum to reflecting the dose delivery pattern including kinetic temporal factor.  The variation between these two approaches was also estimated with geometric perturbation analysis in 1mm scale step. Results: For the selected plan, including the resection target and volumes with prescription range from 24Gy to 15Gy, the values of DEDDI ranged from 0.43cGy/s/CC to 0.179cGy/s/CC and excluding the 2cm target, the values of DEDDI ranged from 8.99cGy/s/cc to 0.05cGy/s/CC; Based on the postoperative plan, consider the volumes with prescription of 18Gy to 10Gy, the values of DEDDI ranged from 0.33cGy/s/CC to 0.221cGy/s/CC. Plotting these two curves in same coordinate system, the cross point was at about 17Gy. Conclusion: Dose Energy Density Distribution Index could be applied to estimate the prescription for postoperative brain metastatic target. Further prescription improvement could be done by validation with clinical outcome data.


Kaile LI (Hagerstown, MD, USA), Arnold ABLE
09:00 - 18:00 #17849 - Radiation therapy and cognitive functioning: long term impact on patients with brain metastasis.
Radiation therapy and cognitive functioning: long term impact on patients with brain metastasis.

Introduction: Although in recent years the interest in impact of radiation therapy (RT) on neurocognitive functioning and quality of life (QoL) has become one of important issues in research and when choosing treatment for patients with brain metastases, the impact for long-term survivors  is still not clear. The main aim of this study is therefore to evaluate long-term neurocognitive and QoL outcomes in patients treated with RT for brain metastases.

Methods: Patients had a neurocognitive and QoL evaluation before RT, 3, 6 and 12-45 months after RT. A neurocognitive battery of tests  was used for neurocognitive and EORTC QoLC30 and BN20 for QoL evaluation. Mini mental state examination (MMSE) and Rey Auditory Verbal Learning Test (RAVLT) were considered in this work. Differences between baseline and follow up scores were analyzed with ANOVA test.

Results: 34 patients were enrolled (median age 52). Most of them had breast cancer as primary tumor (55%). 60% had no neurological symptoms at diagnosis. 9% of patients received whole brain RT (median dose 30Gy)and 91% had stereotactic RT (median dose 21Gy). During treatment no acute toxicities were reported.

33 patients completed baseline evaluation, 26 at 3 months, 19 at 6 months  and 10 between 12-45 months.

Baseline MMSE and RAVLT indicated no neurocognitive deficit in 97% and 74% of patients. Global QoL was 37.37, mean BN20 score was 24.

Comparison with follow-up scores showed no significant changes in MMSE (p = 0.16). Both immediate and delayed recall in the RAVLT significantly changed (p<0.01) with marked increase of scores up to 6 months. No significant changes over time were found in Global QoL and BN20 (p=0,24; p=0,55).

Conclusions. There were no changes in global neurocognitive functioning in long-term survivors. Specifically for verbal memory statistically significant improvement was observed. QoL did not change through the time. 


Milda CERNIAUSKAITE, Valentina PINZI (Milan, Italy), Michela BUGLIONE, Cecilia IEZZONI, Laura FARISELLI
09:00 - 18:00 #17761 - RADIONECROSIS IN PATIENTS RECEIVING STEREOTACTIC RADIOSURGERY FOR BRAIN METASTASES.
RADIONECROSIS IN PATIENTS RECEIVING STEREOTACTIC RADIOSURGERY FOR BRAIN METASTASES.

Aim: To examine factors contributing to radiation necrosis (RTN) in patients receiving stereotactic radiosurgery (SRS) for brain metastases

Methods: Single institution series of 51 consecutive patients with intracranial metastases undergoing SRS.  Follow-up imaging was on standard protocol of MRI 6 weeks post-treatment then 3 monthly thereafter.

Results: Median age at diagnosis 59 years (range 24-86) with median survival of 19.4 months (range 0.9-53.4).  Demographics include 56.9% female, 43.1% male, and 9.8% (n=5) had brain metastases at the time of initial diagnosis.  Histopathology included: lung 37.3%, breast 17.6%, melanoma 11%, colorectal 5.5%, and other malignancy 25.5% (adenoid cystic, sarcoma, prostate, transitional cell, and renal cell).  Craniotomy was performed in 80% (N=41) of patients prior to SRS for at least one intracranial lesion.  De novo SRS was delivered to 82 metastases (85%) and cavity SRS was delivered in 65 cases (44%)

Rate of RTN was 20% (n=10). Diagnosis was based on histopathology in 6 patients, MRI and FET-PET in 1 patient, and MRI alone in 3 patients.  Patients with RTN had the following features: 50% (N=5) had concurrent systemic therapy (doublet therapies including Herceptin and pertuzumab, dabrafenib and trametinib, or androgen deprivation therapy).  One patient with RTN also had whole brain radiotherapy to a dose of 30Gy/10# with a boost of 6Gy/3# to the tumour bed 11 months prior to SRS.   Of the patients with RTN 60% (N=6) were asymptomatic and 40% (N=4) were symptomatic. Decompression surgery was needed in 4 patientsfor symptomatic relief.

Median survival of patients with RTN was 37.5 months (range 9-53) compared to 10.4 months (range 0.9-53.4) in patients without necrosis (P=0.0391).

Conclusion: RTN occurred in 20% of included patients in this series. The presence of necrosis may be prognostic for improved median survival. Further analyses are planned to investigate other contributing factors.


Philippa ELL (Sydney, Australia), Yael BARNETT, Peter EARLS, Louise EMMETT, Michael RODRIGUEZ, Cecelia DE GZELL
09:00 - 18:00 #17881 - Radiosurgery for Brain Metastases: Multicentric Retrospective Analyses.
Radiosurgery for Brain Metastases: Multicentric Retrospective Analyses.

Background and Objectives

Stereotactic radiosurgery (SRS) in brain metastases is a standard strategy to delay or avoid whole-brain irradiation (WBRT) and its associated toxicities. This multicentric retrospective study analyzes results with linear accelerator (LINAC)-based SRS in brain metastasis.

 

Material and Methods

Between January 2016 and November 2018, 355 brain metastases in 109 patients were treated with SRS. All treatments were delivered using a stereotactic LINAC-based SRS. We evaluated toxicity using the common terminology Criteria for Adverse Events v4.0 (CTCAE), survival and local control.

 

Results

109 patients had a median of 3 lesions (1-20). The median dose prescribed to the PTV margin for SRS was 24 Gy (18-30) in 3 fractions (1-5). Median follow-up was 10 months. Distribution by histology 44% lung, 27% breast,10% melanoma, 6%renal, 13% others. Local control (LC) rate was 95%. Overall survival rates were 80%, 60% and 49% at 3, 6 and 12 months respectively with a median OS of 9 months. Adverse events occurred in 60% of the patients, G1 headache being the most frequent symptom and we observed only 5% G2 brain edema that resolved with steroids.

 

Conclusion

In this retrospective, multicentric on radiosurgery for brain metastasis, we conclude that LINAC-based SRS is an effective and well tolerated treatment strategy in patients with brain metastases.


Lucas CAUSSA (Córdoba, Argentina), Leticia ALVARADO, Ofelia PEREZ CONCI, José Máximo BARROS, Jorge CHIOZZA, Ignacio SISAMON, Juan GALARRAGA, Sebastián PIAGGIO, Daniel DAVALOS, Diego FERNANDEZ, Egle AON, Diego FRANCO, Edgardo GARRIGO, Caroline DESCAMPS, Enrique HERRERA, Emilio MEZZANO, Gerardo Gabriel HEINRICH, Maria Fernanda DIAZ VAZQUEZ, Gustavo FERRARIS
09:00 - 18:00 #16747 - Re-irradiation in recurrent high-grade gliomas: A systematic analysis of treatment technique with respect to survival and radionecrosis outcomes.
Re-irradiation in recurrent high-grade gliomas: A systematic analysis of treatment technique with respect to survival and radionecrosis outcomes.

Background 

Re-irradiation may be considered for select patients with recurrent high-grade gliomas (WHO Grade III and IV). Treatment techniques include conformal radiotherapy employing conventional fractionation, hypofractionated stereotactic radiotherapy (FSRT), and single-fraction stereotactic radiosurgery (SRS). 

Methods

A systematic review was performed to identify relevant articles pertaining to re-irradiation of recurrent high-grade gliomas from 1992 to 2018. A population-weighted, pooled multiple regression analysis of publications was performed to evaluate the relationships between re-irradiation technique and median overall survival (OS) and radionecrosis outcomes. 

Results 

Seventy-nine published articles were analyzed, yielding a total of 3738 patients. Across all studies, initial treatment was external beam radiotherapy to a median dose of 60 Gy in 30 fractions, with or without concurrent chemotherapy. On multivariate analysis, there was a significant correlation between OS and radiotherapy technique after adjusting for age, re-irradiation biologically equivalent dose (EQD2), interval between initial and repeat radiotherapy, and treatment volume (P < .0001). Adjusted mean OS was 12.1 months (95% CI, 11.8–12.4) after SRS, 9.9 months (95% CI, 9.4–10.3) after FSRT, and 9.0 months (95% CI, 8.6–9.4) after conventional fractionation. There was also a significant association between radionecrosis and treatment technique after adjusting for age, re-irradiation EQD2, interval, and volume (P < .0001). Adjusted radionecrosis rates were 7.1% (95% CI, 6.6–7.7) after FSRT, 6.2% (95% CI, 5.6–6.6) after SRS, and 1.1% (95% CI, 0.5–1.7) after conventional fractionation. A greater interval between initial and repeat radiotherapy was associated with improved OS (0.25 month greater OS per month interval) (p<0.0001) and decreased RN rate (reduction of 0.23-0.48% per month interval) (p<0.0001).

Conclusions

The published literature suggests that OS is highest after re-irradiation using SRS, followed by FSRT and conventionally fractionated radiotherapy. Whether this represents superiority of the treatment technique or an uncontrolled selection bias is uncertain. The risk of radionecrosis was highest in FSRT followed by SRS and conventional radiotherapy however was acceptably low for all modalities overall. Re-irradiation is a feasible option in appropriately selected patients.


Mihir SHANKER (Brisbane, Australia, Australia), Benjamin CHUA, Catherine BETTINGTON, Matthew FOOTE, Mark PINKHAM
09:00 - 18:00 #17667 - Retrospective audit of the first 10 patients treated with SRS for multiple brain metastases: comparison of multi-isocentres forward planned and mono-isocentre inverse planned techniques.
Retrospective audit of the first 10 patients treated with SRS for multiple brain metastases: comparison of multi-isocentres forward planned and mono-isocentre inverse planned techniques.

The JLGK0901 study demonstrated that stereotactic radiosurgery (SRS) without whole brain radiotherapy in patients with 5-10 brain metastases is non-inferior to that in patients with two to four brain metastases. Based on this result, our centre recently introduced SRS for patients with limited volume multiple brain metastases.

Currently, we plan SRS treatment with the Brainlab iPlan software which uses forward planned conformal static arcs (CSAT). Brainlab Elements planning software uses a set of multiple dynamic conformal arcs (DCAT) to calculate an inverse plan which targets up to fifteen lesions at once with a single isocentre.  Planning time is reduced from days to a matter of hours.

Materials: We performed a comparison of the multi-isocentres and mono-isocentre dosimetry for the first 10 patients that had 4 or more brain metastases (total volume <15cc). To assess plans, the Inverse Paddick Conformity Index (CI) and V12Gy dose-clouds for every treated lesion were calculated and compared as well as mean brain dose. Estimated treatment delivery times were also calculated.   

Results: Overall CIs and V12Gy of 49 treated metastases from 10 eligible patients were analysed. Mean forward planned CSAT CI was 1.62, while the mean inverse planned DCAT CI was 1.40. Mean mono-isocentric CI was superior for every patient. There was no significant difference in the V12Gy dose cloud between the plans: 2.15cc for forward planned vs 2.08cc for inverse planned. Mean brain dose was slightly higher for the mono- versus the multi-isocentric technique: 1.66Gy vs 1.46Gy, respectively. Mean estimated overall treatment delivery time was 6 times longer for multiple isocentres compared to a single isocentre. 

Conclusions: Inverse planned mono-isocentric DCAT SRS can produce at least a comparable dosimetry relative to multi-isocentric CSAT. It is expected to enhance patient experience due to its shorter treatment delivery time.  Adequate corrections to avoid rotational errors are required.


Natalia MITINA (Brisbane, Australia), Yurissa IKEDA, Emma MARRINAN, Jessica CARUSO, Joanne MITCHELL
09:00 - 18:00 #17663 - Stereotactic radiosurgery for the treatment of esophageal carcinoma brain metastases.
Stereotactic radiosurgery for the treatment of esophageal carcinoma brain metastases.

Object:

The authors evaluated the results of stereotactic radiosurgery (SRS) for the treatment of metastatic brain tumors from esophageal carcinoma.

Methods:

We retrospectively analyzed the clinical characteristics and treatment outcomes in 20 patients with metastatic brain tumors from esophageal carcinoma who underwent SRS at the First Affiliated Hospital, Zhejiang University between July 2011 and February 2015.  

Results:

Twenty patients (24 SRS procedures) of a total of 87 tumors underwent Gammaknife SRS. Tumor histologies were adenocarcinoma in 6 patients (30.0%), squamous cell carcinoma in 14 patients (70%). The median age was 65 years (range 58–73). Eleven patients (55%) presented with multiple metastases (range 2–11), and Nine patients (45%) presented with a single metastasis. The median tumor volume was 0.55 cm3 (range 0.004–44.64 cm3) . No complications related to radiosurgical treatment were identified. The local tumor control rate in this group was 94.2 %. The median marginal dose prescribed was 18 Gy(12–22 Gy). The median survival time from the diagnosis of esophageal cancer was 21.5 months and the median survival from SRS was 16 months. A higher Karnofsky Performance Scale (KPS ) at the time of procedure was associated with an increased survival (p = 0.003). After SRS, four patients had subsequent SRS(one for boost therapy, three for new metastatic deposits), One patient underwent craniotomy due to tumor progression. Of the 19 patients who have died, 17 (89.5%) succumbed to systemic disease progression and 2 (10.5 %) neurologic deaths .  

Conclusion:

SRS is an effective and minimally invasive treatment that can prolong survival. Accordingly, SRS could be used as the initial treatment modality, if possible, even in patients with multiple metastases.


Qingsheng XU (Hangzhou, China), Ying TONG
09:00 - 18:00 #17743 - Stereotactic radiosurgery in 1-5 fractions for brain stem metastases: radiobiologic rationale and logistics informing clinical practice.
Stereotactic radiosurgery in 1-5 fractions for brain stem metastases: radiobiologic rationale and logistics informing clinical practice.

Background: Radiotherapy (RT) is often the definitive treatment for brainstem metastases (BSM), and stereotactic radiosurgery (SRS) offers potential advantages over large volume, conventionally fractionated RT. Achieving intracranial control of BSM without causing symptomatic RT-induced inflammation is key to realizing the clinical utility of SRS. The optimal radiosurgical dose-fractionation with the broadest therapeutic window for BSM is unknown.

Materials/Methods: A retrospective review of brain metastases (BM) treated with single fraction SRS or hypofractionated SRS (HF-SRS) in 2-5 fractions using Novalis Tx or Truebeam STX technology between 2012 and 2016 with planning target volume (PTV) overlap of the brainstem was performed. Simultaneous treatment of other BM and prior BM treatment was permitted. Comparison of continuous variables using Kruskal-Wallis test was performed. The imputed balance of tumor control versus potential toxicity for these cases, based on a simple radiobiologic model, is presented.

Results: 98 courses of SRS/HF-SRS among 87 patients met inclusion criteria. The median age and KPS at SRS/HF-SRS was 62 and 80, respectively. Lung (54%), breast (19%), melanoma (14%), and kidney (7%) were the most common primary tumors. Prior treatments included craniotomy (24%), whole brain RT (30%), and prior SRS/HF-SRS (28%). For the BSM, 42 (43%) and 56 (57%) received SRS and HF-SRS, respectively. The most common technique was volumetric modulated arc therapy with a median of 4 arcs. The number of BM treated simultaneously was higher for SRS than HF-SRS (median 4 vs 2, p<0.01). The BSM PTV was larger for HF-SRS than SRS (median 3.6 vs 0.5cm3, p<0.01). The total PTV of all BM was larger for HF-SRS than SRS (median 8.6 vs 3.1cm3, p<0.01). The prescribed dose/fraction was higher for SRS than HF-SRS (median 15 vs 5 Gy, p<0.01). The prescribed total dose was higher for HF-SRS than SRS (median 25 vs 15 Gy, p<0.01). The maximum brainstem dose was higher for HF-SRS than SRS (median 26.6 vs 12.7 Gy on DVH, p<0.01). There was no difference in overall survival (median 7.4 mo SRS vs 5.8 mo HF-SRS, log-rank p=0.19).

Conclusions: SRS/HF-SRS can conformally treat BSM simultaneously with other BM, acknowledging the sensitivity of this eloquent area to RT-induced toxicity. HF-SRS appears to offer a benefit in broadening the therapeutic window for BSM treatment.


Corbin JACOBS (Durham, NC, USA), Kehali WOLDEMICHAEL, Zhanerke ABISHEVA, Jihad ABDELGADIR, Elizabeth HOWELL, Cosette DECHANT, Scott FLOYD, Jordan TOROK, Justus ADAMSON, Peter FECCI, John KIRKPATRICK
09:00 - 18:00 #17668 - The role of adaptive hypofractionated gamma knife radiosurgery in the acute management of brainstem metastases.
The role of adaptive hypofractionated gamma knife radiosurgery in the acute management of brainstem metastases.

Background:

Intrinsic brainstem metastases are life threatening neoplasms requiring prompt and effective intervention. Microsurgery is often not indicated and systemic treatments are deemed ineffective. In the context of radiation therapy, adverse radiation effects (ARE) remain a major concern. A dose adaptive, image-guided, gamma knife based procedure termed as Rapid Rescue Radiosurgery (RRR) offers the possibility of prompt tumor ablation and sustained local control while reducing the risk of ARE-evolvement. We report the results of RRR applied on a group of patients with this particular type of neoplasm.

Methods:                                                      

8 patients with 9 brainstem metastases, underwent three (3) separate, dose-adapted, MRI-guided, Gamma Knife radiosurgery (GKRS) procedures over 7 days. We performed a retrospective analysis of post-RRR effects which included tumor volume dynamics, local recurrence and ARE-development under the period of treatment and at least 6 months after treatment completion.

Results:

Mean peripheral doses at GKRS 1, GKRS 2 and GKRS 3 were 7.4 Gy, 7.7 Gy and 8.2 Gy (range 6-9 Gy) set at the 35-50% isodose lines. Mean tumor volume reduction was -15% between GKRS 1 and GKRS 3 and -56% at first follow-up (usually 4 weeks after GKRS 3). Mean survival from GKRS 1 was 13 months. 4 patients developed radiological signs of ARE but remained next-to asymptomatic. 2 patients were still alive (10 and 23 months from GKRS 1) at the time of paper submission. 1 patient experienced a local recurrence 34 months after treatment; he died 4 months later of both intra- and extracranial disease. The remaining five cases succumbed to systemic disease progression without neurologic deficit.

 

Conclusions:

In this group of patients, RRR proved effective in the management of brainstem metastases in next-to emergency settings achieving rapid tumor volume decrease, rescue of neurological function, limited ARE and sustained response. Yet, distant failure remains a problem. To optimize RRR-treatments, immune-mediated mechanisms aiming to synergize and expand the effects of radiation to distant sites are necessary.


Georges SINCLAIR, Georges SINCLAIR (Reading, UK, United Kingdom), Hamza BENMAKHLOUF, Heather MARTIN, Markus MAEURER, Markus MAEURER, Mustafa Aziz HATIBOGLU, Ernest DODOO, Ernest DODOO, Georges SINCLAIR
09:00 - 18:00 #17670 - The role of adaptive hypofractionated gamma knife radiosurgery in the acute management of fourth ventricle compression due to brain metastases.
The role of adaptive hypofractionated gamma knife radiosurgery in the acute management of fourth ventricle compression due to brain metastases.

 

Background:

20-30% of all intracranial metastases are located in the posterior fossa. The clinical evolution hinges on factors such as tumour growth dynamics, local topographic conditions, performance status and prompt intervention. Fourth ventricle (V4) compression with secondary life-threatening obstructive hydrocephalus remains a major concern, often requiring acute surgical intervention. We have previously reported on the application of adaptive hypofractionated Gamma Knife Radiosurgery in the acute management of critically located metastases, a technique coined by us Rapid Rescue Radiosurgery (RRR). We report the results of RRR in the management of posterior fossa metastases and ensuing V4 decompression.

Case description:

Four (4) patients with V4 compression due to posterior fossa metastases were treated with RRR by means of three (3) separate gamma knife radiosurgical sessions (GKRS) over a period of seven days. Mean V4 volume was 1.02 cm3 at GKRS 1, 1.13 cm3 at GKRS 2 and 1.12 cm3 at GKRS 3. Mean tumor volume during the week of treatment was 10 cm3 at both GKRS 1 and 2, and 9 cm3 at GKRS 3. On average, we achieved a tumor volume reduction of 52% and a V4 size increase of 64% at first follow-up (1 month after treatment completion). Long term follow-up showed continued local tumour control, stable V4 volume and absence of hydrocephalus.

Conclusion:

For this series, RRR was effective in terms of rapid tumour ablation, V4 decompression, and limited toxicity. This surgical procedure may become an additional tool in the management of intractable posterior fossa metastases with underlying V4 compression. More studies involving larger number of patients are warranted.


Georges SINCLAIR, Georges SINCLAIR (Reading, UK, United Kingdom), Georges SINCLAIR, Hamza BENMAKHLOUF, Mustafa Aziz HATIBOGLU
09:00 - 18:00 #16702 - Tumor control and survival in patients with ten or more brain metastases treated with stereotactic radiosurgery: a retrospective analysis.
Tumor control and survival in patients with ten or more brain metastases treated with stereotactic radiosurgery: a retrospective analysis.

Object: 
To assess tumor control and survival in patients who were treated with stereotactic radiosurgery (SRS) for 10 or more metastatic brain tumors. 

Methods: 
Patients treated with SRS for 10 or more total brain metastases at this institution between March 2014 and April 2018 were retrospectively identified. Patient records were reviewed for clinical follow-up data, and post-treatment magnetic resonance imaging (MRI) studies were used to assess tumor control. For tumor control studies, patients were separated into two groups: those who received treatment for 10 or more synchronous metastases and those who received several treatments for 10 or more metachronous lesions. Tumor control was then assessed at intervals of three, six, and nine months. Overall survival was calculated from the first SRS treatment date. The Kaplan-Meier method was used to fit survival curves for the data, and log-rank and Cox proportional-hazards regression were employed to analyze the influence of several variables.

Results: 
Fifty-five patients were treated for 10 or more total brain metastases with SRS. On average, patients were treated for a total of 17.5 metastases, with a median of 10 metastases treated per encounter. Forty patients received synchronous treatment, while 15 patients received metachronous treatment. Median overall survival was 10.9 months. Cox proportional-hazards analysis revealed a significant association between patients receiving larger brain volumes irradiated with 12 Gy and decreased overall survival (p=0.0406); however, significance was lost on multivariate analysis. Among patients who received synchronous treatment for 10 or more metastases, the median percentage of tumors controlled was 100%, 91%, and 82% at 3, 6, and 9 months, respectively. Among patients who received metachronous treatment for 10 or more metastases, the median percentage of tumors controlled after each SRS encounter was 100% at all three time points. 

Conclusions: 
SRS can be used to treat patients with 10 or more total brain metastases with an expectation of tumor control and overall survival that is equivalent to that reported for patients with four or fewer tumors. Development of new metastases leading to repeat SRS is not associated with worsened tumor control or survival. Survival may be adversely affected in patients having a higher volume of normal brain irradiated.


Ehrlich MATTHEW (Lake Success, NY, USA), Jonathan KNISELY, Jenghwa CHANG, Xin QIAN, Anuj GOENKA, Elliot SCHUFF, Michael SCHULDER
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P10
09:00 - 18:00

EPOSTER - 10 Physics
Electronic Poster displayed from June 9 to June 13

09:00 - 18:00 #17763 - A validation method for SF QA through pinpoint ionization chamber measurement.
A validation method for SF QA through pinpoint ionization chamber measurement.

Introduction: Quality Assurance (QA) is a fundamental stage in radiotherapy treatment (RT), but When it comes to small-field (SF) irradiation, common in Stereotactic Radiation Surgeries (SRS), there is a lack of recommendations. Not until recently, with TRS483 (IEAE, September 2017), there was no document guiding SF-QA in a dosimetric perspective. The services that performed dosimetric QA based their methodology in articles published independently. In Brazil, the scarcity of guidelines is even more evident. Objective: We propose a method to implement dosimetric IF-QA of delivered dose calculated by the Treatment Planning System (TPS) and present cases of validation based on comparison to the CLINAC commissioning tables. Methodology: A cross-calibration was performed between two types of ionization chambers (IC), a referred-laboratory calibrated Farmer IC and a Pinpoint IC, in a standard reference field. The correction factor was obtained. The values for the correction by beam quality for small fields were then determined through the measure of TPR20,10 for different sizes of irradiation fields. After that, six SRS plans were reviewed, with treatment fields irradiating the Pinpoint CI. Readings were adjusted by the obtained KQ factors depending on TPR20,10, and the corrections of influence quantities were considered. Results: The values of TPR20,10 are coherent with those presented on TRS483, with a maximum difference of 2,5% for an irradiation field 4x4cm2. Among the reviewed treatment plans, the difference between the dose calculated by the TPS and the measured dose corrected by the factors varied from -2,7% to 1,3%. Discussion: The proposed methodology resulted in close values of estimated dose by the TPS and dose measured by the Pinpoint CI. The data of TPR20,10 and dose for small fields should be verified by Monte Carlo simulations for a more reliable validation. Conclusion: The proposed methodology is feasible, improving SRS treatment security through more reliable SF-QA.


André EZEQUIEL LÔBO DE ABREU, Tiago BATISTA OLIVERA (Ipatinga/MG, Brazil), Gerson Hiroshi YOSHINARI JR., Mariana PARANHOS ALVARENGA, Harley FRANCISCO DE OLIVEIRA
09:00 - 18:00 #17832 - Assessment of difference in dose volume histogram bin calculation for the new version of gamma knife treatment software.
Assessment of difference in dose volume histogram bin calculation for the new version of gamma knife treatment software.

Introduction: In the latest Gamma Knife planning software, Gamma Plan (GP) version 11.1.1, dose volume histograms (DVH) are now binned in 0.1 % at the measurements window compared to 0.5 % as it was before on the previous versions. The effect of this improved calculation can potentially change the prescription dose method especially for centers like ours where the 100% prescription coverage was usually defined using DVH from the measurement window. In this study we compared plans with 99.5 % coverage versus 99.95% coverage using the measurement window. The difference may not look large but it may potentially affect our goal for coverage in order to standardize our planning.

 

Methods: A total of 20 clinically used plans were created with 99.5% and 99.95% coverage by adjusting only the prescribed isodose lines (IDL) which was our standard clinical practice to achieve 100% coverage. Difference between both types of plans were evaluated using dosimetric treatment parameters as a voxel minimum dose, voxel maximum dose, maximum dose of 0.035 cm3 target volume dose, and a mean target dose.  The treatment plans differences in selectivity and gradient indexes were also studied.

 

Results: The increase for a voxel minimum dose, voxel maximum dose, maximum of 0.035 cm3 target volume dose and a mean target dose were in the range of 3 – 6% for 99.95 % coverage of the target compared with 99.5% of coverage.  As a result, by trying to cover an additional 0.45% of the target, we are effectively increasing the dose to the target for the same prescription. For instance, 15 Gy with 99.95% coverage could be more like 16 Gy with 99.5% coverage in terms of similar minimum, maximum and mean doses. Selectivity for the plans with 99.95% coverage decreased, but the gradient index improved.

 

Conclusion: The coverage goal will need to account for the difference in how DVHs are displayed in with the new GP update. This change may result in a clinically significant dose adjustment and needs to be considered for clinical implications and comparison with treatments delivered using old versions of GP.


Gennady NEYMAN (Cleveland, USA), Peng QI, Jennifer YU, Erin MURPHY, Gene BARNETT, John SUH, Samuel CHAO
09:00 - 18:00 #17563 - CBCT-guided cranial radiosurgery validation process by end-to-end test with TLD and film in a SRS head phantom.
CBCT-guided cranial radiosurgery validation process by end-to-end test with TLD and film in a SRS head phantom.

Purpose: The main purpose of this work was to show the availability of perform a frameless cone-beam computed tomography (CBCT)-guided cranial stereotatic radiosurgery (SRS) by an end-to-end (E2E) test with IROC Houston SRS head phantom using the Varian Clinac iX.

Methods and Materials: The head phantom has two inserts, one for the imaging containing the target and the dosimetry insert with film and thermoluminescent dosimeter (TLD). The imaging insert has a nylon sphere embedded in water as the target volume (simulating the tumor). The dosimetry insert contains two orthogonal sheets of Gafchromic passing throug the center of the "tumor" and two TLD within 0.5cm of the center of the target. The phantom with both inserts was imaged with computed tomography (CT) and magnetic resonance imaging (MRI), and a SRS dynamic arc plan was generated to the one with the imaging insert. The purpose of the plan was to cover the target with 25Gy with the prescription isodose being more than 85%. The phantom was localized at the treatment table with CBCT and the imaging insert was changed to the dosimetry one to be irradiated. Comparisons of the planned and the delivered dose to the film and TLD were performed. For the film, the coronal and sagital sheets were analysed with the gamma index with of difference dose 5% and distance-to-agreement (DTA) of 3mm with minimum of 85% of the points meeting the criteria. For the TLD the dose to the center of the target was compared with the plan and must meet the criteria of 95% to 105% of the read dose.

Results: The dosimetric results met the porposed criteria. The gamma index of the of both film sheets (coronal and sagital) agreed with the gamma index in 96% of points. The ratio of the dose to the center of the TLD and of the plan was 0.98.

Conclusions: The end-to-end test procedure proposed by to evaluate the abilities to locate and treat an intracranial target with high precision was performed with success in a frameless setup and CBCT method for positioning.


Anderson MELO (Maceió, Brazil), Landobergue BARROS
09:00 - 18:00 #17845 - Clinical implementation of a dedicated brain treatment planning optimizer for stereotactic treatments.
Clinical implementation of a dedicated brain treatment planning optimizer for stereotactic treatments.

Purpose:

Clinical implementation of a novel dedicated and automated treatment-planning solution for cranial indications, Elements. Single lesions can be targeted with an inversely optimized VMAT approach using automated arc trajectory optimization (Cranial SRS Element, Brainlab, München, Gernmany) while up to fifteen metastastic brain tumors can be automatically targeted with a single isocenter and multiple inversely-optimized dynamic conformal arcs (Multiple Brain Mets SRS Element, Brainlab, München, Gernmany).

Material and Methods:

The very first 25 treated patients were analyzed, each representing a variable number of lesions (1-12). Depending on the number and location of the lesions a dedicated Element was selected and used in order to achieve the specific planning constraints.The plans were evaluated by means of Paddick conformity (CI) and gradient index (GI). Patient specific quality assurance (QA) was performed with gafchromic EBT3 film and portal imager.

Results:

The Elements software tools generated plans with CI of 0.71±0.09 and a gradient index of 3.9±1.4. All plans achieved the organ at risk constraints. A gamma of 3%/3mm was used for the QA. A 98 % and 98,2 % passing rate was found for the EBT3 film and portal imager, respectively. This shows also the good concordance between film and EPID, suggesting that patient specific QA can be performed with the portal imager rather than the time-consuming films.

Conclusions:

The automated dose planning Elements revive dynamic conformal arcs as the paradigm for linac-based stereotactic radiosurgery of multiple brain metastases and at the same time implements an improved VMAT approach for single lesions with the use of automated arc trajectory optimization. This study shows the implementation of this technique in the routine clinical environment with an improved planning and treatment efficiency.


Thierry GEVAERT (Brussels, Belgium), Andrea GIRARDI, Benedikt ENGELS, Marlies BOUSSAER, Chaïmae EL AISATI, Mark DE RIDDER
09:00 - 18:00 #17897 - Commissioning and end-to-end validation for a high dose rate beam for radiosurgery.
Commissioning and end-to-end validation for a high dose rate beam for radiosurgery.

Currently, stereotactic radiosurgery and hypofractionated treatments become increasingly frequent, being the source of many studies. Associated with the new definitions and adjustments for small fields, the commissioning and validation of a high dose rate beam for small field treatments requires an adjustment to the factors suggested by the new IAEA document which infers factors for correction of the readings made by the detectors in the small field situations. A 6MV beam with high dose rate was commissioned and validated for Eclipse, with the AAA algorithm using the blue phantom, a PTW 3D pinpoint ionization chamber and an unshielded diode for the small fields. Following the protocol methodology, the 5x5 field was used as the fmsr field. Thus, the dose profiles: depth dose, inplane and crossplane of the beams were acquired with the two detectors for the square fields of 5 cm to 1 cm to identify the effects suggested by the literature. The output factor was acquired for all symmetrical and asymmetric field sizes with the pin point camera and, with the diode, for the fields equal to and less than 5 cm. Data were treated as recommended by the literature, including current work, and were fed into the planning system. The validation was done initially with a uniform phantom of solid water and already showed good agreement of the field factors and simplified plans, with discrepancies less than or equal to 1%. In an anthropomorphic phantom STEEV by cirs were simulated radiosurgery treatments with non-coplanar 3D and VMAT fields, both showed maximum discrepancies in approximately 1%.


Thiago B SILVEIRA, Maira R SANTOS (Rio de Janeiro, Brazil), Mozart G DUARTE
09:00 - 18:00 #17736 - Comparison between volumetric modulated arc therapy and dynamic conformal arc stereotactic radiotherapy for intracranial lesions.
Comparison between volumetric modulated arc therapy and dynamic conformal arc stereotactic radiotherapy for intracranial lesions.

The purpose of this study is to evaluate the dosimetric differences between treatment plans using dynamic conformal arc therapy (DCAT) from two TPS’s (Varian Eclipse and Brainlab elements) and volumetric modulated arc therapy (VMAT) from Varian Eclipse TPS, via frameless, linear accelerator based stereotactic radiotherapy (SRT) for the treatment of brain lesions for the first use of stereotactic radiotherapy in Algeria Using a Varian iX23 Linear Accelerator, Brainlab's 6D Exactrac Positioning System and Robotics couche, and TPS’s Elements (Brainlab) and Eclipse (Varian). Three plans were developed per each patient, with a total of fifteen patients, utilizing DCAT and VMAT. The plan comparisons of 45 treatment plans include the target coverage, conformity index (CI), homogeneity index (HI), gradient index (GI), and the volume of the normal brain tissue receiving doses of 12 and 5 Gray (Gy). Results of this research outline which planning method may provide benefits or lack thereof depending on the brain lesion location and size, thus providing data in terms of conformity of target coverage as well as lower dose spillage to the rest of the brain. This study also provides dosimetric results regarding advantages and disadvantages of forward versus inverse planning, in addition to the impact of a multi-leaf collimator (MLC) width size. Potentially the results of the study will indicate the most beneficial technique for delivery of SRS treatments for intracranial tumors.


Samir BENCHEIKH, Malika BESBAS, Ryma LOUELH, Mourad BELMESSAOUD, Abdelkader TOUTAOUI (Tizi Ouzou, Algeria)
09:00 - 18:00 #17726 - Contribution of scattered radiation to image formation and imaging dose in CyberKnife radiosurgery.
Contribution of scattered radiation to image formation and imaging dose in CyberKnife radiosurgery.

Purpose: Evaluate the contribution of scattered radiation to radiographic image formation and perform calculations of the imaging dose delivered by the x-ray based image guidance system of a CyberKnife radiosurgery system.

Methods: The CyberKnife image guidance subsystem consisting of two x-ray tubes and two flat panel detectors situated at the ceiling and the floor of the treatment room, respectively, were modeled and used to perform Monte Carlo (MC) simulations for water phantoms of different radii centered at the isocenter, as well as, for intracranial radiosurgery cases. Patient head models were simulated using lattice geometries constructed on the basis of information retrieved from corresponding CT scans. The MCNP6 general purpose MC code was employed to simulate photon transport and score i) the fluence of phantom/patient-scattered photons incident on the image detectors and ii) the imaging dose delivered for different kVp settings.

Results: The contribution of scattered radiation incident on the detector was found to depend on the dimensions of the imaging object and the kVp setting,reaching up to 30% at the center of the detectors for the 30cm diameter phantom and 150kVp. An imaging dose of 0.4mGy for the eye lenses and less than 0.1mGy for the healthy brain was calculated for an image acquisition using both tubes and typical settings of 120kVp and 10mAs.

Conclusions: The scatter contribution in radiographic image of a CyberKnife system is decreased due to the increased distance of 140cm between the patient and each detector. An imaging dose per acquisition of 0.4mGy was found for the eye lenses which corresponds to 4cGy for a treatment using a typical number of 100 acquisitions. Further studies to model the contribution of scattered radiation and improve low contrast resolution which is of interest in extracranial radiosurgery will be performed. 


Panagiotis ARCHONTAKIS, Argyris MOUTSATSOS, Emmanouil ZOROS (Greece, Greece), Eleftherios PAPPAS, Evaggelos PANTELIS
09:00 - 18:00 #17788 - Development of a stereotactic system as a basic concept for diagnostic biopsy as well as lesioning or stimulation of relevant brain structures.
Development of a stereotactic system as a basic concept for diagnostic biopsy as well as lesioning or stimulation of relevant brain structures.

Currently, complex stereotactic systems are used to act in the brain as three-dimensional organ. The biggest barrier of these systems available to date is their high investment requirements (up to 150 TEURO), their enormous weight (up to 5000 g) and their very complex assembly, including the long learning curve.

The aim is to develop a safe and simple stereotactic system that guarantees the same or better precision as traditional systems, but greatly simplifies acquisition and handling.

We developed a system based on a patient-specific 3D platform, which contains a total weight of 300 g. This platform contains all relevant information of the target and entry point and allows a tenth of a millimeter placement of biopsy needle or functional equipment. First, three, max. four small bone screws (frontal/parietal) fixed in the cranial bone followed by the acquisition of a CT or MR dataset. With the planning data, we construct a virtual platform for placement of the desired instruments. This model is 3D printed and attached to the re-exposed bone screws during surgery. This offers the option of a bi-hemispheric operation and helps to reduce the cost per patient by up to 40% of the conventional price.

An initial accuracy study (n = 40) documents a precision of the instrument tip (biopsy needle) of 0.58 mm ± 0.34 mm (ranging from 0.09 mm to 1.17 mm), comparing the target performance based on CT data of planned to actual instruments tip.

The system developed in Germany represents an excellent alternative to traditional stereotactic systems and helps to establish stereotaxy as a routine procedure. Furthermore, these platforms are single use as well as individual for each patient. The implementation of all spatial coordinates in the design of the platform eliminates intraoperatively all adjustment processes and shortens the duration of surgery by up 30%.


Juan Carlos CAMACHO RODRÍGUEZ, Dirk WINKLER (, Germany), Christian FIEDLER, Robert MOEBIUS, Marcel MULLER, Ronny GRUNERT
09:00 - 18:00 #17795 - Evaluation of the Explorer 4D treatment planning system.
Evaluation of the Explorer 4D treatment planning system.

Objectives: The ARI GammaART 6000ND rotating gamma systemwas installed in August 2007 at the University of Debrecen and has been used to treat more than 4500 patients since then. Regular tests are performed by the medical physics group following stringent quality assurance guidelines.The objective of this paper is the assessment of the Explorer 4DTM  treatment planning system (TPS).

Methods:  GAFchromicTMEBT 3 films were used to verify the 50% isodose lines of the TPS. The films were irradiated in a water equivalent phantom and then evaluated with FilmQATMPro software. The actual results were compared with the 50% isodose lines of the TPS. A PTW pinpoint 3D ionization chamber was placed inside a water equivalent phantom to verify the output factors built into the TPS.

Results: Statistical analysis of the results show that the difference between the 50% isodose lines of the TPS and the actual irradiation was maximum 2.35%.  In regards to the output factors, the results show less than 1% deviation from the TPS, except for the 4mm collimator, where the measurements were not reliable.

Conclusions: The results show that the TPS performs within the required tolerances to perform stereotactic treatment planning for intracranial indications.


Tamás HOLLÓ, Gulyás LÁSZLÓ (Debrecen, Hungary), László BOGNÁR, Imre FEDORCSÁK, József Gábor DOBAI
09:00 - 18:00 #16810 - Four-dimensional digital tomosynthesis based on visual respiratory guidance.
Four-dimensional digital tomosynthesis based on visual respiratory guidance.

The aim of this research was to introduce and evaluate a respiratory-guided slow gantry rotation 4D digital tomosynthesis (DTS). For each of 10 volunteers, 2 breathing patterns were obtained for 3 minutes, one under free breathing condition and the other with visual respiratory-guidance using an in-house developed respiratory monitoring system based on pressure sensing. Visual guidance was performed using a 4s cycle sine wave with an amplitude corresponding to the average of end-inhalation peaks and end-exhalation valleys from the free-breathing pattern. The scan range was 40 degrees for each simulation, and the frame rate (FR) and gantry rotation speed (GRS) were determined so that one projection per phase should be included. Both acquisition time (AT) and the number of total projections to be acquired (NPA) were calculated. Applying the obtained respiration pattern and the corresponding sequence, virtual projections were acquired under a typical geometry of Varian on-board imager for two virtual phantoms, modified Shepp-Logan (mSL) and XCAT (extended Cardiac-Torso). For the XCAT, two different orientations were considered, anterior-posterior (i.e., coronal) and left-right (i.e., sagittal). Projections were sorted to 10 phases and image reconstruction was made using a modified filtered back-projection. Reconstructed images were compared with the planned breathing data (i.e., ideal situation) by SSIM (Structural Similarity) and NRMSE (Normalized Root-mean-square Error). For each case, simulation with guidance (SwG) showed motion-related artifact reduction compared to that under free-breathing (SuFB). SwG required less NPA but provided slightly higher SSIM and lower NRMSE values in all phantom images than SuFB did. In addition, the distribution of projections per phase was more regular in SwG. Through the proposed respiratory-guided 4D DTS, it is possible to reduce imaging dose while improving image quality.


Kim DONG-SU, Kim SIYONG, Suh TAE SUK (Seoul, Korea)
09:00 - 18:00 #17719 - Frame-based to frameless brain SRS. Single centre experience in short time technological evolution.
Frame-based to frameless brain SRS. Single centre experience in short time technological evolution.

Mevaterapia medical centre put together a multidisciplinary team to implement frame-based brain SRS using a VARIAN Trilogy LINAC early 2017. Over 2 years a continuous technology upgrade has been performed in order to being able to perform safe frameless brain SRS.

First patient was treated during June 2017, with two treatment workflow considered; single fraction patients with stereotactic frame or hypofractionated patients with BrainLab stereotactic mask. Patient localization was performed based on CBCT imaging using a tolerance criteria 1mm/1°, achieving 6 degree positioning combining Varian couch with couch-mount movements.

During November 2017 ExacTrack imaging system was integrated to our LINAC, and imaging localization transition was carried out from CBCT to ExacTrac based imaging over 2 month. Positioning tolerance criteria was kept 1mm/1°.

In May 2018, we upgrade our treatment couch to BrainLab robotic 6D couch allowing ourselves to perform frameless SRS treatments. Frame-based to Frameless workflow was carried out progressively over 4 month with selected patients in joint decision between radiation oncologist and neurosurgeons. Multiple brain metastasis SRS was incorporated to our clinical protocol and positioning tolerance was set to 0.5mm/0.5°.

In room treatment time over our technological evolution was assessed and compared, considering that positioning tolerance was kept over these 2 years and more than 100 patients. CBCT imaging based treatments were performed in 60±20 minutes, when ExacTrac was implemented with Varian couch total time reduced to 40±10 minutes. Finally, actual in room treatment time with Frameless technology using ExacTrac plus robotic 6D couch is reduced to 30±10 minutes. Total patient time in treatment was reduced in over 40% with equivalent treatment quality and a quantitative increase in patient comfortability.


Florencia MAURI, Leon ALDROVANDI, Ruben Oscar FARIAS, Augusto ALVA, Pablo Marcelo AJLER, Matteo BACCANELLI, Federico Javier DIAZ, Maria Liliana MAIRAL, Claudio Gustavo YAMPOLSKY, Mabel Edith SARDI, Mara Lia SCARABINO (Buenos Aires, Argentina)
09:00 - 18:00 #17566 - Geant4-based Monte Carlo simulation of correction factors for reference dosimetry of the Leksell Gamma Knife Perfexion.
Geant4-based Monte Carlo simulation of correction factors for reference dosimetry of the Leksell Gamma Knife Perfexion.

With the publication of TRS-483 in late 2017 the IAEA has established an international Code of Practice (COP) for reference dosimetry in small and non-standard fields based on a formalism first suggested by Alfonso et al. in 2008. However, data on correction factors for the Leksell Gamma Knife Perfexion is scarce and what little data is available was obtained under conditions not necessarily in accordance with the IAEA’s recommendations. This study constitutes the first systematic attempt to calculate those correction factors by applying the new COP to Monte Carlo simulation using the GEANT4 toolkit. The correction factors were determined for three common ionization chamber detectors, modeled in great detail based on proprietary blueprints provided by their respective manufacturers, in five different phantom materials and using three different physics lists. The results indicated that for chambers with a collector electrode made of low-Z materials, correction factors were within 1% of unity for the liquid water, Solid Water™ and polystyrene phantom materials, whereas chambers with a collector electrode made of heavier elements and electronically denser phantom materials necessitated larger corrections. The correction factors did not differ significantly between the various physics lists. Similarities and differences between the results of this study and previous ones based on EGSnrc and PENELOPE-based Monte Carlo codes were also analyzed and it was found that the results obtained herein were generally in good agreement with the findings of earlier studies that were obtained under comparable reference conditions. The correction factors obtained in this study can be a contribution to a potential revision or update of TRS-483.


Thomas SCHAARSCHMIDT, Tae-Hoon KIM, Young Kyun KIM, Hye Jeong YANG, Kook Jin CHUN, Eun Young KIM, Hyun-Tai CHUNG (Seoul, Korea)
09:00 - 18:00 #17890 - Hypofractionated treatments using Gamma Knife Icon: accuracy evaluation of the daily repositioning.
Hypofractionated treatments using Gamma Knife Icon: accuracy evaluation of the daily repositioning.

The major improvement of Gamma Knife Icon is the possibility to execute frameless treatments to treat large-volume lesions or lesions close to critical organs reducing the side effects to normal tissues.

A possible issue using the frameless modality for hypofractionated treatments is the accuracy and reproducibility of the patient positioning. 

The patient displacement measurements (rotation and translation along the x/y/z axis) have been collected for each fraction and then the data have been analyzed to verify the accuracy and the efficiency of the current positioning procedure.

Between October 2017 and January 2019, 417 patients were treated in Fondazione Poliambulanza, including 65 in frameless mode with the thermoplastic mask, in single or multi-session fractions. In the first 57 hypofractionated treatments (3,4,5 days, for a total of 256 fractions) we studied the error (offset) in the daily repositioning of the patient in the three X-axis, Y, Z both for rotation and for translation. We obtained the following results (the value can be positive or negative depending on the side from which the new positioning moves with respect to the first day): 

- X rotation: mean -0.10°, SD 0.62°; 

- Y rotation: mean 0.08°, SD.53°; 

- Z rotation: mean 0.05°, SD 0.40°; 

- Translation X: mean -0.02 mm, SD 0.25 mm; 

- Translation Y: mean -0.28 mm, SD 0.22 mm; 

- Translation Z: mean -0.04 mm, SD 0.99 mm. 

The most frequent error in translations was found within 0.5 mm; in rotations, within 1°. In translations, the axis most frequently involved is the Y axis (antero-posterior), while the higher error, although less frequent, occurs above all on the Z axis (head-feet). For the rotations, the statistic did not show a preferential axis between X, Y or Z. Overall, the fixing system consisting of the thermoplastic mask and the customized conformable pillow was reliable, easy to use for the operator and was well tolerated by all the treated patients.


Alberto FRANZIN (Brescia, Italy), Chiara BASSETTI, Lodoviga GIUDICE, Cesare GIORGI, Ivan VILLA, Marco GALELLI, Oscar VIVALDI, Mario BIGNARDI
09:00 - 18:00 #17880 - Image processing for radiosurgery using computer deep learning.
Image processing for radiosurgery using computer deep learning.

In radiosurgical operations, the accuracy of planning and drawing of target structures as well as the definition of risk structures is very important.

The planning of the radiosurgery is performed mainly by CT and MRI images, which are transferred after they are merged into the virtual planning system. Visualization and virtual planning greatly assist the subjectivity of hand drawing contour of brain structures by the neurosurgeon for optimization of treatment.

The new proposed system allows to search quickly for the very large amount of information needed to better diagnose and design a further treatment that help the physician in the decision-making algorithm and provide better treatment outcomes for radiosurgery. Priority is given to the processing of image information from CT, MRI and PET considering the different quality of the devices, which is reflected in the different sensitivity and specificity of the results obtained by imaging and clinical methods. This information, if necessary, are displayed in 3D stereoscopy. The processing of sophisticated information system methods by combining the results of multiple imaging (CT, MRI, PET) increase the specificity and sensitivity of the algorithm of interpretation and decision making for the diagnosis and treatment of the patient, which is also a shift towards personalization for the decision algorithm. This system allows through the secure network to communicate between hospitals to diagnose correctly and thus decide the treatment method correctly. At the same time, the system is designed to have the ability to communicate with existing PACS systems in hospitals and "self-deep learning" skills.

Visualization and communication across the hospital network will enable you to prepare radiosurgery with experts from different hospitals, thus increasing the emphasis on the accuracy of the planning process.


Miron ŠRAMKA, Eugen RUŽICKÝ (Bratislava, Slovakia), Alena FURDOVÁ, Štefan KOZÁK, Ján LACKO
09:00 - 18:00 #17842 - Impact of patient-specific MRI distortion correction for stereotactic cranial target definition.
Impact of patient-specific MRI distortion correction for stereotactic cranial target definition.

Introduction

The accuracy of a stereotactic treatment is primarily limited by the least accurate process in the whole chain of events from patient scanning to patient treatment.

The targeting is limited by the accuracy of the CT and MRI images. MRI datasets are subjected to distortions, due to nonlinearity of gradient fields, andmay cause incorrect target definition.

This study aimed to analyze the impact of a patient-specific algorithm, Crainial distortion Elements (Brainlab, München, Germany), rather than a manufacture-specific, to correct spatial distortion in cranial magnetic resonance images.

Methods and materials

Twelve trigeminal patients treated with a single dose of 90 Gy with a 4mm collimator were studied retrospectively.  The gross target volume (GTV) was defined on a 1.0mm T1 MPRAGE and T2 MRI corrected for distortion with a machine-specific algorithm.

For this study, the manufacture-specific corrected MRI was further corrected using a patient-specific distortion correction algorithm that references the treatment planning CT. The GTV were then mapped onto this newly created patient specific corrected MRI dataset.

The original defined target and the corrected deformed object were mutually compared by means of several quantitative measures such as Dice, Jaccard, and Hausdorff indices. The average distance between the two centers of the two GTV was also calculated.

 

Results

On average, a good agreement was found between both GTV resulting in a Dice index of 0.76 (SD 0.23) ranging between 0.13 and 0.92. The Jaccard index, which is an intersection over Union was similar (p> 0.1) to the Dice with an average of 0.66 (SD 0.23) ranging between 0.09 and 0.86. The greatest of all the distances from a point in GTV to the closest point in the other GTV, called the Hausdorff distance, was 0.73 on average (range 0.50-1.80), reflecting good similarity between both GTVs.Average distance between both GTV was 0.43 mm (SD0.26mm), with a minimum of 0.20 mm and a maximum of 1.10 mm. One out of the 12 patients met criteria of “geometric miss”, which was not correlated with clinical outcome.

 

Conclusion

Our study showed that the cranial distortion Elements correct all images even when manufacture-specific corrections fail due to patient specific conditions. In order to avoid any geometrical miss, a patient specific distortion correction must be applied for all cranial indication.


Thierry GEVAERT (Brussels, Belgium), Benedikt ENGELS, Chaïmae EL AISATI, Mark DE RIDDER
09:00 - 18:00 #17751 - Implementation of a national stereotactic radiosurgery chart round: engagement and clinically significant outcomes.
Implementation of a national stereotactic radiosurgery chart round: engagement and clinically significant outcomes.

Introduction

Intracranial and extracranial Stereotactic Radiosurgery (SRS) are highly specialised techniques which require careful and structured implementation.  Here we describe the implementation of a weekly national SRS chart round attended by specialists from 10 geographical locations, held via videoconference. Prior to SRS delivery, all patients had their case presented where clinical, planning and technical details were discussed.

 

Method

Data was collected from weekly run chart rounds between July 2018 and January 2019.  Details recorded included specialty attendances, clinical background, diagnosis, volumes, radiation dose and fractionation, treatment site/location and clinician approach.  Furthermore, consensus recommendations regarding changes to treatment approaches were also recorded.

 

Results

There were 590 attendances split across radiation therapists/dosimetrists (29.0%), radiation medical physicists (27.6%), oncologists (27.3%) and management (16.1%).  There were 118 cases presented. Of these, primary or oligometastatic lung malignancies represented the majority of cases (n=42), followed by brain metastases (n=21 and n=14 for single met and multi-met respectively), bony oligometastases (n=17), non-bone oligometastases (n=11), spine (n=3), benign brain conditions (n=3) and primary brain (n=1).  Across our national network we have had 18 radiation oncologists present at least one case at the chart round with others participating for training and mentorship.  Of the 118 cases presented, there were 29 (24.6%) recommendations made for 21 patients.  These included changes to contours (n=10), dosimetry (n=4), treatment technique (n=1) dose/prescription (n=8) and 6 occasions where standard fractionation or no treatment was recommended.  Three patients had more than one recommendation made.  Cases were re-presented following changes from recommendations.  

 

Conclusion

The implementation of a national SRS chart round, held via videoconference has ensured national protocol compliance to stereotactic treatments across our network.  Furthermore, the chart rounds have allowed clinicians to be provided with mentorship and guidance from nationally and internationally recognised SRS experts which has allowed for increased plan quality and patient outcomes.


Rhys FITZGERALD (Brisbane, Australia), Trent ALAND, David PRYOR, Lee ANDERSON, Andrew FONG, Dominic LUNN, Andrew OAR, Marcel KNESL, Jim JACKSON, Matthew FOOTE
09:00 - 18:00 #17710 - Implementation of a novel non-coplanar arcs technique for stereotactic treatment of brain metastases.
Implementation of a novel non-coplanar arcs technique for stereotactic treatment of brain metastases.

Purpose: Implementation of stereotactic radiosurgery (SRS) treatment for brain metastases in our department with no previous SRS experience, using the dedicated technique HyperArc™, Varian Inc. (HA) on a TrueBeam STx.

Material and Methods: The accuracy of the HA patient positioning system, MV and Cone-Beam computed tomography (CBCT) in conjunction with the 6D robotic couch were evaluated. Brainlab ExacTrac (ET) was used to verify patient positioning prior to each beam and trigger new CBCT correction. Dedicated beam models for millennium and HD multi leaf collimator (MLC) were commissioned. Coincidence of imaging and radiation isocenters was confirmed using Winston-Lutz (WL) test. EBT3 film measurements were done for Picket Fence (PF) test, end-to-end (EE) test using a Max HD phantom and clinical pre-treatment Quality-Control (QC) using a CIRS phantom. The first 21 patients (1-4 brain metastases) have been treated using 4 non-coplanar 180°-arcs in one fraction of 18Gy. A 2 mm margin was applied to the gross target volume delineated on magnetic resonance images. Plans were evaluated with dosimetric indices, total monitor units and overall treatment time (OTT) per fraction.

Results: The CBCT and ET isocenters agreed to within 0.4 mm and 0.3° in translational and rotational directions. The beam models were accurate down to a jaw field of 2 x 2 cm2 with dosimetric leaf gaps of 0.15 cm and 0.09 cm and transmission factors of 1.8% and 1.2% for 6 MV flattening filter free photon beam with the millennium and HD MLC, respectively. The results of WL (max delta <0.7mm), PF and EE (gamma passing rate >95%) tests were within the defined criteria. The mean Planning Target Volume was 3.3 cm3 (range 0.3-16 cm3). Dose constraints were within tolerances for all the patients. Pre-treatment QC resulted in a local gamma passing rate (1mm/5%) above 90% for all the patients. Maximum observed deviation in patient positioning was 3.2mm/2.4°, 11 patients were within treatment tolerance (1mm/1°) throughout treatment. The mean OTT was 33.5 ± 13.5 min.

Conclusion: HA offers fast accurate treatment planning and dose delivery. By omitting MV images, OTT can be decreased by almost half. Next steps are to investigate the possibility of using only the initial CBCT as image verification, and possible benefits of using HD MLC.


Lucie CALMELS (Herlev, Denmark), Susan BLAK NYRUP BIANCARDO, David MC KENZIE GRANT, Maria SJÖLIN, Eva WILKEN, Sune Kristian BUHL, Ulf BJELKENGREN, Mette ANDERSEN, Patrik SIBOLT, Mette PEDERSEN, Hanne LANDGREN, Susanne LIND, Anja NIELSEN, Poul GEERTSEN, David SJÖSTRÖM
09:00 - 18:00 #17722 - Initial experience using a bolus skin-equivalent for calvarial metastases and skull defects using the Leksell Gamma Knife ICON mask based system: The Cleveland Clinic Experience.
Initial experience using a bolus skin-equivalent for calvarial metastases and skull defects using the Leksell Gamma Knife ICON mask based system: The Cleveland Clinic Experience.

Introduction: Our group has previously published on the use of a bolus skin-equivalent layer for treating calvarial and skull base metastases using the Perfexion frame based system (Kotecha et al J NSG (Suppl 2) 121:91-101, 2014). Traditionally used TMR 10 algorithms in Gamma Knife Radiosurgery (GKRS) are not accurate in the first 5 mm from the surface and by adding at least 5 mm of bolus material to the mask and creating an extended skull contour that limitation is removed.

Method: We used a bolus skin-equivalent attached directly to the Leksell Gamma Knife ICON thermoplastic mesh faced mask. The system uses image-guidance utilizing cone-beam CT (CBCT) and infrared tracking to ensure minimal inter- and intra-fractional movement during GKRS and hence can also be used in a fractionated manner. Four patients to date have been treated. The thermoplastic mask system consisted of a customized resin-filled neck rest and a 3-point thermoplastic mask. The area to be treated was outlined on the skin so the correct size of bolus would be utilized. A bolus skin-equivalent of at least 5 mm was positioned over the treatment site and attached directly to the thermoplastic mask to artificially extend the surface to target distance. A localization CBCT was completed after the mask was made and the patients then completed high resolution (1 mm slice) contrasted enhanced MRI images and CT scans without and coregistered to reduce inaccuracies from image distortion.

Results: The four cases treated included a 14 year old (y/o) with osteosarcoma skull metastases treated over 3 fractions, a 69 y/o with renal cancer skull metastases treated over 5 fractions, an 81 y/o with atypical meningioma and skull defect treated over 5 fractions, and a 55 y/o with an anaplastic oligodendroglioma and a skull defect treated in a single fraction. The four cases will be presented in detail outlining the treatment flow. We were able to calculate the skin max point dose (Gy) for 3 patients with all falling below the skin tissue constraints using the Timmerman Tables. There was associated hair loss but no skin dermatitis.

Conclusion: Gamma Knife using the ICON mask based system and a bolus allows treatment of superficial calvarial lesions and patients with superficial tumors and skull defects and provides an option for patients who are not candidates for a frame based Gamma Knife procedure.


Glen STEVENS (Cleveland, USA), Lilyana ANGELOV, Sam CHAO, Gennady NEYMAN, Erin MURPHY, Dani FLAK, John SUH
09:00 - 18:00 #17672 - Integrating navigated Transcranial Magnetic Stimulation (n-TMS) in gamma knife radiosurgery planning.
Integrating navigated Transcranial Magnetic Stimulation (n-TMS) in gamma knife radiosurgery planning.

Background:

To illustrate how navigated transcranial magnetic simulation (n-TMS) can be utilized in the radiosurgical management of brain metastases involving areas of the motor cortex.

Case Descriptions:

Case 1: A 53 year-old woman with metastatic breast cancer developed focal epileptic seizures and weakness in her left hand.  A magnetic resonance imaging (MRI) scan demonstrated a partially cystic 30 mm metastasis in the right precentral gyrus and central sulcus. The lesion was treated with adaptive hypofractionated gamma knife radiosurgery; nTMS - based motor mapping was performed prior to treatment. Follow-up MRI up to 12 months revealed a significant decrease in tumor size without adverse radiation effects (ARE); symptoms resolved within one month post treatment.

Case 2: A 73-year-old man with metastatic lung cancer developed left hand weakness. The corresponding MRI demonstrated a 26 mm metastasis in the right postcentral gyrus and sulcus, 5 mm from the hand motor cortex. The patient underwent preoperative nTMS  motor mapping  prior to single dose gamma knife radiosurgery for both lesions. Follow-up MRI examinations up to 10 months showed tumor control and evolving ARE. Despite the latter, the patient experienced motor function improvement  during follow-up.

Conclusion: 

In our case series, nTMS was safely and effectively integrated in gamma knife radiosurgery (GKRS) planning. Motor mapping allowed sparing of healthy functional tissue. The relation between the type of radiation schedule and possible radiation-induced focal plastic distortions at long term needs consideration and deeper analysis.  Prospective studies involving larger, homogenous group of patients are warranted to further validate the clinical significance of nTMS in GKRS-treatment planning. 


Georges SINCLAIR, Georges SINCLAIR (Reading, UK, United Kingdom), Georges SINCLAIR, Gerald COORAY, Hamza BENMAKHLOUF, Christer LINDQUIST, Mominul ISLAM
09:00 - 18:00 #17811 - Monte Carlo evaluation of the effect of source self-shielding on Gamma Knife dose rate variation.
Monte Carlo evaluation of the effect of source self-shielding on Gamma Knife dose rate variation.

In this work, we analyze the effects of source self-attenuation on the dose rate for a Model C Gamma Knife unit (Elekta, Stockholm. As each source is composed of 20, 1 mm thick individual pellets and the source housing necessarily has a diameter greater than the pellets, it is possible that these pellets can move independently relative to each other. By modeling a large number of different random arrangements of pellets using the Monte Carlo code MCNP6, we were able to construct a probability distribution of the possible dose rates. Using a maximum pellet displacement off of the centerline of 0.25 mm (which assumes the source housing diameter is 0.5 mm greater than the pellet diameter), the FWHM of this distribution is 2.3%. Perhaps more interestingly, the mean dose rate of this distribution is 8% higher than the dose rate obtained when all of the pellets are perfectly aligned, indicating that while randomized arrangements do not vary by much in dose rate, allowing for some offset (and subsequently decreasing the source self-attenuation) can cause an appreciable increase in dose rate.

We then looked at using 2 mm diameter source pellets to match the Gamma Knife hole size, which reduced the number of pellets needed from 20 to 5 (changing the source height from 20 to 5 mm). This change led to a 32.5% increase in dose rate at isocenter for the 18 mm collimator. As we do not have an accurate model of the PerflexionTM system at the time of writing, we were not able to similarly evaluate the newest Gamma Knife generation. However, based on these results, we believe it is worthwhile to investigate the feasibility of modifying the Gamma Knife sources by reducing their dimensions along the beam line in order to reduce the effects of self-attenuation.


Gregory SZALKOWSKI, Tanxia QU (New York, USA), C-K Chris WANG
09:00 - 18:00 #17723 - Patient specific dose verification using a phantom duplicating the patient anatomy created with 3D-printing technology.
Patient specific dose verification using a phantom duplicating the patient anatomy created with 3D-printing technology.

Objective: The aim of this work is to establish and implement a patient specific end to end quality assurance methodology for dose verification in advanced radiotherapy applications using 3D-printing technology.

Methods: Eleven patient VMAT plans including either stereotactic or re-irradiation cases of primary or recurrent brain or head and neck tumors, created in Monaco TPS, were verified. A 3D-printer was used to construct a hollow phantom that duplicates the patient anatomical geometry, including bone structures, using the patients' planning-CT DICOM images. Special inserts were also constructed to position either a semiflex PTW (volume:0.125 cc) or a CC01 IBA (volume:0.01 cc) ionization chamber PTV and OARs. The hollow phantom was subsequently filled with water to simulate normal brain. The phantom was irradiated using the specific patient’s irradiation protocol including the IGRT step using CBCT with Elekta HexaPOD 6D robotic couch.  Phantom CBCT- images were co-registered with the patient-CT images in the TPS to accurately define ionization chamber positions. TPS calculations in the patient anatomy were calculated and compared with corresponding measurements.

Results: An excellent agreement (difference <4%, average=2.7%±1.2%) between measurements and TPS calculations were observed in the low dose gradient/high dose region within PTV. In the OARs region, the degree of agreement between measurements and calculations depend significantly on the definition accuracy of the position of the ionization chamber volume in patient anatomy as well as on the dose gradient in the region of measurement with differences being increased in the high dose gradient regions. In any case, differences < 10% (average=5.4%±2.4%) were observed with the measured dose being always lower than the accepted dose limit for the specific OAR.

Conclusion: The implemented methodology based on 3D-printing technology was found capable to verify the dose in clinically significant regions within the patient without the need of plan recalculation in the phantom anatomy.

 


Nikolaos GIAKOUMAKIS, Pantelis KARAISKOS (Athens, Greece), Chryssa PARASKEVOPOULOU, Efi KOUTSOUVELI, Georgios KRITSELIS, Georgios KOLLIAS
09:00 - 18:00 #17846 - Polyetheretherketone (PEEK) implant can reduce postoperative artefacts and improve accuracy rate of delineation : a test in both pig and human.
Polyetheretherketone (PEEK) implant can reduce postoperative artefacts and improve accuracy rate of delineation : a test in both pig and human.

Background

Spinal stereotactic body radiotherapy (SBRT) delivers high doses of radiation and it is highly conformally focusing the radiation dose on the metastatic bone while sparing spinal cord. Postoperative SBRT dose planning relies on CT and MRI imaging. Polyetheretherketone (PEEK) is a new material of radiolucent character.

Aim is to compare the artefacts in CT and MRI scans caused by PEEK and Titanium rods implanted in pigs and humans.

Methods

In the pig spine specimen three groups of implants were sequentially inserted: a) Two Titanium rods, b) one Titanium rod and one PEEK rod, c) two PEEK rods. CT and MRI scans were acquired of all groups. A region of interest (ROI) was defined in order to measure the imaging noise caused by the rods. CT Houndsfield units (HU) were measured in ROIs and the image-noise were compared by calculating  artefact density standard deviation (SD).

The accuracy of spinal cord identification on MRI scans was compared on two patients who underwent spinal stabilisation.

Results

In the CT scans of pig specimen, the image-noise (artefact density standard deviation) was 63.5 HU for the titanium rods and 6.2 HU for the PEEK rods. There was a significant difference in image-noise between the two groups (P<0.01). The artefacts in the CT scans caused by the implanted rods were considerably lower for PEEK than for Titanium. For the two patients with respectively implanted PEEK and Titanium rods, it was only possible to identify the spinal cord for the patient with PEEK implants.

 Conclusions

PEEK rods created significantly less artefacts than Titanium rods in both CT and MRI scans, thus enabling more accurate spinal cord definition before SBRT. By using this new material, patients could benefit from a more precise and secure SBRT treatment  with less risk of radiation induced side-effects.


Miao WANG (Aarhus, Denmark), Yasmin LASSEN-RAMSHAD, Esben Schjødt WORM, Simon Toftgaard SKOV, Haisheng LI, Anja HARBØLL, Kristian HØY, Ming SUN, Akmal SAFWAT, Ebbe Stender HANSEN, Kestutis VALANCIUS, Simon BUSS, Lise Nørgaard BENTZEN, Thomas BENDER, Morten HØYER, Cody BÜNGER
09:00 - 18:00 #17826 - Spontaneous intraocular air arising after placement of stereotactic frame.
Spontaneous intraocular air arising after placement of stereotactic frame.

Introduction: Although used since the last century, its application still can bring unexpected findings. It can be challenging after a craniotomy, requiring frame rotation and/or pins adjustment to avoid the bone flap. 

Objective: To report the spontaneous appearance of intraocular air immediately after stereotactic frame placement. 

Methods: A 61-year-old woman diagnosed with a left frontal tumor underwent microsurgery, confirming a fibrous meningioma. After complete resection, the tumor relapsed 4 years later. She elected to be treated with radiosurgery. A Leksell model G frame (Elekta, Sweden) was applied with fixation in a more basal manner than usual to avoid the bone flap of the previous left frontal craniotomy. She had eyelid edema immediately after injection of local anesthetic on the right eye. Immediate CT scan after the frame fixation showed the presence of intraocular air on the left eye (same side of craniotomy). This finding was absent on the MRI taken for planning a day earlier. Rigorous assessment did not show a bone fracture or pin slid into the orbit that would justify this finding. Ophthalmological infection was also ruled out. Radiosurgery underwent uneventfully, using a prescription of 15 Gy to the 50% isodose line. The patient reported a scotoma on the following day after radiosurgery. CT scan was repeated 8 days after GK showing complete resolution of intraocular air. Nevertheless, the patient continued to report a blind spot, later confirmed with a visual field exam. The patient was evaluated by a neuro-ophthalmologist who diagnosed a significant retinal pathology on the left eye. Intraocular air occurred ipsilaterally to the tumor and the craniotomy.

Conclusion: This is an unlikely concomitant occurrence of intraocular air accompanied by scotoma following stereotactic frame placement. Neuro-ophthalmologic investigation confirmed the co-existence of underdiagnosed retinopathy.


Juliete MELO DINIZ (SAO PAULO, Brazil), Antônio DE SALLES, Rafael COSTA LIMA MAIA, Aline Lariessy CAMPOS PAIVA, Bruno Henrique DALLO GALLO, Crystian WILIAN CHAGAS SARAIVA, Alessandra GORGULHO
09:00 - 18:00 #17717 - Stereotactic frame-based registrations methods for the Leksell Gamma Knife®.
Stereotactic frame-based registrations methods for the Leksell Gamma Knife®.

Introduction: The Leksell G-frame is designed to localize and immobilize the patient during imaging and treatment with e.g. the Leksell Gamma Knife®. The localization system uses the indicator box with N-shaped fiducials, to create a stereotactic space for tomographic studies used for registration in the Leksell GammaPlan®(LGP). Two new registration algorithms are proposed and evaluated on several tomographic image studies. The purpose is to investigate the registration differences between the LGP registration algorithm and the proposed registration algorithms in images where varying amount of distortion is present.

Materials and methods: 25 CT and MRI studies were stereotactically defined in a Leksell Gamma Plan 11.1 research version from which fiducial information could be exported for evaluation. LGP registers the corners of the stereotactic N derived from least-square fit of fiducials whereas the two proposed algorithms use the fiducial coordinates to minimize the distance of the fiducial to the theoretical fiducial N, either with respect to the mean or quadratic fiducial registration distance, which handles distortions differently. Differences in fiducial registrations and coordinates in stereotactic space were evaluated.

Results: The proposed registration methods proved stable and resulted in smaller mean fiducial distances compared to LGP; Mean Value method MR: 0.479±0.082mm, CT: 0.176±0.047mm; Quadratic method MR 0.484±0.081mm, CT: 0.179±0.050mm compared to LGP MR 0.559±0.088mm, CT 0.353±0.145mm. The quadratic formulation suppresses noise efficiently while the mean formulation reduces the effects of systematic fiducial deviations. The mean and max difference in stereotactical coordinates between registrations based on LGP vs the proposed formulations were 0.4mm and 0.9mm, respectively.

Conclusion: The small shift may be insignificant for most of the image sets analyzed. Larger deviations with LGP registrations (2D error) gave transformations resulting in larger deviation in the stereotactic volume. Further investigations are needed to evaluate stereotactic definitions.


Jonas JOHANSSON (Stockholm, Sweden)
09:00 - 18:00 #17865 - Tears: A Bizarre Cause of Collision in Gamma Knife Radiosurgery.
Tears: A Bizarre Cause of Collision in Gamma Knife Radiosurgery.

Background: With the availability of Perfexion and the Icon model of Gamma knife radiosurgery, no part of the brain is an exception for the treatment. 

Objective: For all practical purposes, the most common cause of the collision is not the patient’s head but the post or screw. Collision warnings distribute mostly at the anterior and the posterior ends of the head and less in the cranio-caudal direction. There is no other plausible source of collision in the radiosurgery. 

Case presentation: We have faced a difficult situation while administering gamma knife treatment to a 7-year-old boy with residual resistant acromegaly. The frame was placed equidistant keeping the nose in the center thereby centralizing the sellar region. All collision checks were confirmed, and no collision was reported, as the lesion was central and easily achieved with the treatment plan. Shortly after starting the treatment, the child got restless and started crying. After a while, the machine stopped the treatment indicating a collision error, but we could not find any source of contact.

Conclusion: The cone inside the treatment area is a collision sensor suspended on sensitive springs. The sensors’ function is to suspend treatment if the cone is displaced such that it creates an electrical connection with the collimator system. This shorting to the ground the trigger to prevent a mechanical collision between the fixated patient and the collimator. The sources are withdrawn to the park position and treatment stops. It seems that the patient’s tears, in this case, were sufficient to trigger the collision sensor. One can wonder if the system has become overly sensitive, in which case it would be recommended to inspect and perhaps change the springs. This case highlights the extreme sensitivity of the gamma gantry to avoid any unnecessary radiation or wrong delivery of the treatment. The treatment of pediatric patients under general anesthesia is another solution for this possible complication.


Manjul TRIPATHI (Chandigarh, India)
09:00 - 18:00 #17654 - The reason for complying with the treatment time limit in plan competition for GKRS.
The reason for complying with the treatment time limit in plan competition for GKRS.

With the purpose of improving the quality of radiosurgery, there were for the first time two treatment plan competitions of brain stereotactic radiosurgery in 2018. They both have 5 target, prescription dose of 20Gy, and treatment time limitation in common. At the last minute 1st plan competition ignored the treatment time limitation on request from the users but 2nd plan competition kept it until the end. We analyzed the result of two competitions and figured out that the decision of keeping the treatment time limit or not was a key to ranking in GKS. ProKnow, 1st competition’s organizer, announced the result on website. It selected the top 50 among all participants with the individual information, acquisition score and the summary of the treatment plan. I analyzed the 7 people’s treatment plan registered in top 50 from the website and added one more plan that was one of my 2 treatment plans presented to the competition but not ranked in it. The result of RadiationKnowledge, 2nd competition’s organizer, took a little more time to be announced on the website and had only one gamma knife treatment plan in top 20 giving only individual information and acquisition score. I could review the plan information because the plan was mine. The first competition did not give the information of the treatment time but give the number of shots instead. We could anticipate the treatment time from the 3 plans that the owner of the plan had sent to me. Among 8 plans only one plan with 18 shots and 103 minutes kept the treatment time limitation. Seeing that the treatment plan with 26 shots had the treatment time of 146 minutes, the others must have exceeded the time limit of 120 minutes. The second competition must have kept the time limit of 90 minutes. The plan only recorded in the top 20 had the treatment time of 89 minutes with 19 shots. Even though the plans taking longer treatment time were certainly GKS planning for clinical treatment, the time limit should have kept to fairly compete in the game and make a right order in ranking. It seemed that the plan competition was to evaluate the ability to meet the condition not to find the highest score. If the first competition’s organizer had commented about this, the participants would have noted that they should comply with the time limit from next plan competition, such as RadiationKnowledge's plan competition.


Weon-Seop SEO (SEOUL, Korea), Chang-Kyu PARK, Seok-Keun CHOI, Bong-Jin PARK
09:00 - 18:00 #17745 - The use of correction factor free detectors to validate ultra-small field dose distributions.
The use of correction factor free detectors to validate ultra-small field dose distributions.

Purpose: Ultra-small field dosimetry (<1cm) is challenging due to perturbation effects and 
volume averaging. Recently, small field correction factors have been introduced to compensate 
for the the varying responses of different detectors in radiosurgical fields. We demonstrate that 
data acquired and validated with detectors not requiring correction factors, such as the W1 
(Standard Imaging, Madison, WI) and Gafchromic film (Ashland, Bridgewater, NJ), yields 
excellent agreement between plans created in the Multiple Met (MME) Element (Brainlab, 
Munich, Germany) and phantom measurements. 
 
Methods: Output factors were acquired on a Truebeam STX (Varian Medical Systems, Palo 
Alto, CA) with a flattening filter free 6 MV beam using an Exradin W1 scintillator. Treatment 
plans for 41 targets were validated in MME: 5 with the W1 and 36 with Gafchromic EBT3 or XD 
film. Target sizes ranged from 0.06 cc to 0.6 cc and 0.03 cc to 1.7 cc for the W1 and film 
validations, respectively. Treatment plans were planned and delivered on MaxHD (IMT, Troy, 
NY) and Baby Blue (Standard Imaging, Madison, WI) phantoms. Phantom alignment was 
performed before and during delivery using Brainlab’s ExacTrac with thresholds of 0.5mm and 
0.5°. 
 
Results: All plans validated with film and the W1 had good agreement with calculations. 
Gamma scores >96% (2%/1mm, 10% dose threshold) were achieved for all film validations for 
targets ranging from 0.03cc to 1.7cc. W1 point dose measurements were <1.5% of calculation 
for all but the 0.06cc target, at which the target size is comparable to the W1 dimensions.  
 
Conclusions: Using a detector with a unity correction factor (or applying proper correction 
factors to an appropriate detector, such as those available in IAEA’s TRS 483) to collect and 
validate data is essential for an accurate machine build.

Lauren WEINSTEIN (South San Francisco, USA), Matthew SKINNER
09:00 - 18:00 #17809 - Use of a Trial Setup to Assess Patient Acceptability for Mask-Based Gamma Knife Treatment.
Use of a Trial Setup to Assess Patient Acceptability for Mask-Based Gamma Knife Treatment.

Purpose: Mask-based stereotactic radiosurgery (SRS) on the Gamma Knife (GK) is facilitated by intra-fraction motion management (IFMM) and cone beam computed tomography (CBCT). The purpose of this study is to evaluate the use of a trial setup during mask simulation to determine patient eligibility and acceptability for mask-based GK-SRS.

Methods: Patients triaged to masked-based GK-SRS undergo a simulation appointment to manufacture a patient-specific mask and headrest, and acquire a reference CBCT for treatment planning. During simulation, while the mask sets on the patient, a trial setup using the IFMM device was performed by tracking a reflective marker on the patient’s nose through the stereoscopic camera. Passive tracking of the marker was performed for 10-20 minutes to assess both the magnitude of patient motion, and patient tolerability to the treatment setup position as large motions tracked via the IFMM system triggers treatment interruption during GK-SRS delivery.

 Results: Mask simulations on the GK were performed on 92 patients. Twelve patients were subsequently aborted for SRS due to various reasons following trial setup: extreme claustrophobia (2), large range of motion on IFMM due to poor performance status (2), triaged to linear accelerator treatments due to number of lesions or lesion size (6), triaged to surgical intervention (1), and patient declined GK-SRS (1). Due to collision risks identified in the pre-planning process, 8 patients were re-simulated with a new mask or foam headrest prior to GK-SRS. The IFMM threshold for GK-SRS was increased from 1.5 mm to 2.0 mm for 5 patients based on motion observed at trial setup.

Conclusions: A trial setup with the mask and IFMM system during the simulation appointment is useful in identifying patient eligibility for mask-based SRS. Identifying patient specific factors, such as claustrophobia and poor performance status, assists with patient comfort measures or triage to other more suitable treatment options.


Winnie LI, Messeret TAMEROU, David SHULTZ, Normand LAPERRIERE, Barbara-Ann MILLAR, David JAFFRAY (Houston, USA), Caroline CHUNG, Catherine COOLENS
09:00 - 18:00 #17742 - Using a high frequency sampling electrometer to measure directly six time related parameters in one acquisition.
Using a high frequency sampling electrometer to measure directly six time related parameters in one acquisition.

This study is to report a novel method to measure six time related parameters: 1) timer accuracy; 2)  timer error; 3) timer linearity; 4) time between two shots; 5) time for sector passing the 4mm cone when traveling to 16 mm cone; 6) transient time that corresponding to shutter dose. This method uses a high frequency sampling electrometer to measure time directly vs the previous method that measure dose and calculate time. Current of every 0.05 sec is collected using a SunNuclear PCElectrometer in the standard GK icon QA setup over one composite acquisition of four shots of 1, 3, 10, and 20 min, respectively. The source sectors start from the sector off position, pass 4mm cone, moves to a 16 mm cone position for nominal exposure time of 1 min, then pass the 4mm cone again, and move back to the sector off position for a short period of time (time between two shots), then repeat the cycle for 3, 10, and 20 min settings, respectively. A MATLAB program was written to graph and calculate 1) timer accuracy of 59.8, 179.7, 599.5 and 1199.1 sec for nominal setting of 60, 180, 600 and 1200 sec, respectively; 2) timer error of 0.40 sec; 3) Timer linearity of R square of 1.0; 4) time between two shots of 4.9 sec; 5) time for sector passing 4mm cone of 0.4 sec; 6) transient time of 0.24 sec for the sectors to reach their full exposure positions.  This transient time is what Gamma Plan uses to account for the shutter dose.  In conclusion we have developed a semi-automatic method to measure time related parameters objectively, accurately, and efficiently by using a programmable high frequency sampling electrometer.


Tanxia QU (New York, USA), Kenneth BERNSTEIN, Douglas KONDZIOLKA
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P11
09:00 - 18:00

EPOSTER - 11 Pituitary
Electronic Poster displayed from June 9 to June 13

09:00 - 18:00 #17590 - Radiosurgery insulin like growth factor 1 immediate response in growth hormone residual adenoma.
Radiosurgery insulin like growth factor 1 immediate response in growth hormone residual adenoma.

Introduction. Patients with pituitary growth hormone secretor benign adenoma has demonstrate a consistent functional response to radiosurgery. This clinical observation present the immediate insulin like growth factor 1 response to ionizing radiation exposure single dose in residual adenoma.

Method. A 49yo male with acromegalic and right hemparesis 4/5 with previous partial resection of pituitary adenoma one year before and vascular intervention for left carotid lesion was programed for radiosurgery. His image studies showed 2.1 cc residual tumor on left cavernous sinus. Five days previous to gamma radiosurgery growth hormone level was 5.04 ng/ml, on treatment day insulin like growth factor 1 was measured previously and inmediatelly after radiation exposure, one and four hours later. 

Results. Insulin like growth factor 1 in ng/ml was as follows: previous 754, immediately after 915, one hour later 954 and four hour later 901. No growth hormone level and fluctuation was considered.

Conclussion. Insulinic growth factor 1 is used in response to treatment follow up in growth hormone pituitary secretory adenomas, his consistency has been tested before. Insulin like growth factor 1 measurement has been reported after surgical procedures previously as a treatment response prognostic factor. In radiosurgery the initial response level rise and his slow return suggest an immediate response at celular level releasing insuline like growth factor 1 and stroma acute microvascular response increasing metabolic evironmental flow and feedback loop of growth hormon secretion, however there is not ready available information related to microscopic morphology, ultrastructural and functional changes in the tumor cells and peritumoral stroma as a result to single dose radiosurgery. In this investigation field is needed basic research updated information wich is not yet available after ionizing radiation exposure in single dose. This justifies enphasize the effort in basic research in supraselar growth hormone secretory adenomas.


Vinicio TOLEDO (GUADALAJARA MEXICO, Mexico), Marco BARAJAS, Carlos PATARROYO, Fernando ZAZUETA
09:00 - 18:00 #17805 - Stereotactic radiosurgery in the combined treatment for functional and nonfunctional pituitary adenomas.
Stereotactic radiosurgery in the combined treatment for functional and nonfunctional pituitary adenomas.

Stereotactic radiosurgery can be used for patients with residual or recurrent pituitary adenoma (PA) that are refractory to surgical and medical therapies.

Materials and methods. 35 patients (19 men and 16 women) with pituitary macroadenoma were treated from 2011 till 2017. 23 patients had single-fraction stereotactic radiosurgery (SRS) on Linear accelerator «Trilogy + BrainLab» and 12 patients had fractinated stereotactic radiosurgery(fSRS) on CyberKnife (CK). The diameter of PA ranged from 1,1 cm to 3,4 cm. 32 patients had previous neurosurgical operations. Hormonally inactive pituitary adenomas were observed in 5 cases. 17 patients had acromegaly (the level of GH was from 24 mmol / l to 216 mmol / l), in 10 cases was prolactinoma (LH level was from 88 ng / ml to 336 ng / ml), in 3 cases was Cushing disease with increased level of ACTH (the level of ACTH ranged from 100 pg / ml to 1250 pg / ml). The marginal doses for the tumors were for LINAC SRS 13 Gy to 17 Gy (median, 14.1 Gy), for CK SRS 18-25 Gy in 3-5 fractions.

Results: The median follow-up of patients was 14 months (range 8-36 months). There were not radiation-induced acute or late toxicities in any case, except for one case of apoplexy in the pituitary gland 4 months after SRS. The tumor had decreased in size in 19 patients and remained stable in 16 patients. 24 patients had a decrease in the level of hormones after radiosurgery.

Conclusion: Single-fraction SRS may represent a convenient approach to patients with small and medium-sized PA away at least 2 mm from the optic chiasm, whereas FSRT is preferred over SRS for lesions >2.5-3 cm in size and/or involving the anterior optic pathway.


Vladyslav BURYK (Sigulda, Latvia), Maris MEZECKIS, Olga CHUVASHOVA, Igors AKSIKS, Dace SAUKUMA, Jelena NIKOLAJEVA, Maris SKROMANIS
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P12
09:00 - 18:00

EPOSTER - 12 Prostate (GU)
Electronic Poster displayed from June 9 to June 13

09:00 - 18:00 #17648 - Early experience and results from the implementation of stereotactic body radiotherapy in localized prostate cancer.
Early experience and results from the implementation of stereotactic body radiotherapy in localized prostate cancer.

Purpose

The purpose of this study is to present the results, in terms of efficacy and safety, of the implementation of Stereotactic Body Radiotherapy (SBRT) as a definitive treatment of patients with localized prostate cancer in Hygeia Hospital, Athens, Greece.

Materials and Methods

Five patients with low-risk prostate cancer, Stage T1-2 with combined Gleason scores of 6 and median PSA below 8ng/ml, without androgen deprivation (ADT), were enrolled for SBRT treatment following a scheme of 35Gy delivered in 5 fractions in a period of two weeks. Assuming an alpha/beta value of 1.5, the biologically equivalent dose is 78Gy. The clinical target volume (CTV) included the prostate and depending on risk stratification, the base of seminal vesicles. Additional margins of 3-5mm were used to form the Planning Target Volume (PTV). Patient plans were calculated on Elekta Monaco TPS and treated on an Elekta VersaHD Linac using a 10 MV Flattening Filter Free (FFF) beam. Patients were given dietary and bladder filling instructions and a rectal enema prior to every fraction. Patient positioning was verified with CBCT image-guidance prior and post treatment. To evaluate the average variation of rectum position, image registration was performed between original CT and each CBCT. Rectum and bladder toxicity was evaluated.

Results

No significant rectal (grade1) or urinary (grade1) toxicity was observed for any of the patients during follow up. The toxicity profile was compared to past conventionally fractionated dose-escalation and hypofractionated studies. This is due to the combination of a strict and well-defined protocol which included careful bladder and rectal preparation, narrow margin expansion together with a strict pre-and post- treatment imaging protocol.

Conclusion

SBRT as a definitive therapy in localized prostate cancer has been successfully applied. All patients demonstrated normal PSA levels and low toxicity while maintaining high quality of life.


Georgios KRITSELIS (ATHENS, Greece), Chryssa PARASKEVOPOULOU, Nikolaos GIAKOUMAKIS, Efi KOUTSOUVELI, Pantelis KARAISKOS, Georgios KOLLIAS
09:00 - 18:00 #17843 - First UK experience of Hydrogels to Enhance Rectal Sparing during Prostate SBRT.
First UK experience of Hydrogels to Enhance Rectal Sparing during Prostate SBRT.

First UK experience of Hydrogels to Enhance Rectal Sparing during Prostate SBRT

Background

The use of hydrogrel spacers to help spare the rectum is growing in popularity in the field of radiation therapy including brachytherapy. In 2015 The London Clinic became the first UK hospital to use hydrogel SpaceoarsTM by AugemixTM. Since then several patients have had them inserted prior to radiotherapy or SABR treatment.

Method

The first three patients were selected who have had SBRT treatment for detailed analysis and follow up. Fiducials and Spaceoar were inserted in one session in day case procedure. The BKTM Ultrasound stepper unit was used transrectally to guide their insertion, which was performed via the transperineal route, whilst the patient was in the lithotomy position. A CT planning scan and MR T1 and T2 sequences were then performed 7 days later for each patient. The resulting scans were imported, fused and planned using MultiplanTM for treatment using PACE protocol(36.25Gy in 5 fractions) on the CyberknifeTM SBRT platform. Dose Volume Histogram (DVH) calculated and volumes are noted at the 37, 36.25, 35, 30, 25 and 20 Gy levels. Three past SBRT prostate patient treatment plans with Spacoar present were compared to the average data set obtained for Spacoar free plans.

Results

Resulting data from the DVHs were compared with the volume in terms of percentage and cubic centimetres. Differences observed were 37Gy spaceoar(n=3) 0.07% 0.07cc without(n=4) 1.53% 1.03cc, 35Gy 0.37% 0.27cc without 3.6% 2.881cc, 30Gy spaceoar 1.93% 1.14cc without 9.55% 6.42cc and 20Gy spaceoar 13.07% 8.29cc without 27.10% 18.48cc.

Conclusions

There was a reduction of dose to rectum as predicted2,3, particularly at the higher dose levels which are thought to be the areas where significant side effects occur. Typically a 1cm gap was generated between the prostate and the rectum. No significant toxicity has been reported over 4 years, in line with predicted results albeit for a small group of patients.


Nigel Ashley RICHMOND (London, United Kingdom), Simon STEVENS, Katrina FINNEGAN, Mark BRAY-PARRY, Jan KONIECZEK, Isabel HO, Joshua GESNER, Steven CRITCHLEY
09:00 - 18:00 #17893 - Quality of life after robotic radiosurgery of primary prostate cancer: sexual domain.
Quality of life after robotic radiosurgery of primary prostate cancer: sexual domain.

Introduction: Sexual domain is important aspect in Quality of Life (QoL) for sexualy active prostate cancer (pCa) patients (pts). Prescribed doses, regimens, treatment techniques and other aspects vary among clinics. Analysis of QoL data in every particular clinic helps in decision making for patients between different treatment methods.

Materials and methods: From June y.2016 to January 2019 26 sexually active patients who had received FSRS to primary prostate cancer filled EPIC Questionaire Sexual domain before treatment and during follow-up starting from 3 months post treatment. Prescribed dose was 35-36.25Gy with homogenous dose distribution (normalised 70-80% isodose line) to prostate (low-risk) or prostate + 1-2cm seminal vesicles (intermediate and high risk pCa) added 5-3mm for PTV. Intermediate and high risk pCa patients were treated focally increasing dose above 40Gy to dominant lesion on MRI/PSMA PET-CT. Follow-up was 3 - 12 months (median 6.5 months). Patients receiving androgen deprivation therapy were excluded. Relation of deterioration in EPIC score with clinical stage and correlation of target volume was analyzed with SPSS Statistics software (Kruskal-Wallis H, Spearman's rank correlation,) . Baseline EPIC score was 158-600 (median 462.5).

Results: Overall EPIC score in Sexual domain was reduced on 4.16-44.50% (median 12.5%) in following months after treatment. For 3 (11.54%) patients EPIC score returned to baseline afterwards, for 14 pts (53.85%) remained deteriorated (median difference -16.6%) and for 9 pts (34.62%) score raised above baseline on 5-35% (median +15.82%). There was no correlation found in EPIC score changes and clinical stage or size of the target volume.

Conclusions: Prostate radiosurgery has different impact on sexual QoL in particular follow-up period. For some patients it showed positive effect what might be linked to psychological aspect of completed treatment and reduced PSA. There were not found risk factors what might be linked with reduced sexual QoL. Further data analysis for correlation of EPIC score changes with radiation dose to anatomical structures, such as neuro-vascular bundle, penile bulb and external urethral sphincter, has to be done in larger population and in longer follow-up to clarify risk factors for reduced sexual QoL.


Maris MEZECKIS (Sigulda, Latvia), Kirils IVANOVS, Egils VJATERS, Sandra LEDINA, Vladislav BURYK
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P14
09:00 - 18:00

EPOSTER - 14 Spine
Electronic Poster displayed from June 9 to June 13

09:00 - 18:00 #17535 - Dosimetric impact of nerve roots sparing in spinal metastases stereotactic body radiotherapy treatment with Cyberknife.
Dosimetric impact of nerve roots sparing in spinal metastases stereotactic body radiotherapy treatment with Cyberknife.

Purpose

The aim of this analysis was to assess whether preservation of nerve roots (NR) doesn’t deteriorate treatment plan of spinal metastasis treated in SBRT. Radiation-induced neuralgia may occurs in 15% of cases, which is painful and a cause of the decrease in patients' quality of life.

Patients and Methods

Data concerning 11 patients treated for spinal metastases at levels between T12 and L5, in one or 3 fractions, were retrospectively studied. The prescribed dose were between 18 and 27Gy. All patients had pre-treatment imaging with CT and MRI scanner in high resolution (CT used for dose calculation, the T1 gado sequence for tumor delineation and the T2 sequence for NR, SC and CE delineation). For each patient two treatment plans were calculated, the first one without dose constraint to NR, and the second one with. All plans were analyzed according to: the tumor coverage, the quality index and the dose constraint to SC and CE. For SC, CE and NR, the nearest maximal dose was recorded. For NR, the mean dose was computed too. Parameters of the two groups were compared by a Student’s t-test and are given with 95% confidence intervals.

Results

For each patient, both plans respect tumor coverage and dose constraint to OAR. The quality index results are similar for both plans in each patient, no significant difference was found. For SC, the mean nearest maximal doses were 12.2Gy and 11.4Gy (P=0.41), respectively for plan without optimization on NR and with, in 3 fractions. For CE, the mean nearest maximal doses were 15.3Gy and 15.7Gy (P=0.49) for single fraction and 23.6Gy and 22.7Gy (P=0.45) for 3 fractions. For NR, the mean nearest maximal doses were 17.8Gy and 14.8Gy (P=0.005) for single fraction and 24.5Gy and 23.3Gy (P=0.21) for 3 fractions. The mean doses to NR were, for single fraction treatment, 14.56Gy and 12.09Gy (P=0.04) and 19.52Gy and 18.44Gy (P=0.37) for 3 fractions treatment.

Conclusion

The decreasing of NR dose constraint allowed to achieve clinically acceptable treatment plans and all quality index obtained were similar. The optimizing of NR dose constraints does not deteriorate the nearest maximal dose to SC and CE. For single fraction, the addition of dose constraint to NR significantly reduces their nearest maximal dose by about 13%. For plans delivered in 3 fractions, this study doesn’t have enough patients to achieve significant results.


Florence BARTIER (AMIENS), Alexandre COUTTE, Michel LEFRANC
09:00 - 18:00 #17709 - Early experience with spine radiosurgery planning and patient specific QA with a dedicated spine SRS treatment planning system.
Early experience with spine radiosurgery planning and patient specific QA with a dedicated spine SRS treatment planning system.

                The initial experiences with the BrainLab Elements Spine Stereotactic Radiosurgery treatment planning system (TPS) are described. Spine Elements includes multi-modality image fusion, spine curvature correction, automatic target and critical structure segmentation, and a VMAT-based treatment planning system capable of Monte Carlo dose calculation. The software was accepted and commissioned in 2018 and five patients have since been treated using a Novalis Tx linear accelerator with the BrainLab ExacTrac system for localization. Of the five patients, three were single fraction SRS (12-16 Gy) and two were fractionated in 3 and 5 fractions. The patient-specific QA results when recomputing the patient plan on an Octavius 4D phantom geometry were analyzed using gamma analysis. Confidence in the initial commissioning was ensured via MPPG 5.a and an IROC Spine phantom accreditation using the Monte Carlo algorithm. Gamma analysis was performed using passing criteria of 3% and 1 mm. Global gamma was used relative to the maximum dose value in the calculated volume. All gamma analysis results comparing an Octavius 1000SRS array measurement with calculation were above 98% using 2%/2mm local gamma. For patient plans, average gamma passing rate was 99.2% with a standard deviation of 1.0%. Median dose deviation across all patients is 1.1% with a standard deviation of 0.3%. Accurate dosimetric results were obtained through IROC accreditation, MPPG 5A, and patient QA plans for the first five patients thereby validating the dose calculation of a novel spine SRS TPS utilizing Monte Carlo.


Daniel SAENZ, Richard CROWNOVER, Niko PAPANIKOLAOU (San antonio, USA)
09:00 - 18:00 #17565 - Evaluation of spine dose during SBRT treatment of spine metastases.
Evaluation of spine dose during SBRT treatment of spine metastases.

Objectives: To evaluate the actual dose received by the spinal cord during SBRT treatment of spine metastases due to the variation in patient position.

Methods: 5 patients with 7 different spine metastases were planned and treated using SBRT technique, the dose delivered using RapidArc modality on Varian linear accelerator 2100CD with Exact couch. All patients were immobilized using SBRT rails and customized vacuum bag, arms were above the head on Posirest arm support, knee and feet support were used. The dose was initially selected to be 24Gy in 3 fractions. Dose constrains for the spinal cord were taken from the AAPM report TG101. To verify the patient setup, 2 orthogonal KV images were used, once position is corrected then CBCT image will be acquired.

Target volume and spinal cord contours were copied from the CT and pasted on the CBCT, they were adjusted to match the bony landmark. Plans were created using the same treatment field with the isocenter positioned as on the actual treatment.

To be able to use the CBCT for dose calculation, CBCT calibration curve was created in the Eclipse TPS. Constancy of the HU is checked as part of the monthly quality control of the linear accelerator.

Results: Doses at the following spine volumes were compared: 1.2cc, 0.35cc, maximum dose and 10% of the partial spine volume. Mean of dose differences in percent were found to be lower in CBCT image for the specified volumes respectively (1.6 ± 2.1, 1.8 ± 2.9, 1.5 ± 4.0 and 0.4 ± 3.0)

Conclusion: SBRT for spine is a safe procedure even though there is small variation in patient setup, it still shows that the dose constrains to the spine are well maintained. Next step is to consider the RTOG631 dose prescription of 16-18Gy in a single fraction.


Marouf ADILI (Riyadh, Saudi Arabia), Abdulaziz ALHAMAD, Bilal MUHAMMAD
09:00 - 18:00 #17620 - Evaluation of spine structure stability at different locations during SBRT.
Evaluation of spine structure stability at different locations during SBRT.

Purpose: To evaluate spine movement and spine position stability during stereotactic body radiotherapy (SBRT).

Methods and Materials: This study included 123 patients treated with spine SBRT. We analyzed different locations within the spine using system log files generated during treatment, which contain information about differences in the pretreatment reference spine positions by CT versus positions during SBRT treatment. We evaluated mean spine motion and intra/interfraction motion. We defined and evaluated spine stability and spine significant shifts (SSHs) during treatment.

Results: We analyzed 462 fractions. For the cervical (C) spine, we observed the greatest shifts in the anterior-posterior (AP) direction (2.48 mm) and in pitch rotation (1.75 deg). The thoracic (Th) spine showed the biggest shift in the AP direction (3.68 mm) and in roll rotation (1.66 deg). For the lumbar-sacral (LS) spine, the biggest shift was found for left-right (LR) translation (3.81 mm) and roll rotation (3.67 deg). No C spine case exceeded 1 mm/1 deg for interfraction variability, but 7 of 54 Th spine cases exceeded 1 mm interfraction variability for translations (maximum value, 2.5 mm in the AP direction). The interfraction variability for translations exceeded 1 mm in 2 of 24 LS spine cases (maximum value, 1.7 mm in the LR direction). Only 13% of cases had no SSHs. The mean times to SSH were 6.5±3.9 min, 8.1±5.9 min, and 8.8±7.1 min for the C, Th, and LS spine, respectively, and the mean recorded SSH values were 1.6±0.66, 1.43±0.33, and 1.46±0.47 mm/deg, respectively.

Conclusion: Positional tracking during spine SBRT treatments revealed low mean translational and rotational shifts. Patient immobilization did not improve spine shifts compared with our results for the Th and LS spine without immobilization. For the most precise spine SBRT, we recommend checking the patient’s position during treatment.


Lukas KNYBEL (Ostrava, Czech Republic), Jakub CVEK, Zuzana CERMAKOVA, Michaela POMAKI, Jaroslav HAVELKA, Kamila RESOVA
09:00 - 18:00 #17870 - Leksell frame fixation at maxilla for treating upper cervical spine lesions: nuances and our experience.
Leksell frame fixation at maxilla for treating upper cervical spine lesions: nuances and our experience.

Background: Traditional restriction of foramen magnum as the lower limit for target location for GKRS makes treatment of upper cervical spinal lesions formidable. Leksell frame fixation above supraorbital margins helps in achieving targets up to axis vertebra level. To target lesions in upper cervical spine with ensured immobility remains a challenging task. We describe our experience of treating lesions located in or extending into upper cervical spine while ensuring immobilisation and the precision of treatment. 

 

Material and Methods: We treated three cases of upper cervical spinal lesions (2 intradural extramedullary tumors and one skull base lesion). To minimize the movement at craniovertebral junction, Philadelphia collar was placed and frame was docked on it. The constant relative head neck position was maintained by keeping glabellar-floor and sternal-floor distance constant. Patient positioning system (PPS) and docking gamma angle were maintained at same values throughout the procedure. 

 

Results: All patients tolerated the procedure well. There was no complication at one-year follow up interval. One patient showed >50% tumour size reduction at one-year follow up. 

 

Conclusion: We tried to push the limits of stereotactic frame by fixing it on maxilla while maintaining immobilization by using strict protocol. Zygomatic process of maxilla might be considered a potential alternate site for frame fixation to target lesions upto C3 vertebra. The well-established dose algorithm for Cyberknife/LINAC system helps in validation of safe dose range for spinal lesions. This proof of concept model also facilitates treatment of lesions in patients with bony defects of previous surgeries (e.g. bifrontal decompressive craniectomy etc.).

 


Manjul TRIPATHI (Chandigarh, India), Kanchan MUKHERJEE
09:00 - 18:00 #17869 - Linac-Based Radiosurgery in Spinal Tumors: Institutional Report.
Linac-Based Radiosurgery in Spinal Tumors: Institutional Report.

Purpose: to report local control and tolerance of stereotactic body radiotherapy (SBRT) in patients with spinal tumors.

 Materials and Methods: SBRT was delivered with LINAC (Linear Accelerator), volumetric modulated-arc therapy (VMAT) and image guided radiotherapy (IGRT). The primary end points were toxicity, clinical local control with radiographic study every 3 month and we use the common terminology of Criteria for Adverse Events v4.0 (CTCAE).

 Results: between September 2016 and November 2018, a total of 28 patients and 41 lesion were irradiated with a median dose of 25Gy(16-50Gy) in 3(1-5) fractions. With a follow up of 15.3 months and a mean age of 62 years old, we found 32(78%) metastatic lesions and 5(12%) primary lesions of spine, all without prior radiotherapy. The most frequent spinal areas were 25 thoracic, 12 lumbar, 2 cervical, 2 sacrum  respectively.  A single fraction was delivered in 11 cases (39%), while a 3-5fractions scheme was used in 17 (61%). The most common histological metastasis lesion was lung and prostate adenocarcinoma. Clinical local control at 10 months was 80% and no cases of Grade 3-4 toxicity were reported.

 Conclusion: SBRT is an effective treatment to achieve local control in spinal metastases. Our results appear comparable to previous reports analyzing spine SBRT.


Daniel DAVALOS, Lucas CAUSSA (Córdoba, Argentina), José Máximo BARROS, Diego FERNANDEZ, Caroline DESCAMPS, Maria Fernanda DIAZ VAZQUEZ, Diego FRANCO, Enrique HERRERA, Emilio MEZZANO, German OLMEDO, Egle AON, Gustavo FERRARIS
09:00 - 18:00 #17752 - The Feasibility of Spinal Stereotactic Radiosurgery for Spinal Metastasis with Epidural Cord Compression.
The Feasibility of Spinal Stereotactic Radiosurgery for Spinal Metastasis with Epidural Cord Compression.

Purpose: To investigate the effectiveness and safety of spinal stereotactic radiosurgery (SRS) in treating spinal metastasis with epidural spinal cord compression (ESCC).

Materials and Methods: During 2013–2016, 149 regions of spinal metastasis in 105 patients treated with single-fraction (12–24 Gy) spinal SRS were reviewed. Cord compression of Bilsky grade 2 (with visible cerebrospinal fluid [CSF]) or 3 (no visible CSF) was defined as ESCC. Local progression (LP) and vertebral compression fracture (VCF) rates after SRS were evaluated using multivariate competing-risk regression analysis.

Results: The 1-year cumulative incidences of LP for Bilsky grades 0 (n = 80), 1 (n = 39), 2 (n = 21), and 3 (n = 9) were 3.0%, 8.4%, 0%, and 24.9%, respectively. ESCC did not significantly increase the LP rate (no LP for grade 2; subhazard ratio [SHR] for grade 3, 4.521; p = 0.246). The 1-year cumulative incidences of VCF for Bilsky grades 0, 1, 2, and 3 were 6.6%, 5.2%, 17.1%, and 12.1%, respectively. ESCC may increase VCF risk (SHR for grade 2, 5.368; p = 0.035; SHR for grade 3, 2.215; p = 0.460). The complete or partial pain response rates after SRS were 79%, 78%, 53%, and 63% for Bilsky grades 0, 1, 2, and 3, respectively (p = 0.008). No neurotoxicity of grade ≥3 was observed.

Conclusions: Spinal SRS for spinal metastasis with Bilsky grade 2 ESCC did not increase the LP rate, was not associated with severe neurotoxicity, and showed moderate VCF and pain response rates.


Yi-Jun KIM, Jin Ho KIM (Seoul, Korea), Kyubo KIM, Hak Jae KIM, Eui Kyu CHIE, Kyung Hwan SHIN, Hong-Gyun WU, Il Han KIM
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Electronic Poster displayed from June 9 to June 13

09:00 - 18:00 #17760 - Analysis of 12 Cases of Solitary Fibrous Tumor/Central Hemangiopericytoma Treated with Gamma Knife.
Analysis of 12 Cases of Solitary Fibrous Tumor/Central Hemangiopericytoma Treated with Gamma Knife.

Objective: To summarize the effectiveness and efficacy of gamma knife in the treatment of solitary fibrous tumor/central hemangiopericytoma. Methods: The clinical data and follow-up results of 12 patients (2/10) with solitary fibrous tumor/central hemangiopericytoma treated with gamma knife from 2006 to 2016 were retrospectively reviewed to perform summary analysis. Results: All patients were followed up for 11 to 47 months, with an average of 29 months, including 10 cases with significantly decreased diameters of tumors at 3 to 4 months after the gamma knife treatment, 4 cases with recurrences and 2 cases with intracranial metastasis. No adverse reactions such as neurological injury or edema reaction were found in all patients after gamma knife treatment. Conclusion: Gamma knife is a safe and effective treatment for solitary fibrous tumor/central hemangiopericytoma, especially for residual or recurrent tumors after operations, with a satisfactory tumor control rate.


Yiguang LIN, Dong LIU (Tianjin, China), Desheng XU
09:00 - 18:00 #17891 - Cisternae Oculomotor Schwannoma Treated With Gamma-Knife.
Cisternae Oculomotor Schwannoma Treated With Gamma-Knife.

Introduction:Cisternae Oculomotor Nerve Schwannomas (ONS) are rare and of difficult surgical approach. These lesions can present as ophthalmoplegic migraine.

Objective:To describe unilateral third nerve palsy without diplopia diagnosed due to an ONS. It was submitted to Gamma Knife Radiosurgery (GKR).

Methods:Detailed review of the literature using Pubmed identified few reports of presumed schwannomas affecting the third A 55-year-old woman presented with progressive abduction of the right eye during the period of 3 years, accompanied of eye irritation and light sensitivity. There was dilation of the right pupil without diplopia with preserved consensual reflex. Magnetic resonance imaging (MRI) revealed an 8.0 x 7.0 mm enhancing lesion occupying the right pre-pontine cistern, 3 mm away from the right optic tract. There was an important atrophy of the right third cranial nerve near the brainstem. Tumor volume was 309.2mm3. She was treated with GKR, the lesion received a total dose of 12Gy prescribed to the 50% isodoseline. Four isocenters of 4 mm collimator were used. Treatment time was 35 minutes. There were no complications and the patient was discharged on the same day. 

Conclusions:GKR is well described for schwannomas. This is a case of atypical location treated with excellent sparing of eloquent structures, specially the optic tract. 


Aline Lariessy CAMPOS PAIVA (Sao Paulo, Brazil), Alessandra GORGULHO, Rafael COSTA LIMA MAIA, Juliete MELO DINIZ, Tomás DE ANDRADE LOURENÇÃO FREDDI, Bruno Henrique DALLO GALLO, Antonio DE SALLES
09:00 - 18:00 #17867 - Current Status of Radiosurgery in India.
Current Status of Radiosurgery in India.

Though established as a treatment modality for various neurosurgical ailments, radiosurgery is yet to establish its firm feet in India. Gamma knife radiosurgery (GKRS) is considered a natural extension to microneurosurgery but there are competitive and supplemental interests. First gamma knife unit in India was established in 1996 at PD Hinduja Hospital, Mumbai shortly followed by AIIMS, New Delhi. At present there are 6 functional gamma knife centres in India. Out of these, 4 are at government teaching institutes while 2 at private centres. 4 centres are working on Perfexion, one with 4C and another with the B model of Gamma knife. There are 6 centres practising cyberknife radiosurgery and many more are yet to come. In comparison to Gamma knife, there are more centres coming up with Cyberknife because of logistic reasons. There is need of many more centres to take care of skewed facility patient ratio. The majority of the patient population is of benign intracranial pathologies and vascular malformations. This is in contrast to the western practice, where intracranial metastasis constitutes the majority of the patient population. One important reason for the same is nearly universal absence of medical insurance and prevailing nihilism in general population. With increasing awareness among neurosurgeons and publicity of non-invasive nature of radiosurgery with publications establishing its efficacy in long term, radiosurgery is now becoming a regular knife in neurosurgical armamentarium. 


Manjul TRIPATHI (Chandigarh, India)
09:00 - 18:00 #17798 - Fractionated radiotherapy for benign brain tumors using mask system of Leksell Gamma Knife Icon.
Fractionated radiotherapy for benign brain tumors using mask system of Leksell Gamma Knife Icon.

Object: Leksell Gamma Knife Icon enables us to apply new methods of immobilization using mask fixation and the option of fractionated treatment. This provides exceptional accuracy and precision of radiosurgery, making it a possibility for many more disease types and many more patients to be treated.

Methods: We retrospectively analyzed 67 patients (69 times) with benign brain tumors who underwent fractionated radiotherapy using mask system of Gamma Knife Icon between September 25th, 2017 and December 31th, 2018 at Rakusai Shimizu Hospital. The most common disease was meningioma (38 patients), followed by vestibular schwannoma (12), craniopharyngioma (7), pituitary adenoma (6) and other schwannomas (4). The reasons of fractionated treatment were large tumor volume (24 patients), recurrence (10) and neurological critical location (45). For higher accuracy, we changed the upper limit of the HDMM system from 1.5mm to 0.5mm for benign tumors.

Results: We selected basically 2.7Gy x 10Fr for benign tumors but specially 1.8Gy x 25Fr for recurrent supracellar lesions for preservation of visual functions. All cases are alive and have no neurological deterioration, except only 2 cases of meningioma underwent repeat fractionated radiotherapy.

Conclusions: Although these results are limited to short periods, survival rated, local control rates and qualitative survival rated in patients unsuitable for SRS, such as those with large, recurrent, and eloquent site lesions, were within the acceptable ranges. Further examination is needed for comparison with staged Gamma Knife radiotherapy, Cyber-Knife and Novalis radiotherapies.

 


Takuya KAWABE (Kyoto, Japan), Manabu SATO
09:00 - 18:00 #17874 - Frame-based and masked stereotactic radiosurgery: a patient experience comparison with the gamma knife icon.
Frame-based and masked stereotactic radiosurgery: a patient experience comparison with the gamma knife icon.

Introduction

Patients undergoing stereotactic radiosurgery (SRS) for intracranial pathology have two technical treatment options: frame-based versus masked. There is sparse information on a patient’s experience between the two types and to what extent a patient’s diagnosis will predicts their SRS experience.

Methods

A retrospective analysis of patients who completed a questionnaire of their experience of framed-based or masked SRS using the Gamma Knife Icon from June through November 2018 at our institution was completed.

Results

Twenty-eight patients undergoing SRS completed the questionnaire, where 61% of the procedures were frame-based and 39% masked. The average age was 61.2 +16.1 years old, 54% of which were male. Pathologies treated were metastasis, meningiomas, vestibular schwannomas, arteriovenous malformations, neurocytoma, pituitary adenoma, and glioblastoma multiforme. Of the patients treated with a frame-based technique, 59% did not find SRS to be uncomfortable. Comparatively, 82% of patients who received masked treatments did not find SRS to be uncomfortable. Frame-based treatment patients rated their pain of frame placement on a visual analog scale (VAS) 1-3 (24%), VAS 4-6 (48%), VAS 7-10 (24%, one patient didn't rate their pain and was excluded). Five patients answered that they didn't tolerate the procedure as expected. Most of the five patients who perceived not tolerating the procedure, were treated using a framed compared to masked method (80% vs. 20%, respectively). Compared to previous surgery or SRS, 7% found their experience of SRS was not tolerable (both of which were frame-based), while 93% of patients would consider repeat SRS if necessary. All patients who received frame-based and masked treatments felt adequately informed about the procedure. The patient experience of discomfort during SRS was higher with benign versus malignant lesions (63% vs. 20%, respectively). Evaluation of pain during frame placement was similar for patients treated for benign versus malignant lesions (median VAS pain: 6 +1.46 [95% CI 4.9 – 7.1], 4 +2.74 [95% CI 2.2 – 5.8], respectively). 

Conclusions

We found that patient experience undergoing frame-based treatment was less tolerable and caused more discomfort in comparison to the masked technique. Patients experienced more discomfort if they were being treated for a benign compared to a malignant pathology.


Troy DAWLEY, Zaker RANA, Anuj GOENKA, Michael SCHULDER (Lake Success, NY, USA)
09:00 - 18:00 #17840 - Gamma Knife Centre of Queensland: the utility of telehealth services.
Gamma Knife Centre of Queensland: the utility of telehealth services.

Introduction

Telehealth is the process of conducting clinic consultations through a variety of videoconferencing platforms.  The Gamma Knife Centre of Queensland (GKCoQ) was established as a statewide service in October 2015 and has utilized telehealth since January 2016.

The Queensland population is approximately 5 million people but covers a land mass of 1.85million km2, comparable to the area of Mexico.  Given such large geographic regions, gaps in health outcomes have been previously demonstrated between Australian patients from city versus rural/remote areas.  The GKCoQ has sought from its inception to offer an inclusive service for all patients using a telemedicine approach.  Rural and remote patients are able to participate from their homes, local doctors’ rooms, or local Hospital and Health Service telehealth-enabled conference room.

The study aims to examine the workload of the GKCoQ unit, explores the proportion of work streamlined through the telehealth approach, and identifies both barriers and enablers of the telehealth program.

Method

Data regarding the geographic distribution of patients utilizing telehealth was examined retrospectively. New cases and review consultations were included. 

Results

Between January 2016 and January 2019, there were 1359 new patients seen in the Gamma Knife unit in total, and 197 (14%) were seen through the telehealth clinic.  There were 568 telehealth consultations in total and the age of patients ranged from 18 to 88 years.  Most patients seen as a telehealth new case elected to continue to utilize telehealth for follow-up.  17% of telehealth consultations were with Australian patients located outside Queensland, and the vast majority of telehealth patients were from rural areas of Queensland and urban centers outside Brisbane.

Conclusion

The telehealth service is advantageous to the GKCoQ in improving healthcare access to Australians in rural and remote regions, and is an effective means of managing the GKCoQ workload while minimizing patient travel and inconvenience.


Kimberley BUDGEN, Mark PINKHAM, Angela MCBEAN, Natalie CLARKE, Frances WILLIAMS, Anescè STAPELBERG, Bruce HALL, Matthew FOOTE (Brisbane, Australia)
09:00 - 18:00 #17835 - Gamma Knife Radiosurgery Strategies for Cystic Lesions and Cyst Formation.
Gamma Knife Radiosurgery Strategies for Cystic Lesions and Cyst Formation.

Introduction: Gamma Knife Radiosurgery (GKR) for cystic-lesion is controversial. Strategies for GKR for these lesions need analyses. The cystic-lesion formation physiopathology is also curious.

Objective: Define strategies of cystic-lesion radiosurgery and mechanisms of cystic lesions after GKR.

Methodology: Analyses of three cases of brain tumors: two with Pilocytic Astrocytoma (PA), one with Pineal Papillary Tumor (PTPR) and cyst formation in an arteriovenous malformation (AVM) treated with embolization and GKR needing microsurgery intervention.

Results: A 9-years-old-girl with PTPR, an 11-year-old boy with PA and a 34-year-old man also with PA had cystic lesions previously submitted to various neurosurgical procedures. They received GKR after stereotactic aspiration and placement of an Ommaya reservoir. Magnetic resonance imaging (MRI) showed remarkable control of the tumors in two of these patients in a bimodal fashion. The 34-year-old patient died due to a sudden cardiac arrest attributed to pulmonary embolism. A 12-year-old boy with a right frontal AVM successfully embolized followed GKR developed after two-years a large cystic lesion occupying the cavity of a pre-treatment bleeding. He required endoscopic ventricular marsupialization and with microsurgery lesion resection.

Conclusion:  Although the present work points out the efficacy of GKR for treatment of PA it is unique for the observation of the bimodal cystic response needing Ommaya reservoir for temporary drainage and the relatively newly described PTPR. The combination of different therapeutic modalities allows for a good quality of life, avoiding multiple large interventions. Cysts secondary to radiosurgery is likely due to edema-induced transudate occupying intra-parenchymal space previously occupied by the treated lesion.


Rafael COSTA LIMA MAIA (São Paulo, Brazil), Alessandra GORGULHO, Fabrício CORREA LAMIS, Crystian WILIAN CHAGAS SARAIVA, Antonio DE SALLES
09:00 - 18:00 #17866 - Hypofractionated radiosurgery with Gamma Knife Icon®.
Hypofractionated radiosurgery with Gamma Knife Icon®.

Introduction:

Gamma Knife Radiosurgery (GKRS) yields superior conformity and selectivity. However, large lesions and lesions abutting organs at risk can not be treated safely in a single fraction. To overcome this, one can make use of fractionation. Gamma Knife Icon® with mask immobilization allows to take advantage of (hypo)fractionation in addition to the advantage of its high conformity and selectivity.  In this study, we report on our experience with (hypo)fractionated GKRS.

Material and Methods:

Between January 2016 and November 2018, we have performed 335 Gamma Knife procedures with mask immobilization to treat 83 targets in 73 patients. A dose of 13 to 25 Gy, prescribed to the isodoseline covering 100% of the target, was delivered in 1 to 5 fractions. Fourteen single fraction procedures were performed with mask immobilization because of preferences of the patients. The major indications for fractionation were large volume (43 targets) and or targets abutting cranial nerves (34 targets). Other indications were ill-defined lesions and previous craniotomies. The most common lesions treated were meningioma (43 patients), metastases (26 patients), plexus papilloma (4 patients), vestibular schwannoma (3 patients) and  pituitary adenoma (2 patients). All patients had follow-up in our center with MRI scan as long as clinical meaningful .

Results:

Mean follow-up was 12 months (range 1-31 months). Eight of the 73 patients experienced complications: cranial neuropathy (5 patients), symptomatic edema (2 patients), seizures (1 patient). Twenty-two patients (of which 15 with metastases) died (mean survival 10,2 months, range 2-22,5 months). All patients with a benign disease had local control.

Conclusions:

Gamma Knife Icon® with mask immobilization allows to treat large lesions and lesions abutting organs at risk. It yields high local control rates and minimal toxicity rates. (Hypo)fractionated GKRS can be an alternative to (stereotactic) radiotherapy or to surgery in selected patients.


Patrick HANSSENS, Patrick HANSSENS (Tilburg, The Netherlands), Guus BEUTE, Suan Te LIE, Jeroen VERHEUL, Bram VAN DER POL, Liselotte LAMERS, Diana GROOTENBOERS, Jannie SCHASFOORT - VAN DEN TILLAART, Wim DE JONG
09:00 - 18:00 #17877 - Primary dose fractionated gamma knife radiosurgery for large volume glomus jugulare tumours.
Primary dose fractionated gamma knife radiosurgery for large volume glomus jugulare tumours.

Objective:Stereotactic radiosurgery is emerging as optimal primary treatment modality for glomus jugulare tumours (GJT). This study evaluates efficacy and safety of dose fractionated gamma knife radiosurgery (DFGKRS) in treatment of glomus jugulare tumours not amenable for single session GKRS.

Material and Methods:Between 2012 and 2017, 10 patients of glomus jugulare tumours were treated with DFGKRS in 2 or 3 sessions. The Leksell G frame was kept in situ during the whole procedure. The tumour volumes on pre- and posttreatment imaging were compared utilizing the Leksell Gamma Plan treatment plan software to assess tumour progression. Pre- and posttreatment symptoms and complications were recorded.

Results: The mean radiological follow up was 39 months. The mean marginal dose for three fractions and two fractions was 7.64 Gy @ 50% and 11.2 Gy @ 50 % respectively. The mean tumour size was 29.9cc at treatment and 21.9cc at follow-up. Tumour control (defined as stable or reduced tumour volume at follow up) was achieved in all patients (100%). Out of 110 potential neurological problems (signs/ symptoms) evaluated (11 in each patient), 56 (50.9%) were present preoperatively. Of them, 27 (48.2%) improved and 29 (51.8%) stabilised after treatment. There were 2 new onset neurological problems (out of 110, 1.8%) attributable to treatment. 

Conclusion:DFGKRS is feasible for glomus jugulare tumours (GJT) with a fair tumour control rate and acceptable toxicity (CTCAE grade 1-2). DFGKRS should be preferred over surgery or radiotherapy in GJT not amenable for single session GKRS.

 


Amanjot KAUR (Mohali, India), Navneet KAUR
09:00 - 18:00 #17711 - Radiosurgery for cranial and spinal haemangioblastomas: monoinstitutional analysis.
Radiosurgery for cranial and spinal haemangioblastomas: monoinstitutional analysis.

PURPOSE. Though primary therapy for Hemangioblastomas (HB) is surgical resection, for patients with subtotally excised or unresectable lesions and for patients with poor clinical status who are not good candidates for surgery, as well as those wishing a minimally invasive approach, radiotherapy (RT) or radiosurgery (SRS) can be an effective alternative. RT and SRS have been associated with good rates of local control in a 60–90% range, especially in patients with VHL. The aim of this study is to evaluate the efficacy and safety of SRS for patients with diagnosis of intracranial and spinal HB in terms of local control and toxicity.

METHODS. We conducted a retrospective analysis of 22 patients with a total of 37 HB: 23 intracranial HB and 14 spinal HB treated at our Institute from January 2012 until February 2017.

A regular clinical and radiological follow-up with MR imaging was scheduled at 4–6 month intervals after SRS procedure. The toxicity was recorded based on CTCAE 3.0v. The radiosurgical procedures were performed using a CyberKnife system, characterized by a 6MV linac mounted on a robotic arm for multiple, non-isocentric, non-coplanar beams sets delivery. Statistical analysis was carried out using SPSS 21.

RESULTS. Twenty-two patients were followed for a median of 42 months (range 3–72 months). Median age at the time of SRS was 44 years (range 19-79), 8 patients were female and 14 male.

The diagnosis of HB was based on the histological findings, except in 7 patients without surgical removal. Seven patients had multiple lesions and 30 patients had a single lesion. The mean prescription dose was 18 Gy (range, 10-25 Gy) in 1-5 fractions with median isodose line of 81% (range, 73-88%).Two patients (9%) developed a recurrence, 12 patients (55%) showed stable disease and 8 (36%) partial response. There was no significant toxicity after treatments.

CONCLUSION. SRS, both in single and multi-fractions settings, is potentially attractive for patients with VHL disease where multiple HB may develop either concurrently or sequentially and may be difficult to treat or retreat with repeated surgery and/or conventional radiation techniques without the risk of toxicity. Our results show that SRS can be considered a safe and effective treatment for intracranial and spinal HB.


Valentina PINZI, Anna VIOLA, Elena DE MARTIN, Cecilia IEZZONI, Marcello MARCHETTI, Laura FARISELLI (milan, Italy)
09:00 - 18:00 #17651 - Repeat gamma knife radiosurgery for cavernous sinus hemangiomas: a report of 3 cases.
Repeat gamma knife radiosurgery for cavernous sinus hemangiomas: a report of 3 cases.

Background: Gamma knife radiosurgery(GKRS) is well established in the management of cavernous sinus hemangiomas(CaSHs) alternative to microsurgery. Tumor regrowth, however, is occasionally encountered, and treatment modality is usually controversial in such cases. The role of repeat GKRS in these situations is still unclear. The goal of this study was to investigate whether repeat GKRS is an effective and safe treatment for recurrent CaSHs after initial GKRS.Methods: Between January 2008 and November 2009, 42 patients haboring CaSHs were treated using a Leksell Gamma Knife model C at Gamma Knife Center of Huashan Hospital. Of these, 2 patients (4.8%) had regrowth of the residual tumor and 1 patient habored still large volume of tumor after initial GKRS. Repeat GKRS was performed in all three patients, who had more than 100 months of follow-up. There were 2 female and 1 male patients with a median age of 41 (range, 7-54) years old. The median follow-up period after repeat GKRS was 11 months, and the median interval between these interventions was 99 (range, 74-122) months. The median tumor volume was 8.98 and 5.80 ml at the initial and second GKRS treatments, respectively. Patients received a median prescription dose of 13.5 Gy and 14.0 Gy at first and second interventions, respectively.Results: The median follow-up was 110 months (range, 100-128 months). At last follow-up, we report no cases of failure in repeat GKRS for CaSHs. All three patients demonstrated again a significant reduction in tumor volume. The median tumor volume reduction was 65.7% (range, 35.4%-70.1%) and 51.1% (range, 33.2%-53.1%) after initial and repeat GKRS treatments compared with the pre-GKRS volume, respectively. Post-GKRS clinical improvement was achieved in all three patients (100%). No radiation-induced neurological deficits or delayed complications secondary to GKRS were observed during the long follow-up period. Conclusions: This is the first report to address repeat GKRS for CaSHs. Repeat GKRS can result in further tumor volume reduction of residual CaSHs years after initial GKRS. During long-term follow-up, regrowing of remnant CaSHs after GKRS can be detected. Repeat GKRS seems to be a safe and effective treatment in patients harboring regrowth of small CaSHs that have previously been treated with GKRS.


Xuqun TANG (Shanghai, China), Li PAN, Hanfeng WU, Nan ZHANG, Jiazhong DAI
09:00 - 18:00 #17617 - Significance of record maintenance and keeping backups for Radiosurgery patient’s data.
Significance of record maintenance and keeping backups for Radiosurgery patient’s data.

Significance of record maintenance and keeping backups for Radiosurgery patient’s data.

Objective: Radiosurgery patients are generally considered to survive long and quite often require repeat treatment  procedures in future. Therefore, it is highly recommended for centers performing radiosurgery to keep backup strategies in the paced paperless technology era.

Methods: The “Perfexion” Gamma knife unit was installed at PSMMC in Sep. 2013 as the first unit in the kingdom. A total of 110 patients have been treated till October 2018. This unit was installed under the administration of Radiation Oncology department, which requires to keep a record of every radiotherapy treated patient in Varian record and verification system “ARIA” through electronic PDF files of approved radiosurgery plans, alongside a hard copy of documents as conventional manual file of the respective patient. This helps forming a reasonable backup system in case electronic counterpart faces any form of strain.

Unfortunately, on September 2016, an unplanned power shut down led to the permanent damage to the primary hard disc as well as the second backup hard disc, which was physically located at the same premises as the main planning system.

 Despite support team’s utmost efforts, no electronic records could be retrieved.

Results: 67 patients who were treated by Sep. 2016 got all their electronic records lost from the primary server. The only available information was based on the “ARIA”  which saved it from this unprecedented event. In order to identify targets and their formations, a procedure was adopted to extract information from shots configurations based on records in the later. Clinical records were extracted back from the prospective database collected upon the manual traditional files.

Conclusion: It is highly recommended to keep a scientific base as a backup strategy for radiosurgery data which can disappear in an extraordinary state.


Bilal MUHAMMAD, Marouf ADILI (Riyadh, Saudi Arabia), Saleh BAMAJBOUR, Abdulaziz ALHAMAD
09:00 - 18:00 #17656 - The imaging cost of matching the treatment accuracy between frame and frameless stereotactic linac radiosurgery.
The imaging cost of matching the treatment accuracy between frame and frameless stereotactic linac radiosurgery.

Objective:To compare the intrafraction motion and the setup imaging time between 2 cohorts of patients (frame-based and frameless) treated with linac stereotactic radiosurgery at Tom Baker Cancer Centre.

 Methods:We conducted a retrospective single-institution review of 40 patients treated in a single fraction with linac stereotactic radiosurgery. Twenty patients were immobilized using the Brainlab frame system (Brainlab Munich, Germany) and 20 patients were immobilized using the open face mask Orfit system (Orfit Industries, Wijnegem, Belgium). Initial setup for each patient was completed by acquiring a cone beam CT (CBCT) and an automatic match until shifts and rotations were within our 0.5mm and 0.3° tolerances. A CBCT and automatic match was also performed between each arc to determine the intrafraction motion. Additional CBCTs required to meet the matching tolerance level were also acquired and shifts were recorded for both cohorts, and this was used to calculate the extra time taken for treatment.  

 Results:The mean shifts and rotations (± one standard deviation) between the 2 cohorts (framed and frameless respectively) were -0.1±0.1 mm and 0.0±0.2 mm (vertical), 0.0±0.1 mm and 0.0±0.2 mm (lateral), 0.0±0.1 mm and 0.0±0.3 mm (longitudinal), 0.0±0.1 ° and 0.1±0.3 ° (pitch), 0.0±0.1 ° and 0.0±0.1 ° (roll), 0.0±0.1 ° and 0.0±0.2 ° (yaw). An unpaired t-test showed there was no significant difference in the shifts and the rotations between the two immobilization systems. An average of 0.2 and 1.4 additional CBCT scans per isocentre were required for framed and frameless treatments, respectively, for patients to be within match tolerances for treatment.  This translates to an average increase in treatment time of 1.2 min (framed) and 8.4 min (frameless) using 6 min as the average time for acquiring, matching and applying moves per CBCT at our institution.

 Conclusion:The same level of geometrical accuracy can be achieved with either framed or frameless immobilization. This accuracy comes at the cost of extra imaging time, which is significantly higher for frameless SRS. The number of additional scans required for framed patients suggests that CBCT in between arcs may not be necessary; however, CBCT between arcs is essential for frameless patients to achieve the desired accuracy in SRS due to increased intrafraction motion with this form of immobilization.


Nicolas P PLOQUIN (Calgary, Canada), Alana HUDSON, Gerald LIM, Shaun LOEWEN, Salman FARUQI
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09:00 - 18:00 #16744 - RADIATION MACULOPATHY AFTER ONE-DAY SESSION STEREOTACTIC RADIOSURGERY IN PATIENTS WITH UVEAL MELANOMA.
RADIATION MACULOPATHY AFTER ONE-DAY SESSION STEREOTACTIC RADIOSURGERY IN PATIENTS WITH UVEAL MELANOMA.

INTRODUCTION: Radiotherapy/surgery (SRS) is the standard treatment care for patients with uveal melanoma. In Slovakia we use one-day session stereotactic radiosurgery at linear accelerator C LINAC. One of the most serious and vision-threatening complications after SRS is the radiation retinopathy, which divides into maculopathy and peripheric retinopathy. The clinical signs include microanerysms, teleangiectases, hard exsudates, cotton wool spots and macular edema, neovascularisation, and vitreous hemorrhage . Radiation macular edema can be classified by optical coherence tomography into cystoid or noncystoid edema.
MATERIAL AND METHODS: The retrospective analysis of maculopathy in a group of 168 patients with uveal melanoma after one-day session stereotactic radiosurgery on linear accelerator C LINAC in a period 2007-2016.
RESULTS: Therapeutic dose to the tumor was 35.0Gy. The prevalence of the radiation maculopathy was 29% with the median time from the irradiation to maculopathy in 16 months. Median radiation dose on the macula was 37.0 Gy. Variables statistically significantly associated with the maculopathy were: radiation dose (p=0.0016), postequatorial location of the tumor (p=0.0271), tumor touch of the macula and better visual acuity before treatment (p=0.00076). The tumor touch of the macula was strongly associated with the visual acuity loss (bivariate analysis -p=0.0006).

Five patients underwent intravitreal application of the bevacizumab as a treatment of the radiation maculopathy, without improvement of the visual acuity.


The radiation dose on a macula is the key determinant for radiation-induced maculopathy, other variables were related to distance of the tumour to the macula, so the radiation dose on the macula was higher indirectly. Better visual acuity before treatment as a risk factor for maculopathy can be a consequence of a) earlier diagnostics of tumor with proximity to the posterior pole (uveal melanoma stage T1) b) frequency of the secondary enucleation afetr SRS was 1.6 times higher in patients without maculopathy (uveal melanoma stage T2-T3 tumors) 

CONCLUSION: Radiation complications can lead to visual acuity loss and secondary enucleation. Radiation maculopathy is a consequence of higher radiation dose to the macula. The treatment modalities of radiation maculopathy are rather ineffective.


Alena FURDOVA (Bratislava SLOVAKIA, Slovakia), Iveta WACZULIKOVA, Miron SRAMKA, Gabriel KRALIK, Martin CHORVATH
09:00 - 18:00 #17756 - Stereotactic radiosurgery (SRS) in choroidal melanoma: experience and cost efficiency.
Stereotactic radiosurgery (SRS) in choroidal melanoma: experience and cost efficiency.

Objectives

To analyze local control (LC), disease free survival, toxicity and cost effectiveness of SRS treatment of choroidal melanoma.

 

Material and methods

Between 2003 and 2017, 7 patients with choroidal melanoma were treated in a private hospital in Spain. Mean age at diagnosis was 60 years (43-79 years). The mean tumor volume was 0.49 cm3 (0.13-0.93) and distant disease was ruled out.

The first step is to fix the ocular rectus muscles at the Leksell frame doing a retrobulbar blockage with local anesthesia. The delineation of the tumor was made by fusion of magnetic resonance (MRI) and computerized tomography (CT) in stereotactic conditions. The minimum marginal dose administered was 35 Gy in a single session. The treatment is with a linear accelerator (LINAC) with cones. It is an outpatient procedure with estimate duration of 3 hours. The overall cost of the procedure is around $-9,000, compared to $-16,125 of brachytherapy.

 

Results

Mean follow up of 64 months (13-186), 100% local control rate has been reached without any enucleation. One patient developed distant disease (hepatic metastasis) one year after SRS. MRI complete radiological response was observed in two patients, three had maximum partial response (≥ 50%) and two a minor partial response (≤ 50%). The maximum dose in crystalline was 13.63 Gy and 27.9 Gy in optic nerve.  Follow-up, one of the patients required cataract surgery, another had retinal detachment 5 years latter and posterior macular edema with a significant decrease in visual acuity. Neovascular glaucoma presented 9 months after SRS in a patient with a previous cataract surgery, improved after intravitreal antiangiogenics.

 

 

 

Discussion

SRS is safe with acceptable toxicity. Survival and LC is equivalent to other techniques, is a cost efficiency procedure, alternative to enucleation and brachytherapy, that allows the treatment of larger tumors and close to the optic nerve.


Luis LARREA (Valencia, Spain), Enrique LOPEZ-MUNOZ, Veronica GONZALEZ, Paola ANTONINI, Maria BANOS-CAPILLA, Jose BEA-GILABERT
09:00 - 18:00 #17779 - The first application of gamma-knife radiosurgery for diffuse choroidal hemangioma in a patient with Sturge-Weber syndrome.
The first application of gamma-knife radiosurgery for diffuse choroidal hemangioma in a patient with Sturge-Weber syndrome.

Purpose: to present a case of successful Gamma-knife radiosurgery (GKRS) of the single eye with diffuse choroidal hemangioma (DCH) in a child with Sturge-Weber syndrome.

Methods: A 4.5-year old girl was referred to our center with port-wine stains of the face, leptomeningeal angiomas and bilateral DCH. The right eye was presented with DCH of 6.6 mm in thickness with no signs of exudation.

The left eye was diagnosed with DCH of 6.8 mm in thickness, total retinal detachment and vision loss. Ruthenium brachytherapy was performed but retinal detachment increased.

Within 5 months follow-up the right eye developed retinal detachment up to 6.6 mm in height. GKRS was used as the last opportunity to save the eye and improve vision. Dosimetric plan included double PTVs of 18 Gy @ 57% and 18 Gy @ 50% excluding central retina, and will be presented.

Results: During 8 months of follow up choroidal tumor thickness decreased from 6.6mm to 3.0mm with retinal detachment resolution that provided child a good vision in the only seeing eye. Irradiation “tracks” according to the planning were seen on the eye fundus examination without radiation damage of central retina. No complications were revealed within the follow-up.

Conclusion: This exceptional case presents the first to our knowledge experience of GKRS of DCH in a child with Sturge-Weber syndrome. GKRS allowed to irradiate intraocular vascular tumor precisely and save the eye with vision improvement. Further experience is essential.


Andrey YAROVOY (Moscow, Russia), Andrey GOLANOV, Roman LOGINOV, Vera YAROVAYA, Valery KOSTJUCHENKO, Amina CHOCHAEVA