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) (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) (London, UK)
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 (Rochester, MN, 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

Monday 10 June

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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) (New York, USA)
07:48 - 08:06 Motion Management. Anderson PASSARO (Medical Physicist) (São Paulo, BRAZIL)
08:06 - 08:24 Evidence Review. Jin Ho KIM (Associate Clinical Professor) (Seoul, KOREA)
08:24 - 08:42 Resection of Thoracic Metastases. Rui HADDAD (BRAZIL)
08:42 - 09:00 MR Guided SBRT for Lung Tumors. Ben SLOTMAN (Professor and Chairman) (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) (Durham, NC, USA)
07:52 - 08:14 Inverse Treatment Planning. Marc LEVIVIER (Chef de Service) (Lausanne, SWITZERLAND)
08:14 - 08:36 Dose Painting/Delivery Automation. Richard POPPLE (Medical Physicist) (Birmingham, USA)
08:36 - 09:00 Automatic Segmentation of Structures in the Brain. Crystian SARAIVA (Medical Physicist) (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) (Sao Paulo, BRAZIL), Ian PADDICK (Physicist) (London, UK)
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) (Sao Paulo, BRAZIL), John KIRKPATRICK (Professor - Radiation Oncology & Neurosurgey) (Durham, NC, USA), Ian PADDICK (Physicist) (London, UK)
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) (Oxford, UK)
09:35 - 09:50 Can Radiobiology help us further refine SRS treatments? John KIRKPATRICK (Professor - Radiation Oncology & Neurosurgey) (Durham, NC, USA)
09:50 - 10:05 Imaging of Radiation Necrosis. Yael MARDOR (Research) (Ramat-Gan, ISRAEL)
10:05 - 10:20 Oncogenesis & Stereotactic Radiation: What We Know. Jonathan KNISELY (Lake Success, 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) (Région de la baie de San Francisco, USA), Patrick KUPELIAN (Professor) (Palo Alto, USA), Ben SLOTMAN (Professor and Chairman) (AMSTERDAM, THE NETHERLANDS)
10:45 - 11:00 MR GUIDED SRS/SBRT: Technical Overview. Ben SLOTMAN (Professor and Chairman) (AMSTERDAM, THE NETHERLANDS)
11:00 - 11:15 Realtime Adaptive Therapy: Workflow Considerations. Frank LAGERWAARD (Radiation Oncologist) (Amsterdam, THE NETHERLANDS)
11:15 - 11:30 Beyond Anatomical Imaging: The Promise and Challenges. Caroline CHUNG (Associate Professor, Radiation Oncology) (Houston, USA)
11:30 - 11:45 Clinical Indications & Results. Lauren HENKE (Radiation Oncologist) (St. Louis, USA)
11:45 - 12:00 Clinical Trials and Research Overview. Arjun SAHGAL (Professor) (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 Brookn 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 CIPKINA, 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 (Durham, 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, 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, UK), 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, UK), 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, UK), 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

Monday 10 June

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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) (FRANCE)
13:20 - 13:35 Elekta Unity™ Installation and Initial Clinical Usage at the University of Iowa. Mark SMITH (Iowa City, USA)
13:35 - 13:50 Managing the Increasing Demand for Intracranial Radiosurgery Treatments in an integrated Oncology and Neurosurgical Setting. Matthew FOOTE (Co-Director) (Brisbane, AUSTRALIA)
13:50 - 14:05 4D Image Guidance and Other Motion Management Techniques for Lung SBRT. Farkhad MANAPOV (Munich, GERMANY)
14:05 - 14:15 Discussion.
Segovia Break Out
14:30

Monday 10 June

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A27
14:30 - 15:30

PARALLEL SESSION
BENIGN BRAIN TUMORS UPDATE

Moderators: Laura FARISELLI (director) (milano, ITALY), Leonardo FRIGHETTO (Neurosurgeon) (Porto Alegre, BRAZIL), Eduardo LOVO IGLESIAS (Brain and Spine Radiosurgery Program) (San Salvador, EL SALVADOR)
14:30 - 14:45 Long Term Outcomes. Zhiyuan XU (Gamma Knife) (Charlottesville, USA)
14:45 - 15:00 Combination Therapy. Bruce POLLOCK (Physician) (Rochester, USA)
15:00 - 15:15 Repeat Radiosurgery. Gus BEUTE (Neurosurgeon) (Tilburg, THE NETHERLANDS)
15:15 - 15:30 Is Earlier Better? Jean REGIS (PROFESSEUR) (MARSEILLE, FRANCE)
Segovia Plenary

Monday 10 June

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B27
14:30 - 15:30

PARALLEL SESSION
SPINE

Moderators: Lily ANGELOV (Staff Neurosurgeon) (Cleveland, USA), Lucas Ignacio CAUSSA (MD) (Córdoba, ARGENTINA), Scott SOLTYS (ISRS 2019) (Stanford, CA, USA)
14:30 - 14:40 Patient Selection for Spine SBRT. Matthew FOOTE (Co-Director) (Brisbane, AUSTRALIA)
14:40 - 14:50 Status of clinical trials for de novo metastases. Samuel RYU (Professor) (Stony Brookn NY, USA)
14:50 - 15:00 Re-irradiation Spine SBRT. Sten MYREHAUG (Radiation Oncologist) (Toronto, CANADA)
15:00 - 15:10 Consensus Contouring Guidelines for Spine SRS. Kristin J REDMOND (Associate Professor of Radiation Oncology and Molecular Radiation Sciences) (Baltimore, MD, USA)
15:10 - 15:20 Radiation for spinal chordoma. Scott SOLTYS (ISRS 2019) (Stanford, CA, USA)
15:20 - 15:30 Radiosurgery for Benign Pathologies. Kita SALLABANDA (Asoc.Prof.) (Madrid, SPAIN)
Segovia Break Out

Monday 10 June

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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

Monday 10 June

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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 (Asoc.Prof.) (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: Lily 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) (Rochester, MN, USA), Paulo OPPITZ (Neurosurgeon) (Porto Alegre, BRAZIL), Scott SOLTYS (ISRS 2019) (Stanford, CA, USA)
17:00 - 17:15 Designing Studies. Debra Nana YEBOA (Radiation Oncologist) (Houston, USA)
17:15 - 17:30 Perfecting Article Writing and Publication. Isaac YANG (Associate Professor) (Los Angeles, USA)
17:30 - 17:45 Interpreting Statistics: Common Pitfalls to Avoid. David PRYOR (Radiation Oncologist) (Brisbane, AUSTRALIA)
17:45 - 18:00 Remember the Patient. Lily ANGELOV (Staff Neurosurgeon) (Cleveland, USA)
Segovia Plenary

Monday 10 June

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B291
17:00 - 18:00

BREAST SYMPOSIUM

Moderators: Laura FARISELLI (director) (milano, 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) (San Francisco, USA)
17:20 - 17:40 Focal Radiation Techniques (incl. IORT). Lorenzo LIVI (Full Professor, Head of Radiation Oncology Unit) (Florence, ITALY)
17:40 - 18:00 SBRT Clinical Trials and Research Overview. Allisson Barcelos BORGES (Radiation Oncologist) (Brasilia-DF, BRAZIL)
Segovia Break Out

Monday 10 June

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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) (Glasgow, UK)
17:15 - 17:30 HyperArc™ for Cranial SRS: First Year Indications & Outcomes on the EDGE® at UAB. Evan THOMAS (BALLER) (BIRMINGHAM, USA)
17:30 - 17:45 RapidArc™ Radiosurgery and SGRS – The Brazilian Experience. Samir HANNA (São Paulo, BRAZIL)
17:45 - 18:00 VMAT on the EDGE® for H&N and other Extracranial Targets: The Henry Ford Experience. Farzan SIDDIQUI (Detroit, USA)
18:00 - 18:15 Frameless Functional Linac-Based Radiosurgery: Focus on Essential Tremor. Evan THOMAS (BALLER) (BIRMINGHAM, USA)
18:15 - 18:30 Immunotherapy plus SRS/SBRT: Increasing the Probability of the Abscopal Effect. James WELSH (Chicago, USA)
El Pardo I