Sunday 28 May
08:00

Sunday 28 May

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ISRS Course
08:00 - 12:00

ISRS Educational Course
Basic principles of Radiosurgery

Moderators: Antonio DE SALLES (Professor - Chief) (Sao Paulo, BRAZIL), Arjun SAHGAL (Professor) (Toronto, CANADA)
08:00 - 08:25 08:00 – 08:25 - Principles of radiosurgery. Laura FARISELLI (director) (milano, ITALY)
08:25 - 08:50 08:25 – 08:50 - Radiobiology. Dennis SHRIEVE (Professor and Chair) (Salt Lake City, USA)
08:50 - 09:15 08:50 – 09:15 - QA & Imaging. Ian PADDICK (Physicist) (London, UK)
09:15 - 09:40 09:15 – 09:40 - Intracranial benign lesions. Douglas KONDZIOLKA (New York, USA)
09:40 - 10:00 09:40 - 10:00 - Coffee break.
10:00 - 10:25 10:00 – 10:25 - Brain Malignancies. Patrick HANSSENS (Radiation Oncologist) (Tilburg, THE NETHERLANDS)
10:25 - 10:50 10:25 – 10:50 - Functional Radiosurgery. Alessandra GORGULHO (Director of Research Affairs) (Sao Paulo, BRAZIL)
10:50 - 11:15 10:50 – 11:15 - Spinal Radiosurgery. Samuel RYU (Professor) (Stony Brookn NY, USA)
11:15 - 11:40 11:15 – 11:40 - Body Radiosurgery. Ben SLOTMAN (Professor and Chairman) (AMSTERDAM, THE NETHERLANDS)
11:40 - 12:00 11:40 - 12:00 - Panel discussion.
Parallel 1- Prince
12:00

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Lunch
12:00 - 12:30

Lunch Break

12:30

Sunday 28 May

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LUD
12:30 - 14:30

ISRS EDUCATIONAL COURSE - LECTURES BY DEVICES USERS

Moderators: Alessandra GORGULHO (Director of Research Affairs) (Sao Paulo, BRAZIL), Patrick HANSSENS (Radiation Oncologist) (Tilburg, THE NETHERLANDS)
12:30 - 14:30 Keynote speaker 1. Ian PADDICK (Physicist) (London, UK)
12:30 - 14:30 Keynote speaker 2. Thierry GEVAERT (Head of Medical physics) (Brussels, BELGIUM)
12:30 - 14:30 Keynote speaker 3. Christoph FÜRWEGER (Munich, GERMANY)
12:30 - 14:30 Keynote speaker 4. Peter HOUSTON (Physicist) (Glasgow, UK)
Parallel 1- Prince
14:30

Sunday 28 May

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HON
14:30 - 16:30

ISRS EDUCATIONAL COURSE - Hands-On With Main Systems

Moderators: Alessandra GORGULHO (Director of Research Affairs) (Sao Paulo, BRAZIL), Patrick HANSSENS (Radiation Oncologist) (Tilburg, THE NETHERLANDS)
Parallel 2- Queen
17:00

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OPEN
17:00 - 18:15

Opening Ceremony
Special Conference: Mathieu Jaton, CEO Montreux Jazz Festival.

17:00 - 18:15 Welcome addresses to ISRS 2017.
17:00 - 18:15 Special Conference: Mathieu Jaton, CEO Montreux Jazz Festival.
Born in 1975 in Vevey, music lover and graduate of the Ecole Hôtelière de Lausanne. Mathieu Jaton was hired by the Montreux Jazz Festival in 1999, at 24, to head up Marketing and Sponsoring; he became the Festival’s General Secretary in 2001. Working at the Festival alongside Claude Nobs, who had become his mentor, he developed the values that have always defined him: a flair for hospitality, and a deep passion for music.
Following the passing of Claude Nobs in 2013, he assumed direction of the Fondation du Festival de Jazz de Montreux, of the Montreux Jazz Artists Foundation, and Montreux Jazz International SA. He presently also serves on the boards of the Ecole de Jazz et de Musique Actuelle (Lausanne) and the Mühle Hunzinken (Rubigen) and is a member of the Association Label Suisse.
Through an array of projects, Mathieu Jaton has been guiding the Festival towards its future for four years while ensuring continuity in the savoir-faire and values that make Montreux so unique in the world of music.
Stravinski Auditorium
Monday 29 May
07:30

Monday 29 May

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BS3
07:30 - 08:30

BREAKFAST SEMINAR
Guidelines

Coordinator: Arjun SAHGAL (Professor) (Toronto, CANADA)
Moderators: Philippe BIJLENGA (Genève, SWITZERLAND), Douglas KONDZIOLKA (New York, USA)
07:30 - 07:35 Update of the ISRS Guideline Initiative. Arjun SAHGAL (Professor) (Toronto, CANADA)
07:35 - 07:40 Vestibular Schwannomas. Ian PADDICK (Physicist) (London, UK)
07:40 - 07:45 Trigeminal Neuralgia. Constantin TULEASCA (Resident) (Lausanne, SWITZERLAND)
07:45 - 07:50 Tremor. Roberto MARTINEZ-ALVAREZ (Neurosurgeon) (Madrid, SPAIN)
07:50 - 07:55 De Novo Spine SBRT. Zain HUSAIN (USA)
07:55 - 08:00 Re-irradiation Spine SBRT. Sten MYREHAUG (Radiation Oncologist) (Toronto, CANADA)
08:00 - 08:05 Cavernous Sinus Meningioma. Cheng-Chia LEE (Attending physician) (Taipei, TAIWAN)
08:05 - 08:10 Epilepsy. Aileen MC GONIGAL
08:10 - 08:15 Limited Brain Metastases. Arjun SAHGAL (Professor) (Toronto, CANADA)
Parallel 1- Prince

Monday 29 May

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BS2
07:30 - 08:30

BREAKFAST SEMINAR
WFSBS Session / Extracranial Head & Neck Radiosurgery: Glomus Tumors

Coordinator: Roy Thomas DANIEL (Médecin Cadre) (Lausanne, SWITZERLAND)
Moderators: Sebastien FROELICH (Paris, FRANCE), Jeremy ROWE (Sheffield, UK)
07:30 - 08:30 Extra-cranial glomus tumors of the head and neck. Christian SIMON (SWITZERLAND)
07:30 - 08:30 Jugulare-Tympanicum glomus tumors radiosurgery : long term results. Jeremy ROWE (Sheffield, UK)
07:30 - 08:30 Carotid & Carotido-jugular glomus tumors radiosurgery: experience with LGK Icon. Cyrille CAPEL (Marseille, FRANCE)
Parallel 2- Queen

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BS1
07:30 - 08:30

BREAKFAST SEMINAR
Functional Radiosurgery: Technical nuances in Capsulotomies

Coordinator: Giorgio SPATOLA (Neurosurgeon) (Marseille, FRANCE)
Moderators: Antonio DE SALLES (Professor - Chief) (Sao Paulo, BRAZIL), Motohiro HAYASHI (Associate professor) (Tokyo, JAPAN)
07:30 - 07:45 Gamma knife Radiosurgery for OCD: results on 12 consecutive patients. Giorgio SPATOLA (Neurosurgeon) (Marseille, FRANCE)
07:45 - 08:00 Capsulotomy: Description of target. Ian PADDICK (Physicist) (London, UK)
08:00 - 08:15 Connectivity-based parcellation of the anterior limb of the internal capsule: targeting applications in psychiatric neurosurgery. Pranav NANDA (Medical Student) (New York, USA)
08:15 - 08:30 'Radiosurgical Capsulotomy for OCD – A Dosimetric Analysis of 92 Treatments. Roberto MARTINEZ-ALVAREZ (Neurosurgeon) (Madrid, SPAIN)
Parallel 3- BB King
08:45

Monday 29 May

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PS1
08:45 - 10:00

PLENARY SESSION 1

Moderators: Paul KRACK (Bern, SWITZERLAND), John KIRKPATRICK (Professor - Radiation Oncology & Neurosurgey) (Durham, NC, USA), Ian PADDICK (Physicist) (London, UK)
08:45 - 08:55 Radiobiology fundamentals of BED. John HOPEWELL (invited speaker) (Oxford, UK)
08:55 - 09:05 Changing the dose prescription to compensate for single fraction treatment time extension. Bleddyn JONES (UK)
09:05 - 09:15 Influence of source activity on outcome in Gamma Knife. Constantin TULEASCA (Resident) (Lausanne, SWITZERLAND)
09:15 - 09:25 Pros & Cons: BED dose planning - Is treatment time a key issue mandatory to integrate at time of doseplanning ? Yes. John HOPEWELL (invited speaker) (Oxford, UK)
09:25 - 09:35 Pros & Cons: BED dose planning - Is treatment time a key issue mandatory to integrate at time of doseplanning ? No. Bodo LIPPITZ (Co-Director) (Hamburg, GERMANY)
09:35 - 09:45 Special Lecture: Radiosurgery for Tremor. Tatiana WITJAS (neurologist) (marseille, FRANCE)
09:45 - 09:55 #9994 - Stereotactic radiosurgery for newly diagnosed and recurrent chordomas of the skull base and spine.
Stereotactic radiosurgery for newly diagnosed and recurrent chordomas of the skull base and spine.

 

Purpose/Objectives:

With conventionally fractionated radiotherapy, local failure typically occurs in over 30% of chordomas by 3 years. Given that the alpha/beta ratio for these slowly growing tumors is likely low, we investigated if dose escalation through hypofractionated stereotactic radiosurgery (SRS) may improve local control.

Methods/Materials:

An IRB-approved retrospective review identified 35 consecutive patients with new or recurrent chordoma treated to 36 sites (n=25(69%) in skull base, n=11(n=31%) in spine) with SRS (in 1 to 5 fractions) from 2000 to 2016. SRS treated 22 newly diagnosed tumors (61%) following surgery and 14 (39%) tumors recurrent after radiotherapy (n=11) or surgery alone (n=3). The median SRS dose for newly diagnosed tumors was 40 Gy in 5 fractions (range, 20-45 Gy in 1-5 fractions) for a median EQD2 (equivalent dose in 2 Gy fractions, assuming an alpha/beta of 4) of 80 Gy4 (range, 64-134 Gy4) and 29 Gy in 5 fractions (range, 18-50 Gy in 1-5 fractions) for a median EQD2 of 51 Gy4 (range, 24-117 Gy4) to recurrent tumors. Local control (LC) within or adjacent to the SRS field, regional control (RC) within the surgical corridor or in the draining lymph nodes, distant control of metastatic disease (DC) and overall survival (OS) were estimated with the Kaplan-Meier method, censored at last follow-up. Acute and late toxicity were assessed via CTCAE V4.0.

Results: Newly diagnosed chordomas had a median follow-up of 32 months (range, 8-142 months) and a 3-year LC of 88% (95% confidence interval (CI), 59-97%), RC of 92% (CI, 56-98%) and DC of 89%. With a median follow-up of 24 months (range, 5-193 months), recurrent tumors had a 3-year LC of 92% (CI, 54-97%), RC of 54% (CI, 24-76%) and DC of 86%. At last follow-up, 20 of 22 newly diagnosed patients were still alive (91%), but 7 of 13 recurrent patients (54%) were deceased, for a median OS of 94 months. Late toxicities occurred in 6 patients (17%): cranial neuropathy (grade 2 in three patients and grade 3 in one patient), vertebral body compression fracture (grade 2), and treatment induced trigeminal neuralgia (grade 2).

Conclusions: With a 3 year overall local control of 88%, these early data suggest that dose escalation through hypofractionated SRS provides rates of local control comparable or higher than historical series of fractionated radiotherapy for selected, smaller tumors, and supports a low alpha/beta ratio for chordoma.  Measures to improve regional control for recurrent tumors are warranted.

 

Evan WHITE, Abdulrazag AJLAN, Qiao QIAO, Laurie TUPPER, Kiran KUMAR, Iris GIBBS, Steven HANCOCK, Steven CHANG, Griffith HARSH, Robert DODD, Atman DESAI, John RATLIFF, Victor TSE, Marco LEE, Dylann FUJIMOTO, Aika SHOO, John ADLER, Scott SOLTYS (Stanford, USA)
Stravinski Auditorium
10:00

Monday 29 May

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BREAK0
10:00 - 10:30

Coffee Break

10:30

Monday 29 May

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OSP18
10:30 - 11:30

Parallel session - Various 1

Moderators: Guilherme BULGRAEN DOS SANTOS (CHILE), Laura FARISELLI (director) (milano, ITALY), Bruce POLLOCK (Physician) (Rochester, USA)
10:30 - 10:40 #9847 - Stereotactic radiosurgery for non-functioning pituitary adenoma touching/compressing the optic chiasm: median 12-year post-treatment imaging follow-up results analyzed using competing risk analysis.
Stereotactic radiosurgery for non-functioning pituitary adenoma touching/compressing the optic chiasm: median 12-year post-treatment imaging follow-up results analyzed using competing risk analysis.

Objectives: Debate continues as to whether stereotactic radiosurgery (SRS) or fractionated stereotactic radiotherapy (FSRT) should be chosen for patients with non-functioning pituitary adenomas (NFPAs) touching or even compressing the optic chiasm. We describe our long-term follow-up results with SRS for such patients.

Methods: This institutional review board-approved, retrospective study used our prospectively accumulated database including 27 patients (14 females, 13 males, mean age; 61 [range; 19-85] years) who underwent gamma knife SRS between 1998 and 2006 for NFPAs touching/compressing the optic chiasm. Twenty-six patients had undergone surgical removal; once in 16, twice in eight and four times in two. The median tumor volume was 5.2 (range; 1.8-50.8) cc. To avoid excess irradiation to the optic apparatus (OA), the tumor was not totally covered with the selected peripheral doses. Instead, the lower part of the tumor was covered with a 50% or a 60% isodose gradient; i.e., 49-98% (mean; 84%, median; 88%) of the entire tumor received the selected doses. Median doses at the tumor periphery and the OA were 7.6 Gy and 11.0 Gy (ranges; 3.2-10.9 Gy and 8.7-12.9 Gy), respectively.   

Results: Seven patients (26%) were confirmed to be deceased due to unrelated diseases at a median post-SRS period of 150 (range: 15-174, IQR: 83-154) months. Follow-up MRI showed tumor growth in two patients (7.4%) at the 11th and 134th post-SRS month; the former underwent surgery and the other SRS. Excluding these two patients, the latest follow-up MRI examinations which were performed 13-216 (mean: 139, median: 156, IQR: 116-172) months after SRS showed no size changes in five (18.5%) and shrinkage in 22 patients (74.1%), i.e., the crude incidence of tumor growth control was 92.6% and cumulative incidences of tumor growth-free survival estimated with a competing risk analysis were 96.3%, 96.3% and 91.7% at the 60th, 120th and 180th post-SRS month. Neither SRS-induced optic neuropathy nor endocrinological impairment occurred.

Conclusion: In patients with NFPAs touching or even compressing the optic chiasm, SRS achieves good long-term results. The opinion that FSRT is the only appropriate treatment is thus unwarranted. 

Yamamoto MASAAKI (Hitachi-naka, JAPAN), Kawabe TAKUYA, Watanabe SHINYAN, Takao KOISO, Aiyama HITOSHI, Sato YASUNORI, Bierta E. BARFOD
10:40 - 10:50 #9969 - Long-term results of single-session stereotactic radiosurgery for non-vestibular cranial nerve schwannomas.
Long-term results of single-session stereotactic radiosurgery for non-vestibular cranial nerve schwannomas.

Introduction:

Non-vestibular schwannomas (NVS) are rare intracranial tumors representing <10% of all cranial nerve schwannomas. For small to medium-size tumors, radiosurgical treatment in a single session is often preferred to surgical resection. The aim of the present study is to analyze the long-term tumor control and morbidity of a series of 30 NVS treated in our center and followed prospectively.

Materiel & Methods:

The data of a series of 30 patients were analyzed. Affected cranial nerves included cranial nerve III (n=1), V (n=8), VI (n=2), VII (n=8), IX-X-XI (n=9), and XII (n=2). Median age was 47. Two patients had neurofibromatosis. A functional deficit of the cranial nerve was present at the time of irradiation for 23 patients (77%). Seven patients (23%) had undergone previous microsurgical resection. All patients were treated by a single-session procedure with a Gamma Knife C or Perfexion. The median tumor volume and margin dose were 1.1cc (range, 9.9-0.02cc) and 12Gy (range, 10-15Gy).

Results:

The median follow-up was 6.2y (range, 2-11.5y). We found a significant (i.e., >10% of the initial volume) reduction of the tumor volume during follow-up for 17 patients (57%), and a stable volume for 13 patients (43%). No patient had MR-defined tumor growth during follow-up. We observed a transient worsening of the function of the cranial nerve in the first months after radiosurgery in 2 patients with a facial nerve schwannoma, which was treated successfully with corticoids. No patient developed permanent worsening of the affected cranial nerve, and no other morbidity occurred. Five patients had an improvement of their functional deficit: diplopia resolved for 2 patients with NVS of cranial nerve III and VI, and trigeminal neuralgia resolved for 3 patients with NVS of nerve V.

Conclusions:

Based on our experience of 30 patients successfully treated for a NVS by single-session radiosurgery, we concluded that this treatment is very efficient and can be safely delivered in a single session for patients with small to medium-size NVS.

Nicolas MASSAGER (Brussels, BELGIUM), Cecile RENIER, Daniel DEVRIENDT
10:50 - 11:00 #10077 - Gamma knife radiosurgery for intracranial ependymomas.
Gamma knife radiosurgery for intracranial ependymomas.

Ependymomas are rare tumors of the central nervous system developing from ependymocytes. Surgery is the reference treatment, supplemented by adjuvant radiotherapy in case of incomplete excision. At the time of the recurrence, a second surgery is preferred, but not always feasible. In these cases, the therapeutic options are limited and radiosurgery seems a good therapeutic alternative.

We present a retrospective series of 21 patients treated by radiosurgery for 33 post-surgical recurrences of ependymomas at the University hospital of Lille, France, between 2003 and 2015. The diagnosis of ependymoma was carried out according to the WHO criteria and the indication of radiosurgical treatment validated by a multidisciplinary staff. The treatments were performed with a Leksell Gamma Knife model 4C. For each patient, the data collected were age, sex, WHO grade of the tumor, number of surgeries, location of recurrence, time between surgery and radiosurgery, prescribed dose and target volume . The overall survival after radiosurgery is 100% at 1 year, 91% after 3 years. Progression-free survival was 85% at 1 year, 80% at 2 years, 64% at 3 years and 51% at 5 years. The local control of lesions treated by radiosurgery is 100% at 1 year, 85% at 2 years, 76% at 5 years and 55% at 10 years. The average duration of follow-up was 4.2 years.Among the different variables analyzed, only the WHO grade of the tumor had a significant impact on local and regional control of the disease (p 0.03 and p <0.001).

In our series, radiosurgery is a treatment of choice of ependymoma recurrences with a good rate of local control. Patients with Grade 2 ependymomas have better local and regional control of the disease.

Jean-Michel LEMÉE, Philippe MENEI, Serge BLOND, Maximilien VERMANDEL, Nicolas REYNS (LILLE)
11:00 - 11:10 #10081 - Endocrine Deficits after Pituitary Adenoma Radiosurgery: Dosimetric Analysis based on Patients treated with the Gamma Knife Perfexion.
Endocrine Deficits after Pituitary Adenoma Radiosurgery: Dosimetric Analysis based on Patients treated with the Gamma Knife Perfexion.

Objective: Endocrine deficits are the most frequent complication after pituitary adenoma radiosurgery (SRS).  The clinical and dosimetric factors associated with pituitary insufficiency remain unclear despite more than 30 years of clinical usage.

Methods: Retrospective review of 97 patients having single-fraction SRS from 2007 until 2014.  Eligible patients had no history of prior radiation, normal age and gender specific pituitary function before SRS, and at least 24 months of endocrine follow-up.  Forty patients (41%) had hormone secreting tumors; 57 patients had non-secreting tumors (59%).  The median prescription isodose volume was 2.8 cm3 (range, 0.5-30.5); the median tumor margin dose was 20 Gy (range, 12-27.5).  The median follow-up after SRS was 48 months (range, 24-107).

Results: Twenty-seven patients (28%) developed pituitary insufficiency at a median of 22 months (range, 4-69) after SRS.  The 2-year and 5-year rates of new endocrine deficits were 17% and 31%, respectively.  Multivariate analysis found men (risk ratio, 2.38; P=0.04), smaller gland volume (risk ratio, 0.99; P=0.02), and increasing mean gland dose (risk ratio, 1.31; P<0.0001) to be predictive of new endocrine deficits.  Further analysis using receiver operating curves showed the least to most sensitive dosimetric variable for predicting new endocrine deficits were gland volume (AUC 0.65, P=0.01), volume of gland receiving 12 Gy (Vgland12) (AUC 0.68, P=0.02), volume of gland receiving 14 Gy (Vgland14) (AUC 0.71, P=0.01), volume of gland receiving less than 14 Gy (Vgland<14) (AUC 0.83, P<0.0001), mean gland dose (AUC 0.83, P<0.0001), and volume of gland receiving less than 12 Gy (Vgland<12) (AUC 0.85, P<0.0001).  The incidence of new deficits based on mean gland dose were <10 Gy, 1/40 (3%); 10-15 Gy, 12/35 (34%); ≥15 Gy, 14/22 (64%).  The incidence of new deficits based on Vgland<12 were >300 mm3, 1/31 (3%); 100-300 mm3, 12/49 (25%); <100 mm3, 14/17 (82%).   

Conclusion: Endocrine deficits after pituitary adenoma SRS increase in a time and dose dependent manner.  Reducing the radiation exposure to the identifiable gland whenever feasible should lower the incidence of new hormonal deficits after pituitary adenoma SRS.  The primary weakness of this analysis is the high probability of inter-observer variability in pituitary gland definition.          

Bruce POLLOCK (Rochester, USA), Christopher GRAFFEO, Michael LINK, Scott STAFFORD, Robert FOOTE
11:10 - 11:20 #9766 - Stereotactic radiosurgery for patients with ten or more brain metastases.
Stereotactic radiosurgery for patients with ten or more brain metastases.

OBJECT: To evaluate the efficacy of Gamma Knife radiosurgery (GKRS) as treatment in patients with 10 or more metastatic brain tumors.

METHODS: Between February 2014 and January 2016, 20 patients were treated with GKRS for 10 or more brain metastases. We retrospectively analyzed the data from these patients, with survival and tumor control as primary endpoints. Brain volumes treated with 8 Gy and 12 Gy were measured to explore volume of treated tissue as a contributing factor to tumor control. Pre-treatment and post-treatment magnetic resonance imaging (MRI) studies were reviewed at intervals of 3 months, as were patient records on site.

RESULTS: Of the 20 patients treated, 3 were excluded due to insufficient follow-up data. For the 17 included patients the median age was 61 (range 19-76). These patients were treated for a total of 323 tumors, with a median of 17 tumors per patient (10-34). The median survival for these patients was 12.5 months (1.3-16.9). Patient survival was censored at the time of data collection, and the true upper limit of survival is higher than recorded here. The mean percent of brain volume treated was 0.9, with a median of 0.41 (0.07 – 3.38). The mean percent of brain volume that received a dose of 12 Gy was 5.0 (0 – 21.0), and of 8 Gy was 9.0 (1.0 – 31.0). For each of the first three 3-month intervals, the median percent of tumor control was 97%, 96%, and 100%, respectively in the patients with available data.

CONCLUSIONS: GKRS effectively treats and controls brain tumors, even in patients presenting with 10 or more tumors simultaneously. The number of tumors initially present was not found to have a significant correlation with general tumor control.

Elliot SCHIFF, Luke SWASZEK, Jonathan KNISELY (Lake Success, USA), Aditya HALTHORE, Sussan SALAS, Nina KOHN, Michael SCHULDER
11:20 - 11:30 #10658 - The Development of a Quality Assurance Program for CyberKnife M6 in Chile.
The Development of a Quality Assurance Program for CyberKnife M6 in Chile.

Objectives: Robotic technology, image guidance based on sophisticated tracking software and small-field dosimetry issues are incorporated into the CyberKnife® Robotic Radiosurgery System (CK M6). Upon commissioning and external beam auditing (by Equal ESTRO in our case), performance evaluation procedures should be carried out for each of the CK subsystems. Standardization of a quality assurance (QA) program of CyberKnife for suitable circumstances in Chile has not been established. In this research, we investigated the development of a QA program for CyberKnife and evaluated the feasibility of its application.

Methods: Considering all the subsystems involved in producing a CK M6 treatment, a list based on bibliographical recommendations was established and divided depending on the periodicity of QA tests to be carried out. All these developed Quality Check (QC) lists were later categorized into two groups: machine QA and patient-specific QA. An IBA (myQA®) comprehensive SQL quality control management database was used to schedule every single task and tabulate its expected results and tolerances including daily QA, monthly QA and yearly QA. Purpose and outcome are described and tracked for each test. In order to verify the validity of the established QA program, this QC list was applied strictly during the past year of operation. The acceptable tolerance was based on the careful comparison of values required by the CyberKnife manufacturer and QA results in different publications. The acquired measurement results were evaluated for the analysis of the current QA status and for the verification of the propriety for the developed QA program.

Acquired x-ray images were fed into 6D target locating software to calculate patient translations and rotations. A head-neck phantom, placed at different predefined positions on a treatment couch, was used to evaluate accuracy and precision of the target locating software for the fiducial, 6D skull, Xsight™ spine tracking methods. The dosimetric characteristics of the 6MV beam were also measured. Finally, beam delivery precision and total clinical accuracy were evaluated for the fiducial, 6D skull, Xsight™ spine tracking methods.

Results: The current QA status of the CyberKnife was evaluated from the accuracy of all measurements in relation with the application of the established QA program. Each measurement result was verified to have good agreement within the acceptable tolerance limit of the developed QA program. The Target locating software was found able to define the position of the imaging objects for translations and rotations respectively with an accuracy of 0.2mm and 0.2. The results revealed sub-millimeter beam-delivery precision and dose placement total accuracy for the fiducial, skull and XsightTM spine tracking methods.

Conclusion: Performance evaluation procedures were carried out for a CK M6. The system was controlled for mechanical accuracy of the manipulator, image quality, kV parameters of the TLS as well as for linac 6MV beam characteristics and beam output parameters. The results revealed sub-millimeter beam-delivery precision and dose placement total accuracy for the fiducial, skull and XsightTM spine tracking methods. It is considered that the developed QA program in this research could establish the standardization of QC methods for CyberKnife and confirms the accuracy and stability for image-guided stereotactic radiotherapy. 

Karla TORZSOK (Santiago, CHILE), Alvaro RUIZ , Marcelo PICCIOLI, Guilherme BULGRAEN, Filippo MARANGONI, Herve BROQUE, Franklyn REGGIO, Hugo MARSIGLIA
10:30 - 11:30
Parallel 1- Prince

Monday 29 May

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OSP28
10:30 - 11:30

Parallel session - WFSBS: Skull Base

Moderators: Siviero AGAZZI (Tampa, USA), Moncef BERHOUMA (LYON, FRANCE), Lucia SCHWYZER (Senior Physician) (Aarau, SWITZERLAND)
10:30 - 10:40 #9907 - Upfront hypofractionated frameless stereotactic radiotherapy for large petroclival meningioma.
Upfront hypofractionated frameless stereotactic radiotherapy for large petroclival meningioma.

Background: Large petroclival meningiomas are extremely challenging tumors because of their intimate location with critical neurovascular structures. Microsurgical resection is often associated with significant morbidity. For this, combined surgical/radiosurgical treatment is advocated. In this study, we evaluate the outcomes of petroclival meningiomas treated with hypofractionated CyberKnife SRS as a primary treatment modality.

Methods: A series of 32 patients with a petroclival and sphenopetroclival meningiomas with a volume >8cc were treated with upfront hypofractionated radiosurgery between 2007 and 2016 at the CyberKnife Center of the University of Messina, ITALY. Patients received a dose of 25-45 Gy in 5-15 fractions. Outcome measures included progression-free survival, neurological and quality of life outcome.

Results: At mean follow up of 56 months (range 6-114), tumor volumes increased in 12% of patients, remained stable in 44%, and decreased in 44%. Kaplan-Meier actuarial progression free survival rates at 3, 5, 8, and 10 years were 100, 89, 82, and 80% respectively. No complications were recorded except from medically controlled trigeminal neuralgia that occurred in 15.6% of patients. At last clinical follow-up, 90.6% of patients demonstrated no change or improvement in their neurological condition and quality of life.

Conclusions. In our series, we used upfront frameless stereotactic radiotherapy for the most challenging tumor of the skull base. Tumor control was achieved in 87.5% of patients without impairment of neurological status or quality of life. Even though further studies are necessary, hypofractionated stereotactic radiation therapy may change the paradigm of treatment of skull base meningioma.

 

Alfredo CONTI (Messina, ITALY), Antonio PONTORIERO, Giuseppe IATÌ, Federica MIDILI, Carmelo SIRAGUSA, Anna BROGNA, Stefano PERGOLIZZI
10:40 - 10:50 #9939 - Long term follow up of jugular glomus treated with radiosurgery.
Long term follow up of jugular glomus treated with radiosurgery.

The treatment of paraganglioma of the jugular foramen remains controversial due to its high morbidity, given the anatomical position, the presence of major vessels and cranial nerves that are often found within the lesion. 

Although benign, these tumors sometimes present rapid growth and the neurological symptoms that accompany are hearing loss, cerebral nerves palsies and tinnitus.

For many years surgery, with or without previous embolization has been the treatment of choice, but the inability to do a complete resection, and complications have made surgeons think of alternative treatments such as radiotherapy and most recently radiosurgery. One of the major uncertainties that have always accompanied radiosurgery as treatment for jugular glomus is its effectiveness and long-term results. We present a series of 29 patients treated with radiosurgery, over 50% of patients had undergone surgery, with a mean of 73 months (> 6 years), a symptomatic tumor control 96.5%, and morbidity post irradiation of 13% (Grade I RTOG). According to our data and that found in contemporary literature, radiosurgery has replaced surgery as the primary treatment of jugular foramen paragangliomas. 

Kita SALLABANADA DIAZ (Madrid, SPAIN)
10:50 - 11:00 #9965 - Long-term outcome of low dose (≦12 Gy) gamma knife radiosurgery for skull base meningiomas.
Long-term outcome of low dose (≦12 Gy) gamma knife radiosurgery for skull base meningiomas.

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

Methods: 295 patients treated with GKS (median treatment volume: 6.9 cm3, median prescribed marginal dose: 12 Gy, range 8 -12 Gy) were followed for a mean of 104 months (range 6 - 252 months). 22 patients with large volume tumors were treated by two-staged radiosurgery (volume fractions).

Results: Local tumor growth control was 85%, Actuarial rates of progression-free survival at 5, 15, and 15 years were 90%, 82%, and 74%, respectively. 6% were malignant transformation of tumors. Univariative analysis revealed only without preGKS surgery was positive factor and age, sex tumor volume, treatment dose, staged surgery were not significant for tumor control. The clinical outcome was improved in 15% and unchanged in 64% of patients. The radiation induced neuropathy occurred 7.8% (22 patients). The trigeminal neuralgia considering most devastating symptoms was improved or disappeared in 60% (6/10patients), but new trigeminal neuralgia was occurred in 3.7%(11 patients).

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

Yoshiaysu IWAI (Osaka, JAPAN), Kenichi ISHIBASHI, Kazuhiro YAMANAKA
11:00 - 11:10 #9966 - Current and future for treatment strategy of skull base hemangiopericytoma in stereotactic radiosurgery: Advantage of use pathological micro-anatomy.
Current and future for treatment strategy of skull base hemangiopericytoma in stereotactic radiosurgery: Advantage of use pathological micro-anatomy.

Rationale Hemangiopericytoma (HP) is well known as one of very rare intracranial tumors, and especially skull base one which is very close to the cavernous sinus should be too difficult to be cured by microsurgery alone because of much abundant feeding arteries. If there is residual tumor, it will have often opportunity to develop extracranial metastases. In addition, we should do stereotactic radiosurgery to prevent tumor regrowth. In our institute, we have tried to install and investigate pathological micro-anatomy in Gamma plan to grasp relationship between the tumor and surround vital structures, and hope to prevent tumor shrinkage without any neurological deficit.

Materials and Methods We already treated 11 HP cases with Gamma knife surgery (GKS) after surgical resection, and median prescribed dose was 12 (10-25)Gy. Among of them, 36.4%(4/11) could be controlled, but 54.5%(6/11) experienced extracranial metastases. The clinical results were failure, and then we have investigated micro-anatomy to detect tumor origin and its extension much more precisely to make complete dose planning. In detail, we irradiated higher dose (80% isodose area) to the tumor origin as a priority target, and also cover the tumor as much as possible to make tumor necrotizing due to feeding arterial occlusion pathologically.

Result We experienced another case whose tumor was located in the Meckel’s cave which was looked like trigeminal schwannoma, but the onset was very progressive abducens nerve palsy. At that moment, we investigated micro-anatomy in Gamma plan, but didn’t make clear diagnosis. So we decided to do surgical resection to define pathology with maximal volume reduction. We couldn’t remove sufficiently because of terrible bleeding from the tumor, and did GKS for residual with 24Gy as prescribed peripheral dose according to the micro-anatomical simulation. The patient experienced no deficit with tumor disappearance at 6 months later to GKS, and has to be observed much longer follow-up.

Conclusion We will progress the knowledge and clinical experiences of GKS based on pathological micro-anatomy to establish heavy particle microsurgery system to provide patients complete remission to prevent extracranial metastases.

Motohiro HAYASHI (Tokyo, JAPAN)
11:10 - 11:20 #10239 - Gamma Knife radiosurgery for glomus jugular tumors. Results on 51-treated patients followed-up for al least 36 months.
Gamma Knife radiosurgery for glomus jugular tumors. Results on 51-treated patients followed-up for al least 36 months.

Objective. To assess efficacy and safety of Leksell Gamma Knife Radiosurgery (LGKRS), in terms of tumor control (TC) and permanent symptomatic adverse radiation effects (AREs) (end points); to identify some prognosticators significantly influencing the end-points in patients affected with glomus jugular tumors (GJTs). 

Methods. Between April 1996 and December 2013, 51 consecutive patients with GJTs underwent LGKRS at our Department and were followed up for at least 3 years. Males/females ratio was 10/40; mean age was 56.6 years (20-82). In 21/50 (42%) patients, an endovascular embolization was performed and 19/50 (38%) cases underwent one or more surgical procedures before LGKRS. At the time of treatment, GJTs were classified according to the Glasscock–Jackson (G-J) grading as follows: Grade I 11 patients (23%), Grade II 23 (46%), Grade III 6 (11%), and Grade IV 10 (20%). Mean and range dose planning parameters were as follows: gross target volume (GTV: 0.22 mL, 0.06-0.70), prescription dose (PD: 16.8 Gy, 12.0-24.0), prescription isodose (PI: 49.70 %, 40-55), maximum dose (MD: 32.62 Gy, 24-48) and shot number (13.3, 2-33). On GK day, stereotactic localization was performed using volumetric and T1 fat saturated MRI sequences. Uni-multivariate logistic regression analysis was performed to evaluate which of the following independent variables – G-J grading, pre-LGKRS endovascular treatment, pre-LGKRS surgery, GTV and PD, adjusted for age and sex – could potentially influence the end points.

Results. Median survival was 53.9 months (37.7-183.50). At last clinical follow-up, an improved or stable neurological examination was observed on the whole series with no symptomatic AREs. TC was achieved in 96.0% of cases (48/51) with an actuarial progression-free survival rate of 97% at 10 years. No malignant transformation or radiation induced tumors were observed. Statistical analysis showed that G-J Grade II (p=0.043) was the only prognosticator positively affecting the probability of TC in such patients.  

Conclusion. Despite the particularly critical location of GJTs, long-term outcomes show that LGKRS reveals to be an extremely effective and safe primary or adjuvant treatment in such tumors, as well.

Antonio NICOLATO (Verona, ITALY), Michele LONGHI, Emanuele ZIVELONGHI, Mariano VITELLI, Roberto FORONI, Pierpaolo BERTI, Elisa Francesca Maria CICERI, Stefano DALL'OGLIO , Francesca DUSI, Paolo Maria POLLONIATO, Giuseppe Kenneth RICCIARDI, Giampietro PINNA, Carlo CAVEDON, Mario MEGLIO, Nicola TOMMASI
11:20 - 11:30 #10451 - Gamma Knife radiosurgery for recurrent WHO grade 2 meningiomas.
Gamma Knife radiosurgery for recurrent WHO grade 2 meningiomas.

Objectives

WHO grade 2 meningiomas are aggressive tumors associated with a high recurrence rate leading to repeated surgical procedures, which can seriously worsen a patient’s neurological status. Although radiosurgery is an increasingly popular technique, its role in the management of grade 2 meningiomas has yet to be defined. In this study the authors aimed to evaluate radiosurgery in achieving control of proven tumor progression occurring after resection of grade 2 meningiomas.

Methods 

This retrospective study included consecutive patients, between 2000 and 2015, treated by gamma knife radiosurgery (GKRS) for radiologically proven progression of a previously surgically treated grade 2 meningioma.

Results

Thirty patients were eligible for analysis. There were 10 men and 20 women with a mean age of 59 years. The mean radiation dose was 15.2 Gy (range 12–21 Gy), and the mean target volume was 5.4 cm3 (range 0.194–14.2 cm3). Thirty-eight radiosurgical procedures were performed in the 30 patients. The mean progression-free survival after radiosurgery was 32.4 months among those with progression in a target irradiated volume and 26.4 months among those with progression in any intracranial meninges. With a mean follow-up of 56.4 months (range 12–108 months), the 12-, 24-, and 36-month actuarial local control rates for all patients were 75%, 52%, and 40%, respectively, and the regional control rates were 75%, 48%, and 33%. A single case of transient hemiparesis completely resolved without sequelae.

Conclusions 

Radiosurgery appears to be a safe and effective treatment for the local control of delayed progression after resection of a WHO grade 2 meningioma. Higher radiation doses similar to those applied for malignant tumors should be recommended when possible.

Henri-Arthur LEROY (Lille), Nicolas REYNS, Jean-Paul LEJEUNE, Serge BLOND, Rabih ABOUKAÏS
Parallel 2- Queen
11:30

Monday 29 May

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OSP2
11:30 - 12:30

Parallel session - Functional 1: Movement Disorders

Moderators: Paul KRACK (Bern, SWITZERLAND), Douglas KONDZIOLKA (New York, USA), Tatiana WITJAS (neurologist) (marseille, FRANCE)
11:30 - 11:40 #10263 - Vim’s Anatomical Landmarks: Indirect Targeting vs. Direct Visualization at 7T MRI.
Vim’s Anatomical Landmarks: Indirect Targeting vs. Direct Visualization at 7T MRI.

The ventro-intermediate thalamic nucleus (Vim) is a commonly used target in functional neurosurgery, such as Deep Brain Stimulation and Gamma Knife thalamotomy, for treatment of drug-resistant tremor.  Unfortunately, the routinely used clinical Magnetic Resonance Imaging (MRI) does not allow its direct visualization. Consequently, the targeting strategies are indirect, such as atlas-based registration and stereotactic coordinates. Recent findings have shown the potential of the susceptibility-weighted imaging (SWI) acquired at 7T for imaging the thalamic nuclei with Vim being one of them. The aim of this study is to compare the localization of the target points defined by the quadrilateral of Guiot, as used in daily clinical practice, with the visual Vim-area on SWI at ultra-high field.

Data was collected from five young healthy subjects (25±2 y.o., 3 males). At 3T (TimTrio SIEMENS Scanner) we acquired the standard imaging protocol for Gamma Knife thalamotomy (GKT) including T2-weighted (TR/TE=3200/402 ms, 0.5x0.5x1mm3)  and T2-weighted CISS (TR/TE=6.18/2.75 ms, 0.4375x0.4375x0.44 mm3) images, and at 7T (Siemens Medical Solutions) we acquired the SWI sequence (TR/TE=28/20 ms, 0.375x0.375x1mm3). Guiot targeting was performed bilaterally, six times for each subject using the 3T images. The left and the right Vim-area were manually delineated based upon the intensity variation observed from the SWI as well as the Schaltenbrand and Wahren stereotactic atlas. Both of these tasks were carried out in MITK 3M3 software.

The Vim was outlined for nine out of ten thalami, while the last one was difficult to discriminate due to a presence of a blood vessel. The volumes of the delimitated Vim-area are in the interval [76.3, 83.3] mm3 conforming its size expectations. The quadrilateral of Guiot showed to be highly reproducible with a maximum intra-subject variability of 1.1mm. Additionally, these points were always inside the manually delineated Vim and predominantly in the ventral part of the outlined volume showing a tendency of their localization.

This study reports for the first time, to the best of our knowledge, a validation of the clinical targeting against subject-related imaging reference. Moreover, we observed that the clinically used Guiot targeting points are confined in the ventral part of the visually distinguishable Vim as provided by SWI acquired at ultra-high field. Further studies with larger datasets, such as tremor patients and their electrophysiological confirmation, should validate these findings.

Elena NAJDENOVSKA (Lausanne, SWITZERLAND), Constantin TULEASCA, Jose P. MARQUES, Joao JORGE, Daniel GALLICHAN, Philippe MAEDER, Jean-Philippe THIRAN, Marc LEVIVIER, Meritxell BACH CUADRA
11:40 - 11:50 #10260 - Exploring Local Diffusion MRI Properties for Vim Localisation: Evaluation in Clinical Cases.
Exploring Local Diffusion MRI Properties for Vim Localisation: Evaluation in Clinical Cases.

The difficulty to directly visualize the Ventro-intermediate thalamic nucleus (Vim) on the currently routine MRI leads to the application of indirect targeting methods in stereotactic neurosurgical procedures, such as Gamma Knife Surgery (GKS) and Deep Brain Stimulation (DBS), for a treatment of drug-resistant tremor.

There has been a growing effort for automated targeting in the image-processing community based on diffusion-MRI. This technique enables the depiction of the different structural-connectivity properties and therefore, the specific fiber orientation inside each thalamic nucleus.

Our group proposed an automated and robust method across healthy subjects and tremor patients for parceling the thalamus in seven main groups of nuclei while exploring the local diffusion information from the spherical harmonics representation of the orientation distribution functions (ODFs) in k-means clustering framework. One of the resulting parcels is the Ventral-Lateral-Ventral group (VLV) enclosing all motor-related nuclei including the Vim. We aim at further automatic subdivision of the VLV cluster. To this end, within the VLV, we first built a k-nn graph with edges corresponding to the respective ODFs distances and then, we performed a partition in 3 sub-clusters using the NCut algorithm.

The proposed subdivision was compared to the radiological response in the follow-up images of 17 patients treated for tremor with GKS unilaterally. The MRI protocol included pre-operative diffusion-weighted images with 64 (or 72) gradient direction, b=1000s/mm2 and voxel-size: 2.2x2.2x2.2mm3, pre-operative and post-operative MPRAGEs with isotropic resolution of ~1mm3 - all of them acquired at 3T. In general, the sub-partition followed a spatial-distribution pattern and for 12 out of 17 cases we observed that one specific sub-cluster encloses entirely or the major part of the contrast enhancement corresponding to the GKS target appearing on the follow-up images.

The evaluation of the sub-partition outcome was further extended in one additional tremor patient treated with DBS, bilaterally. Similar pre-operative MRI data, as for the GKS-treated patients, was acquired. We observed that in each hemisphere both initial targeting point and the final electrode position are inside the anticipated sub-cluster. The final left and right position are 5 and 1 mm distant from the corresponding sub-clusters’ centroids, respectively.

This study shows that the diffusion-MRI-based sub-clustering of the VLV thalamic nuclei could potentially allow, in an automated manner, to narrow the area of Vim’s localization. Our preliminary results will be further investigated in a larger patients dataset, treated by either GKS or DBS, and on diffusion images with higher spatial resolution.

Elena NAJDENOVSKA (Lausanne, SWITZERLAND), Constantin TULEASCA, Jocelyne BLOCH, Philippe MAEDER, Nadine GIRARD, Tatiana WITJAS, Jean RÉGIS, Jean-Philippe THIRAN, Meritxell BACH CUADRA, Marc LEVIVIER
11:50 - 12:00 #10371 - Staged Bilateral Thalamic Radiosurgery for Patients with Bilateral Tremor.
Staged Bilateral Thalamic Radiosurgery for Patients with Bilateral Tremor.

Objective: Gamma knife thalamotomy (GKT) is a well-established treatment for medically refractory tremor patients who are at risk for invasive procedures. The purpose of this study was to evaluate whether staged bilateral GKT provides benefit and acceptable risk to patients suffering from disabling bilateral tremor.

 

Methods: At a median interval of 22 months, 11, patients underwent staged bilateral GKT during a 17 year period (1999-2016). Eight patients had essential tremor (ET), two had Parkinson’s disease (PD) related tremor, and one had Multiple-sclerosis (MS) related tremor. For the 1st GKT, a median maximum dose of 140 Gy was delivered to the posterior-inferior region of the nucleus ventralis intermedius (VIM) through a single isocenter with 4-mm collimators. Patients who benefitted from unilateral GKT were eligible for a contralateral GKT. For the 2nd GKT, a median dose maximum of 130 Gy was delivered to the opposite VIM nucleus to a single 4-mm isocenter. We used the Fahn-Tolosa-Marin (FTM) clinical tremor rating scale to score tremor, drawing, writing and drinking before and after GKT. We used the Karnofsky performance scale (KPS) to grade quality of life and activities of daily living before and after the GKT.

 

Results: All patients had improvement in tremor after 1st GKT. The median time to last follow-up after the 1st GKT was 35 months (range, 11-70 months). No patients had tremor recurrence or diminished tremor relief. One patient experienced new temporary neurological deficit (contralateral lower extremity hemiparesis) from the 1st GKT which improved on corticosteroids. The median time to last follow-up after the 2nd GKT was 12 months (range, 2-70 months). Nine patients had improvement in at least one FTM score after the 2nd GKT. Two patients had tremor arrest and complete resolution of function. No patient experienced tremor recurrence or diminished tremor relief after the 2nd GKT. No patient experienced new neurological or radiological adverse effect from the 2nd GKT. Statistically significant improvements were noted in the KPS following the 1st and 2nd GKT.

 

Conclusions: Staged bilateral GKT provides effective relief for medically refractory, disabling, bilateral tremor without increased risk of neurological complications. It is an appropriate strategy for carefully selected medically refractory bilateral tremor patients ineligible for deep brain stimulation.  

Ajay NIRANJAN (Pittsburgh, USA), Sudesh RAJU, Edward MONACO III, John FLICKINGER, L. Dade LUNSFORD
12:00 - 12:10 #10395 - Correlations between the clinical results and the MR characteristics of the thalamic lesion in Vim Gammaknife radiosurgery for tremor.
Correlations between the clinical results and the MR characteristics of the thalamic lesion in Vim Gammaknife radiosurgery for tremor.

Objective: This study aims at reporting the correlation between the clinical results and the one-year postoperative MR neuro-imaging characteristics of the thalamic lesion after Gammaknife radiosurgery for  tremor.


Methods: Between April 2004 and March 2015, a Vim Gammaknife thalamotomy was performed in 319 patients for essential or Parkinsonian tremor in Marseille University hospital with a very stereotyped procedure. A neuro-imaging and clinical assessment was performed at one year FU for 253 patients. The volume of the lesion defined as the whole area of post-contrast enhancement was calculated for each patient in mm3, the pattern of lesion determined and the amount of edema evaluated according to a semi-quantitative scale. A comprehensive clinical evaluation by expert neurologists was performed at the same time.  Statistical analysis was performed using R software (Version 1.0.136/2016 RStudio, Inc)


Results: Imaging data were analyzable and reviewed for a total of 169 patients at one year follow-up. Among these patients, data from neurological clinical evaluation were obtained for 91 patients. The median percentage of tremor reduction was 70% (0-100%, SD:30%).  The median volume of the lesion at 12 months FU (+/- 3 months) was 91,45 mm3 (Mean = 104, Min:0, Max :1120, SD:284) . A correlation was established between the volume of the lesion and the percentage of tremor reduction (Pearson's coefficient of correlation r =+ 0,26 (p=0,0178). In patients regarded as clinical failure (< 45% of tremor improvement), the lesion volume was significantly smaller than in patients deemed responders (> 45% tremor reduction) ,p <0,0001).The amount of edema surrounding the lesion was found to be significantly related to the clinical improvement (p = 0.022). The “cocade” pattern enhancement type was strongly related to good outcome (p<0,001) and the absence of enhancement to the absence of improvement (p<0,00001 ,62% versus 0,07%).

Conclusions: These data confirm our previous results derived from 50 patients with blinded analysis of clinical outcome (Witjas and al. Neurology, 2015). Even though a significant correlation does exist between lesion volume, edema and clinical improvement, concordance is far from being very strong and linear between the imaging and clinical responses. These findings prompt to look for additional factors in order to better characterize the effects of Gammaknife that might also rest upon a delayed non-lesional neuromodulatory mechanism. These fascinating questions are of utmost importance and currently under investigation in our department.

Romain CARRON (Marseille Cedex 5), Tatiana WITJAS, Cornel TANCU, Giorgio SPATOLA, Jean RÉGIS
12:10 - 12:20 #10599 - Voxel-based morphometry after Gamma Knife thalamotomy of the Vim for tremor could help discriminating clinical responders from non-responders the Vim nucleus for tremor.
Voxel-based morphometry after Gamma Knife thalamotomy of the Vim for tremor could help discriminating clinical responders from non-responders the Vim nucleus for tremor.

Constantin Tuleasca1,3,9, MD, Tatiana Witjas4,5, MD, Elena Najdenovska2, MSc, Antoine Verger6, MD, Nadine Girard7, MD-PHD, Jerome Champoudry8, MSc, Jean-Philippe Thiran3,9, PHD, Meritxell Bach Cuadra2, PHD, Marc Levivier1,9, MD, PHD, Eric Guedj*6, MD, AND Jean Régis*8, MD


Objective: To assess for the first time structural brain changes, by voxel-based morphometry (VBM), before and after unilateral Gamma Knife thalamotomy (GKT) for drug-resistant tremor. To identify differences between clinical responders and non-responders to GKT.

Methods: Thirty-eight patients (mean age 71.8 years) with severe refractory right essential tremor (ET) were treated with unilateral left GKT. Targeting of ventro-intermediate nucleus (Vim) was performed with Leksell Gamma Knife using a single 4-mm collimator and 130 Gy.  Neurological, neuropsychological and neuroimaging (3 Tesla, including 3D T1 weighted) assessment had been done at baseline and 1 year after GKT. Clinical responders were considered those improved in tremor score (Fahn-Tolosa-Marin) with at least 45%.

Results: Thirty-one (81.6%) patients were responders (R) and 7 (18.4%) non-responders (NR). With regard to GM changes after GKT, independently of clinical answer, atrophy was present in extensive areas (right globus pallidus, left putamen, left thalamus, right anterior and medio-dorsal thalamus, cerebellar, right premotor and supplementary motor area, left and right visual association cortex, right ventral temporal, left parahippocampal and posterior cingulate gyrus). The interaction between R - NR with time showed brain plasticity in R remote areas, within left temporal pole (BA 38) and cluster including left occipital cortex (BA 19), visual areas V4 and V5, parahippocampal place area (punc<0.005, k>120).

Conclusions: Our results show brain plasticity after unilateral left GKT. Responders present changes in areas involved in motion, mainly locomotor monitoring towards the local and distant environment, suggesting the requirement to recruit in the targeting specific visuomotor networks.

Constantin TULEASCA (Pully, SWITZERLAND)
12:20 - 12:30 #10616 - Bilateral GammKnife Thalamotomy for severe Essential Tremor.
Bilateral GammKnife Thalamotomy for severe Essential Tremor.

Objective: To assess the feasibility and tolerance of bilateral Gamma Knife thalamotomy (GKT) in Essential Tremor (ET)

Background: Unilateral GKT is an established treatment for severe tremors. However, essential tremor is usually bilateral. The persistence of contralateral tremor may induce an impairment in activities of daily living (ADL). Bilateral procedures with thermocoagulation were contraindicated because of the risk of balance, cognitive or speech problems. As the lesion induced by radiosurgery within the VIM is progressive and limited, we proposed a study on bilateral GKT. Here are the preliminary results.

Methods: 15 patients (8 women) with severe ET who had benefit from a first GKT and who had a severe permanent contralateral tremor were included. Patients were included if there was no impairment in their balance or speech and if the neuropsychological assessment was stable. The 2nd GKT was performed at least 18 months after the first GKT. Patients were assessed before and quarterly for at least 12 months after GKT2, with tremor rating scale, neuropsychological and gait/balance assessments and MRI. VIM lesioning was performed with Leksell Gamma unit with a single exposure through a 4mm collimator. Radiosurgical dose was 130Grays.

Results:  here are the preliminary results for 9 patients who completed the study at 1 year. Tremor score on the treated hand was improved by 57%. The improvement of ADL was 95%. Cognitive score and gait assessment were stable. No patient had hypophonia or dysarthria. Two patients were not significantly improved. One patient had a side effect related to GKT2. She developed hemiataxia and dysarthria induced by a hyperresponse pattern 11months after GKT.

Conclusions: These preliminary results on bilateral GKT for severe ET in a selected cohort of patients shows that the procedure is feasible without a major risk of cognitive or balance problems. However, a longer follow-up is needed

Tatiana WITJAS (marseille), Romain CARRON, Jean Philippe AZULAY, Jean REGIS
Stravinski Auditorium

Monday 29 May

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OSP3
11:30 - 12:30

Parallel session - Metastases 1

Moderators: Igor LATORZEFF (MD) (Toulouse, FRANCE), Luis SCHIAPPACASSE (Consultant in Radiation Oncology) (Lausanne, SWITZERLAND), Masaaki YAMAMOTO (Gamma Knife) (Hitachi-naka, JAPAN)
11:30 - 11:40 #9858 - Pattern of Failure after Resection and Post-Operative Radiosurgery to the Surgical Cavity.
Pattern of Failure after Resection and Post-Operative Radiosurgery to the Surgical Cavity.

Objectives

Stereotactic radiosurgery (SRS) after surgical resection of brain metastases has been shown to be an effective alternative to whole brain radiation for local control.  In this study we assessed local failure patterns after post-op SRS to the surgical bed of completely resected brain metastases.

Methods and Materials

In a phase III randomized study (NCT00950001), 132 patients, who had no more than 3 brain metastasis with at least one completely resected were randomized to SRS or observation (OBS).  Complete resection was verified by postoperative magnetic resonance imaging (MRI) and SRS was delivered to the cavity by post-op day 30.  Using the Elekta Perfexion Gamma Knife unit, SRS was delivered with a 1 mm margin and the  prescription dose was target volume dependent which ranged from 12 to 16 Gy.  Tumor recurrence in the resection cavity or its immediate vicinity was identified on routine follow up MRI.  The first MRI that identified recurrence was imported into the Leksell GammaPlan software and registered with the cavity treatment planning MRI.  The recurrence was contoured and its position was evaluated relative to the prescription isodose line.  The location of recurrence was classified into three categories; 1) “in-field”, 2) “cross-field” and 3) “marginal” if the recurrence volume was within, crossed, or adjacent to the prescription isodose line, respectively.  The minimum dose delivered to the area of recurrence was quantified.

Results

12 of the 64 patients randomized to SRS had local recurrence after SRS.  Five cases failed in-field, 4 cases were cross-field and 3 cases were marginal.  The minimum dose received by the volume showing in-field failure during SRS delivery ranged from 12 to 20 Gy.  All marginal failures were notable for having dural involvement with the recurrence occurring adjacent to the prescription isodose line.

Conclusion

The factors contributed to failure after SRS are complicated.  In-field failures may be due to an inadequate prescribed dose or a biologic resistance to radiotherapy.  Marginal failures maybe related to inadequate margins.  A larger margin, particularly along the dura may help increase local control with SRS after surgery.  Cross-field failures are likely multifactorial due to factors allowing to both in-field and marginal failures.  Evaluation of the clinical factors and comparison to the failures within the OBS arm are ongoing.

Xin WANG (Houston, USA), Ganesh RAO, Jing LI, Mary MCALEER, Susan MCGOVERN, Amol GHIA, Erik SULMAN, Paul BROWN, Sherise FERGUSON, Amy HEIMBERGER, Frederick LANG JR, Ian MCCUTCHEON, Sujit PRABHU, Raymond SAWAYA, Jeffrey WEINBERG, Salmaan AHMED , Dershan LUO, Anita MAHAJAN
11:40 - 11:50 #9977 - Stereotactic radiosurgery for treatment of patients with 10 or more brain metastases.
Stereotactic radiosurgery for treatment of patients with 10 or more brain metastases.

Objectives: For patients with up to 10 brain metastases (BM), studies increasingly support excellent disease control and toxicity outcomes with stereotactic radiosurgery (SRS) in lieu of whole brain radiotherapy (WBRT) or as salvage therapy for recurrence after WBRT. Outcomes for patients with 10 or more metastases treated with SRS remain unclear. We report our institutional experience of treatment of patients with 10 or more brain metastases at first SRS treatment session.

Methods:  We identified 97 patients with 10 or more brain metastases (BM) receiving fixed-frame SRS (FFSRS) without WBRT for newly-diagnosed or recurrent BMs at our institution between September 1998 and December 2013. We reviewed treatment-related outcomes of overall survival (OS), treated lesion freedom from progression (FFP), freedom from new metastases (FFNM), and adverse radiation effect (ARE).

Results: Among the 97 FFSRS-treated patients, the median age was 56 (range 17-84) and median KPS 80 (range 40-90). Primary histologies within the cohort were breast (38), lung (28), melanoma (22), and other (9). Median number of BM per patient was 12 (IQR 11-16). Median total treatment volume was 4.3 cc  (IQR 2.3-11.5 cc). Forty-three patients received FFSRS without WBRT as upfront BM radiotherapy and 54 as salvage therapy after prior WBRT, with median OS 7.8 and 8.8 mo, respectively. Sixty patients had available follow up imaging. FFP at 1 year with 95% confidence intervals for upfront vs. salvage FFSRS was 70% (49-84%) vs. 55% (30-74%) by patient and 94% (91-96%) vs. 86% (81-90%) by lesion. FFNM at one year for upfront vs. salvage FFSRS was only 9% (2-22%) vs. 14% (4-30%). At progression, 40 patients received additional FFSRS, 20 (21%) had WBRT, and one had partial brain radiotherapy. Symptomatic ARE was observed in 1% of 1018 treated lesions over the patients’ disease course. Seven patients experienced symptomatic ARE.

Conclusions: Our institutional experience demonstrates excellent local control following FFSRS for patients with 10 or more BM as upfront therapy or at recurrence following prior WBRT. Rates of ARE were modest, consistent with prior studies. Expectedly, these patients with large burden metastatic disease had a high rate of new metastases often requiring salvage SRS or WBRT.

Steve BRAUNSTEIN (San Francisco, USA), Michael GARCIA, Jean NAKAMURA, Shannon FOGH, Lijun MA, Phillip THEODOSOPOULOS, Michael MCDERMOTT, Penny SNEED
11:50 - 12:00 #10008 - Implications of HER2 status on local control and adverse radiation effect after stereotactic radiosurgery for brain metastases from breast cancer.
Implications of HER2 status on local control and adverse radiation effect after stereotactic radiosurgery for brain metastases from breast cancer.

Objectives:  To determine the implications of HER2/neu-amplification (HER2) status on local control and adverse radiation effect (ARE) after stereotactic radiosurgery for the treatment of brain metastases from breast cancer.

Methods:  We retrospectively reviewed all Gamma Knife radiosurgery cases from 1998-2013 for the treatment of brain metastases from breast cancer at our institution. Newly-diagnosed brain metastases treated with radiosurgery alone and new or recurrent brain metastases after prior radiotherapy were included, and resection cavities, lesions treated with prior radiosurgery, and lesions with no imaging follow-up were excluded from this analysis. Hormone receptor status was determined based on pathology reports from the primary breast tumor. Freedom from progression (FFP) and cumulative incidence of ARE for all treated lesions were determined using the Kaplan-Meier method with censoring at last imaging. Univariate analysis by lesion was performed using the log-rank test.

Results:  1314 newly-diagnosed or recurrent brain metastases in 204 breast cancer patients were included for analysis. The median imaging follow-up was 9.0 months. Actuarial 1- and 2-year FFP probabilities by lesion were 89% and 79% overall. HER2 positive status was associated with worse FFP; 1-year and 2-year FFP probabilities were 85% and 75% for HER2 positive tumors versus 95% and 86% for HER2 negative tumors (p<0.0001). Further stratification of HER2-positive lesions by ER status showed no significant difference in FFP or ARE, whereas among HER2 negative tumors, 1- and 2-year FFP probabilities were 97% and 91% for ER positive versus 92% and 80% for ER negative metastases. A dose-response relationship was seen in HER2-positive lesions (p<0.001). In HER2 positive lesions, the use of systemic therapy within 1 month of radiosurgery was associated with improved tumor control (p = 0.0007) and did not increase the risk of ARE. The cumulative incidence of ARE at 1 and 2 years was low at 2% and 6% for HER2 positive tumors versus 2% and 3% for HER2 negative tumors (p=0.11).

Conclusions:  Radiosurgery for HER2-positive brain metastases from breast cancer appears to be associated with poorer tumor control with low incidence of ARE.  Treatment intensification with dose escalated radiosurgery or concurrent treatment with systemic therapy should be considered.

Jason W CHAN (San Francisco, USA), Yao YU, Steve E BRAUNSTEIN, Jean L NAKAMURA, Shannon E FOGH, Lijun MA, Philip V THEODOSOPOULOS, Michael W MCDERMOTT, Penny K SNEED
12:00 - 12:10 #10064 - Hypofractionated stereotactic radiotherapy for the treatment of brain metastases: analysis of 400 cases.
Hypofractionated stereotactic radiotherapy for the treatment of brain metastases: analysis of 400 cases.

Objectives:  To analyze radiographic and survival outcomes in a large cohort of patients with brain metastases who received hypofractionated stereotactic radiotherapy (HSR) with a focus on short-term and long-term tumor response, complications and mortality.  

Methods: Patients with brain metastases who underwent HSR between 2010 and 2016 were included in the study. Radiation treatments were performed with Gamma Knife 4C and Perfexion (Elekta AB, Stockholm, Sweden), Cyber Knife (Accuray, Sunnyvale, CA, USA) and linear accelerator TrueBeam STX (Varian Medical Systems, Palo Alto, CA). The indications for HSR were determined by the presence of large volume tumors or proximity to critical brain structures. Patients with multiple brain metastases were subjected to a combination of HSR and stereotactic radiosurgery (SRS). Radiation schemes were selected depending on the number of metastases, size, location, proximity to critical brain structures, histological type of primary cancer and patient general condition. Following treatment the patients underwent control MRI examination with standard protocols (2 mm T2 and 1 mm T1 with double contrast enhancement) at 8 weeks and then every 3 months. The median follow-up time after HSR was 9 months.

Results: The study revealed that the application of HSR for the treatment of large volume or critically located brain metastases provided a high level of local control (12-month local control rate was 86 %).  Shrinkage of tumor volume by more than 50% was observed in a vast majority of patients with radiosensitive tumor histology, which resulted in considerable improvement of the patients’ neurological condition. Complications in the form of radiation necrosis occurred in 20% of patients at a median of 7.6 months after HSR. History of previous brain irradiation increased the risk of radiation necrosis (HR=3.4, p<0.001). For the entire cohort 12-month and 24-month overall survival rates after HSR were 45% and 24% respectively. There was no statistically significant difference in the median survival of the patients receiving HSR alone and those receiving HSR plus SRS. Mortality within 2 months after HSR was 10% and was associated with neurological deterioration or systemic disease progression. The best survival results were obtained in patients belonging to the first RPA-class who achieved one-year survival in 73% of the cases.

Conclusion: HSR and its combination with SRS is an effective treatment strategy for patients with brain metastases having at least one large unresectable lesion or a lesion located in/near critical brain structures.

Pavel IVANOV (Saint-Petersburg, RUSSIA), Irina ZUBATKINA, Alexandr KUZMIN, Dmitriy NIKITIN, Georgij ANDREEV, Anton KUBASOV, Ivan PLUGAR, Fedor SCHEPINOV
12:10 - 12:20 #10269 - The role of number metastasis in the diagnosis specific graded prognostic assessment (ds-GPA) for lung, renal cell carcinoma (RCC) and melanoma.
The role of number metastasis in the diagnosis specific graded prognostic assessment (ds-GPA) for lung, renal cell carcinoma (RCC) and melanoma.

Background: The diagnosis specific graded prognostic assessment (ds-GPA) model is one of the most prevalent methods of prognostication for patients with cerebral metastases. The ds-GPA models for lung, RCC, and melanoma each contain number of metastases as one of the prognostic inputs. Recent literature has revealed that the impact of number of metastases has on patient outcomes is often overshadowed by the impact of cumulative intracranial volume (CITV) and other clinical variables. With this in mind, we wished to test if a simplification of the ds-GPA model for lung, renal cell carcinoma (RCC), and melanoma was non-inferior to the original model.

Objective: We wished to examine the hypothesis that binarizing the number of metastases to 1 and greater than 1 is non-inferior to the three bin model used for patients with lung, melanoma, and RCC cerebral metastases after accounting for the other components of their respective ds-GPA model.

Methods: Our patient cohort of interest consisted of 4348 patients (3745 lung, 321 RCC, 282 melanoma) from the United States, Japan, and Australia who underwent SRS for one or more brain metastases We used the statistical metrics net reclassification index (NRI) and integrated discrimination improvement (IDI) in order to examine the ds-GPA model for lung, RCC, and melanoma against a similar model with the only change being the number of metastases category binarized. Through use of these statistical measures we were able to compare the effect of replacing the 1, 2-3, and >3 metastases grouping with 1 and >1.

Results: We found that for lung, RCC, and melanoma no difference between the original ds-GPA and the simplified version was detectable even after controlling for the other elements of each pathology’s respective model (NRI and IDI CI’s capturing 0 with p >.05 for each tumor type). In fact, when subgroups of patients with similar tumor pathology were further stratified by institution/location, we found instances where the simplified model was superior to the original ds-GPA.  

Conclusion: We found that simplifying the number of metastasis portion of ds-GPA model for lung, RCC, and melanoma was non-inferior to their respective, original ds-GPA models.

 

Mir Amaan ALI (Huntington Beach, USA), Brian HIRSHMAN, Kate CARROLL, Alexander SCHUPPER, Michael BRANDEL, Bayard WILSON, James PROUDFOOT, Steven GOETSCH, Bob CARTER, Gerald FOGARTY, Angela HONG, Toru SERIZAWA, Masaaki YAMAMOTO, Clark C CHEN
12:20 - 12:30 #10376 - A randomised clinical trial of the 4mm vs. the 8mm collimator for GKR of brain micro-metastases: Interim analysis.
A randomised clinical trial of the 4mm vs. the 8mm collimator for GKR of brain micro-metastases: Interim analysis.

Introduction

Gamma Knife Radiosurgery (GKR) of large numbers of micrometastases can be time consuming. Beam on time can often become the limiting factor in being able to treat every lesion in a particular patient. One technique to reduce beam on time is to use a larger collimator to a high isodose. This controversial technique decreases the dose gradient inside and outside the target. However, it is uncertain whether this makes a clinical difference, when target and treatment volumes are so small.

Objective

To investigate whether there is a difference in clinical efficacy between treating micro-metastases with GKR using the 4mm or 8mm collimator.

Methods

So far 33 patients undergoing GKR for brain metastases have consented to participate in this trial. Micro-metastases (defined here as under 0.14cc and maximum diameter under 6mm) were randomised to a single shot with either the 4mm or the 8mm collimator. Brainstem lesions and lesions within 11mm of one another were excluded. A marginal dose of 25Gy was prescribed for all lesions

Primary outcome was radiological local control at 12 months post GKR, or at the last imaging follow-up if death occurred during the first year post-GKR.

Results

72 eligible lesions were identified in 20/33 subjects and underwent randomisation. 38 lesions were randomly assigned to the 4 mm collimator and 34 to the 8 mm collimator.

A marginal dose of 25Gy was prescribed for all lesions. The mean Prescription Isodose was 73.4% (43-93) for the 4mm group and 95.7% (88-99) for the 8mm. 

The outcome has been reached by 66% of the micro-metastases and at least one follow up was available for 81% of the lesions. The mean follow-up time was 7.6 months (2.1-18.9). No lesion has shown definite enlargement (up to 30% TV increase) and no radiological evidence of oedema or radionecrosis has been detected. In the 4mm group, 40% of the lesions remained unchanged and 60% got reduced or disappeared. Similarly, in the 8mm group 45% were stable and 55% reduced/disappeared.

Seven patients developed new metastatic lesions at follow up and one of them underwent WBRT. 60% (12) patients have died, three of them from progressive intracranial metastatic disease, at a mean time of 6 months (0.3-11.3) post-GKR.

Conclusions

Initial results suggest that optimisation of treatment time for small lesions may be achieved by using the 8mm collimator without compromising clinical efficacy.  Further recruitment and follow up is needed.

Ian PADDICK (Streatley, UK), Alvaro ROJAS-VILLABONA, Cornel TANCU, Naomi FERSHT, Katherine MISZKIEL, Rolf JAGER, Neil KITCHEN
Parallel 1- Prince

Monday 29 May

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OSP1
11:30 - 12:30

Parallel Session - WFSBS: Vestibular Schwannomas 1

Moderators: Gus BEUTE (Neurosurgeon) (Tilburg, THE NETHERLANDS), Pierre-Hugues ROCHE (Marseille, FRANCE), Karl SCHALLER (Genève, SWITZERLAND)
11:30 - 11:40 #10104 - Gamma Knife radiosurgery in acoustic neuroma – the Vienna series.
Gamma Knife radiosurgery in acoustic neuroma – the Vienna series.

Objective: We present long-term follow-up data after Gamma Knife radiosurgical (GKRS) treatment of acoustic neuroma.

Patient and Methods: Six-hundred and eighteen patients were radiosurgically treated for acoustic neuroma between 1992 and 2016 at the Department of Neurosurgery, Medical University Vienna. Patients with neurofibromatosis and patients who could not yet have a one year follow-up were excluded from the study. Thus, we present data of 557 patients with spontaneous acoustic neuroma and long-term follow-up data on 426 patients with a minimum follow-up of two years. Koos grades at time of diagnosis and at time of GKRS were evaluated. Patients were assessed according to the Gardner-Robertson hearing scale and House-Brackmann facial weakness scale prior to GKRS, and at times of follow-up. Data were evaluated retrospectively.

Results: 452 patients (81%) were treated radiosurgically alone and 105 patients (19%) were treated combined microsurgically-radiosurgically. Whereas the combined treatment was favored especially prior to 2002, the percentage of only radiosurgically treated cases has significantly increased since then. The overall complication rate after GKRS was low. The complication rate after GKRS further declined in the last decade. A significant enlargement of the ventricular system (hydrocephalus) after GKRS was only observed among patients harboring Koos grade III or IV tumors. One case of malignant transformation after GKRS was diagnosed (0.2%). Radiological outcome after GKRS revealed stable or decreased neuromas in the vast majority of cases including all Koos grades. The rate of non-functional hearing was already rather high prior to GKRS. At last follow-up, preservation of functional hearing was achieved in 52% of patients classified as Gardner-Robertson grade I or II prior GKRS.

Conclusion: GKRS is a safe and effective treatment in patients of all Koos grades. Advancements in the radiosurgical treatment especially over the last decade have led to a low complication rate and excellent outcome.

Brigitte GATTERBAUER (Vienna, AUSTRIA), Klaus KITZ, Josa M. FRISCHER
11:40 - 11:50 #10211 - Genetics in Vestibular Scwannomas - a comparison of native tumors and tumors treated by SRS.
Genetics in Vestibular Scwannomas - a comparison of native tumors and tumors treated by SRS.

Objective Vestibular schwannoma (VS) is a benign tumor with associated morbidities and reduced quality of life. Except for mutations in NF2, the genetic landscape of VS remains to be elucidated. Little is known about the effect of Gamma Knife radiosurgery (GKRS) on the VS genome. The aim of this study was to characterize mutations occurring in this tumor to identify new genes and signaling pathways important for the development of VS. In addition, the authors sought to evaluate whether GKRS resulted in an increase in the number of mutations.

Methods Forty-six sporadic VSs, including 8 GKRS-treated tumors and corresponding blood samples, were subjected to whole-exome sequencing and called tumor-specific DNA variants. Pathway analysis was performed using the Ingenuity Pathway Analysis software. In addition, multiplex ligation-dependent probe amplification was performed to characterize copy number variations in the NF2 gene and microsatellite instability testing was done to investigate for DNA replication error.

Results With the exception of a single sample with an aggressive phenotype that harbored a large number of mutations, most samples showed a relatively low number of mutations. A median of 14 tumor-specific mutations in each sample were identified. The GKRS-treated tumors harbored no more mutations than the rest of the group. A clustering of mutations in the cancer-related axonal guidance pathway was identified (25 patients), as well as mutations in the CDC27 (5 patients) and USP8 (3 patients) genes. Thirty-five tumors harbored mutations in NF2 and 16 tumors had 2 mutational hits. The samples without detectable NF2 mutations harbored mutations in genes that could be linked to NF2 or to NF2-related functions. None of the tumors showed microsatellite instability.

 

Conclusions The genetic landscape of VS seems to be quite heterogeneous; however, most samples had mutations in NF2 or in genes that could be linked to NF2. The results of this study do not link GKRS to an increased number of mutations

Aril HÅVIK (Bergen, NORWAY)
11:50 - 12:00 #10310 - Rate of residual tumor growth after primary subtotal resection (STR) and the role of upfront versus salvage stereotactic radiosurgery for sporadic vestibular schwannomas.
Rate of residual tumor growth after primary subtotal resection (STR) and the role of upfront versus salvage stereotactic radiosurgery for sporadic vestibular schwannomas.

Background: Modern clinical studies have converged upon “maximal safe resection” as the optimal surgical strategy for moderate-to-large vestibular schwannomas, however data on the long-term outcomes of residual tumor is lacking and the best treatment strategy for residual disease is an open question. The goal of this study was to review our rates of residual tumor growth, and the response to salvage versus upfront SRS.

Methods: This retrospective single-institution study included all sporadic vestibular schwannomas treated primarily with subtotal resection at our institution from 2002 – 2015. Patients with less than 1 year of follow-up imaging were excluded. Patients treated with upfront SRS after surgery were analyzed separately. The primary outcome was tumor stability or growth requiring salvage treatment, and response to salvage treatment (surgery or SRS).

Results: 295 patients underwent primary surgery for vestibular schwannoma at our institution between 2002 and 2015. A subtotal resection was performed in 140 of these cases. 49 cases were excluded due to <1 year follow-up imaging. 17 cases received upfront SRS after surgery (12 cases Gamma Knife, 12Gy; 5 cases CyberKnife, 25Gy in 5 fractions). There were 2 failures requiring salvage surgery 1.6 and 2.6 years after SRS (88% control rate at 1.8 median follow-up after SRS). Of the remaining 74 residual tumors managed with observation after STR, 57 (77%) remained stable at a median 4.1 years after surgery.  17 tumors (23%) progressed and required salvage treatment at a median of 2.8 years after STR. 11 were treated with Gamma Knife (12.5 Gy) at a median interval of 2.6 years after surgery, and all remained clinically stable over a median follow-up of 2.3 years after salvage SRS. One was treated with Cyber Knife (18Gy in 3 fractions) and went on to require a second surgery 3 years later. 4 residual tumors were treated with salvage surgery at a median interval of 5 years after STR, and one was lost to follow-up.  The control rate of salvage SRS was 92% at 2.3 years median follow-up.

Conclusion:  A majority (77%) of residual vestibular schwannomas will remain stable after a primary subtotal resection. Both upfront and salvage SRS had good control rates (~90%) in our series. Further study is needed to define the role of upfront versus salvage SRS after a primary STR.

Jonathan BRESHEARS, Carlene PARTOW, Tarik TIHAN, Michael MCDERMOTT, Patricia SNEED, Steven CHEUNG, Philip THEODOSOPOULOS (San Francisco, USA)
12:00 - 12:10 #10330 - Correlation between pre-treatment growth rate and tumor control of vestibular schwannomas after gamma knife radiosurgery in the dutch database.
Correlation between pre-treatment growth rate and tumor control of vestibular schwannomas after gamma knife radiosurgery in the dutch database.

Introduction
Prognostic factors of tumor control after Gamma Knife Radiosurgery (GKRS) for vestibular schwannoma (VS) are largely unknown. Recently, it has been reported that the growth rate of VS before treatment is indicative of the chance that radiosurgery achieves tumor control. Such findings may have important implications for treatment strategies and may lead to advise for either microsurgery or higher marginal doses for fast growing tumors. However, studies on this important aspect are limited and show conflicting results. Moreover, the available studies are hampered by methodological limitations such as limited patient numbers and follow-up and two-dimensional assessment of tumor size. The objective of this study is to identify a possible correlation between pre-treatment growth rate and tumor control after GKRS in a large database with sufficient follow-up and volumetric tumor assessments.

Methods
In the prospectively collected database of the Gamma Knife Center Tilburg, 445 patients with VS, treated between 2002 and 2014, that showed documented growth before treatment and who have had a minimum follow-up of 2 years after treatment, were identified. Tumor volumes before, at and after treatment were assessed. GKRS was performed in a uniform way, with a dose of 12-13Gy prescribed to the isodose line covering 90-99% of the target. Failures were defined as tumor progression on 2 consecutive MRI’s beyond 2 years after GKRS, or as judged by the radiosurgical team. Volume doubling times (VDT) before treatment were correlated with the observed tumor control rates and volumetric responses after treatment.

Results
Until now 266 of the 445 patients with documented pre-treatment tumor growth have been analyzed. 25 Patients were lost to follow-up. The median follow-up was 4 years. 25 Patients showed a radiological failure. The 5- and 10-year actuarial control rates were 91% and 78% respectively. VDT varied from 3 to 344 months, with a median of 16 months. Using the Mann-Whitney-U test, the VDT of tumors that showed tumor control is significantly higher than those that failed (p=0.01). After stratifying for VDT at the median, slow growing tumors showed a 5- and 10-year actuarial control rate of 97% and 89%, where the fast growing tumors had a 5- and 10-year control rate of 85% and 68% (p=0.009).

Conclusion
This study clearly shows that the pre-treatment growth rate correlates with the observed tumor control after GKRS. Fast growing tumors are less likely to show tumor control. This finding might justify alterations in the management of VS.

Patrick LANGENHUIZEN, Svetlana ZINGER, Patrick HANSSENS, Henricus KUNST, Jef MULDER, Sieger LEENSTRA, Peter DE WITH, Jeroen VERHEUL (Tilburg, THE NETHERLANDS)
12:10 - 12:20 #10351 - V-REX: Vestibular Schwannoma – Radiosurgery or Expectation. A prospective single blinded randomized study.
V-REX: Vestibular Schwannoma – Radiosurgery or Expectation. A prospective single blinded randomized study.

Background: Class I level evidence for treatment of Vestibular Schwannoma is generally lacking. One particular issue that has been put forward as an argument against radiosurgery for this tumor is that it is so quiescent that the effect of radiosurgery only reflects its natural course. In 2014, we introduced a randomized trial to measure the effect of radiosurgery against natural course.

Study design: The study will include 100 patients with newly diagnosed unilateral VS with diameter 5-20mm, age 19-69. Patients are randomized to  up-front Gamma Knife radiosurgery or observation by serial MRI. They are followed annually for 4 years. The study is blinded to observer (study radiologist and study physician). The primary endpoint is tumor growth measured as relative to baseline size and volume doubling time at four years. Secondary endpoints include Gardner Robertson hearing Class, need of additional treatment  and adverse effects. Patients fill out the PANQOL and EQ-50 forms at each control.

Results: The study has included 80 patients per February 2017 and has so far lost one patient who withdrew. One patient who was randomized to radiosurgery declined such treatment and is followed according to intention-to-treat principle.  The practical setup and the experiences learned from the study design will be presented.

Morten LUND-JOHANSEN (Bergen, NORWAY), Øystein TVEITEN, Finnkirk MONICA, Frederik GOPLEN, Jonas LINDH, Annette STORSTEIN
12:20 - 12:30 #10406 - Salvage treatment of vestibular schwannoma: Repeat gamma knife radiosurgery.
Salvage treatment of vestibular schwannoma: Repeat gamma knife radiosurgery.

Object: Although several small individual series on repeat Gamma Knife radiosurgery (GKS) for recurrent vestibular schwannoma (VS) following prior GKS have been published, we aim to systematically aggregate data from the literature as well as from our own institutions to better understand the safety and efficacy of repeat GKS for VS.

Methods: All patients that underwent repeat GKS of sporadic VS at two tertiary academic referral centers between 2006 and 2016 were eligible for study. An aggregated dataset of previously published cases plus our own data were analyzed. A cohort of patients treated with salvage microsurgery (MS) following failed GKS were used as comparison. 

Results: Sixteen patients from our own institutions were included for analysis. Five patients were previously treated with MS. Mean age at first treatment was 60.1 years, mean time between first and second treatment was 50 months (4.2 years). Mean tumor volume at the first treatment was 0.539 cm³, at the second treatment 1.407 cm³. Mean follow-up after the second GKS treatment was 34 months. Five patients had serviceable hearing (AAO-HNS=A/B) before the initial treatment, none of these had preserved their serviceable hearing after the second treatment. Thirteen patients had good facial nerve function as evaluated by the House-Brackmann grade (HB≥2) before the initial treatment. None of the 13 patients with HB≥2 had worsened facial nerve function after the first GKS treatment. Of 10 patients with a complete dataset, one had worsened facial nerve function after the second GKS treatment. There were no new reported cases of trigeminal neuralgia. Overall, in 12 patients with complete follow-up: 5 tumors grew despite the second GKS treatment, 7 patients have tumor control so far. The combined dataset with patients previously reported in the literature included 88 patients: 86.4% accomplished tumor control after a mean follow-up of 43.2 months, 18.5% maintained functional hearing, 97.4% maintained good facial nerve function, 4.4% developed trigeminal neuralgia. All patients treated with salvage microsurgery accomplished tumor control 26 months after salvage, 73% had good facial nerve outcome. 

Conclusion: Salvage treatment of vestibular schwannoma is challenging. Repeat GKS treatment provide poorer tumor control than what can be expected from initial GKS treatment and poorer tumor control than salvage microsurgery, few patients maintain good hearing. The risk of facial and trigeminal nerve dysfunction however, is low - and lower than what can be expected from salvage microsurgery.

Oeystein TVEITEN (Bergen, NORWAY), Matthew L CARLSON, Colin L DRISCOLL, Michael J LINK, Stephanie C WISE, Morten LUND-JOHANSEN
Parallel 2- Queen
12:30

Monday 29 May

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Lunch0
12:30 - 14:00

Lunch Break

14:00

Monday 29 May

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OSP6
14:00 - 15:00

Parallel Session - Metastases 2

Moderators: Nicolaus ANDRATSCHKE (Consoultant) (Zürich, SWITZERLAND), Steve BRAUNSTEIN (Faculty) (San Francisco, USA), Arjun SAHGAL (Professor) (Toronto, CANADA)
14:00 - 14:10 #9929 - Stereotactic radiosurgery alone in patients with ≥5 brain metastases.
Stereotactic radiosurgery alone in patients with ≥5 brain metastases.

STUDY'S OBJECTIVE :

The use of upfront stereotactic radiosurgery (SRS) as the sole treatment for patients with more than five brain metastasis (BM) is still a matter of debate. However, this approach seems to gain momentum. In this study we report our results using SRS alone in patients with ≥ 5 BM as the initial treatment.  

 

METHODS :

103 patients underwent SRS between 2005 - 2016 for the treatment of ≥ 5 BM at our institution. 30% were male, 70% were female and the median age at SRS was 58. Primary histology was NSCLC in 57% of patients, breast cancer in 28%, melanoma in 12% and colorectal in 3%. All patients were divided by their KPS and by the RPA classification;12% were class 1, 82% class 2 and 6%class 3. 55 (53%) patients had previous irradiation for 1-4 BM. The mean number of treated BM was 7 (5 – 19) and the mean cumulative BM volume treated was 3.6 cc (0.06 – 27.7). We performed subgroups analyses based on these characteristics. Extracranial disease status prior to SRS was classified as stable in 28% versus progressive in 72%.

 

RESULTS :

Median follow-up after SRS was months 5.1 months (0- 57). Local control, based on RANO criteria, was achieved in 75% of patients. Median overall survival (OS) was 6 months. 72% developed new distant metastases. Multivariate analyses revealed that cumulative volume of treated BM (p=0.0128), stable extracranial disease status (p=0.00195) and RPA (p=0.0221) were independent prognostic factors for OS. Specifically, patients with a cumulative volume of treated BM £ 6 cc (OR: 2.54, p=0.006, IC95: 1.3 – 4.99) had better prognosis. The total number of BM had no impact on survival (p= 0.206). No factor was found to be predictor for local recurrence. RPA was also significant (p=0.0265) in terms of distant recurrence in multivariate analyses.

 

CONCLUSION :

This study suggests that SRS is a reasonable option for the management of patients with ≥5 brain metastases, especially when the cumulative treatment volume is £ 6 cc, as it was associated with favorable OS and local control.

Élodie HAMEL-PERREAULT (Sherbrooke, CANADA), Laurence MASSON-CÔTÉ, David MATHIEU
14:10 - 14:20 #9954 - Significant tumor shift in patients treated with stereotactic radiosurgery for brain metastasis.
Significant tumor shift in patients treated with stereotactic radiosurgery for brain metastasis.

Introduction: Linac-based Stereotactic Radiosurgery (SRS) for brain metastases may be influenced by the time interval between treatment preparation and delivery, related to risk of anatomical changes. We studied tumor position shifts and its relations to peritumoral volume edema changes over time, as seen on MRI.

 

Methods: Twenty-six patients who underwent SRS for brain metastases in our institution were included. We evaluated the occurrence of a tumor shift between the diagnostic MRI and radiotherapy planning MRI. For 42 brain metastases the tumor and peritumoral edema were delineated on the contrast enhanced T1weighted and FLAIR images of both the diagnostic MRI and planning MRI examinations. Center of Mass (CoM) shifts and tumor border were evaluated. We evaluated the influence of steroids on peritumoral edema and tumor volume and the correlation with CoM and tumor border changes.

 

Results: The median values of the CoM shifts and of the maximum distances between the tumor borders obtained from the diagnostic MRI and radiotherapy planning MRI were 1.3 mm (maximum shift of 5.0 mm) and 1.9 mm (maximum distance of 7.4 mm), respectively. We found significant correlations between the absolute change in edema volume and the tumor shift of the CoM (p<0.001) and tumor border  (p=0.040). Patients who received steroids did not only had a decrease in peritumoral edema, but also had a median decrease in tumor volume of 0.02cc while patients who did not receive steroids had a median increase of 0.06cc in tumor volume (p=0.035).

 

Conclusion: Our results show that large tumor shifts of brain metastases can occur over time. Because shifts may have a significant impact on the local dose coverage, we recommend minimizing the time between treatment preparation and delivery for Linac based SRS.

Eline HESSEN (Amsterdam, THE NETHERLANDS), Laurens VAN BUUREN, Jasper NIJKAMP, Kim DE VRIES, Wai Kong MOK, Luc DEWIT, Anke VAN MOURIK, Alejandro BERLIN, Uulke VAN DER HEIDE, Gerben BORST
14:20 - 14:30 #9958 - Phase I study of spinal cord constraint relaxation with single session spine stereotactic radiosurgery (SSRS) in the primary management of patients with inoperable, previously unirradiated metastatic epidural spinal cord compression (MESCC).
Phase I study of spinal cord constraint relaxation with single session spine stereotactic radiosurgery (SSRS) in the primary management of patients with inoperable, previously unirradiated metastatic epidural spinal cord compression (MESCC).

Objectives:  We seek to establish the feasibility of using 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 no prior history of radiation at the site of interest were enrolled on this prospective Phase 1 single institution protocol.  Single fraction SSRS was delivered to a histology dependent prescription dose of 18 or 24 Gy.  Spinal cord constraint relaxation was performed from an initial allowable Dmax cohort of 10 Gy only if tumor progression occurred.  If the risk of radiation induced spinal cord myelopathy (RM) remained lower than the risk of tumor progression, then the cord Dmax was elevated in 2 Gy increments to a maximum of 16 Gy in the final cohort.  Patients were monitored every 3 months with follow-up visits, MRI scans and validated patient reported outcome surveys.

 

Results: Thirty-two patients enrolled on the trial of which 4, 12, 8 and 8 were in the 10 Gy, 12 Gy, 14 Gy and 16 Gy cord Dmax cohorts, respectively.  The most common histology was renal cell carcinoma (n=12).  The most common GTV prescription dose was 18 Gy (n=17) followed by 24 Gy (n=15).  The median age was 62.7 yrs (range 35-81 yrs).  At baseline, there were 10 sites with MESCC Grade 1B, 10 sites with Grade 1C, 9 sites with Grade 2, 2 sites with Grade 1A, and 1 site with Grade 3 epidural extension of disease.

 

The median overall survival of the cohort was 28.6 mos (95% CI 19.6, NR).  Of the 32 patients treated with SSRS, 4 were lost to follow-up without post-SSRS evaluation.  Of the remaining 28 patients, the 1-year LC was 80.5% and median LC was not met.  With a median clinical follow-up of 17.2 months (range 3-35.7 mo), there were no cases of RM.  In the cohort receiving a cord Dmax of 16 Gy, there were no cases of RM with a median follow-up of 15.4 mo (range 6.4-21.0 mo).

 

Conclusions: SSRS is a safe and effective tool in patients with MESCC.  Cord constraint relaxation may be considered in inoperable patients with MESCC.

Amol GHIA (Houston, USA), Nandita GUHA-THAKURTA, Kenneth HESS, James YANG, Stephen SETTLE, Hadley SHARP, Jing LI, Mary Francis MCALEER, Claudio TATSUI, Erik SULMAN, Eric CHANG, Paul BROWN, Lawrence RHINES
14:30 - 14:40 #9998 - Outcomes of stereotactic radiosurgery for motor-region brain metastases.
Outcomes of stereotactic radiosurgery for motor-region brain metastases.

Objectives:  Our institution utilizes conservative stereotactic radiosurgery (SRS) dosing and reduces dose by ~1-2 Gy for motor region metastases because of toxicity concerns, but this may compromise local control.  Here we evaluate freedom from progression (FFP) and risk of adverse radiation effect (ARE) after Gamma Knife SRS for primary motor cortex or frontoparietal brain metastases to consider dosing recommendations.

Methods:  Within a cohort of brain metastases with follow-up imaging treated at our institution 1998-2013 with SRS alone upfront or SRS for recurrence after prior radiotherapy, we compared actuarial FFP and risk of ARE for motor cortex or frontoparietal (“motor”) vs. non-motor frontal or parietal (“non-motor”) lesions.  FFP and ARE were measured from the date of SRS with censoring at last follow-up imaging.

Results:  Among 3920 brain metastases treated with SRS alone upfront or SRS for recurrence, 143 were coded as motor cortex, 75 frontoparietal, and 1727 non-motor frontal or parietal.  The median dose was 18 Gy for 218 “motor” metastases vs. 19 Gy for 1727 “non-motor” metastases (Wilcoxon rank-sum p < 0.0001).  Lesion quadratic mean diameter (QMD) was highly significantly associated with both FFP and ARE.  For newly-diagnosed motor vs. non-motor metastases with QMD <0.75 cm, 0.75-2.0 cm, or >2.0 cm, 1-year FFP probabilities with 95% confidence intervals were 95% (85-98%) vs. 94% (91-96%), 88% (73-95%) vs. 88% (83-91%), and 71% (39-89%) vs. 62% (48-72%) with corresponding 1-year ARE probabilities of 2% (0-11%) vs. 1% (0-3%), 0% vs. 5% (3-9%), and 8% (1-43%) vs. 0%.  For recurrent motor vs. non-motor metastases with QMD <0.75 cm, 0.75-2.0 cm, or >2.0 cm, 1-year FFP probabilities were 79% (60-89%) vs. 94% (89-97%), 63% (24-86%) vs. 80% (70-86%), and 50% (1-91%) vs. 70% (32-89%) with 1-year ARE probabilities of 0% vs. 1% (0-6%), 32% (12-69%) vs. 5% (2-11%), and 0% vs. 23% (8-52%).  For recurrent metastases, motor location was associated with significantly worse FFP (Cox proportional hazards p = 0.029 and hazard ratio = 2.07, stratified by QMD category), with a trend toward higher risk of ARE (p = 0.09; hazard ratio = 2.76).  At least 18.5 Gy was needed to give equivalent FFP for recurrent motor-region metastases.

Conclusions:  Local control was worse for recurrent motor-region vs. non-motor metastases, and disappointing for lesions > 2 cm.  Given the consequences of uncontrolled tumor and generally low risk of symptomatic ARE, we suggest radiosurgical management of motor-region metastases with at least 18.5 Gy, or hypofractionation.

Penny K SNEED, Steve E BRAUNSTEIN (San Francisco, USA), Jean L NAKAMURA, Shannon E FOGH, Lijun MA, Philip V THEODOSOPOULOS, Michael W MCDERMOTT
14:40 - 14:50 #10038 - Stereotactic radiosurgery for the treatment of adrenal oligometastases.
Stereotactic radiosurgery for the treatment of adrenal oligometastases.

Purpose: To evaluate the efficacy and safety of adrenal oligometastases treated with hypofractionated stereotactic radiosurgery in a single institution.

Methods and Materials: Between August 2013 and September 2016, we treated 34 adrenal metastases from 29 patients. All lesions except one was treated with linear accelerators, the residual 1 lesion was treated with robotic radiosurgery. Motion management strategy for linear accelerator based treatments was the internal tumor volume formation with 4 dimensional computed tomography and fiducial placement and tracking with the robotic radiosurgery. The prescription dose was 50 Gy in 5 fractions for all patients. The response evaluations were performed with PET-CT after 3 months and upper abdominal CT or MRI evert 3 months afterwards. Local control was defined as metabolic response of the first PET-CT imaging and no progression in size afterwards.

Results: The local control and survival analyses were performed on the patients who have at least 3 months of follow up. The majority of the patients had lung cancer primary. The median age of the patients were 58 (43-84), all but one patients were male. The median follow up was 24 months (2-40 months). In 1 patient local progression was detected after 11 montjs, the rest are still under local control. Six, 12 and 24 months local control rates were 100%, 96% and 96% respectively. Twelve patients were alive during the analysis. Overall survival rates of 6, 12 and 24 months were 84%, 57% and 10% respectively from the time of the first diagnosis and 93%, 83% and 69% from the diagnosis of adrenal metastases. None of the patients experienced any acute of late toxicity.

Conclusion: Stereotactic radiosurgery for adrenal oligometastases is a non-invasive, safe and effective local treatment strategy without any compromise in systemic therapy. It is being used as a standard approach in our hospital.  

Hale Basak CAGLAR (Istanbul, TURKEY), Rashad RZAZADE , Dogu CANOGLU, Esra KUCUKMORKOC, Nadir KUCUK
14:50 - 15:00 #10339 - Clinical outcome of Stereotactic Body Radiation Therapy for the treatment of abdomino-pelvic lymphnode recurrence in oligometastastic patients.
Clinical outcome of Stereotactic Body Radiation Therapy for the treatment of abdomino-pelvic lymphnode recurrence in oligometastastic patients.

Purpose: the aim of this study is to evaluate local control, overall survival and pattern of toxicity for oligometastatic patients with isolated lymphnode recurrence treated with Stereotactic Body Radiation Therapy (SBRT) and Volumetric Modulated Arcs (VMAT).

Materials and methods:  Seventy-one patients were treated for a total of 79 lesions from 2009 to 2015. Dose prescription was 45Gy in 6 daily fractions for all patients. Delivery was performed with VMAT and flattening filter free beams (FFFs). Dosimetric analysis was carried on the treatment plans while clinical outcome was assessed by means of actuarial analysis. Treatment response was assessed by means of the RECIST criteria. Toxicity was recorded according to the common toxicity criteria version 4.0.

Results:  with a  median follow of 1.5 years (range: 0.2-6.2), 45 patients (63.3%) had solitary metastasis while 26 (36.6%) had multiple lesions.  Primary tumour was located in the gastrointestinal tract in 59.1% of patients. Local control was achieved in 97.5% of the lesions with an actuarial rate at 1 year of 83%.  Progression free survival at 1 year was 86% while overall survival was 93%.  Only 2 patients (3%) developed grade 2 gastro-intestinal toxicity, no grade 3 cases were observed.

Conclusion: SBRT with VMAT technique and FFFs can be considered a well tolerated treatment with adequate clinical response in this group of patients confirming its appropriateness in the oligometastatic setting.

Ciro FRANZESE (Milano, ITALY), Tiziana COMITO, Luca COZZI, Davide FRANCESCHINI, Lucia DI BRINA, Pierina NAVARRIA, Giuseppe Roberto D'AGOSTINO, Pietro MANCOSU, Stefano TOMATIS, Antonella FOGLIATA, Marta SCORSETTI
Stravinski Auditorium

Monday 29 May

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OSP5
14:00 - 15:00

Parallel Session - Physics 1

Moderator: Daniel SCHMIDHALTER (Medical Physicist) (Bern, SWITZERLAND)
14:00 - 14:10 #9891 - Assessment of image distortion for three different MR scanners by three different phantoms.
Assessment of image distortion for three different MR scanners by three different phantoms.

Objectives: Geometric accuracy of stereotactic MR imaging is one of major requirements for any successful intracranial stereotactic procedure. In this study we want to evaluate image distortion for three different Siemens MR scanners and also test and compare three different phantoms and methodology of measurement.

Methods and materials: Following three different phantoms are used for MR image distortion measurement in this study: 1) in-house made cylindrical Perspex phantom with 59 and 63 glass rods for axial and coronal inserts, respectively, 2) commercial PTGR phantom consisting 21 three-dimensional cross-hairs filled with contrast medium and 3) CIRS 3D Anthropomorphic Skull Phantom filled with matrix of 3 mm diameter rods spaced 1.5. cm apart. For all three phantoms rods or points with rigid geometrical positions are well imaged by different scanning MR protocols. All phantoms can be also fixed in the Leksell stereotactic frame and thus stereotactic imaging procedures can be reproduced following exactly the same steps as for a real patient, including also the stereotactic image definition in the Leksell GammaPlan. Three different Siemens MR scanners were measured in this study: 1.5 T Avanto, 1.5 T Symphony and 3T Skyra.  

Results: The measured distortions proved satisfactory accuracy precision for stereotactic localization for all three scanners. The mean radial (total in all three X, Y, Z coordinates) distortion for these MR scanners for a major imaging protocol (T1 weighted 3D imaging) measured by PTGR phantom were 0.8 mm, 1.1 mm and 1.1 mm, respectively. Similar results were obtained also by other two phantoms. Detailed comparison of all three phantoms and different methodology of measurement is work in progress.

Conclusion: Generally in all experiments with various phantoms there was detected dependence of the MR image distortion on the type of the MR scanner, slice orientation and imaging protocol. Image distortions are also property of each particular scanner, the worst distortion was observed for 3T Skyra. In the case of a clinical case with obvious or suspected MR image distortion we suggest always CT stereotactic imaging as an independent method.

 

This study was supported by Ministry of Health, Czech Republic - conceptual development of research organization (Nemocnice Na Homolce - NNH, 00023884)

Josef NOVOTNY (Prague 5, CZECH REPUBLIC), Veronika PASTYKOVA, Tomas VESELSKY
14:10 - 14:20 #9934 - Assessment of Co-registration Accuracy of Gamma Knife Icon Cone Beam Computed Tomography.
Assessment of Co-registration Accuracy of Gamma Knife Icon Cone Beam Computed Tomography.

Purpose: The accuracies of co-registration between the stereotactic images and the cone beam CT (CBCT) images of Gamma Knife Icon were assessed and parameters to enhance the accuracy were studied.

Materials and Methods: The accuracy of the co-registration procedure was evaluated by co-registering CBCT images taken at various situations to a reference CBCT. Then, stereotactic CT images of an anthropomorphic head phantom were obtained and co-registered to the CBCT images taken at arbitrarily moved positions. The coordinates of fifteen landmarks inside the phantom were measured. The co-registration accuracy between CBCT and stereotactic MR images were studied using the images of 41 patients who had CBCT images and stereotactic MR images together. Positions of anterior commissure (AC) and posterior commissure (PC) were measured both in the fiducial marker based system and the CBCT based system. In order to assess the effect of image distortion in the MR images, co-registration was performed with four different ranges in the patient head and their accuracies were compared.

Results: Co-registration between CBCT images showed deviations of 0.2 +/- 0.1 mm. After co-registration of stereotactic CT images to the CBCT images, the mean and standard deviation of the coordinate values in the left-right (x-axis), anteroposterior (y-axis), and craniocaudal (z-axis) direction was 0.0 +/- 0.3 mm, -0.3 +/- 0.2 mm, and 0.0 +/- 0.2 mm, respectively. The overall mean three dimensional deviation was 0.4 +/- 0.1 mm and it was not related with the distance from the center (p = 0.685). Co-registration of MR images to CBCT images were related with larger errors. The three dimensional difference of AC coordinates was 1.1 +/- 0.3 mm and that of PC was 0.9 +/- 0.3 mm. These differences were statistically correlated with the movement of coordinate systems calculated by the co-registration procedure. The target coverage ratios in the CBCT based system was lower than those in the fiducial marker based system, 92.2 +/- 7.1 % versus 97.9 +/- 1.7 % (p = 0.000). A region of co-registration (ROC) covering skull base area produced smaller co-registration error than other regions (p = 0.000).

Conclusion: Image co-registration error of GK Icon CBCT was similar with the registration error of the fiducial markers and the resolution of the images. In order to reduce the co-registration error, a portion of the MR images including skull base area is recommended for co-registration.

Hyun-Tai CHUNG (Seoul, KOREA), Tae-Hoon KIM, Jin Wook KIM, Sun Ha PAEK, Dong Gyu KIM
14:20 - 14:30 #9935 - Quality Assurance of Gamma Knife Icon Radiosurgery.
Quality Assurance of Gamma Knife Icon Radiosurgery.

Purpose: Quality assurance results of Gamma Knife IconTM (GKI) for one year were analyzed to assess the accuracy of frameless Gamma Knife surgery and stability of the system.

Methods: Routine QA works on the radiological part such as absolute dose rate measurement, verification of couch movement, absolute comparison between calculated and measured dose distribution, end-to-end test of positional accuracy were performed. The image quality of the cone-beam CT (CBCT) of GKI was measured biweekly with Catphan® 503 phantom. The positional accuracy of CBCT was assessed daily using four ball bearings on a manufacture provided phantom. The accuracy of the high definition motion management (HDMM) system was also assessed with a home-made device using a micrometer.

Results: Measured dose rates coincided with calculated values with mean error of 0.68 +/- 0.08% and measured half-life of cobalt 60 was 5.301 +/- 0.040 years. Gamma index pass rates with 3.0%/1.0mm criterion were greater than 99.1% for all single shots. A virtual target plan showed 98.6 +/- 1.6% gamma index pass rates at various locations in an anthropomorphic phantom. Positional accuracy of the radiation focus at the center and at an extreme position were 0.08 +/- 0.06mm and 0.06 +/- 0.05mm, respectively. For one year, the mean offset of the focus was 0.1 +/- 0.0 mm. The mechanical accuracy of the CBCT coordinate system was stable for one year (0.06 +/- 0.02mm deviation). For 2.5 mGy CTDI images, contrast to noise ratio was 1.13 +/- 0.3, and uniformity was 14.6 +/- 0.7%. For 6.3 mGy CTDI images, they were 1.78 +/- 0.08 and 14.5 +/- 0.7%, respectively. The slope of the HDMM values with respect to the real movement was 1.03 +/- 0.01 along the x-axis and 1.00 +/- 0.03 along the z-axis. The end-to-end test on the positional accuracy of the mask based irradiation was 0.9 +/- 0.3mm in an anthropomorphic phantom. Image co-registration showed 0.4 +/-0.1 mm deviation between CT and CBCT images and 1.0 +/- 0.3mm deviation between MR and CBCT images.

Conclusions: Overall accuracy of a millimeter order was verified for a frameless gamma knife surgery by various quality assurance works.

Hyun-Tai CHUNG (Seoul, KOREA), Tae-Hoon KIM, Jin Wook KIM, Sun Ha PAEK, Dong Gyu KIM, Kook Jin CHUN
14:30 - 14:40 #10115 - Extracranial doses on Leksell Gamma Knife Perfexion – in vivo TLD study on 80 patients.
Extracranial doses on Leksell Gamma Knife Perfexion – in vivo TLD study on 80 patients.

Objectives: Main purpose of this study was to perform an assessment of extracranial patient doses received during treatment on Leksell Gamma Knife (LGK) Perfexion. Results were compared with published data from previous gamma knife systems (model B and C).

Methods and materials: Extracranial doses were measured for 80 patients treated on the LGK Perfexion. Thermoluminescent dosimeters (TLDs) were positioned on patients at seven different following locations: eyes, thyroid, chest, abdomen, pelvis, knee and ankle. Measured data were evaluated and analyzed in terms of parameters that may affect extracranial doses. Following parameters were considered for analyses: prescribed dose, total irradiation time, distance between isocentre and position of TLDs, volume of prescribed isodose, total integral dose in target volume and total integral dose in brain.

Results: Mean extracranial doses delivered to patients in this study were: eyes (151.2 mGy), thyroid (10.1 mGy), chest (4.1 mGy), abdomen (1.2 mGy), pelvis (0.73 mGy), knee (0.30 mGy) and ankle (0.11 mGy). Significant dependence of extracranial doses was observed on total irradiation time, distance between isocentre and position of TLDs, volume of prescribed isodose, total integral dose in target volume and total integral dose in brain. In comparison with previous LGK models (B and C), there was observed a significant decrease of the extracranial doses in LGK Perfexion in the range of two to twenty times lower (depending on measured anatomical location).

Conclusion: Measured extracranial doses are generally very low and thus safe for treated patients. Observed measured doses are far below dose limits for deterministic effects. In comparison with previous LGK systems, Perfexion appears to be much safer with significantly lower extracranial doses.

Blanka KOTRCOVA, Petra KOZUBIKOVA, Michal SCHMITT (, CZECH REPUBLIC), Josef NOVOTNY
14:40 - 14:50 #10131 - Patient positioning accuracy in Gamma Knife radiosurgery with mask fixation and cone beam CT.
Patient positioning accuracy in Gamma Knife radiosurgery with mask fixation and cone beam CT.

Purpose: The Leksell Gamma Knife ICON introduces a mask fixation capability for patient setup and an optical tracking system for patient position monitoring. The purpose of this study is to evaluate the treatment target positioning accuracy at different stages of the mask-based Gamma Knife radiosurgery (GKRS) procedures.

Methods: CBCT imaging was applied to 11 patients who underwent multi-session mask-based GKRS and 7 patients with single session frame-based GKRS. A reference CBCT image set was obtained for each patient before the first session using the 6.3mGy dose setting. Setup CBCT images were acquired for each mask patient before each fraction using the 2.5mGy dose setting and repeated whenever a treatment pause was triggered by the motion surveillance system that tracks a fiducial marker attached to the patient nose. The treatment target positioning accuracy within the workflow of a mask-based GKRS is analyzed in terms of: 1) the registration change between the planning MR images and the reference CBCT images as obtained from the frame based GKRS with CBCT imaging;  2) the inter-fraction patient positioning accuracy determined from the registration changes for different fractions of a mask-based GKRS; 3) the intra-fraction patient positioning accuracy calculated as the difference between the registration changes for the initial setup scan and the intra-fraction CBCT scan following a treatment pause.

Results: The averaged values of the absolute translational changes in the X,Y,Z directions and the rotational changes along the X,Y,Z axes from the MR/CBCT image registrations for the 7 frame-based cases are 0.16mm,0.1mm,0.28mm and 0.41°,0.19°,0.12°, respectively. The corresponding numbers for the 41 inter-fraction registrations are 0.82mm,0.72mm,1.48mm,0.74°,0.78°, and 1.37°. The averaged values of the absolute differences in the translational and rotational changes between the 17 intra-fraction scans and the corresponding initial setup scans are 0.38mm,0.44mm,0.70mm and 1.12°,0.35°,0.86°, respectively. The smallest set of differences observed for the 17 treatment pauses are 0.01mm,0.03mm,0.03mm, and -0.16°,0.1°, -0.09°. This indicates minimum head movement despite some movement of the patient nose.

Conclusions: The registration changes between the planning MR images and the reference CBCT images are in general much smaller than those between the reference and the setup CBCT scans. The largest discrepancies in the CBCT registrations are usually seen in the Z direction for the translation changes or along the Z axis for the rotational changes. The optical tracking system may report a false alarm in some cases, owing to the inaccurate correlation between the nose reflector and the patient’s skull.

Andy (Yuanguang) XU, Joshua SILVERMAN (New York, USA), Kevin DU, Indra DAS, Douglas KONDZIOLKA
14:50 - 15:00 #10268 - A monolithic silicon detector array for small field QA in Stereotactic Radiotherapy: DUO.
A monolithic silicon detector array for small field QA in Stereotactic Radiotherapy: DUO.

“A monolithic silicon detector array for small field dosimetry in Stereotactic Radiotherapy: DUO”

 

Introduction:  Stereotactic radiosurgery (SRS) commissioning and quality assurance (QA) are challenging as the technique uses extremely small, highly collimated photon beams, which require high geometric precision and dosimetric accuracy1. Silicon diode arrays have a number of advantages including: real time operation (compared to film) and high spatial resolution and small size (compared to ionizing chambers) 2, which make their implementation advantageous for SRS QA. This work aims to characterize the monolithic silicon diode array named “DUO” designed for stereotactic QA.

 

Methods: DUO is a silicon monolithic detector manufactured on a p-type substrate, designed by CMRP at UOW as shown in figure 1. The pixels are arranged in two cross linear arrays with 256 individually readout pixels for each arm. The pixel pitch is 0.2 mm and the overall detector area is 52 × 52 mm2. DUO is placed on a 0.5 mm thick tissue equivalent printed circuit board. Characterization of DUO was performed, and used to measure 6MV beam profiles, percent depth dose and output factor for Elekta SRS cone collimators from 5 to 50 mm diameter on an Axesse ELEKTA Linear accelerator with Agility head. The DUO measurements were compared with results obtained with EBT3 films and Stereotactic field diode (SFD).

Results: The output factor agrees within 1% when compared with EBT3, and 2% with SFD for all cone sizes. The profiles of SRS cones show agreement in the FWHM and (20-80) % penumbra with EBT3 within 1% and 0.6 mm, respectively. The measured depth dose response agreed to within 1.5%, compared to EBT3 for depths beyond the build-up region.

Conclusions: DUO is a suitable detector for stereotactic dosimetry as it has excellent resolution 0.2 mm in a direction of steepest dose gradient, on time data analysis and provides both in-plan and cross-plan measurements. The good agreement with EBT3 films measurements confirms its accurate and precise data.

References

  1. Alfonso, R., Andreo, P., Capote, R., Huq, M. S., Kilby, W., Kjäll, P. & Ullrich, W. (2008). A new formalism for reference dosimetry of small and nonstandard fields. Medical physics, 35(11), 5179-5186.
  2. Wong, J. H. D., Knittel, T., Downes, S., Carolan, M., Lerch, M. L. F., Petasecca, M., & Rosenfeld, A. B. (2011). The use of a silicon strip detector dose magnifying glass in stereotactic radiotherapy QA and dosimetry. Medical physics, 38(3), 1226-1238.

 

Khalsa AL SHUKAILI (New South Wales, AUSTRALIA), Stephanie CORDE, Marco PETASECCA, Anatoly ROSENFELD, Michael LERCH
Parallel 1- Prince

Monday 29 May

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OSP4
14:00 - 15:00

Parallel Session - WFSBS: Meningiomas

Moderators: Carmen ARES MOLINA (MD) (Geneva, SWITZERLAND), Moncef BERHOUMA (LYON, FRANCE), Mahmoud MESSERER (Médecin hospitalier) (SWITZERLAND), Maximilian RUGE (Vice-Chairman, Head of Oncological Stereotaxy and Radiosurgery) (Cologne, GERMANY)
14:00 - 14:15 Meningiomas. Moncef BERHOUMA (LYON, FRANCE)
14:15 - 14:20 #9746 - Clinical Outcome of Gamma Knife Radiosurgery for Skull Base Meningiomas after Surgery: Effect for Residual Tumors and Preservation of Cranial Nerve Function and Recurrence Rates.
Clinical Outcome of Gamma Knife Radiosurgery for Skull Base Meningiomas after Surgery: Effect for Residual Tumors and Preservation of Cranial Nerve Function and Recurrence Rates.

Objectives: To evaluate long-term outcome of residual skull base meningiomas after gamma knife (GK) with our conservative strategies, avoiding excessive irradiation to cranial nerves. 

Methods: Sixty-nine patients (51 women, mean age 57.9 y/o) were included and 55 of them underwent surgery before GK. The mean follow-up period was 98.0 months (median 106.2). The mean tumor volume was 5.74ml (0.2-25.6).  Forty-eight patients had residual tumors in the cavernous sinus region.  The mean marginal and maximal doses were 13.2Gy (10-15) and 26.4Gy. To prevent cranial nerve injuries, the doses for the lateral wall of the cavernous sinus were set below 13Gy, and those near the superior orbital fissure were below 18Gy.

Results: Tumor regrowth was observed in 7 patients and the other two showed recurrence outside the irradiation areas. Additional treatments were done in six patients; repeated surgery for three including two with large-sized residual tumors (>18 ml), and repeated GK for three including two with recurrence outside the irradiated areas. No regrowth was observed in the patients without preceding surgeries. The actuarial progression free survival rate was 88.0%, and the actuarial tumor volume decrease rate was 38.7 % at 10years.  Malignant transformation were not observed. Preexisting abducens nerve paresis got worsened in one patient. Improvement of visual or oculomotor function was observed in four patients. Tumor volume >10ml was significantly associated with tumor regrowth.

Conclusion: GK with our conservative planning is safe and effective over the long term for skull base meningiomas.

 

Satoka SHIDOH (Isesaki, JAPAN), Masahito KOBAYASHI, Takayuki OHIRA, Ryosuke TOMIO, Tadashige KANO, Kazunari YOSHIDA, Takeshi KAWASE
14:20 - 14:25 #9986 - Stereotactic radiosurgery for the treatment of meningiomas eligible for complete resection.
Stereotactic radiosurgery for the treatment of meningiomas eligible for complete resection.

Objective:

Microsurgical resection is the first recommended treatment for meningiomas especially if sufficient resection can be achieved (Simpson Grade I&II). Stereotactic radiosurgery (SRS) is established as treatment option for meningiomas considered inoperable due to critical localisation or involvement of vulnerable structures. In this study, we evaluated the efficacy and safety of SRS in cases where a Simpson Grade I or II resection could be achieved but either patient´s wish or condition excluded surgery.

 Methods:

In this retrospective single-center analysis (1995-2014) we included all patients who underwent single fraction LINAC based SRS for microsurgically resectable (Simpson Grade I&II) cranial meningiomas with clinical follow-up of ≥6 months. Histologically confirmed WHO II&III tumors were excluded. We analyzed local tumor control by magnetic resonance imaging, early (first 6 month after SRS) and late treatment related complications, including symptomatic peritumoral edema requiring steroids (rated by the Common Terminology Criteria for Adverse Events; CTCAEv4.03). Local control was estimated by Kaplan-Meier method.

Results:

85 patients (f:m=65:20, mean age 60 years) were treated with LINAC-SRS for 92 supra- (67.4%) or infratentorial (32.6%) meningiomas localized in skull base (63.0%), convexity (20.7%), parafalcine (14.1%) or other areas (2.2%). Treatment indication was based on documented tumor growth in 71.7 % or recurrence after surgery in 28.3%. Mean follow-up was 68.7 ±48.8 months. Mean tumor volume was 4.1 ±3.6ml, mean radiation parameters were 13.2 ±2.2 Gy surface dose at 65.8 ±13.9% isodose level. The estimated 2-,5-, and 10-year tumor control rate was 99%, 93% and 93%, respectively. Local recurrence was observed in one case after 180.4 months (1.2%) and loco-regional (out of dose) recurrence in five patients after 17.7–155.7 months (5.9%). Minor early complications (headache, dizziness) occurred in 4.7%; one patient suffered from seizures. Late complications encompassed permanent deterioration of cranial nerve function in two cases (CTCAE:1;2) and transient seizures in one patient. Temporary steroid use due to symptomatic peritumoral edema was observed in 7.1%.

 

Conclusion:

SRS can be considered as treatment alternative for patients with meningiomas eligible for Simpson Grade (I&II) resection either refusing or harboring contraindications to microsurgery. SRS treatment provides reasonable long term tumor control with low morbidity rates.

Juman TUTUNJI, Stefan GRAU, Roland GOLDBRUNNER, Harald TREUER, Martin KOCHER, Maximilian RUGE (Cologne, GERMANY)
14:25 - 14:30 #10162 - Stereotactic radiosurgery (SRS) for intracranial meningiomas.
Stereotactic radiosurgery (SRS) for intracranial meningiomas.

Introduction

Many intracranial meningiomas are at eloquent sites where surgical resection poses considerable risk of neurological deficit.  The objective of this study is to review of the use of Stereotactic Radiosurgery (SRS) for these lesions in a single centre.

 

Materials and Methods

This ratified Ethics approved study audits a disease-specific database for all patients with meningioma consecutively treated by linear accelerator-based SRS.  Head fixation was via a BRW Head-Ring using Radionics-Software for planning with a rigid quality assurance evaluation throughout the whole process.  Dose delivery was via a “cone” based approach for “spherical” lesions, or via a mini-multi-leaf-collimator (MMLC) to larger or more irregular shaped lesions.  Dose range was 11-16Gy. Statistical evaluation was conducted using SPSS_v24 and survival analysis was performed using the Kaplan-Meier product limit method.

 

Results

From 1st May 1991 to 31st July 2015, 270 meningiomas were treated in 235 patients (19 patients with ≥2 tumours).  Females constituted 73% (n=172) of patients treated, with a median age of 54 years (range 7-87).  For eligible intracranial meningiomas, the cavernous sinus was the most frequently involved site (47%, n=127), followed by the petrous ridge (37%, n=101), and clivus (13%, n=36), though many lesions involved multiple anatomical sites.  The most common presenting feature was diplopia (26%, n=70), followed by involvement of cranial nerve (CN) VI (19%, n=52), headache (16%, n=44) and involvement of CN V (16%, n=44).  Cone-based treatment delivered a median dose of 14.0Gy to a median volume of 2.8cm3 in 167 patients.  MMLC based intensity modulated radiosurgery delivered a median dose of 13.5Gy to a volume of 7.2cm3 in 103 patients.  Median follow-up of all patients was 6.9 years.  Patients receiving SRS had 5- and 10-year progression-free survival and overall survival rates of 91% and 84%, and 90% and 82% respectively. For 35 patients with demonstrated progression, median time to failure was 3.6 years (range 0.01 to 21.6 years).  Cause-specific survival rates were 96% at 5 years, and 92% at 10 years post-SRS.  Fifty-one percent of patients presenting with headache had improvement post SRS (54/107), 54% reported improved diplopia (38/70), and 48% had improvement in CN VI function (25/52).  Few patients had worsened symptoms post-SRS.  Three patients had worsened trigeminal nerve involvement, and four patients had worsened headaches post-SRS (<4%). 

 

Conclusion:  Single session SRS provides a convenient, effective, and safe means of treating many intracranial meningiomas.  

Robert SMEE (, AUSTRALIA), Janet WILLIAMS, Rebecca VENCHIARUTTI
14:30 - 14:35 #10186 - Hearing Preservation after gamma knife radiosurgery for cerebellopontine angle meningiomas: single center study.
Hearing Preservation after gamma knife radiosurgery for cerebellopontine angle meningiomas: single center study.

Background

The presence of the hearing apparatus in the vicinity of cerebellopontine angle (CPA) meningiomas makes hearing function, theoretically, at risk during gamma knife treatment.

Objective

To assess the hearing function after gamma knife treatment of CPA meningiomas and assess factors affecting the hearing outcome. Hearing preservation, to the best of our knowledge, has never been separately addressed in studies involving gamma knife radiosurgery for CPA meningiomas.

Methods

In this study, we included patients with CPA meningiomas with serviceable hearing and tumor extension in to the region centred on internal auditory meatus. These included 66 patients that underwent a single session of gamma knife radiosurgery between 2002 and 2014. The most common presenting symptoms were facial pain, facial numbness, vertigo and disequilibrium. All the patients had serviceable hearing before treatment (Gardner-Robertson (GR) grade 1 and 2). Fifty-seven patients (86%) had GR grade 1 hearing and 9 patients (14%) had GR grade 2 hearing. The median tumor volume was 7 cc (1.5-41.4 cc) and median prescription dose was 12 Gy (10-12 Gy). The median maximum cochlear dose was 6 Gy (1.5-11.1 Gy). The median follow up was 33 months (6-149 months).

 

Results

At the last follow up, the tumor was stable in 38 patients (58%), shrank in 26 patients (39%) and progressed in 2 patients (3%). The tumor control rate was 97%. The hearing remained stable in 59 patients (89%) and worsened in 7 patients (11%). The GR grade, after treatment, decreased from grade 1 to 2 in 6 patients and from grade 2 to 3 in one patient. In all the patients, the hearing remained serviceable except one patient. Hearing preservation was determined to be maintained serviceable hearing according GR hearing score. The hearing preservation rate was 98%. The 5- and 10-year serviceable hearing preservation rate was 82% and 75%, respectively. The median time to hearing deterioration was 14 months (6-22 months).The median maximum cochlear dose in the patients with preserved and worsened hearing was 6 Gy and 5.5 Gy, respectively. No statistical significance was found. Two patients developed symptomatic edema. In one patient, the symptoms were temporary and in the other, symptoms were due to tumor progression.

 

Conclusion

Gamma knife radiosurgery for CPA meningiomas provides excellent hearing preservation in addition to high tumor control rate.

Amr EL-SHEHABY (CAIRO, EGYPT), Wael REDA, Khalid ABDEL KARIM, Ahmed NABEEL, Reem EMAD ELDIN, Sameh TAWADROS
14:35 - 14:40 #10227 - Survival Outcomes of patients underwent LINAC-Based Stereotactic Radiosurgery for Radiation- Associate Meningioma – Comparative Case Control study.
Survival Outcomes of patients underwent LINAC-Based Stereotactic Radiosurgery for Radiation- Associate Meningioma – Comparative Case Control study.

Objective: Our goal was to compare the clinical and imaging outcomes of Radiation Associate Meningiomas (RAM's) patients with those of Sporadic Meningiomas (SM’s) patients who underwent Stereotactoc Radiosurgery.

Methods: Fifty-three patients harboring 102 RAM’s and 163 patients with 204 SM’s were treated consecutively by stereotactic radiosurgery in our institution between March 2004 and 2012. Clinical and radiological follow-up (mean 42.53 months) was completed in all patients. Study groups were compared for age, sex and for previous microsurgery. Multifocal meningiomas observed in 31 (58.5%) and 31 (19%) patients with RAM’s and SM’s respectively (p<0.001). Fifteen  (28.3%) RAM’s and 17 (10.4%) SM’s patients had either atypical or malignant histology (p=0.003). Average initial tumor volume was 5.99 and 4.43 cc (RAM’s, SM’s respectively). Clinical data were collected from hospital records. Radiological control rate was assessed by volumetric measurements on Ax3DT1+Gd. MR data sets at the end of follow-up using the iPlan Image 5.2 (BrainLab AG). Local tumor control (LC), disease progression free survival (PFS) and overall survival (OS)  were calculated as well.

Results: The mean reduction in tumor volume at the end of follow-up was  1.46 (24%) and 0.65cc (15%) in the SM group and the RAM group respectively.

LC was 89.6% in the SM, compared to 72.5% in the RAM (P<0.001). The PFS in the SM was 85.3% with a mean time of 99.05 months (95% CI, 91.12 to 106.96), and 46.2% in the RAM with a mean time of 61.83 (95% CI 51.9- 71.7) (p<0.001). The OS in the SM group was 95.7% with mean survival time of 122.2 months (95% CI, 118.7 to 125.7), compared with 81.1% in the RAM group with mean survival time of 103.7 months (95% CI, 92.6 to 114.78) .

COX's analysis found that age>60, previous irradiation, previous surgery, multiplicity and histology had a negative impact on OS and PFS.

Conclusion: Radiosurgery was found to be an effective treatment for RAM and SM. When compared to spontaneous meningiomas, radiation-associate meningiomas manifest with significantly higher multifocal disease and tendency for WHOII/III histology. Stereotactic radiosurgery for RAM’s results more frequently in radiological recurrent disease particularly in non-benign meningiomas. However, in RAM’s patients whose tumor affect critical structures and/or are poor surgical candidates, stereotactic radiosurgery may provide satisfactory clinical and radiological control rates.

Kobi WEISSMEHL, Marc WGODA, Annete WYGODA, Nadia PAT, Yigal SHOSHAN (Jerusalem, ISRAEL)
14:40 - 14:45 #10261 - Long-term clinical and volumetric outcomes of patient treated with stereotactic radiosurgery for parasagittal meningiomas: The impact of meningioma histology.
Long-term clinical and volumetric outcomes of patient treated with stereotactic radiosurgery for parasagittal meningiomas: The impact of meningioma histology.

Background: The proximity of meningiomas to the superior sagittal sinus and bridging veins complicates gross-total resection of parasagittal meningiomas. Sub-total resection may result in continuous meningioma growth with repeat surgery that may associated with higher morbidity. Stereotactic Radiosurgery (SRS) has emerged as a common treatment option for parasagittal meningiomas, and provides a relatively safe, minimally invasive treatment that decreases the need for surgery. Still, the optimal approach for parasagittal meningiomas, the long term volumetric outcome and prognostic factors following SRS remain unclear. 

Objective: To review our long term volumetric results for the treatment of parasagittal meningiomas with LINAC-based radiosurgery, and determine possible factors affecting prognosis.

Methods: We retrospectively reviewed our prospectively collected data base of patients treated at our institution between 2004-2013. Volumetric assessment of all follow-up MR-image data-sets were performed using the iPlan Image software (BrainLab AG). Kaplan-Meier analysis was used to determine survival. Cox regression analysis was used to identify independent prognostic factors. 

Results: Our cohort consisted of 44 patients with 46 parasagittal meningiomas. There were 29 pts(66%) with WHO grade I tumors and 15 pts(34%) with WHO grade II tumors. Female gender was 65.5% and 20% in our WHOI and WHOII meningioma patients respectively. Previous surgery was performed in 71.74% of the tumors, while 40.9% of the patients suffered from pretreatment neurological symptoms. The mean follow-up time was 47.23 months. Local control (LC) was achieved in 100% of the WHO I group, compared to 62.5% in the WHO II group (p<0.001). The five-year progression-free survival (PFS) rate was 79.4% and 26.3% in the WHOI and WHO II groups, respectively (p<0.001). Five-year year overall survival (OS) rate was 95.8% and 74.2% in the WHOI and WHO II groups, respectively (p<0.034). 15.9% of patients suffered from symptomatic peritumoral edema which was transient in all but one patient. The mean volumetric tumor reduction was 26.25% and 5.13% for WHOI and WHOII meningiomas, respectively. Histological grade and pretreatment neurological symptoms were found to be a significant unfavorable prognostic factor for LC and PFS in our patients. Other factors such as tumor volume, or previous craniotomy were not found to have a significant effect on outcome. 

Conclusions: Stereotactic Radiosurgery for parasagittal WHO I and WHO II meningiomas offers a relatively safe and effective treatment modality, with good long term volumetric local tumor control, PFS and OS. WHO II meningiomas display significantly worth outcomes.

Benjamin ULIEL, Marc WGODA, Annete WYGODA, Nadia PAT, Yigal SHOSHAN (Jerusalem, ISRAEL)
14:45 - 14:50 #10373 - Planned subtotal resection followed by GKR for complex skull base meningiomas: Lausanne experience.
Planned subtotal resection followed by GKR for complex skull base meningiomas: Lausanne experience.

Objective: We retrospectively reviewed all patients operated for skull base meningiomas, who benefited from a combined approach (planned subtotal surgery followed by Gamma Knife surgery (GKS) on the remnant tumor). We focused on clinical outcome and oncological control.

Methods: All cases treated by this approach, between 2010 to 2016, were operated by the senior neurosurgeon (R.D.) in Lausanne University Hospital.

Results: From 103 patients were operated for a skull base meningioma, 11 fitted the selection criteria, median age 58 years (44-88). Median follow-up was 25 months (1-49 months). Tumor locations were: petroclival (55%), clinoidal region (18%), spheno-orbital (9 %) and cerebello-pontine angle (18 %). Clinical presentation was as follows: visual impairment (28%), diplopia (18%), hypoacusia (28%), gait impairment (18%), low cranial nerve disturbances (9%). Multi-staged surgery (multiple surgical approaches: cranaial and/or endonasal) was used in 3 cases. Ten cases resulted in WHO grade I and one in WHO grade II. Six patients (55%) were stable or improved considering with respect to their preoperative status, 2 (18%) experienced visual improvement but developed a mild ophthalmoparesis, 3 (27 %) worsened. One experienced severe autonomic dysfunction that necessitated stopping the surgical excision. The same patient in the immediate post-operative period had posterior fossa swelling with cervico-medullary compression requiring EVD positioning and posterior fossa decompression. One patient required wound revision. The mean dose delivered by GKS was 12.4 Gy (median 12, 12-14 Gy) at the 50% isodose line. The mean target volume was 5.14 cc (1.7-7.6 cc) and mean prescription isodose volume 5.75 cc (2.3-9.04 cc). Volume-staged GKS was necessary in 4 cases. Clinical adverse radiation effects were noted in one patient, who developed trigeminal pain and trigeminal hypoesthesia, 6 months after GKS, due to perilesional oedema, currently under corticosteroid. After a median follow-up of 25 months (6-49 months) after GKS, available for 10 patients, 60% of tumors regressed in size and 40 % remained stable.     

Conclusion: Skull base meningiomas requiring combined treatment are challenging lesions, with non-neglectable morbidity. Performing planned subtotal resection in order to make GKS possible seems to be a valid strategy to achieve local control while limiting neurological morbidity. Surgical chiasmopexy proofed to be very useful in those cases with residual tumor close to optic pathways, to limit the radiation dose received by the former. In cases when single fraction GKS is not suitable, hypofractionnation with the new Leksell Gamma Knife ICON can be a valuable alternative.  

Giammattei LORENZO (, SWITZERLAND), Constantin TULEASCA, Luis SCHIAPPACASSE, Maud MARGUET, Francois-Xavier BORRUAT, Marc LEVIVIER, Roy Thomas DANIEL
14:50 - 14:55 #10381 - Gamma-Knife radiosurgery as first line treatment for benign cavernous sinus meningioma: a multicentric prospective study.
Gamma-Knife radiosurgery as first line treatment for benign cavernous sinus meningioma: a multicentric prospective study.

Objective:

Gamma knife radiosurgery (GKRS) is a consistent option for the treatment of cavernous sinus meningioma (CSM). We propose a multicentric prospective study reporting the local tumor control and clinical outcomes after GKRS as first line treatment for CSM.

Methods

From January 2010 to August 2016, all patients treated in Lille and Lausanne by first-line GKRS for a benign cavernous sinus meningioma were included. The exclusion criteria were: non-typical radiological lesion, multiple meningiomas. Clinical outcomes (including visual acuity, oculomotricity and trigeminal dysfunction), dosimetric data (treatment dose, treated volume, selectivity / conformity index) and imaging follow-up were reported.

Results

A total of 85 patients were treated. The median age at diagnosis was 52 y/o (range 24-84). The median follow-up was 27 months. The median target volume was 3.49 cm3. The pre-GKRS deficits were: oculomotor palsy in 55%, trigeminal dysfunction in 39% and a visual acuity decrease in 8%. The median prescribed dose was 14 Gy, at the 50% isodose line, with a median of 14 shots. The mean conformity and selectivity index were respectively of 97% and 75%. After GKRS, 45 % of patients improved their clinical situation, 42 % were stable. Three (3,6%) patients worsened their previous deficit at last follow-up. No new deficit was reported. Tumor volume decreased in 49% of patients and was stable in 49% of cases. One patient harbored a tumor volume increased while improving his pre-GKRS symptoms (no additional treatment needed).

Conclusion

GKRS is safe and effective modality to treat benign CSM. At last follow-up, 87% of patients were clinically improved or stabilized with a local tumor control reached in 99% of patients.

Henri-Arthur LEROY (Lille), Constantin TULEASCA, Serge BLOND, Marc LEVIVIER , Nicolas REYNS
Parallel 2- Queen

Monday 29 May

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3D SK1
14:00 - 15:00

Small groups WFSBS session 1
3D Skull-base Anatomy for safe Radiosurgery

Keynote Speaker: Siviero AGAZZI (Tampa, USA)

These 3 identical sessions will use HD 3D cadaveric dissections slides (from the Rhoton Collection) as well as HD 3D intra-operative video recordings to illustrate the intricate anatomy related to radiosurgical targeting of skull-base tumors and trigeminal neuralgia. The session will focus on four key anatomical regions:
- the sella / parasellar space and cavernous sinus for the targeting of meningiomas, pituitary adenomas and craniopharyngiomas
- the cerebellopontine angle and Meckel's cave for the targeting of trigeminal neuralgia
- the internal auditory canal / facial-vestibulo-cochlear complex for targeting of vestibular schwannomas
- the jugular foramen for targeting of schwannomas and paragangliomas.
The target audience is radiation oncologists, physicists and neurosurgeons treating skull-base tumors with radiosurgery

Parallel 3- BB King
15:00

Monday 29 May

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OSP9
15:00 - 16:00

Parallel Session - Functional 2: Trigeminal Neuralgia

Moderators: Romain CARRON (MEDECIN) (MARSEILLE, FRANCE), Bertrand DEBONO (FRANCE), Motohiro HAYASHI (Associate professor) (Tokyo, JAPAN)
15:00 - 15:10 #9979 - Gamma Knife Radiosurgery for Idiopathic Trigeminal Neuralgia; does the status of offending vessels influence on outcome?
Gamma Knife Radiosurgery for Idiopathic Trigeminal Neuralgia; does the status of offending vessels influence on outcome?

OBJECTIVE To determine pain control and side effects after gamma knife radiosurgery (GKRS) for classical idiopathic trigeminal neuralgia (TN) with or without neurovascular compression (NVC).

METHODS This study included 47 patients with type 1 idiopathic TN and Barrow Neurological Institute (BNI) pain class IV or V that were treated with GKRS as a first-treatment modality between January 2005 and March 2015. A retrospective analysis was made of NVC status, pain control, side effects, recurrence, and cross-sectional area.

RESULTS During the median 21.5 months follow-up (range, 3–119 months), 36 (76.6%) patients showed good outcomes (improved to below BNI class IIIa). Twenty two patients did not show NVC (group A) and 25 had NVC present (group B). Good outcomes were not different in two groups (group A: 19/22; group B: 17/25)(p = 0.138). The numbers of cases in BNI class I or II, and recurrences were not significantly different between the two groups (p = 0.532, 0.786, respectively). The mean areas, measured at the target coordinate, were 8.64 ± 2.59 mm3 (range, 2.81–12.74 mm3) in non-deviated cases (n = 27) and 2.59 ± 1.68 mm3 (range, 0.80–5.29 mm3) in deviated (n = 10). Side effects were significantly more frequent in deviated cases (8/10; 80%) than in non-deviated (7/27; 25.9%) (p = 0.003).

CONCLUSION NVC is not a predictive factor for pain control after GKRS for the treatment of idiopathic TN. Side effects may occur more frequently in patients with NVC at the target coordinate when a dorsal root entry zone is used, but the subjective symptoms are not always bothersome.

Hyun Ho JUNG (Seoul, KOREA)
15:10 - 15:20 #10049 - Role of trigeminal nerve length in determination of adequate dosing and target planning using CyberKnife stereotactic radiosurgery.
Role of trigeminal nerve length in determination of adequate dosing and target planning using CyberKnife stereotactic radiosurgery.

Objective: CyberKnife stereotactic radiosurgery (SRS) is routinely used for treatment of trigeminal (TG) neuralgia by non-isometric, conformational high-dose administration to the corresponding nerve root-core. Given its proximity to the brain stem, nerve-core treatment optimization has required careful selection of dose and distance to achieve efficacy without compromising safety. We consider how the cisternal nerve length contributes to divergent outcomes in two treatment plans. 

Methods: We conducted a retrospective, single-institution review of 91 patients treated with CyberKnife for TG neuralgia in during 1/2005 to 5/2007 (Plan A, N = 47) and 1/2009 to 8/2013 (Plan B, N=44). Plan A (vs B) conservatively targeted the nerve core at 2 mm (vs 2.5 mm) and set the maximum brainstem dose to 10 Gy. The primary outcome was pain control at follow-up. Select secondary outcomes included changes in Barrow Neurologic Institute (BNI) pain and numbness scores. Length of the cisternal TG nerve, max brainstem dose, prior treatments, SRS treatment planning, and demographics were recorded. Univariate, multivariate and receiver operating characteristic curve analyses were performed.

Results: Patients were followed for a mean 23 months, and 62% were naïve to prior treatment. CK was administered in one fraction (92%) to a median and max dose of 60 and 75 Gy, respectively. Plans A and B exhibited treatment failure, durable improvement, and pain recurrence in 17.6%, 29.4%, and 52.9% vs 8.5%, 70.2%, 21.3%, respectively. BNI pain scores improved for 55.8 vs 78.7%, respectively while BNI numbness scores increased for 65.1% vs 38.3%, respectively. Nerve length, volume, and max brainstem dose were 7.48 vs 10.3 mm, 0.034 vs 0.036 cc, and were 33.7 and 48.8 Gy, respectively. Length significantly predicted any pain improvement under Plan A, but not Plan B, which was better predicted by treatment history (AUC = 0.82). Under Plan A, shorter nerves demonstrated a corresponding decrease in treated volume and under Plan B, longer nerves were less likely to have bothersome post-SRS numbness.

Conclusion: Our analysis demonstrates the ongoing challenge with predicting CyberKnife SRS treatment outcomes for TG neuralgia, and highlights how individualized consideration of TG nerve anatomy should assume an increased role in future patient selection. While patients who present with longer TG nerves may already be optimal candidates, those with shorter lengths and additional favorable history, will possibly benefit from a more aggressive dosing protocol.

Michael ZHANG (Mountain View, USA), Matthew SCHOEN, Layton LAMSAM, Geoff APPELBOOM, John ADLER, Steven CHANG
15:20 - 15:30 #10192 - Gamma Knife radiosurgery for glossopharyngeal neuralgia: a bicentric experience of 21 patients.
Gamma Knife radiosurgery for glossopharyngeal neuralgia: a bicentric experience of 21 patients.

Objective: Glossopharyngeal neuralgia (GPN) is a very rare pathology (0.7-0.8/100.000). Patients usually describe short episodes of paroxysmal pain, beginning at the base of the tongue and pharynx and irradiating towards the neck and the internal ear. We aim at reviewing our bicentric experience (Marseille and Lausanne University Hospital) in patients treated with Gamma Knife surgery (GKS) for idiopathic GPN.

Methods: Between 2003 and 2015, 21 patients were treated with 25 procedures. Eleven were women and 10 were men. All cases fulfilled the pharmaco-resistance criteria. Were analyzed patients with at least 6 months follow-up. GKS using a Gamma Knife (model B or C or Perfexion) was performed, based on both MRI and computer tomography targeting. A single 4-mm isocenter was positioned in the cisternal portion of the glossopharyngeal nerve at a mean distance of 14.6 +/- 3mm (range 9.3-23.5) anteriorly to the emergence of the nerve. The target was placed in the cisternal part for 2 and close to the glossopharyngeal meatus in 23 procedures. The mean maximal dose was 81.4+/-6.7 Gy (range 60-90). Three cases have had previous microvascular decompression (MVD), which was effective for 2, 8 and 13 years, respectively.

Results: The mean follow-up period was 5.2 +/- 3 years (range 0.9-12.1). At 3 months follow-up, 91.6% of the cases were pain free (BNI classes I to IIIA). At one year, 81.8% were still pain free (BNI classes I to IIIA), with 60% of them being BNI class IA. Recurrence appeared in 59.1%, in a mean time of 13.6 +/-10.4 months (range 3.1-36.6). Of them, 35% were controlled with medication and 25% (3 cases, 4 procedures) underwent a new radiosurgical procedure after 7, 17, 19 and 30 months, respectivelly. From these cases, two needed another open surgical procedure, with one undergoing a termocoagulation and another a neurotomy. At last follow-up, 16 cases (80%) were still pain free (BNI I-IIIA, 60% BNI IA). No complication was reported.

Conclusion: As in all cranial neuralgias, the reference technique remains MVD, as it addresses the cause (e.g. the neurovascular conflict). Radiosurgery is a valuable alternative, less invasive, with a very high rate of efficacy, in the absence of complications. The most important aspect is that the fifth nerve is easily identifiable, while the ninth nerve remains more challenging, so as its targeting. A multidisciplinary approach including a neurologist and neuroradiologist might be necessary, both for diagnosis and imaging purposes.

Pierre-Yves BORIUS (Paris), Constantin TULEASCA , Xavier MURACIOL, Luis SCHIAPPACASSE , Antoine DORENLOT , Michele ZEVERINO , Anne DONNET , Marc LEVIVIER , Jean REGIS
15:30 - 15:40 #10210 - Image-guided Robotic Radiosurgery for Trigeminal Neuralgia: three-year follow-up results in 207 patients.
Image-guided Robotic Radiosurgery for Trigeminal Neuralgia: three-year follow-up results in 207 patients.

Introduction : A cohort of 207 patients affected by Trigeminal Neuralgia (TN) was treated by Cyberknife radiosurgery and regularly followed for at least 36 months .

Methods: Patients with typical TN and severe drug-resistant pain (grade IV-V on the Barrow Neurological Institute [BNI] scale and numerical rating scale [NSR] scores >5) were selected and treated with image-guided robotic radiosurgery (Cyberknife, Accuray Inc., Sunnyvale, Ca). The treatment was delivered in single session using a non-isocentric technique, a 5-mm collimator and the trigeminal node set.  A 5-6 mm segment of the nerve was contoured as treatment target. A 58/60 Gy dose was prescribed to the 80% isodose. Clinical re-evaluation was performed at 3, 6, 12, 18, 24 and 36 months. BNI and NRS scales have been used to assess the pain level before the treatment and during the follow-up. The BNI facial numbness scale was used to assess the development of sensory disturbances following the treatment.  

Results: 6 months after the procedure 191 out of 207 patients (92%) were pain-free (BNI I-IIIa). Mild hypoesthesia (grade II BNI) was reported by 14 (6.7%) and severe bothersome hypoesthesia (BNI grade IV) by 1 (0.5%). 11 patients reporting no improvement after treatment (5.3%) underwent a second procedure. Twenty-five out of 207 (12%) pain-free patients who experienced recurrent pain within 3 years from the treatment underwent retreatment with restoration of analgesia. Peak of recurrent pain was found 12 months after the first procedure (13 patients), while other 7 recurred after 18 months and 5 after 24 months. Overall, 36 patients underwent second treatment (17%). All of them developed stable pain relief while the rate of moderate and somewhat bothering (grade III BNI) versus to severe and very bothersome hypoesthesia (grade IV BNI) was, respectively, 13 and 6. Follow-up MR imaging showed focal contrast enhancing restricted over the target region in 16 patients without significant association with pain control or hypoesthesia. Brainstem edema was found in one case (the only patient developing BNI grade IV hypoesthesia). Actuarial pain control rate  after 6, 12, 24 ,36 months was, respectively, 92%, 90%, 77% and 71%. Rate of moderate and severe sensory disturbance was 9.2%.

Conclusions: Cyberknife radiosurgery targeting a 5-6 mm segment of the TN with a prescribed dose of 58-60 Gy is a safe and effective treatment for TN providing high pain control rates with an acceptable risk of sensory complications, which are typically found after re-irradiation.

Pantaleo ROMANELLI, Alfredo CONTI (Messina, ITALY), Giancarlo BELTRAMO, Livia BIANCHI, Meccio FLAVIA, Achille BERGANTIN, Antonio PONTORIERO, Anna MARTINOTTI
15:40 - 15:50 #10455 - Gamma Knife Radiosurgery for medically refractory trigeminal neuralgia: long terms outcomes.
Gamma Knife Radiosurgery for medically refractory trigeminal neuralgia: long terms outcomes.

Objective:

To analyze the long-term outcomes for medically refractory trigeminal neuralgia (TN) treated by Gamma Knife Radiosurgery (GKRS) in our institution.

Methods:

We included 309 patients treated consecutively by GKRS for medically refractory TN, between 2011 and 2014, in Lille University Hospital. Clinical baseline, treatment parameters and functional outcomes (using Barrow Neurological Institute (BNI) Pain Intensity Score) were reported.

Results:

The mean age was 62 y/o (range, 23 to 86). 13% of patients harbored a pre-GKRS hypoesthesia. A vascular conflict was reported in 230 (82%) patients. The mean dose was 90 Gy at the 100% isodose line, delivered at a mean distance to the root-entry zone of 9.6 mm. The mean dose to the first 10 mm3of the brainstem was 9.7 Gy. The mean delay before clinical improvement was 4.8 weeks. Patients with BNI

Conclusion 

GKRS is effective to treat medically refractory TN, with half of patient free of medication at last follow-up, with a very low morbidity.

Henri-Arthur LEROY (Lille), Benjamin POMMIER, Gustavo TOUZET, Serge BLOND, Nicolas REYNS
15:50 - 16:00 #10467 - Image-guided Robotic Radiosurgery for Trigeminal Neuralgia: three-year follow-up results in 207 patients.
Image-guided Robotic Radiosurgery for Trigeminal Neuralgia: three-year follow-up results in 207 patients.

Introduction : A cohort of 207 patients affected by Trigeminal Neuralgia (TN) was treated by Cyberknife radiosurgery and regularly followed for at least 36 months .

Methods: Patients with typical TN and severe drug-resistant pain (grade IV-V on the Barrow Neurological Institute [BNI] scale and numerical rating scale [NSR] scores >5) were selected and treated with image-guided robotic radiosurgery (Cyberknife, Accuray Inc., Sunnyvale, Ca). The treatment was delivered in single session using a non-isocentric technique, a 5-mm collimator and the trigeminal node set.  A 5-6 mm segment of the nerve was contoured as treatment target. A 58/60 Gy dose was prescribed to the 80% isodose. Clinical re-evaluation was performed at 3, 6, 12, 18, 24 and 36 months. BNI and NRS scales have been used to assess the pain level before the treatment and during the follow-up. The BNI facial numbness scale was used to assess the development of sensory disturbances following the treatment.  

Results: 6 months after the procedure 191 out of 207 patients (92%) were pain-free (BNI I-IIIa). Mild hypoesthesia (grade II BNI) was reported by 14 (6.7%) and severe bothersome hypoesthesia (BNI grade IV) by 1 (0.5%). 11 patients reporting no improvement after treatment (5.3%) underwent a second procedure. Twenty-five out of 207 (12%) pain-free patients who experienced recurrent pain within 3 years from the treatment underwent retreatment with restoration of analgesia. Peak of recurrent pain was found 12 months after the first procedure (13 patients), while other 7 recurred after 18 months and 5 after 24 months. Overall, 36 patients underwent second treatment (17%). All of them developed stable pain relief while the rate of moderate and somewhat bothering (grade III BNI) versus to severe and very bothersome hypoesthesia (grade IV BNI) was, respectively, 13 and 6. Follow-up MR imaging showed focal contrast enhancing restricted over the target region in 16 patients without significant association with pain control or hypoesthesia. Brainstem edema was found in one case (the only patient developing BNI grade IV hypoesthesia). Actuarial pain control rate  after 6, 12, 24 ,36 months was, respectively, 92%, 90%, 77% and 71%. Rate of moderate and severe sensory disturbance was 9.2%.

Conclusions: Cyberknife radiosurgery targeting a 5-6 mm segment of the TN with a prescribed dose of 58-60 Gy is a safe and effective treatment for TN providing high pain control rates with an acceptable risk of sensory complications, which are typically found after re-irradiation.

 

Pantaleo ROMANELLI , Conti ALFREDO (Milano, ITALY), Giancarlo BELTRAMO, Livia Corinna BIANCHI, Isa BOSSI ZANETTI, Flavia MECCIO, Achille BERGANTIN, Antonio PONTORIERO, Anna Stefania MARTINOTTI
Stravinski Auditorium

Monday 29 May

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OSP8
15:00 - 16:00

Parallel Session - Physics 2

Moderators: Catherine COOLENS (Faculty Physicist) (Toronto, CANADA), Fang-Fang YIN (Medical Physicist/Professor) (Durham, NC, USA)
15:00 - 15:10 #8981 - Technical, Dosimetry and Treatment Descriptions of the First 200 Patients Using the First Completely Automated, Stereotactic Intracranial Radiosurgery Rotating Gamma Ray Unit (Infini) in the American Continent.
Technical, Dosimetry and Treatment Descriptions of the First 200 Patients Using the First Completely Automated, Stereotactic Intracranial Radiosurgery Rotating Gamma Ray Unit (Infini) in the American Continent.

Introduction

During the 1990’s other companies (OUR) in Asia begun developing stereotactic gamma ray machines that rotated, needing a significant less amount of cobalt 60 sources (25 or 30) with the same dosimetry characteristics than the Gamma Knife units of that time. Recently the first fully automated rotating gamma ray unit called the Infiniâ by Masep (Schenzen, China) has been installed in El Salvador Central America and 204 patients have been treated so far. The purpose of the current communication is to evaluate the technical singularities of this system and to briefly review basic dosimetry and patient treatment process in order to better understand this relatively new intracranial stereotactic radiosurgery machine.

 

Technical characteristics.

There are six rows containing 5 cobalt sources each, that are focused at the isocenter rotating at one cycle per minute. The mechanical precision of the machine was 0.4 mm on average of all collimators tested (0.11 for the 4mm, 0.16 for the 8mm, 0.17 for the 14mm and 0.20 for the 18mm collimator) the offset registered at 15Gy on all axis was 0.0 as measured along the different profiles. Initial dose rate was 3.89 Gy per minute, dose at the center of the target at the anthropomorphic phantom was 0.97 (criteria 0.95-1.05) with a treated volume of 0.95 (criteria 0.75-1.25) with a minimum dose to target of 1.05 (criteria >0.90). The treatment bed is fully automatized as well as collimator change on all 4 diameters, it has a treatment range of 180,180,230mm in the X,Y,Z respectively and with dose sculpturing capabilities do to independent beam switch to off position every 5⁰.

 

Pathology and treatment characteristics.

Thus far 204 patients have been treated: 85 (42%) benign tumors, 44 (22%) with malignant tumors, 38 (19%) vascular lesions of diverse types and 34 (17%) with “functional” indications such as trigeminal neuralgia, tremor and pain.

 

Conclusions.

Infini® is a reliable machine with mechanical characteristics at least comparable to its better known predecessor, the Gammaknife®. By obtaining the same results with substantially less amount of cobalt sources makes the machine more efficient.  

 

Victor CACEROS, Mario MINERVINI, Fidel CAMPOS, William REYES , Eduardo LOVO (San Salvador, EL SALVADOR)
15:10 - 15:20 #10183 - Respiratory Induced Online Correlation Model Uncertainties In Synchrony Tracking System of Cyberknife.
Respiratory Induced Online Correlation Model Uncertainties In Synchrony Tracking System of Cyberknife.

Purpose: Synchrony Tracking System (STS) is used to predict and create online correlation model for respiratory induced internal target motion and external markers on the chest wall during treatment. In this study we aimed to evaluate the limits and uncertainties of correlation model system with respect to dosimetric deviations for several plans of Cyberknife radiation therapy system (CKS) by using end to end (E2E) test.

Methods: Isocentric plan with fiducial and E2E centroid error results in mm were assumed as reference. Next, isocentric and non-isocentric synchrony plans with phase difference (PD) and with no PD were achieved. The plans with no PD were only irradiated in synchrony phantom. On the other hand, plans with PD were irradiated in synchrony phantom and external markers were placed on the second respiratory phantom in order to create random phase difference during irradiations. Phase shift was obtained by changing the velocity of inhale and exhale periods of second respiratory phantom after linear or nonlinear correlation model generated by the system. E2E centroid error results were analyzed for all plans in order to find out the dosimetric deviations with respect to each other.

Results: The total targeting error (TTE) of isocentric fiducial plan from E2E test was 0.12 mm as reference result for no motion induced irradiation. TTE of isocentric and non-isocentric synchrony plans with no PD were 0.35 mm and 0.99 mm respectively for linear correlation model (LCM). TTE of isocentric and non-isocentric synchrony plans with PD were 3.95 mm, 4.17 mm respectively for LCM.

Conclusion: Incoherent internal target translation and orientation movement or global body inconsistency cause variations in dosimetric parameters such as source skin distance and depth. This can affect wider and inaccurate irradiation volume during non-isocentric synchrony irradiation even with no PD. Also suboptimal correlation models and predictions between internal target and external markers during PD induced respiratory motion cause much more inaccurate and dosimetric deviated irradiations. These results offer to create accurate, optimal and correct linear or nonlinear correlation models between internal target and external markers during clinical treatments with synchrony tracking system.

Gorkem GUNGOR (ISTANBUL, TURKEY), Orbay ASKEROGLU, Gokhan AYDIN, Banu ATALAR, Bulent YAPICI, Enis OZYAR
15:20 - 15:30 #10221 - Quality Assurance of InCise™2 Multileaf Collimator for CyberKnife M6™ System.
Quality Assurance of InCise™2 Multileaf Collimator for CyberKnife M6™ System.

Objective: To report quality assurance (QA) procedures and results for the newly released InCise2™ Multileaf Collimator (MLC) installed on our CyberKnife M6™ System.

 Methods: Accuray recently released its second version of Multileaf Collimator (MLC), InCise™2 MLC, for clinical use on CyberKnife M6™ System. As one of the test sites, we not only did a thorough evaluation of InCise™2 MLC during commissioning, but also generated a system of QA procedures to ensure the MLC performance and short term and long term stability. Our MLC QA program includes daily, monthly and annual tests. A patient-specific QA for each case treated with MLC is also performed with a pinpoint chamber and film measurements. A Picket Fence test in a standard perch position is performed daily for a quick check of MLC positioning accuracy. For monthly QA, we performed a MLC Garden Fence test for leaf / bank positioning in standard (A/P) and clinically relevant non-standard positions. Total system and delivery accuracy with MLC is also assessed with End-to-End tests monthly. In annual QA, besides the tests in monthly QA, we also check the consistency of dosimetric parameters, including MLC leaf transmission, MLC beam profiles, output factors and tissue-phantom ratios, etc. Data for more than one and half years was analyzed to assess the MLC short term and long term stability.

 Results: No significant MLC positioning errors (>0.5mm) were observed with visual inspection from daily Picket Fence tests. Based on monthly Garden Fence tests, mean leaf position offsets were -0.05±0.13mm for X1 leaf bank and -0.08 ± 0.12mm for X2 leaf bank. No significant difference on mean leaf positioning offsets was observed between different leaf orientations. The change of mean leaf position offsets with time was less than 0.2mm, indicating a stable MLC positioning accuracy. Total system accuracy with MLC was 0.43±0.21mm as shown in the monthly End-to-End tests. All measurements for the dosimetric parameters were stable and well within the manufacturer specifications. Point dose measurements for more than 30 patients agreed with calculation within 3%, and all film measurements passed 3%/2mm Gamma evaluation for more than 95% of the measurement points.

 Conclusion: QA procedures were setup for the Incise™2 MLC installed on CyberKnife M6™. Our QA results indicate that the Incise™2 MLC has a good short term and long term stability.

Yong YANG (Stanford, USA), Lei XING, Anthony LO, Lei WANG
15:30 - 15:40 #10309 - A revised PTV method to improve conformality for SRS and SBRT conformal dynamic arc plans.
A revised PTV method to improve conformality for SRS and SBRT conformal dynamic arc plans.

Objective:

SBRT and SRS plans require highly conformal dose to the planning target volume (PTV) to spare adjacent normal tissues. Conformal dynamic arc technique can achieve very sharp dose falloff and efficeint delivery. It is routinely used in our institution for SBRT and SRS treatments. However, the conformality is usually not as good as inverse planned volumetric modulated arc therapy (VMAT) technique. Therefore, a simple revised PTV method is presented in this study to improve the conformality of dynamic arc plans.

Materials and Methods:

Twelve SBRT (target volume range 8 ~ 108cc) and thirteen brain SRS patients (target volume range 0.7 ~ 47cc) were selected in this study. SBRT plans were created using coplanar arcs and SRS plans were created using three to six non-coplanar arcs using Varian Eclipse treatment planning system (version 13.5). The linear accelerator (LINAC) was a Varian Truebeam equipped with 5mm multi-leaf collimator (MLC). For each case, an original plan was generated by fitting MLC to the PTV and normalized to “100% prescription dose covers 95% of PTV”. Then the 100% isodose volume was converted into a structure (100%IDV). At any radial angle ϴ from contour geometry center in each axial slice, the radius of PTV is defined as R1(ϴ) and radius of 100%IDV is defined as R2(ϴ). The distance between them is calculated as D(ϴ) = R2(ϴ)-R1(ϴ). Then a new PTV radius is calculated as R’(ϴ) = R1(ϴ) - D(ϴ). A revised PTV contour was then generated, and a new plan was developed by fitting the MLC to the revised PTV. Paddick conformity index (PCI) and gradient index(GI) were compared for each case between the original and revised plans. GI is defined as the ratio of 50%IDV/100%IDV.

Results:

For the SBRT plans, the revised plan improved PCI by 10% on average (PCI increased from 0.79 ± 0.05 to 0.87 ± 0.04), and no change on GI (4.11 ± 0.25 vs 4.10 ± 0.33 ). For SRS plans, both original and revised plan were renormalized to 99% PTV coverage. PCI improved by 11% on average (PCI increased from 0.73 ± 0.06 to 0.81 ± 0.07), and no change on GI (2.94 ± 0.51 vs. 2.92 ± 0.55 ).

Conclusion:

Revised PTV method is simple and effective to improve conformality of conformal dynamic arc plans for most SBRT and SRS patients, except for some very irregular concave shape target.

Lei FU (Philadelphia, USA), Yan YU, Haisong LIU
15:40 - 15:50 #10355 - Dosimetric verification of MLC based CyberKnife treatments using Monte Carlo.
Dosimetric verification of MLC based CyberKnife treatments using Monte Carlo.

Objectives

Today’s procedures to perform patient-specific quality assurance (QA) for multi-leaf collimator (MLC) based CyberKnife stereotactic radiotherapy are generally based on dose measurements for every treatment plan. This work describes an alternative approach, which makes use of Monte Carlo (MC) techniques to independently calculate dose distributions.

Methods

A vendor-independent MC based dose calculation framework using the EGSnrc MC simulation code system was developed and validated for CyberKnife MLC treatments. Each beam of the treatment plan with its corresponding MLC field shape compiled to an EGS++ geometry is simulated using EGSnrc with a phase space based beam model, creating a pre-patient phase space file for each beam. The framework then samples particles from all beams (weighted according to the treatment plan) and performs energy deposition scoring in the patient CT using DOSXYZnrc. MC calculations were validated against measured depth dose curves (DD) and dose profiles in water in units of cGy per Monitor Unit for several MLC fields. The framework was then validated by comparing MC calculated dose to film measurement for a clinical prostate treatment plan applied to a solid water phantom. Further, for another clinical prostate case, MC dose calculations were compared to TPS dose calculation using a finite size pencil beam algorithm. Both film and TPS dose were compared to MC calculations by gamma analysis with a 10% (global) low‑dose threshold using 2% (global) dose difference / 1 mm distance to agreement criteria.

Results

Measured and MC calculated dose profiles and DD in water agreed within 3% and 1 mm. MC calculations showed good agreement to the film measurement with 93.4% of voxels passing gamma evaluation. Comparing TPS dose to MC calculated dose showed a gamma pass rate of 93.1% despite dose differences of up to ±10% (global) near bones and metal fiducials.

Conclusion

An alternative to measurements for patient-specific QA was successfully developed and validated against measurements.

Paul-Henry MACKEPRANG (Bern, SWITZERLAND), Diem VUONG, Werner VOLKEN, Dominik HENZEN, Daniel SCHMIDHALTER, Marco MALTHANER, Silvan MUELLER, Daniel FREI, Daniel M. AEBERSOLD, Michael K. FIX, Peter MANSER
15:50 - 16:00 #10388 - Impact of the skull definition on Leksell Gamma Knife IconTM radiosurgery treatment delivery.
Impact of the skull definition on Leksell Gamma Knife IconTM radiosurgery treatment delivery.

Objective:

To define the skull volume for Gamma Knife radiosurgery (GKRS) dosimetry, there are two possibilities in IconTM: manual skull scaling measurements and image-based skull definition. We evaluate if dose calculation significantly differs depending on these 2 techniques.

Methods

We included 48 GKRS treatments performed from July 2016 to January 2017 in Lausanne University Hospital, distributed among four groups: convexity lesions (18), parenchymal deep-seated lesions (13), vestibular schwannomas (11) and trigeminal neuralgias (6). For each treatment, we recorded the beam-on time (min), target volume coverage (%), prescription isodose volume (cm3) and maximal dose (Gy) to the nearest organ at risk if relevant (e.g. cochlea) according to each of the 2 skull definition techniques. The image-based contours were performed using CT-scan, which provides more reproducible segmentation than MRI. During this period, the mean dose rate was 3.72 Gy/min.

Results

Between the manual measures and image-based contours, the beam on time varied of +1.27% (corresponding to 27 sec) (p <0.001 Wilcoxon signed rank test), the target volume coverage varied of -0.04% (0.6 mm3) (p=0.09), the prescription isodose volume varied of -0.07% (12 mm3) (p=0.22) and the maximal dose to organ at risk varied of -0.37% (0.016 Gy) (p=0.6). Using image-based contours, the mean increase of dose delivery was theoritically of +1.674 Gy per treatment (if no blocked sectors).

Conclusion

The beam on time is significantly increased using image-based contours in comparison with manual skull measurements, resulting in an increase of the total dose delivery per treatment. The other dosimetric parameters did not differ significantly.

Henri-Arthur LEROY (Lille), Constantin TULEASCA, Maud MARGUET, Michele ZEVERINO, Marc LEVIVIER
Parallel 1- Prince

Monday 29 May

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OSP7
15:00 - 16:00

Parallel Session - WFSBS: Other Skull Base

Moderators: Sebastien FROELICH (Paris, FRANCE), Mahmoud MESSERER (Médecin hospitalier) (SWITZERLAND), Selcuk PEKER (Surgeon) (Istanbul, TURKEY), Takahiko TSUGAWA (doctor) (Nagoya, JAPAN)
15:00 - 15:15 Skull Base. Sebastien FROELICH (Paris, FRANCE)
15:15 - 15:20 #9885 - Gamma Knife radiosurgery for facial nerve schwannomas.
Gamma Knife radiosurgery for facial nerve schwannomas.

Object

The aim of this study was to determine the efficacy and safety of gamma knife radiosurgery for the treatment of the patients with facial nerve schwannoma.

Methods

Twelve patients with facial nerve schwannoma underwent gamma knife radiosurgery and their clinical and radiographic data have been evaluated. Females outnumbered males with a ratio of 2:1 and the mean age of the patients was 44 years (range 19-73 years). Most common symptoms were facial palsy (10 of 12 patients) and hearing loss (7 of 12 patients). 5 patients presented with headache. 2 of these 12 patients had prior resection and 1 patient had biopsy taken. Mean tumor volume was 3.1 cc (range 0.4-7.4 cc) and mean margin dose applied to the tumor was 11.9 Gy (range 11-13 Gy).

Results

The mean follow-up period was 44.2 months (range 13-84 months). Tumor control was achieved in all patients. Remission in 4 patients, stable in 8 patients. During follow-up 10 of 12 patients had no change in their facial function, 2 of 12 patients had their function worsened, no patients developed new facial palsy. 11 patients who had servicable hearing retained their hearing, 1 patient who was bilateral deaf since 1 year-old remained deaf.

Conclusions

Gamma knife radiosurgery is an effective and safe treatment modality for patients with either primary or residual facial nerve schwannomas. This treatment modality has showed excellent results in terms of tumor control and facial nerve funcitonal outcomes. These results show us that gamma knife radiosurgery is a good primary treatment option for small to mid sized tumors, patients with good facial function and patients with servicable hearing.

Alperen SIRIN (Istanbul, TURKEY), Meric SENGOZ, Meltem YILMAZ, Selcuk PEKER
15:20 - 15:25 #9931 - Trigeminal schwannomas: systematic review of management with SRS.
Trigeminal schwannomas: systematic review of management with SRS.

Trigeminal schwannomas are rare skull base tumors. A direct microsurgical approach usually results in some neurological deficits or complications. Stereotactic radiosurgery (SRS) has emerged as a treatment alternative to microsurgery. To conduct an analysis assessing the effect and complications of SRS in trigeminal schwannomas, a systematic review of all cases of trigeminal schwannomas treated with SRS was performed. The search revealed 10 papers with a total enrollment of 398 patients whose follow-up data obtained from 1999 to 2016. The mean age was 47.13 years old. Average tumor size ranged from 3.96-8.7 cm3 (mean 5.74 cm3). Of 290 patients with tumor location information, tumors were located predominately in the middle fossa (type A) in 98 cases and predominately in the cerebellopontine angle (type B) in 77 cases. Tumors extended into both the middle and posterior fossa (type C) in 111 cases and extended extracranially to the orbit, maxillary sinus or infratemporal fossa (type D) in 4 cases. The average prescription dose was 14.37Gy (range 13.1-16.4Gy). The mean follow-up period was 60.73 months (range 42.5-98 months). The most recent MR images demonstrated average tumor control rate was 90.95%, tumor shrinkage in 228 patients (57.29%), tumor progression occurred in 36 patients (9.05%). There was no significant correlation between lesion volume and tumor shrinkage. Thirteen patients (3.27%) had no symptom before SRS. Among all cranial nerve impairments before SRS, facial hypesthesia was the most common symptom in 270 (70.13%), facial pain in 94 (24.42%), diplopia in 84 (21.82%). Symptoms improvement was achieved in 179 (46.49%) among 385 patients with cranial nerve impairments before SRS. Forty-five (11.31%) patients had symptoms worsened and/or additional cranial nerve disturbance. SRS is an alternative for trigeminal schwannomas confirmed by typical imaging.

Hua Guang ZHU (Shanghai, CHINA), Enmin WANG, Xin WANG
15:25 - 15:30 #9989 - Gamma Knife radiosurgery in acoustic neuroma – the Vienna series.
Gamma Knife radiosurgery in acoustic neuroma – the Vienna series.

Objective: We present long-term follow-up data after Gamma Knife radiosurgical (GKRS) treatment of acoustic neuroma.

Patient and Methods: Six-hundred and eighteen patients were radiosurgically treated for acoustic neuroma between 1992 and 2016 at the Department of Neurosurgery, Medical University Vienna. Patients with neurofibromatosis and patients who could not yet have a one year follow-up were excluded from the study. Thus, we present data of 557 patients with spontaneous acoustic neuroma and long-term follow-up data on 426 patients with a minimum follow-up of two years. Koos grades at time of diagnosis and at time of GKRS were evaluated. Patients were assessed according to the Gardner-Robertson hearing scale and House-Brackmann facial weakness scale prior to GKRS, and at times of follow-up. Data were evaluated retrospectively.

Results: 452 patients (81%) were treated radiosurgically alone and 105 patients (19%) were treated combined microsurgically-radiosurgically. Whereas the combined treatment was favored especially prior to 2002, the percentage of only radiosurgically treated cases has significantly increased since then. The overall complication rate after GKRS was low. The complication rate after GKRS further declined in the last decade. A significant enlargement of the ventricular system (hydrocephalus) after GKRS was only observed among patients harboring Koos grade III or IV tumors. One case of malignant transformation after GKRS was diagnosed (0.2%). Radiological outcome after GKRS revealed stable or decreased neuromas in the vast majority of cases including all Koos grades. The rate of non-functional hearing was already rather high prior to GKRS. At last follow-up, preservation of functional hearing was achieved in 52% of patients classified as Gardner-Robertson grade I or II prior GKRS.

Conclusion: GKRS is a safe and effective treatment in patients of all Koos grades. Advancements in the radiosurgical treatment especially over the last decade have led to a low complication rate and excellent outcome.

Brigitte GATTERBAUER (Vienna, AUSTRIA), Josa M. FRISCHER
15:30 - 15:35 #10039 - Stereotactic LINAC radiosurgery in the treatment of vestibular schwannomas : results of a single center.
Stereotactic LINAC radiosurgery in the treatment of vestibular schwannomas : results of a single center.

OBJECTIVE

The objective of this study was to estimate the clinical and radiological outcome of patients treated by radiosurgery for vestibular schwannomas (VS) in the Toulouse Radiosurgery Unit.

 

METHODS

The records of patients with VS treated between january 2008 and december 2012 in the Toulouse Radiosurgery Unit (Novalis 600N®, BrainLab) were retrospectively analysed. Patients with neurofibromatosis type 2 were excluded. All patients had at least a 36 months-follow-up (FU) with a control MRI every 6 months.

 

RESULTS

1- Patients characteristics. 119 patients were treated with a mean FU of 75±17mo. Mean-age was 61±13 years and 59.7% were female. At the time of radiosurgery, 42.6% of patients had serviceable hearing and 8.8% some degree of facial palsy. A previous surgery was found in 15.3% of the population. Mean KOOS grade was 2.5±0.7 and mean volume was 1.1±1.1cc (range: 0.1 – 5.4cc). Median prescription dose to the tumor margin was 11.1±0.91 Gy.

2- Control rate with at least 36 mo-FU was 91.8%. The results differ with the Koos grade : 100% for grade 1, 92.7% for grade 2, 93.5% for grade 3, 77.8% for grade 4.

3- Cranial nerves complications. A permanent facial palsy (new or worsening of a pre-existing palsy) was found in 5.6% of patients. Trigeminal nerve symptoms appeared in 8.4% (9/107 patients) but 5/6 patients with pre-treatment symptoms were improved. Both complications were significantly related to the increase of volume at 6 months (respectively p<0.02 and p<0.01) and to the KOOS grade (p<0.04 and p<0.03).

 4- Serviceable hearing was maintained in 56% of patients (data for 25 cases).

5- Tumor volume. An increase of volume was found at 6 months in 71.6% of cases. It was predictive of failure if superior to 60% of the initial volume with a sensitivity of 62% and a specificity of 89% on ROC analysis.

 

CONCLUSION

-       LINAC-Radiosurgery with Novalis is an effective treatment of VS with a tumor control obtained in 91.8% of cases.

-       The variation of size on the first control MRI could be predictive of the outcome issue and morbidity.

Jean SABATIER (Toulouse Cedex), Violaine DELABAR, Jean-Albert LOTTERIE, Pierre DUTHIL, Sylvie MONFRAIX, Franck THOUVENY, Bertrand DEBONO, Jean-Yves PLAS, Philippe BOUSQUET, Anne-Christine JANUEL, Jean-Christophe SOL, Vincent LUBRANO, Igor LATORZEFF
15:35 - 15:40 #10042 - Gamma knife radiosurgery for hemangiopericytoma.
Gamma knife radiosurgery for hemangiopericytoma.

Background Intracranial hemangiopericytoma(HPC) is a rare tumors that composes under 0.5% of all primary brain tumors.  This tumor is notable for aggressive clinical behavior such as high rate of recurrence after surgical resection and proclivity for extracanial metastases. Formerly this tumor type was categorized into meningioma variants.  Even now classification of this tumor and the relationship to solitary fibrous tumor are still controversial.   For the management of recurrent intracranial tumors, we applied Gamma Knife radiosurgery (GKRS) in case tumors were well-circumscribed and less than 3centimeters in diameter.   In this study we evaluated the efficacy and the role of GKRS considering control of intracranial HPC.

Materials and Methods Between April 2004 and April 2016, we treated 12 patients with intracranial HPC by GKRS.   All patients underwent surgical resection prior to GKRS. Two patients had been treated with conventional fractionated external beam radiotherapy (EBRT) before GKRS and one patient had been treated with linac-based stereotactic radiosurgery (SRS) before GKRS. The mean age of the patients at first GKRS was 44.8 (range, 16 to 75) years. During follow up five patients out of 12 underwent total 15 repeat GKRS for newly developed tumors or tumor regrowth.  The mean volume of all tumors treated by GKRS was 3.6 (range, 0.2 to 23.6) ml and the mean prescription dose at the tumor margin was 17.1 (range, 13 to 20) Gy.

Results The median follow-up time was 70.3 months (range 4 to 160 months). Ten patients out of 12 were alive at the last follow-up visit without any serious neurological deficit.   One patient presented extracranial metastasis and died from cerebrospinal dissemination of the tumor at 71 months after the 1st GKRS.  Another patient died from a colon cancer during the follow-up. The 3-, 5-, and 7-year overall survival rate of the patients was 87.5, 87.5 and 58.3% respectively. Five patients out of 12 developed extracranial metastssis (lung, liver, pancreas, bone).  The 3-, 5-, and 7-year progression free survival (PFS) rate after initial GKRS was 55.6, 27.8 and 27.8% respectively

Conclusions Though PFS rate is relatively low, GKRS is thought to be an effective management option for patients with recurrent hemangiopericytoma.

 

Takahiko TSUGAWA (Nagoya, JAPAN), Tatsuya KOBAYASHI, Chisa HASHIZUME, Sachko KATO, Yoshimasa MORI
15:40 - 15:45 #10203 - First intention radiosurgery and combined approaches in trochlear and abducens nerve schwannomas.
First intention radiosurgery and combined approaches in trochlear and abducens nerve schwannomas.

Introduction

Most of intracranial nerve schwannomas arise from the cranial nerve (CN) VIII. In these cases, for small to medium-size tumors, radiosurgery has proven its safety and efficacy both for tumor control and function preservation over the last four decades. There are, however, less common schwannomas involving the CN III, IV and VI. The former can be very disabling for patients, due to the associated palsies and decreased quality of life due mainly to vision problems. We prospectively evaluated the safety and efficacy of Gamma Knife surgery (GKS) in these rare cases.

Methods

Five patients with CN IV (3 patients) and VI (2 patients) schwannomas were treated in Lausanne University Hospital between 2010 and 2015. Three were treated with upfront GKS. However, due to a large tumor volume (7.9 cc), one (VIth CN) was referred for planned subtotal excision to our skull-base surgeon, followed by GKS (combined approach). All cases had neuroophtalmological evaluation at baseline and at 6 and 12 months and on annual basis after. In one case, a type II neurofibromatosis was diagnosed.

Results

The mean follow-up period was 29 months (range 6-54). The mean target volume at the time of GKS was 1.51 cc (range 0.086-5.8). Initial clinical presentation was only diplopia in four cases and cavernous sinus syndrome in one. The mean marginal dose was 12 Gy (range 12-12). The mean prescription isodose volume was 1.71 cc (range 0.131-6.7). The mean maximal dose to the optic pathways was 1.5 Gy (range 0.1-6.6). Following GKS, at last follow-up, all patients presented clinical alleviation, with disappearance of baseline symptoms. However, one of them had an additional surgical intervention (left superior oblique tendon folding). Tumor control (all with decrease in volume) was achieved in 100%. The particular case, which had combined approach, presented postoperatively with transient IVth, Vth and VIth CN palsies, which completely recovered 3 months later. 

Conclusions

Our data suggests that first intention GKS is a safe and effective treatment option for patients with CN IVth and VIth schwannomas, with high rates of both clinical alleviation and tumor control. In cases where the initial tumor volume is too large for first intention GKS, combined approaches can be performed, with favorable and comparable outcomes. Patients require further careful follow-up evaluation for eventual neurological deterioration and/or tumor progression. 

Jean-Nicolas COMPS (, SWITZERLAND), Iulia PECIU-FLORIANU, Constantin TULEASCA, Luis SCHIAPPACASSE, Zeverino MICHELE, Roy Thomas DANIEL, Marc LEVIVIER
15:45 - 16:00 Invasive pituitary adenomas. Emmanuel JOUANNEAU (LYON, FRANCE)
Parallel 2- Queen

Monday 29 May

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3D SK2
15:00 - 16:00

Small groups WFSBS session 2
3D Skull-base Anatomy for safe Radiosurgery

Keynote Speaker: Siviero AGAZZI (Tampa, USA)
See Session 3D Skull-base Anatomy 1 for description.
Parallel 3- BB King
16:00

Monday 29 May

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break9
16:00 - 16:30

Coffee Break

16:30

Monday 29 May

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OSP12
16:30 - 17:30

Parallel Session - Vascular 1

Moderators: Evandro DE SOUZA (since 2008) (São Paulo, BRAZIL), Ajay NIRANJAN (neurosurgeon) (Pittsburgh, USA)
16:30 - 16:40 #9894 - "De novo" arteriovenous malformations after treatment with gamma Knife radiosurgery in pediatric patients.
"De novo" arteriovenous malformations after treatment with gamma Knife radiosurgery in pediatric patients.

Introduction

The concept of "de novo" arteriovenous malformations (AVM) remains a poorly understood condition. It has been documented, observing follow-up radiological studies, that AVMs are dynamic lesions. However, this concept is exceptional in the literature after radiosurgery treatment.

Material and methods

108 pediatric patients have been treated for their AVM with Gamma Knife stereotactic radiosurgery. Seven have developed "de novo" AVM on the periphery of the treatment performed in a retrospective study.

Results and conclusions

The mean follow-up period after the radiosurgical treatment of the 7 AVMs with "de novo" AVM was 14.5 years, diagnosing these entities at 5 years of Gamma Knife in 71% of the patients. The mean age at treatment was 7.45 years (3.4-13.6), 5 males and 2 females. About the location of AVMs, one was profound and the rest superficial, with eloquence in 5 of them. The Spetzler-Martin grades were II, III and IV in 2, 3 and 2 patients respectively. In the first treatment the mean volumen of the nidus is 2.6 cc and the mean radiosurgical dose is 20 Gy. Only one patient had hemorrhage at 7 years of radiosurgery. All but one patient has been treated subsequently. The mean volumen of "de novo" AVMs is 8.2 cc. This study corroborates the possibility of developing "de novo" AVM predominantly in childhood, after achieving obliteration of the volumen treated with radiosurgery.

Isabel CUERVO-ARANGO HERREROS (Salinas, SPAIN), Nuria MARTÍNEZ MORENO, Jorge GUTIÉRREZ SÁRRAGA, Germán REY PORTOLÉS, Roberto MARTÍNEZ ÁLVAREZ
16:40 - 16:50 #9895 - Obliteration rate of arteriovenous malformations in pediatric patients with or without previous embolization.
Obliteration rate of arteriovenous malformations in pediatric patients with or without previous embolization.

Objective:

Evaluate the obliteration rate of arteriovenous malformations (AVM) and clinical results after radiosurgery in pediatric patients with and without previous embolization.

Method:

Of the hundred patients undergoing radiosurgery with Gamma Knife, thirty patients had been embolized prior to radiosurgery. All patients have a minimim follow-up of three years. The rate of obliteration, hemorrhage and clinical outcome after radiosurgery were analyzed between the two groups under study.

Results and conclusion:

Nidus obliteration was achieved in 63% of patients in the non-embolized AVM group (Group A) and in 59% of the previously embolized AVM group (Group B). During the first three years after radiosurgery, three patients in group A suffered hemorrhage, without sequelae; and one patient in group B, with clinical worsening. In group A, three more patients presented hemorrhage at 7,8 (death) and 10 years of treatment, and in group B one patient at 10 years, passing away. The ratio of the obliteration rate to the AVM volume has been in group A: < 3 cc: 70%, 3-10 cc: 63% and > 10 cc: 20%; and in group B: 73%,60% and 0% for the same volumes, respectively. The clinical situation regarding treatment has worsened in five patients in group A and in two patients in group B, remaining stable or improving in the rest. The relation of appearance of "de novo" AVM between group A and B has been 5 to 1, producing delayed hemorrhage in two of these patients in group A.

Partially embolized AVM in pediatric patients are susceptible to successful treatment with Gamma Knife, without significant differences in the obliteration rate between the two groups.

Isabel CUERVO-ARANGO HERREROS, Nuria MARTÍNEZ MORENO, Jorge GUTIÉRREZ SÁRRAGA, Germán REY PORTOLÉS, Roberto MARTÍNEZ ÁLVAREZ (Madrid, SPAIN)
16:50 - 17:00 #9909 - Time-Staged Gamma Knife Radiosurgery for Large Arteriovenous Malformation.
Time-Staged Gamma Knife Radiosurgery for Large Arteriovenous Malformation.

Object.

We retrospectively analyzed our experience with time-staged Gamma Knife radiosurgery (GKRS) for large arteriovenous malformation (AVM)s.

Methods.

Between 1998 and 2016, 835 patients were treated with GKRS for cerebral AVMs. Among the 835 patients, 113 patients had large AVMs with volumes larger than 14 cm3.

After exclusion of patients who followed up less than 3 years, a total of 89 patients were enrolled in this study. All patients were treated with a planned time-staged GKRS.

The median age was 32 years (range, 4-60). The most common presentation was seizure (n=22). Fifty-four patients underwent a second GKRS and 11 patients underwent a third GKRS.

The median volume was 22 cm3 (range, 14-59) at first GKRS, 11 cm3 (range, 0.4-33.8) at second GKRS and 2.5 cm3 (range, 0.3-17.4) at third GKRS.

The median marginal dose was 13 Gy at first GKRS, 12Gy at second GKRS and 16 Gy at third GKRS. Nidus obliteration of AVMs was confirmed using transfemoral cerebral angiography (TFCA).

The median clinical follow-up after first GKRS was 76 months.

 

Results.

Among the 82 patients who underwent a TFCA following first GKRS, complete nidus obliterations were obtained in 12 patients.

Fifty-four patients underwent a second GKRS with a post-GKRS median interval of 39 months. Thirty-three of 54 patients had a 3-year follow-up TFCA.

Complete nidus obliteration was confirmed in 18 of 33 patients. Eleven of 33 patients underwent a third procedure with a median interval of 39 months.

Eight of 11 patients underwent a TFCA at 3 years after GKRS. Five of 8 patients had a complete nidus obliteration.

Therefore, the overall nidus obliteration rate in this study was 60% (35 of 58 eligible patients).

During follow-up period, a hemorrhage developed in 15 patients (17%) including 5 cases of major bleeding and 10 cases of minor bleeding.

Only one patient died of intracerebral hemorrhage after GKRS. Symptomatic adverse radiation effects were detected in 12 (13%) of 89 patients.

However, permanent morbidity rate was 1% at the last follow-up. No patients in this study developed a delayed cyst formation following GKRS.

Conclusions.

The management of large AVMs is still challenging. In this study, a time-staged GKRS for large AVMs shows a relative high obliteration rate and a low complication rate.

Although long-term follow-up and repeat GKRS are needed to achieve complete obliteration, a time-staged GKRS might be an effective and safe treatment option in the management of large AVMs. 

Dong Gyu KIM (Seoul, KOREA), Youngbeom SEO, Jin Wook KIM, Hyun-Tai CHUNG, Sun-Ha PAEK
17:00 - 17:10 #10379 - Stereotactic radiosurgery as first-line treatment for non-hemorrhagic arteriovenous malformations in the pre-ARUBA era: long-term functional outcomes and obliteration rates.
Stereotactic radiosurgery as first-line treatment for non-hemorrhagic arteriovenous malformations in the pre-ARUBA era: long-term functional outcomes and obliteration rates.

Objectives

The management of non-hemorrhagic arteriovenous malformations (AVMs) remains a greatly debated topic, even more so since the ARUBA trial. We report on the long-term outcomes and obliteration rates after Gamma Knife radiosurgery (GKRS) treatment for such AVMs.

Methods

We retrospectively analyze data from a series of 101 patients harboring unruptured AVMs treated by GKRS as first-line treatment in our University Hospital between April 2004 and September 2011. Inclusion criteria were: age > 18 years old, no clinical history suggestive of acute hemorrhage, no bleeding stigma on the pre-treatment MRI and/or CT scan, minimal follow-up > 3 years. Exclusion criteria were: pediatric population, volume-staged GKRS, prior embolisation or surgical management.

Results

Mean age at presentation was 38.9 years (range 19-64). The main initial symptoms were: epilepsy in 50% of patients and headache in 27% of patients. Mean follow-up was 9.9 years (range 3-13 years). Median target volume was 1.9 cm3 (IQR, 0.8-3.3 cm3), median Spetzler-Martin grade: 2 (IQR, 1 to 2), median Pollock-Flickinger score: 1.067 (IQR, 0.8-1.3), median Virginia score: 1 (IQR, 1 to 2). Median treatment dose was 24 Gy at 50%. 17 patients benefited from a second GKRS after 3 years follow-up without obliteration. Hemorrhage during the post-treatment follow-up was reported in 11 patients (annual risk of 1.1%). Transient post-GKRS morbidity was reported in 4.9% with persistent neurological deficit in 2.9% of patients. The obliteration rate was 72%, based on cerebral angiography and/or MRI. At last follow-up 95% of patients had a mRS ≤1 and 88% of patients were free of symptoms. Concerning epilepsy, 84% of patients were seizure-free at last follow-up.

Conclusions

GKRS as first-line treatment for unruptured cerebral AVMs achieves high obliteration rates while maintaining patient autonomy and even improving their clinical symptoms (e.g. epilepsy).

Nicolas REYNS (LILLE), Henri-Arthur LEROY, Pierre-Jean LERESTE, Jean-Paul LEJEUNE, Iulia PECIU-FLORIANU, Serge BLOND
17:10 - 17:20 #10384 - Covering 75% of Nidus with 23 Gy or higher dose improves obliteration of arteriovenous malformations following stereotactic radiosurgery.
Covering 75% of Nidus with 23 Gy or higher dose improves obliteration of arteriovenous malformations following stereotactic radiosurgery.

Introduction: It has been shown that higher margin dose given to the AVM nidus correlates with higher AVM obliteration rates, with the maximum obliteration rate observed at 25 gy. However, it is not always possible to prescribe such higher margin doses as these can lead to higher rates of adverse radiation effects (AREs) especially in large volume AVMs.  Theoretical dose modeling indicated that it is possible to expand specific isodose volumes (e.g. 70% of the maximum dose) closer to prescription isodose without a substantial increase in 12 gy volume. The purpose of this study was evaluate if a higher dose covering a higher volume of AVM nidus correlates with improved nidus obliteration.

 

Methods: For this retrospective, single-institution analysis, the authors reviewed their experience in 43 patients who had Gamma Knife surgery between 2007 and 2013. Patients with multiple AVMs, prior Gamma Knife treatment, planed stage treated AVMs, AVMs larger than 10 cm3, or lacking at least three years of follow-up data were excluded. Nidus volume, margin doses, 12 Gy volume, and absolute doses covering various percentages of nidus volume were determined using Leksell GammaPlan® software. The average marginal dose was 20 gy (range: 16-23 gy), and the average AVM nidus volume was 3.44 cm3 (range: 0.2579-9.13 cm3).  AVM obliteration was confirmed by MRI and/or Angiography.  Comparisons between groups were performed using Mann-Whitney U Test and Pearson’s c2 test of independence.

 

Results: Of the 43 patients, a total of 37 (86%) patients had complete obliteration of the AVM over an average follow-up time of 36 months (range: 11-79 months). Our analysis indicated that higher obliteration rates were achieved in patients who received greater than 23 gy to more than 75% of nidus volume (p = 0.036). Patents who received greater than 23 gy to 75% of nidus volume did not have increased risk of ARE (p=0.82). Similarly obliteration rates were significantly better (p=0.025) for patients with expanded 70% isodose volume (more than 43% nidus covered with 70% isodose line). Expanded 70% isodose volume was not associated with increased risk of AREs (p=0.56).

 

Conclusion: Higher dosage (23 gy or higher) delivered to at least 75% AVM nidus volume or expanded 70% isodose volume are associated with higher obliteration rates following AVM radiosurgery without increasing the likelihood of AREs. 

Ajay NIRANJAN (Pittsburgh, USA), Kyle ATCHESON, Edward MONACO III, Hideyuki KANO, John FLICKINGER, L. Dade LUNSFORD
17:20 - 17:30 #10396 - Predictive factors in cavernous malformation series treated with gamma knife radiosurgery.
Predictive factors in cavernous malformation series treated with gamma knife radiosurgery.

Background

Cavernous malformations (CMs) natural history has remained unclear several years. This lack of knowledge has made treatment decisions difficult. Indeed, the use of stereotactic radiosurgery (SRS) is nowadays controversial. The purpose of this paper is to analyze factors implicated in bleeding  and adverse radiation effects in patients treated with Gamma Knife Radiosurgery (GKRS).

Methods

The authors reviewed ninety-five cavernous malformations prospective database, 57 women and 38 men, underwent GKRS for high-surgical-risk CMs. The median malformation volume was 1570mm3. The median tumor margin dose was 11,87 Gy and the mean tumor maximum dose was 19,56 Gy. Statistical analysis was performed with IBM SPSS software version 20.0 and R Core Team software version 2013.

Results

Ninety-five cavernous were situated in: brainstem (64), thalamus/basal ganglia (12) and hemispheric eloquent areas (19). All patients had experienced at least one symptomatic bleeding before treatment. Imaging follow-up after SRS revealed lesion volume regression in 39 CMs. The pretreatment annual hemorrhage rate was 3,06% compared with 1,4% during first 3 years latency interval, and 0,16% thereafter (p-value = 0.004). Four patients developed new location-dependent neurological deficits and three patients had edema-related headache after radiosurgery. All of them presented full recovery.

In spite of univariate analysis didn't findstatistically significant association between marginal dose and post-treatment bleeding, Multiple Regression Model, with Akaike`s Information Criterion including sex, showed finally statistically significant association between lower marginal dose and bleeding (p-value=0,03) and no association between target volume and bleeding (p-value=0,13).

Volume and coverture dose show a weak negative correlation with adverse radiation effects (AREs) (ρ = -0.260, p-value = 0.011). Using Multiple Regression analysis, AREs couldn´t be related to prescribed radiation dose, brainstem location nor multiple pre-treatment hemorrhages.

In Multiple Regression Model, size reduction seemed to relate with patients age (p-value: 0,042) and maximum dose levels  (p-value: 0,028).

Conclusions

Marginal dose was the only variable that showed statistically high significant influence on bleeding rate in multiple regression analysis (p-value = 0.030). A lower marginal dose seems to be related with post-treatment rebleeding.

Highly conformal GKRS with lower margin dose average (margin dose average: 11.3 Gy) could be related to safety of this treatment in recent series. In spite of descriptive analysis showed a trend towards relating adverse radiations effects with higher margin dose, we didn't find statistically significant association in our study. This result could be due to the scarce number of AREs and post-treatment bleeding events in our series.

 

 

 

 

 

 

 

 

Remedios LÓPEZ SERRANO, Roberto MARTÍNEZ (Madrid, SPAIN), Nuria E. MARTÍNEZ
Stravinski Auditorium

Monday 29 May

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OSP11
16:30 - 17:30

Parallel Session - Physics 3

Moderators: Andreas MACK (Chief Physicist Radiosurgery) (Zürich, SWITZERLAND), Maud MARGUET (Medical Physicist) (Lausanne, SWITZERLAND), Josef NOVOTNY (Head of department) (Prague, CZECH REPUBLIC)
16:30 - 16:40 #9014 - Optimized orthovoltage stereotactic radiosurgery.
Optimized orthovoltage stereotactic radiosurgery.

Objective: For some stereotactic radiosurgery (SRS) treatment sites, delivering a homogeneous dose to the target volume has been associated with reduced adverse effects and toxicities. Previous work has indicated that lowering the beam energy from the standard megavoltage range to the orthovoltage range results in the improvement of various plan quality metrics in SRS. Modulation of beam energy, even across a small field, may further serve to create homogeneous, conformal dose distributions in orthovoltage SRS delivery. The objective of this work was to build and characterize an orthovoltage energy-modulated SRS system in order to achieve dose distributions approaching rectangular functions.

Methods: Previous work described the design of cone-based, filtered orthovoltage energy-modulated SRS system using mathematical optimization techniques and Monte Carlo simulations. This system uses a NIST-traceable 250 kVp irradiator with an auxiliary cone/filter system that was constructed using both in-house machining techniques as well as the commissioning of an outside prototyping firm capable of binderjetting, an additive manufacturing technique, using tungsten. Four nondivergent cone collimators were constructed from free machining brass to be used optionally along with four epoxy-infiltrated bonded tungsten filters of variable thicknesses. Radiochromic EBT3 film measurements of the system were performed in a custom, thin-window water phantom to compare dose distributions derived from open cones to those from filtered cones. Films were scanned with a prototype laser densitometry system.

Results: Measured beam profiles showed that the modulated beams could more closely approach rectangular function dose profiles compared to the open cones, based on quantification of profile flatness and penumbra. This result remained consistent for all four cones and for the three different depths tested. This result confirms previous computational work indicating the benefit of orthovoltage energy fluence modulation.

Conclusion: Both computational and measurement results showed that filtered orthovoltage SRS prototypes are able to achieve dose distributions approaching rectangular function distributions at depth, therefore establishing the feasibility and efficacy of a full future treatment platform that relies on fluence modulation in the orthovoltage energy range to manipulate resulting dose distributions.

Jessica FAGERSTROM (Madison, WI, USA), Wesley CULBERSON, Larry DEWERD
16:40 - 16:50 #9866 - Metal artifact reduction with Dual Energy CT for Gamma Knife Radiosurgery in pacemaker patients.
Metal artifact reduction with Dual Energy CT for Gamma Knife Radiosurgery in pacemaker patients.

Metal artifact reduction with Dual Energy CT for Gamma Knife Radiosurgery in pacemaker patients

Purpose: Pacemaker patients with brain metastases who are to undergo Gamma Knife (GK) radiosurgery are typically simulated with CT as they are not usually MRI compatible. Since the patients are framed and fixated with either titanium (Ti) or aluminum (Al) pins to the skull, metal induced artifacts by the Ti or Al pins are unavoidable. This can result in obscuration and suboptimal evaluation of brain lesions. Conventional single-energy CT (SECT) with metal artifact reduction (MAR) and newer dual energy CT (DECT) with high keV mono-energy imaging are promising techniques for reduction of metal artifacts. The purpose of this study is to assess the effectiveness of these two methods in metal artifact reduction to enable optimal treatment planning in pacemaker patients undergoing GK radiosurgery.

Methods and Materials: An anthropomorphic head phantom (Radiology Support Devices) fixated with one pair of Ti and one pair of Al pins was scanned with SECT and DECT on GE HD 750 64-slice CT, and SECT on Philips large bore 16-slice CT. Both metal artifact reduction techniques of MAR and DECT on GE, and OMAR (orthopedic MAR) on Philips were compared. The scan and reconstruction parameters are as follows (in the order of [kVp/mA/Collimation (mm)/Pitch/CTDIVol (mGy)/Thickness (mm)/Recon]): Philips LB16 [120/482/16x0.75/0.438/65.4/1/UC & UC+OMAR]; GE HD750 [120/220/32x0.625/0.531/65.2/1.25/Standard & Standard+MAR]; and GE HD750 [(80,140]/375/32x0.625/0.531/67.0/1.25/140keV DECT].

Results: Metal artifact reduction when using Ti fixation was best achieved by DECT followed by MAR, then SECT and lastly OMAR (DECT> MAR > SECT > OMAR). In case of Al fixation DECT was again the best, SECT was as good as MAR, and OMAR was the worst (DECT > SECT = MAR, > OMAR). More metal artifacts were introduced by Ti than Al pins. For Al pins, while DECT could reduce artifacts, OMAR introduced more artifacts than SECT, and MAR was not effective for artifact reduction.

Conclusions: There were fewer artifacts introduced by Al than Ti. DECT was more effective than MAR in reducing metal artifacts for both Ti and Al. OMAR should not be used in CT acquired for simulation in GK pacemaker patients. Pacemaker patients undergoing GK radiosurgery may be best served by frame fixation using Al pins in combination with DECT because of the least amount of metal artifact generated, and therefore likely better visualization of metastases in the underlying brain parenchyma.

Dershan LUO (Houston, Texas, USA), Nandita GUHA-THAKURTA, Xin WANG, Eun HAN, He WANG, Jing LI, Tinsu PAN
16:50 - 17:00 #9919 - Two independent dosimetry audits and comparison of TMR10 and Convolution calculation algorithms in the Leksell Gamma Knife treatment planning.
Two independent dosimetry audits and comparison of TMR10 and Convolution calculation algorithms in the Leksell Gamma Knife treatment planning.

Objectives: Purpose of this study was to make a dosimetry audit after Leksell Gamma Knife (LGK) Co-60 sources reload. Comparison of TMR10 and Convolution calculation algorithms in the Leksell GammaPlan (LGP) was also made by measurement in heterogeneous anthropomorphic phantom.   

Methods and materials: Dosimetry audits were performed by two institutions: 1) National Radiation Protection Institute, Prague, Czech Republic (NRPI) (on-site audit) and 2) The MD Anderson Dosimetry Laboratory (MDADL), Houston, USA (postal audit). Measurements were made in three different phantoms: 1) ABS Elekta plastic spherical phantom, 2) adapted anthropomorphic Alderson Rando phantom and 3) Stereotactic Radiosurgery Head phantom from MDADL. Calibration of the LGK unit was verified in the Elekta phantom by two independent PTW 31010 ion chambers. Altogether six measurements in two different orientations were made. Then comparison between planned and delivered dose in anthropomorphic Alderson Rando phantom was done for a test treatment plan calculated by both TMR10 and Convolution algorithms. Mean dose in two PTW 31010 ion chambers positioned close to heterogeneous area in the phantom was measured. All these measurements were performed on-site by NRPI medical physicists. Additionally, irradiation of MDADL head phantom was made. The head phantom consisted of imaging insert with nylon ball target to obtain imaging for treatment planning and then the insert was exchanged to a dosimetry insert with TLDs and Gafchromic films for dosimetry measurements. After on-site irradiation, the phantom was sent back to MDADL for an evaluation.      

Results: Deviation between measured and reported calibration dose rate in the ABS plastic phantom was 0.7 %. Deviation in mean dose measured by ion chamber positioned within target volume in heterogeneous anthropomorphic head phantom was -1.1 % and 2.5 % for TMR10 and Convolution algorithms, respectively. Results from MDADL are not yet ready at the time of writing this abstract. Convolution algorithm generally calculated always longer irradiation times by 2-3 % on average compared to TMR10. This fact was also supported by measurement results. Based on results from this study the statement that Convolution algorithm provides more accurate calculation is not supported.      

Conclusion: To perform dosimetry independent audit after a new LGK installation or after Co-60 source reload belongs to a good medical physics practice. Both on-site and postal audits were used in this study. Very reasonable agreement was observed for reported calibration dose rate. Also measurements for target volume mean dose in anthropomorphic heterogeneous phantom for both algorithms showed reasonable results. 

Josef NOVOTNY (Prague 5, CZECH REPUBLIC), Irena KONIAROVA, Ivana HORAKOVA
17:00 - 17:10 #9956 - Lessons learnt during a national cross-platform radiosurgery end-to-end audit.
Lessons learnt during a national cross-platform radiosurgery end-to-end audit.

The purpose of this work was to assess the dosimetric accuracy of SRS in the UK for linac-based (LB), Tomotherapy (TT), Cyberknife (CK) and Gamma Knife (GK) radiosurgery. 

The methodology developed for this assessment employed an anthropomorphic phantom with realistic tissue densities. The simulated scenario featured an irregular 8 cm3 lesion located anterior to the brainstem. The case was presented to 26 UK centres who developed 28 treatment plans: 16 LB, 7 GK, 4 CK and 1 TT. An end-to-end test was conducted for each plan, incorporating immobilisation, scanning, planning and treatment delivery following the local protocol. Previously characterised dosimeters (EBT-XD film and alanine pellets) were placed inside the phantom to measure absolute dose inside the target and brainstem, for comparison with Treatment Planning System (TPS) predictions. Film measurements were compared to TPS dose planes using gamma-analysis. 

Alanine measurements showed that LB (including TT) had the largest range in percentage difference to the TPS of 5.2% (-1.3% to +3.9%) with a mean of +0.5%. CK had a range of 2.6% (+1.4% to +4%), with the highest mean difference in comparison to the other platforms (+2.5%). GK showed the smallest range at 2.4% (-0.8% to +1.5%) being comparable to that of CK, with the smallest mean percentage difference (+0.4%) comparable to that of LB. Similar trends were observed in the brainstem with alanine measurements showing a range from -1% to +3.6% (mean= +1.3%), 0% to +1.9% (mean= +0.9%) and -1.1% to +0.9% (mean= +0.1%), for LB, CK and GK respectively. Film measurements showed comparable results between centres, regardless of the platform used. For 3%-2 mm Local-gamma, all except two films showed passing rates above 75%.  For 5%-1 mm Global-gamma, all except 2 films showed passing rates above 90%. Large variations were observed in prescription practices, delivery techniques and plan quality.

This audit enabled a comparison of all UK centres in terms of the dosimetric accuracy achieved during treatment delivery. The LB group showed the largest variations in agreement to the TPS, related to more heterogeneous practices within the group, compared to smaller variations seen in CK, and more consistent practices seen in GK. Good overall agreement with the TPS was observed with 2 centres falling above 3.6% (2sd). The results suggest that good agreement with predicted dose distributions is achievable by all modalities. The variations in prescription practices, techniques and plan quality highlight the need for standardisation in SRS practice.

Alexis DIMITRIADIS (London, UK), Russel THOMAS, Anthony PALMER, David EATON, Jonathan LEE, Rushil PATEL, Ileana SILVESTRE PATALLO, Andrew NISBET, Catharine CLARK
17:10 - 17:20 #9991 - Radiation protection considerations when equipping a robotic SBRT delivery device with a new collimator type.
Radiation protection considerations when equipping a robotic SBRT delivery device with a new collimator type.

Purpose

Shielding considerations for both, primary and secondary radiation must be revised when switching from a conventional linear accelerator to a Cyberknife (CK). In this context two important parameters to be investigated are the direction distribution of the primary radiation and the modulation factor (MF) of treatment plans, which is linked to secondary radiation. This work assesses the impact of a novel multi leaf collimator (MLC) on the required radiation shielding of the CK analyzing the clinically applied treatment beams.

 

Methods

For 364 patients (163 fixed cones, 180 iris collimator, 21 MLC) the delivered beams were projected onto the boundaries of a 9.5x5.9x3.9 m3 vault in order to obtain a monitor unit (MU)-weighted spatial distribution of the treatment beams. This was accomplished by a previously developed framework, which extracts the beam directions, the corresponding number of MUs and the employed collimator of all treatment beams delivered by the CK. In addition, the total delivered MUs and the prescribed dose were stored in the database for each treatment beam. Using this information, the MF, defined as the ratio of delivered MUs divided by the prescribed dose, was assessed for each treatment plan and used collimator type.

 

Results

Compared to all considered treatments, the MLC beams delivered slightly more MUs to the wall to the left and right of the patient (13.0% vs of 12.0%) and the floor (73.5% vs 71.0%). None of the analyzed MLC beams hit the wall at the patient’s feet in contrast to 5.3% of MUs for all treatments. However, comparing the MLC beams only with all extra-crainal beams, the differences for the wall at the patient’s feet vanish.

The mean MF for the treatments without MLC is 8.5 MU/cGy, while the mean MF for the treatment using the MLC is 6.3 MU/cGy. Taking only the extra-cranial treatments into account, the mean MF for the treatment with and without using the MLC is 7.1 MU/cGy and 10.4 MU/cGy, respectively.

Conclusion

The MLC, which was mainly used for extra-cranial treatments, has a minor influence on the direction distribution of the treatment beams compared with the differences arising from treating cranial or extra-cranial entities. If the MLC is employed, the larger field sizes available together with the segmented delivery lead to a reduction of the MF for the considered cases.

Dominik HENZEN (Bern, SWITZERLAND), Daniel SCHMIDHALTER, Claudia ZANELLA, Werner VOLKEN, Paul-Henry MACKEPRANG, Marco MALTHANER, Michael Karl FIX, Peter MANSER
17:20 - 17:30 #10394 - First stereotactic radiosurgery patient treatment using an MLC-based virtual cone.
First stereotactic radiosurgery patient treatment using an MLC-based virtual cone.

Purpose: The virtual cone is a standardized MLC control point sequence designed to mimic the dose distribution of a 4 mm cone. It was developed to facilitate rapid treatment planning and quality assurance for treatment of small lesions using an MLC equipped linear accelerator. We report on the first patient treatment using the virtual cone.

Methods: The virtual cone is comprised of an MLC control point sequence having multiple non-coplanar arcs and a dose rate that varies as a function of gantry angle. The patient was immobilized using an open-face thermoplastic mask and received a treatment planning CT scan having 1 mm slice spacing. The target volume, a solitary metastasis defined using MR images, was 0.021 cm3 (diameter 3.4 mm). The virtual cone sequence was imported and dose was calculated on a 1 mm grid using Eclipse AAA version 13.6 (Varian Medical Systems, Palo Alto, CA). The plan was normalized such that 99% of the target volume received at least 20 Gy. Measurement using radiochromic film in a phantom was done prior to treatment to confirm dosimetric and geometric accuracy.  The patient was localized prior to treatment using orthogonal kV images followed by cone-beam CT and was monitored during radiation delivery using optical surface monitoring.

Results: The ratio of the measured dose to the calculated dose was 1.02. The 2-dimensional magnitude of the difference between the measured and calculated dose distributions was 0.13 mm. After correction for the systematic offset, the maximum distance between the measured and calculated prescription isodose contour was 0.26 mm. These results were consistent with preclinical end-to-end studies using an anthropomorphic skull phantom.  The maximum dose was 143.9%, corresponding to a prescription isodose line of 69%. Dose calculation dominated the treatment planning time, requiring 22 min on a cluster of calculation servers, whereas importing the plan and placing isocenter was less than 5 min. Delivery of the plan for the QA measurement required 12 min. 

Conclusion:  The virtual cone is an efficient technique for treatment of small spherical dose target volumes. Because the control point sequence is standardized, patient specific QA measurements will not be necessary in routine clinical use.  Integration of the virtual cone directly into the treatment planning system along with improved dose calculation efficiency will make planning using this technique extremely efficient, potentially allowing for same day treatment. Planned clinical applications of the virtual cone include trigeminal neuralgia and treatment of essential tremor.

Richard A. POPPLE (Birmingham, USA), Evan M. THOMAS, Xingen WU, Markus BREDEL, Ivan A. BREZOVICH, Barton L. GUTHRIE, James M. MARKERT, John B. FIVEASH
Parallel 1- Prince

Monday 29 May

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OSP10
16:30 - 17:35

Parallel Session - WFSBS: Vestibular Schwannomas 2

Moderators: Alison CAMERON (Consultant Clinical Oncologist) (Bristol, UK), Emmanuel JOUANNEAU (LYON, FRANCE), Jeremy ROWE (Sheffield, UK)
16:30 - 16:40 #9906 - Frameless three-fraction radiosurgery for large vestibular schwannomas.
Frameless three-fraction radiosurgery for large vestibular schwannomas.

Background: Large acoustic schwannomas (VS) are tumors with a diameter of >3 cm or a volume >8 cm3. They are usually considered not amenable to conventional, single-fraction stereotactic radiosurgery (SRS) because a large section of the brainstem may be exposed to harmful doses of radiation. The problem can be avoided by using a hypofractionated irradiation scheme.

Methods: Twenty-five patients with VS of >8 cm3 (range 8-24 cm3, median 9.5 cm3) were treated from August 2007 to January 2016 at the CyberKnife center at the University of Messina, Italy. All patients underwent 3-fraction radiosurgery with a total dose ranging 18-19.5 Gy.

Results: Follow-up period ranged from 12 to 106 months (median 48 months). Radiological growth control was achieved in 88% of cases: 11 tumors (44%) displayed no relevant size variation; 11 (44%) showed a >50% volume shrinkage. Three patients (12%) needed salvage tumor resection. No patient presented worsening of trigeminal sensory disturbances or facial nerve dysfunction. No patient had serviceable hearing before treatment. Five patients (20%) developed hydrocephalus after treatment or showed deterioration of the preoperative ventricular enlargement with new neurological symptoms. All 5 patients were treated with ventriculo-peritoneal shunts with full recovery. Actuarial progression-free survival rates at 1 year and 5 years were 97% and 83%, respectively.

Conclusions: The current and other published results suggest that hypofractionation may extend the indication of SRS to VS larger than 8 cm3. The tumor control rate is not significantly different from smaller tumors. Hydrocephalus is the only complication recorded in our series. This complication is related to preoperative ventricular size and can be easily and effectively treated with minor surgery. Even though the limited experience and short follow-up currently available in the literature do not provide sufficient support for widespread application of hypofractionated SRS in younger patients with large VS, further studies on the issue are warranted.

 

Alfredo CONTI (Messina, ITALY), Antonio PONTORIERO, Giuseppe IATÌ, Carmelo SIRAGUSA, Anna BROGNA, Federica MIDILI, Stefano PERGOLIZZI
16:40 - 16:50 #10010 - Impact of neuro-imaging on GTV definition in radiosurgical treatment of acoustic neuroma.
Impact of neuro-imaging on GTV definition in radiosurgical treatment of acoustic neuroma.

Objective:

Acoustic neuromas (AN) have a close proximity to radiosensitive critical structures (i.e. inner ear, cranial nerves). Single fraction radiosurgical (SRS) treatment requires precise definition of the target volume as well as the surrounding critical structures (CS). Therefore, various imaging modalities are available with cranial computed tomography (CT) and different magnetic resonance imaging (MRI) sequences. The aim of this study was to evaluate to what extent this affects the definition of gross tumor volume (GTV) and identification of CS. There are no clear guidelines for the imaging modality to be used for delineation of GTV and CS in SRS, so far.

Methods:

The GTV, anterior-posterior and transverse diameter of the internal acoustic canal (IAC) were conducted with a variety of different image modalities (plain CT window widths, T1 TFE 3D, T2 TSE 2D, T1 FFE 3D, T2 DRIVE 3D) in 73 patients and compared with each other. Furthermore, the identification rate of CS (trigeminal nerve, labyrinthine artery) was evaluated. The obtained GTVs were compared to the respective T1 TFE 3D volume for every individual. Significance in volume changes were verified using Wilcoxon signed-rank test.

Results:

The average deviation from the GTV obtained in T1 TFE 3D imaging was 43.4 ± 23.1% (for CT brain window), 18.7% ± 21.3 (T2 TSE 2D), 27.7% ± 17.9 (T2 DRIVE 3D) and 15.5 ± 10.4 (T1 FFE 3D). All deviations were significant (p <0.0001). The anterior-posterior and transverse diameter of IAC showed significant (p<0.0061) differences between T1 TFE 3D imaging and CT brain and bone window and T2 weighted MRI. The rate of inner ear identification was 99% in T2-weighted sequences and 100% in CT bone window. The identification rate of the trigeminal nerve was 97% in T2-weighted MRI compared to 34% in CT brain window.

Conclusion:

Various imaging modalities are available for the definition of the GTV and CS. However, differences in the predefined GTV (up to 43% in CT and 18% in T2-MRI respectively) significantly depend on the image modalities in use. How far these differences affect dosimetry remains unclear and should be part of further investigations.

Daniel RUESS (Koeln, GERMANY), Fenja FRITSCHE, Alexandra HELLERBACH, Harald TREUER, Martin KOCHER, Maximilian I. RUGE
16:50 - 17:00 #10065 - Is multisession radiosurgery more effective than singlesession radiosurgery to preserve the hearing in patients affected by a sporadic vestibular schwannoma? Preliminary results from a prospective randomizeed clinical trial.
Is multisession radiosurgery more effective than singlesession radiosurgery to preserve the hearing in patients affected by a sporadic vestibular schwannoma? Preliminary results from a prospective randomizeed clinical trial.

Objective. The treatment strategy for the patients affected by sporadic vestibular schwannomas is recently changing and the number of patients which undergo radiosurgery as a primary treatment modality for such lesions is continuously increasing.

While the question about the best treatment is waiting for more definitive results, the attention is actually focusing on the hearing function sparing.

The aim of the present study is to investigate about the potential advantages of multisession radiosurgery(mRS) compared to single session radiosurgery(sRS) in terms of hearing preservation.

Patients and methods. The present is an “ad interim” analysis of a prospective randomized clinical trial.

The primary end-point of the study is the difference in term of hearing preservation between patients treated with mRS and sRS because of a sporadic acoustic neuroma.

The conditions for patient eligibility are:

- sporadic acoustic neuroma diagnosis.

- Age≥18 years old

- KPS≥70

- Serviceable hearing(class A/B from the AAOHNS classification)

- Written consent

All the enrolled patients are clinically, radiologically and audiometrically evaluated.

The volumetric analysis of the tumor is always performed.

Results. At the time of the present analysis 52 patients have undergone a radiosurgical treatment. The mean follow-up period is 27 months. Twenty-nine patients had a sRS and 25 had a three fraction mRS.

In term of hearing preservation, no differences were observed between the two groups. A significant difference was observed between the patients that were class A at the treatment time compared to class B. Indeed, only 10% of the class A patients compared to 53% of the class B patients lost the serviceable auditory function during the follow-up period.

The volumetric analysis showed that most part of the tumors(86%) had a shrinkage or a stabilization. The 14% of the patients experienced a tumor enlargement, at least in the first two follow-up MRIs. No significant differences were observed between the patients treated with mRS and sRS.

Conclusions. At our knowledge, the present clinical trial is the first one comparing two different radiosurgical regimens in terms of hearing sparing.

While we are waiting for the definitive results of the present study, the preliminary ones suggest that mRS has no advantages compared to sRS in terms of hearing preservation.

Similarly to surgical studies, the data suggest that the better is the auditory function at the moment of the treatment, the more probable is the hearing preservation.

The volumetric analysis confirms the good tumor control rate.

Marcello MARCHETTI (Milano, ITALY), Valeria CUCCARINI, Davide BOSETTI, Valentina PINZI, Laura FARISELLI
17:00 - 17:10 #10157 - Influence of volumetric parameters of the IAC on hearing for patients with vestibular schwannomas.
Influence of volumetric parameters of the IAC on hearing for patients with vestibular schwannomas.

Introduction:

Anatomical parameters of the petrous bone and tumor could perhaps predict clinical findings in patients with vestibular schwannoma. This information might be important to determine the optimal parameters of the dosimetric planning and to estimate hearing outcome.

Materiel & Methods:

We have retrospectively analyzed anatomical and clinical parameters on a series of 656 patients treated radiosurgically for a vestibular schwannoma. Hearing status was evaluated with the Gardner-Robertson classification. The high-resolution CT at bone windows and high-resolution MRI-T2 and MRI-T1gadolinium have been used to analyze linear and volumetric measurements of the IAC and the part of the tumor located into the IAC. We estimate the erosion of IAC bone by comparison of the ipsi- and controlateral IAC volume. We correlate the IAC volume and linear measurements with the % of IAC occupied by the tumor. We compare the bony erosion of the IAC and % of intrameatal tumor with hearing level before Gamma Knife irradiation and hearing status at last follow-up.  

Results:

The pre-treatment anatomical and audiological data of all patients were analyzed in LGP 10.0, and the patients were followed prospectively for tumor control and hearing outcome. The volume of IAC at the side of the schwannoma was increased in comparison with the controlateral side in 87% of cases, and was increased by more than 120% of the controlateral IAC volume in 66% of cases. We found an extremely significant association (p<0.0001) between the ratio Vol IACipsi/Vol IACcontra and the volume of tumor located into the IAC, as well as the % of tumor volume located into the IAC. The pre-radiosurgical ipsilateral hearing level (GR grade and useful/not useful hearing status) was significantly associated (p=0.034 and p=0.0032, respectively) with the volume and the % of tumor volume located into the IAC. Therefore, the ratio Vol IACipsi/Vol IACcontra and the % of tumor volume located into the IAC are parameters related to hearing loss and could be used in the decision process for treatment or wait-and-scan.

Conclusions:

The IAC can be eroded by the intracanalicular part of the schwannoma. Volumetric parameters of the IAC and intrameatal volume of the tumor are significantly related to patients hearing status and some cut-off of these parameters can be used to decide when the wait-and-scan attitude must be stopped in favor of radiosurgical treatment.

Cecile RENIER (Brussels, BELGIUM), Nicolas MASSAGER, Carine DELBROUCK, Philippe DAVID, Daniel DEVRIENDT, Stephane SIMON
17:10 - 17:20 #10205 - Acute clinical adverse radiation effects after Gamma Knife surgery for vestibular schwannomas.
Acute clinical adverse radiation effects after Gamma Knife surgery for vestibular schwannomas.

OBJECTIVE Vestibular schwannomas (VSs) represent a common indication of Gamma Knife surgery (GKS). While most studies focus on long-term morbidity and adverse radiation effects (AREs), none describe the acute clinical AREs that might appear on a short-term basis. These types of events are investigated, and their incidence, type, and outcomes are reported in the present paper. METHODS The included patients were treated between July 2010 and March 2016, underwent at least 6 months of follow-up, and presented with disabling symptom during the first 6 months after GKS that affected their quality of life. The timing of appearance, as well as type of main symptom and outcome, were noted. The prescribed dose was 12 Gy at the margin. RESULTS Thirty-five (22%) of 159 patients who fulfilled inclusion criteria had acute clinical AREs. The mean followup period was 30 months (range 6-49.2 months). The mean time of appearance was 37.9 days (median 31 days; range 3-110 days). In patients with de novo symptoms, more frequent were vertigo (n = 4; 11.4%) and gait disturbance (n = 3; 8.6%). The exacerbation of a preexisting symptom was more frequently related to hearing loss (n = 10; 28.6%), followed by gait disturbance (n = 7; 20%) and vertigo (n = 3, 8.6%). In the univariate logistic regression analysis, the following factors were statistically significant: age (p = 0.002; odds ratio [OR] 0.96), hearing at baseline by Gardner-Robertson (GR) class (p = 0.006; OR 0.21), pure tone average at baseline (p = 0.006; OR 0.97), and Koos at baseline (Koos Grade I used as reference) (for Koos Grade II, OR 0.17 and p = 0.002; for Koos Grade III, OR 0.42 and p = 0.05). Fractional polynomial regression analysis showed a nonlinear relationship between the outcome and the radiation dose rate (minimum reached at a cutoff of 2.5 Gy/minute) and the maximal vestibular dose (maximum reached at a cutoff of 8 Gy). The clinical acute AREs disappeared in 32 (91.4%) patients during the first 6 months after appearance. Permanent and somewhat disabling morbidity was found in 3 (1.9% from the whole series): 1 each with complete hearing loss (GR Class I before and V after), hemifacial spasm (persistent but alleviated), and dysgeusia. CONCLUSIONS Acute effects after radiosurgery for VS are not rare.  In most cases, none of these effects are permanent, and they will ultimately improve or disappear with steroid therapy. Permanent AREs remain very rare.

Constantin TULEASCA (Pully, SWITZERLAND), Mercy GEORGE, Mohamed FAOUZI, Luis SCHIAPPACASSE, Henri-Arthur LEROY, Zeverino MICHELE, Roy Thomas DANIEL, Raphael MAIRE, Marc LEVIVIER
17:20 - 17:30 #10353 - Volumetric changes in growing vestibular schwannomas post stereotactic radiosurgery.
Volumetric changes in growing vestibular schwannomas post stereotactic radiosurgery.

Introduction

Previous publications suggest that vestibular schwannomas (VS) which grow rapidly prior to stereotactic radiosurgery (SRS) are more likely to continue growing after treatment. However this is based either on potentially inaccurate tumour length or small patient numbers.  In University Hospitals Bristol (UHBristol) the majority of patients with VS have treatment after documented growth.  The aim of this study is to accurately describe the volumetric changes pre- and post-SRS of growing VS and investigate if the tumour’s growth kinetics are predictive of these changes.

Method

Patient cohort consisted of patients with VS treated with SRS who had a MRI scan within 24 months prior to SRS demonstrating growth and minimum 2 years MRI follow-up.  To ensure volumetric accuracy, MRI scans >1.5mm slice interval were excluded.  Scan closest to 1 year pre-treatment, treatment day and all post treatment scans were imported into Oncentra Planning System (Elekta, Stockholm).  VS was contoured to establish tumour volume at all timepoints (pre, day 0, and 1/2/3 year post SRS). The rate of volume change of the VS was calculated per month and statistical analysis utilised Pearson Correlation.

Results

60 consecutive patients with VS were treated at UHBristol with SRS 10/2013-12/2014.  3 were excluded due to lack of growth on scans 4-8 months prior to treatment and 14 due to inadequate pre-treatment scans. 43 patients had 173 scans contoured. Tumours were treated on Perfexion Gamma Knife (Elekta, Stockholm) with mean 12.3Gy to 50% isodose with 99% coverage, conformity index 0.83 and gradient index 2.85.

At 4-22 months pre-treatment the mean VS volume was 1.36cc; at SRS 1.94cc; at 1 year 1.19cc; and 2 year 1.08cc.  Pre-treatment tumours grew mean +8.2%/month [+0.29-+36.8%/month].  38 patients had adequate scans at 1 year and 43 at 2 year post-SRS.  At 1 year post treatment overall rate of growth was -2.9%/month [-6.7-+3.3%/month]: 86.8% smaller; 5.3% stable; 7.9% grew but rate of growth reduced from +9.3%/month to +2.2%/month.  At 2 years compared to treatment day mean growth was -1.9%/month [-3.4-+2.3%/month]: 88.4% shrank; 4.7% grew then stabilised; 4.7% initially shrank then grew; 2.3% continued to grow at a slower rate.

There was no correlation between rate of growth prior to after SRS, nor between rate of shrinkage at 1 year to 2 year.

Conclusion

Despite growth pre-treatment, most VS shrink in the first 2 years post SRS.  The rate of pre-treatment growth does not predict post treatment continued growth or degree of shrinkage.

Hannah M REED, Georgina GULLICK, Alison L CAMERON (Bristol, UK)
17:30 - 17:35 #10344 - Gamma Knife surgery for facial nerve schwannomas.
Gamma Knife surgery for facial nerve schwannomas.

Background: Facial nerve schwannomas are rare tumors and account for less than 2% of intracranial neurinomas, despite being the most common tumors of the facial nerve. The optimal management is currently under debate and includes observation, microsurgical resection, radiosurgery (RS) and fractionated radiotherapy. RS might be a valuable alternative, as a minimally invasive technique, in symptomatic patients and/or presenting with tumor growth.

 

Methods: We review our series of 4 consecutive cases, treated with Gamma Knife surgery (GKS), during the period July 2010 and January 2017. Clinical and dosimetric parameters were assessed. GKS was performed in all cases using the Leksell Gamma Knife Perfexion.

 

Results: The mean age at the time of GKS was 44 years (range 34-56). The mean follow-up period was 42 months (range 12-60). The first symptom was facial palsy in 2 (50%) cases and hemifacial spasm in 2 (50%). All had a facial palsy at baseline, one with House-Brackmann (HB) II, 2 with HB III and one with HB VI. The mean target volume at the time of GKS was 0.360 cc (range 0.030-0.638) and the mean prescription isodose volume was 0.462 cc (range 0.052-0.805). The mean maximal dose delivered was 12 Gy at the 50% isodose line. The mean dose received by the cochlea was 3.8 Gy (range 0.1-10). The mean number of isocenters was 6.5 (range 1-10). One patient benefited from a staged-volume GKS. At last follow-up, facial palsy remained stable in 2 cases (one HB II and one HB III), and improved in 2 (one from HB III to HB II; one from HB VI to HB II). Regarding hemifacial spasm, both patients presenting one at baseline had a decrease in its frequency and intensity.

 

Conclusion: In our experience, RS and particularly GKS appear to be an appropriate therapeutic option in the management of these tumors. However, it should be also accompanied by a rehabilitation program, in collaboration with specialized colleagues, so as to give the patients the best chances for recovery. Radiosurgery remains a minimally invasive technique and with a small risk of functional decline, which should be putted in balance with the patient’s baseline clinical status and tumor characteristics.   

Jean-Nicolas COMPS (, SWITZERLAND), Antonio TARABAY, Constantin TULEASCA, Mercy GEORGE, Luis SCHIAPPACASSE, Maud MARGUET, Raphael MAIRE, Marc LEVIVIER
Parallel 2- Queen

Monday 29 May

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3D SK3
16:30 - 17:30

Small groups WFSBS session 3
3D Skull-base Anatomy for safe Radiosurgery

Keynote Speaker: Siviero AGAZZI (Tampa, USA)
See Session 3D Skull-base Anatomy 1 for description.
Parallel 3- BB King
Tuesday 30 May
07:30

Tuesday 30 May

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BS4
07:30 - 08:30

BREAKFAST SEMINAR
Targeting Optimization

Moderators: Alessandra GORGULHO (Director of Research Affairs) (Sao Paulo, BRAZIL), Adrian MERLO (SWITZERLAND), Niklaus SCHAEFER (SWITZERLAND)
07:30 - 08:30 Multidisciplinary imaging in targeting optimization for skull base meningiomas. Antonio NICOLATO (Neuroradiosurgeon) (Verona, ITALY)
07:30 - 08:30 Principle of Selective Interstitial radiation therapy. Niklaus SCHAEFER (SWITZERLAND)
07:30 - 08:30 Targeted alpha therapy for malignant gliomas WHO II-IV. Adrian MERLO (SWITZERLAND)
Parallel 1- Prince

Tuesday 30 May

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BS5
07:30 - 08:30

BREAKFAST SEMINAR
Motion Management Techniques for SBRT of Lung & Liver

Coordinator: Fang-Fang YIN (Medical Physicist/Professor) (Durham, NC, USA)
Moderators: Jeffrey D BRADLEY (St Louis, USA), Samuel RYU (Professor) (Stony Brookn NY, USA)
07:30 - 08:30 Speaker 1: Techniques and processes for Motion Management Techniques of Lung & Liver. Fang-Fang YIN (Medical Physicist/Professor) (Durham, NC, USA)
07:30 - 08:30 Speaker 2: Motion considerations for lung SBRT. Jeffrey D BRADLEY (St Louis, USA)
07:30 - 08:30 Speaker 3. Jackie WU (Professor) (Durham, USA)
Parallel 2- Queen

Tuesday 30 May

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BS6
07:30 - 08:30

BREAKFAST SEMINAR
Standardization

Coordinator: Caroline CHUNG (Associate Professor, Radiation Oncology) (Houston, USA)
Moderators: Evelyn HERRMANN (Radiation Oncology) (Bern, SWITZERLAND), Dheerendra PRASAD (Professor and Medical Director) (Buffalo, USA)
07:30 - 08:30 Standardization: essential steps towards quality, collaboration and cutting edge progress. Caroline CHUNG (Associate Professor, Radiation Oncology) (Houston, USA)
07:30 - 08:30 Geometrical accuracy and quality assurance of MRI protocols for gammaknife treatments. Uulke VAN DE HEIDE (THE NETHERLANDS)
07:30 - 08:30 Global assessment of current practices & vision for convergence. Dheerendra PRASAD (Professor and Medical Director) (Buffalo, USA)
Parallel 3- BB King
08:45

Tuesday 30 May

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PS2
08:45 - 10:00

PLENARY SESSION 2

Moderators: Adrien COSINSCHI (Radiation Oncologist) (Vevey, SWITZERLAND), Bruce POLLOCK (Physician) (Rochester, USA), Pierre-Hugues ROCHE (Marseille, FRANCE)
08:45 - 08:55 Data Blitz: Updates on Functional Radiosurgery. Romain CARRON (MEDECIN) (MARSEILLE, FRANCE)
08:55 - 09:05 Special Lecture: Introduction to Diffusion MR image processing. Jean-Philippe THIRAN (Director) (Lausanne, SWITZERLAND)
09:05 - 09:15 Minimal requirements for safe Frameless Radiosurgery. Johan CUIJPERS (Head of Physics) (Amsterdam, THE NETHERLANDS)
09:15 - 09:25 Pros & Cons - Progression versus pseudoprogression: Is stability of Vestibular Schwannoma before SRS a major predictor of tumor control? Yes. Bruce POLLOCK (Physician) (Rochester, USA)
09:25 - 09:35 Pros & Cons - Progression versus pseudoprogression: Is stability of Vestibular Schwannoma before SRS a major predictor of tumor control? No. Philip THEODOSOPOULOS (Neurosurgeon) (San Francisco, USA)
09:35 - 09:45 Pros & Cons - Very big Vestibular Schwannomas: Is limited better than extended resection in combined approaches? Yes. Roy Thomas DANIEL (Médecin Cadre) (Lausanne, SWITZERLAND)
09:45 - 09:55 Pros & Cons - Very big Vestibular Schwannomas: Is limited better than extended resection in combined approaches? No. Pierre-Hugues ROCHE (Marseille, FRANCE)
Stravinski Auditorium
10:00

Tuesday 30 May

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break10
10:00 - 10:30

Coffee Break

10:30

Tuesday 30 May

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PS3
10:30 - 11:30

PLENARY SESSION 3

Moderators: Roy Thomas DANIEL (Médecin Cadre) (Lausanne, SWITZERLAND), Yoshiaysu IWAI (Neurosurgery, Radiosurgery) (Osaka, JAPAN), Antonio NICOLATO (Neuroradiosurgeon) (Verona, ITALY), Karl SCHALLER (Genève, SWITZERLAND)
10:30 - 10:40 Recent developments in Proton Therapy Technology: a critical thinking approach. David WIKLER (BELGIUM)
10:40 - 10:50 Pros & Cons - Who has the bragg'ing rights: Are Protons superior to Stereotactic Photons in Chordomas and Chondrosarcomas? Yes. Damien WEBER (Villigen, SWITZERLAND)
10:50 - 11:00 Pros & Cons - Who has the bragg'ing rights: Are Protons superior to Stereotactic Photons in Chordomas and Chondrosarcomas? No. Dheerendra PRASAD (Professor and Medical Director) (Buffalo, USA)
11:00 - 11:10 Limits of resection in skull-base tumors. Paul GARDNER (Pittsburg, USA)
11:10 - 11:25 Proton-beam irradiation of ocular tumors. Leonidas ZOGRAFOS (SWITZERLAND)
Stravinski Auditorium
11:30

Tuesday 30 May

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OSP15
11:30 - 12:30

Parallel Session - SRS versus Alternative Focal Approaches

Moderators: Javier FANDINO (SWITZERLAND), Adrian MERLO (SWITZERLAND), Jason SHEEHAN (Charlottesville, USA)
11:30 - 11:45 HIFU in tremor. Howard EISENBERG (USA)
11:45 - 12:00 HIFU for brain tumors. Daniel COLUCCIA (SWITZERLAND)
12:00 - 12:15 Tumor Treating Fields in neuro-oncology. Andreas HOTTINGER (Lausanne, SWITZERLAND)
12:10 - 12:30 Focal therapies in prostate tumors. Massimo VALERIO (Lausanne, SWITZERLAND)
Stravinski Auditorium

Tuesday 30 May

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OSP14
11:30 - 12:30

Parallel Session - Imaging

Moderators: Antonio DE SALLES (Professor - Chief) (Sao Paulo, BRAZIL), Thomas MINDERMANN (Neurosurgeon) (Zürich, SWITZERLAND)
11:30 - 11:40 #8971 - 11C-Methionine PET for distinguishing recurrent brain metastases from radiation necrosis: Limitations of diagnostic accuracy and long-term results of salvage treatment.
11C-Methionine PET for distinguishing recurrent brain metastases from radiation necrosis: Limitations of diagnostic accuracy and long-term results of salvage treatment.

Background: Imaging features of radiation necrosis (RN) are similar to those of local recurrence (LR) of brain metastases (BM) on conventional diagnostic imaging technique. 11C-Methionine PET (MET-PET) has reportedly been useful to provide a differential diagnosis between LR and RN. The aim of this study was to investigate the diagnostic performance of MET-PET and the mid- to long-term results of subsequent management.

 

Methods: The eligible subjects were enlarging contrast-enhanced lesions (>1cm) on MR imaging after any kind of radiotherapy for BM, suggesting LR or RN but difficult to differentiate. From August 2013 to September 2016, MET-PET was performed for 35 lesions in 30 patients (median age: 63 yrs). Tracer accumulation in the regions of interest was analyzed as standardized uptake value (SUVmax) and lesion/normal tissue SUVmax ratios (LNR) were calculated. The cut-off value of LNR was provisionally set at 1.40. Salvage treatment strategies determined based on MET-PET diagnosis and treatment results were investigated. The diagnostic accuracy of MET-PET was analyzed by Receiver operating characteristic (ROC) curve analysis.

Results: Median interval from primary radiotherapy to MET-PET was 21 months and 13 lesions had received radiotherapy twice or more. The MET-PET diagnoses were LR 17 and RN in 18 lesions. In the median follow-up time of 15 months, final diagnoses were confirmed in 31 lesions (Histological 16, Clinical 15). Mean LNR of LR and RN were 1.70 ± 0.31, 1.13 ± 0.25, respectively. Sensitivity, Specificity, positive predictive value and negative predictive value were 80%, 88%, 86%, 82%, respectively. ROC curve analysis indicated the optimal LNR cut-off value as 1.39 (AUC: 0.89). LNR of 5 lesions incorrectly diagnosed by MET-PET were ranged within 1.4 ± 0.2. Salvage treatment for 17 lesions predicted as LR were surgical resection in 7, radiosurgery in 8. Of 18 lesions predicted as RN, 6 were surgically treated and 3 needed repeat bevacizumab treatment. In 4 lesions which failed to obtain diagnostic conclusion, salvage treatment based on MET-PET diagnosis did not provide significant improvement and treatment strategies had to be changed.

Conclusions: 11C-Methionine PET appeared to have a reliable diagnostic performance for distinguishing LR from RN. The provisional LNR cut-off value of 1.4 in our institution was found to be relevant. Limitations of diagnostic accuracy should be recognized in cases with LNR close to the cut-off value.

Shoji YOMO (Tokyo, JAPAN)
11:40 - 11:50 #9983 - Differentiating post-SRS radionecrosis from tumor progression using MRI Arterial Spin-Flow Labelling (ASL): Quick, colorimetric, quantifiable and necessary baseline blood flow data used to evaluate SRS treatment of brain metastases and predict outcomes.
Differentiating post-SRS radionecrosis from tumor progression using MRI Arterial Spin-Flow Labelling (ASL): Quick, colorimetric, quantifiable and necessary baseline blood flow data used to evaluate SRS treatment of brain metastases and predict outcomes.

The radiographic differentiation of post-SRS radiation change versus tumor progression is a major issue for any SRS center. We have been using non-Gd+ ASL as a reliable pulse sequence to help decide on the dominant tissue in these lesions and have used this data to assist in the decision for further treatment for four years now. Recent published data confirms that post-SRS elevated flow can be a very reliable predictor of recurrent tumor but the largest study failed to establish baseline data, and we have found that up to 40% of pre-treatment brain metastasis do not have elevated flow at baseline, therefore these tumors would not be expected to have elevated flow when they re-occur. If a baseline is not established, then these ‘low flow’ metastasis would be mistaken as radiation change upon follow-up. We have contacted multiple international centers to join in a larger data pool to verify our initial findings and establish an optimal statistical data base and promote this two-minute pulse sequence characterization to be used with confidence.

Elisheva LAMBERT (Tel Aviv, ISRAEL), Dr. Stephen HOLMES
11:50 - 12:00 #10001 - Integration of MR Guided Linear Accelerator for Treatment of Multiple Brain Metastases with Single-Isocenter using Stereotactic Radiosurgery.
Integration of MR Guided Linear Accelerator for Treatment of Multiple Brain Metastases with Single-Isocenter using Stereotactic Radiosurgery.

Objectives

The purpose of study was to investigate the treatment planning capabilities for multiple brain metastases using stereotactic radiosurgery with a shared isocenter on an integrated 0.35T magnetic resonance imaging guided Linear Accelerator (MR-Linac) platform.

 

Methods

The MR-Linac consists a 0.35T double donut superconducting MRI and a ring-gantry mounted Linac system.  The Linac has a 6X flattening filter free (FFF) beam with a dose rate up to 600 MU/min. The multileaf collimator (MLC) has a novel double-stack design to achieve a 4 mm spatial resolution which is half of the leaf width. The treatment planning process for two patients with 3 brain metastatic lesions and one patient with 2 lesions were studied. Single-isocenter IMRT plans with 10-15 beams were used to generate treatment plans for multiple metastases in a coplanar setting. The isocenter was placed around the geometric center among the lesions. All plans were calculated with 1 mm dose grid resolution using a fast Monte Carlo algorithm with a prescription dose of 18 Gy for each lesion.  The IMRT optimization employed the same Monte Carlo algorithm for calculating the dose distribution at each iteration step.  2.4 millions histories were simulated to achieve a statistical uncertainty of 2%, on average, at Dmax.

Plan quality was evaluated using the conformity index (CI), homogeneity index (HI) and gradient index (GI). The volume of normal brain that received 4, 8, and 12 Gy (V4, V8, and V12, respectively), as well as the mean dose were used to evaluate the dose to the normal brain. The total MUs, segments, and beam on time, were also recorded.

 

Results

The average planning target volume was 0.34 cm3 (range 0.06-0.74 cm3). The CI, HI and GI of each plan were 1.31/1.23/5.93, 1.61/5.98/5.27, and 1.31/1.23/5.27 respectively.  V4Gy, V8Gy, V12Gy of normal brain of each plan were 1.02/0.34/0.14, 3.32/0.58/0.22, 1.27/0.20/0.02 %. The mean dose of normal brain tissue for all three patients were 0.37, 0.78 and 0.60 Gy. The total MU of each plan was 5510, 7488, and 6547 and the corresponding beam on time was 9, 12, and 11 minutes.  Monte Carlo based dose calculation required less than 5 minutes.

 

Conclusions

A novel double-stacked MLC design was able to achieve a finer leaf width, which provided better dose conformity to target lesions under 1.0 cm3. This preliminary investigation demonstrated that excellent plan quality was achievable on the MR-Linac to treat multiple brain metastases with a single isocenter.

Ning WEN (Detroit, USA), Anthony DOEMER, Carri GLIDE-HURST, James VICTORIA, Iwan KAWRAKOW, Qixue WU, Liu CHANG, Farzan SIDDIQUI, M. Salim SIDDIQUI, Indrin CHETTY, Benjamin MOVSAS
12:00 - 12:10 #10256 - Radiomics analysis for assessing concurrent stereotactic radiosurgery and bevacizumab treatment of recurrent malignant gliomas.
Radiomics analysis for assessing concurrent stereotactic radiosurgery and bevacizumab treatment of recurrent malignant gliomas.

This study explored the use of radiomics features as potential biomarkers for predicting the outcome of recurrent malignant gliomas (MG) patients treated by concurrent stereotactic radiosurgery (SRS) and Bevacizumab (BVZ). Thirteen patients with recurrent MG were retrospectively studied. Lesions with <3 cm in diameter were treated in a single fraction and 3-5 cm in diameter were treated in 5 fractions. BVZ was administered immediately before SRS and 2 wks later. MRI studies, including T1- and T2-weighted, dynamic contrast-enhanced (DCE) and diffusion weighted (DW), were performed before SRS, 1 week and 2 months after the completion of SRS. Functional paremeters including apparent diffusion coefficient ADC, micro-vascular transfer constant Ktrans, brain blood flow FB, and blood volume vB were analyzed. Radiomics analysis extracts imaging features (a total of 252 radiomics features) and correlates features with outcomes. Statistical tests were performed with Bonferroni correction to evaluate the change of functional parameters and texture features 1 week and 2 months after SRS. The changes between different WHO grades were evaluated. Correlation tests were used to examine the relationships between changes of functional parameters/radiomics features and patient survival time after SRS. Selected features were used to predict the patient survival time after treatment using Support Vector Regression (SVR) with leave one out cross validation (LOOCV). The median survival time was 13.7 months after treatment. Radiomics analysis was also performed in normal tissues receiving 12 Gy or above. DCE results showed that GTV blood flow dynamics parameters Ktrans(p=0.02) and vB(p=0.04) significantly decreased at 2 months after SRS. No functional parameters reflected statistically significant treatment response at 1 week after SRS. 20 radiomics features from anatomical T1w gray level images and 25 features from functional parameters maps (Ktrans:18, ADC:7) showed significant changes 2 months after SRS. Among these features, 7 Ktrans features and 3 ADC features reflected significant difference as early as 1 week after SRS between WHO Grade 3/4 patient groups. The changes of 16 radiomics features (Ktrans:11, FB:5) at 2 months after SRS were significantly correlated with patient survival time. Using 2 selected signature features from T1w scans and 3 from DCE parametric maps, 9 out of 13 patients’ survival time could be accurately predicted. The preliminary results demonstrate the effectiveness of using radiomics features for predicting early treatment response. The results also suggest the potential application of radiomics features as potential biomarkers for individualized treatment regime optimization.

Fang-Fang YIN (Durham, USA), Chunhao WANG, Wenzhen SUN, Zheng CHANG, John KIRKPATRICK
12:10 - 12:20 #10411 - Tractography in gamma knife anterior capsulotomy planning.
Tractography in gamma knife anterior capsulotomy planning.

Objective: The role of tractography in Gamma Knife Capsulotomy (Gamma-C) planning is still unclear. The anterior internal capsule (AIC) tractography could demonstrate the most important fibers necessary to be severed to achieve best results and reduce complications.

 

Methods: In this study, the AIC of 20 patients undergoing functional neurosurgery for diverse diagnosis was defined bilaterally in the Iplannet Stereotaxy Software (Brainlab, Germany). The 40 AIC tractography were divided in two halves based on coronal views. The direction of the fibers was studied in the two segments with the objective to define which portions of the fibers would be reached by a single isocenter placed in the ventral most portion of the AIC, and which fibers would be reached if added a second isocenter to obtain an oval shaped distribution in the direction of the ventral-dorsal portion of the AIC. The isocenters were adjusted based on Gamma Plan® Treatment Planning System - TPS (Elekta, Sweden).

 

Results: Significant difference was observed between both plans, with the single isocenter reaching substantially fibers directed to the ventral-mesial-orbitofrontal fibers, while the two isocenters plan achieved also fibers directed to the lateral-frontal cortex. Classical capsulotomy suggests that these lateral fibers should be also reached, based on size of the lesion, oval in shape.

 

Conclusions: The routine use of DTI tractography of the AIC may be important to the planning of Gamma Knife capsulotomy. DTI tractography, as well as anisotropy showing the capsule promises the have important role in Gamma-C. In the case of Gamma-C it allows for objective definition of dose constrains to the internal capsule and the fibers to be reached. It may direct the procedure based on severity of the disease, as well as its dominant symptomatology.

Antonio DE SALLES, Alessandra GORGULHO, Joao Gabriel GOMES (Sao Paulo, BRAZIL), Anderson PASSARO
12:20 - 12:30 #10430 - Stereotactic diffusion tensor imaging tractography for gamma knife stereotactic radio-surgery - Evolution of technique & application.
Stereotactic diffusion tensor imaging tractography for gamma knife stereotactic radio-surgery - Evolution of technique & application.

Integration of modern neuroimaging into treatment planning has increased the therapeutic potential and safety of stereotactic radiosurgery. We previously reported our method of integrating stereotactic diffusion tensor imaging (DTI) tractography into conventional treatment planning for Gamma Knife radiosurgery (GKRS). The aim of this study is to address  some of the technical limitations of our previously reported techniques in a larger series

Methods: Seventy patients who underwent GKRS composed the study cohort. DTI images were obtained at the time of standard GKRS protocol MRI (T1 and T2 weighted) for treatment, with the patient’s head secured by a Leksell stereotactic frame. All studies were performed using a 1.5-T magnet with a single-channel head coil. DTI was performed with diffusion gradients in 32 directions and coregistered with the volumetric T1-weighted study. DTI postprocessing by means of commercially available software allowed tensor computation and the creation of directionally encoded color, apparent diffusion coefficient & fractional anisotropy mapped sequences. In addition, the software allowed visualized critical tracts to be exported as a structural volume and integrated into GammaPlan as an “organ at risk” during shot planning. Combined images were transferred to GammaPlan and integrated into treatment planning.

Results: Stereotactic DTI images were successfully acquired in all patients, with generation of correct directionally encoded color images. Tract generation was straightforward and reproducible, particularly for axial tracts such as the optic radiation and the arcuate fasciculus. In our original dtudy we noted that Corticospinal tract visualization was hampered by artifacts from the base of the stereotactic frame, but this was overcome by adjusting the gradient parameters. Coregistration of the DTI series with the T1-MR treatment volume at imaging is essential for the generation of correct tensor data. Most patients had pathology in the vicinity of eloquent tracts and/or the cortex. One patient with mesial temporal AVM developed delayed worsening of a pre-existing hemianopia. no other neurological deficits due to radiation were recorded at follow-up.

Conclusions: Reports in the medical literature have suggested that white matter tracts (particularly the optic radiation and arcuate fasciculus) are more vulnerable to radiation during SRS than previously thought. Integration of stereotactic tractography into GK-SRS represents a promising tool for preventing GK-SRS complications by reduction in radiation doses to functional organs at risk, including critical cortical areas and subcortical white matter tracts & further increase our knowledge of critical cerebral structure radiation tolerances to better improve the therapeutic potential and safety of SRS

Cormac GAVIN (London, UK), H. Ian SABIN
Parallel 1- Prince

Tuesday 30 May

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OSP13
11:30 - 12:30

Parallel Session - WFSBS: Hypofractionation in skull-base

Moderators: Patrick HANSSENS (Radiation Oncologist) (Tilburg, THE NETHERLANDS), Oscar MATZINGER (Vevey, SWITZERLAND), Piero PICOZZI (Director) (MILANO, ITALY)
11:30 - 11:40 #9896 - Predictors of local control and comparison of single versus fractionated stereotactic radiotherapy for meningiomas – A Single institutional experience.
Predictors of local control and comparison of single versus fractionated stereotactic radiotherapy for meningiomas – A Single institutional experience.

OBJECTIVES  : To assess the predictors for local control and to compare  outcomes of  Linac  based SRS(stereotactic radiosurgery) with  FSRT(fractionated stereotactic radiotherapy) for meningiomas

 

METHODS AND MATERIALS : 45 patients of meningioma treated using LINAC based SRS and FSRT were retrospectively analyzed in our institute  diagnosed( radiological diagnosis =30, and biopsy proven =15) between 2007 to 2016. Male to female ratio was 17: 28 .12 patients were treated radically with SRS  and 33 patients (20 were radically treated, 8 received adjuvant radiation and 5 had radiation on recurrence, post surgery) were treated with FSRT. Patients who received re-irradiation were not included in the study. The median age group in SRS arm was 50 years ( range 32 -72 years)and in FSRT arm  55 years(30- 76 years) The median dose for SRS  was 15Gy (range 12-16Gy), and for FRST it was 25Gy (range 25-30Gy).The median PTV volume in SRS arm was 3.25cc ( range 0.75 to 10.5cc), and in FSRT arm 13.25cc  (range 10.45 to 65.3cc). The patients were followed by clinical examination as well as serial imaging with MRI (Magnetic resonance imaging).

 

RESULTS : The median follow up of the entire cohort was 54 months( range 6 – 84months).The median follow up of SRS arm and FSRT  arm was 48 months(range 12- 72months) and 72 months( range 6- 84months)  respectively . The overall survival was 100% in both the groups.  The 5 year local control was equivalent in both SRS and FSRT arm (91.6 vs 90.2%)(p =0.512). On univariate analysis  of the whole cohort, we found that age ,gender and PTV volume were predictors for local control. Local control was better for age group < 60 years ( p = 0.043). Females had longer time to relapse than males (p =0.026).The 5 year Local control was 100% for a tumor volume of ≤ 15cc and 91.1% for  a tumor volume of  >15cc (p= 0.044). No radiation late damage or any adverse events were observed during follow up period in both the arms.

 

CONCLUSION  : SRS and FSRT are equally effective  in terms of local control and complication rates. SRS is better for smaller volumes. FSRT is suitable for larger volumes,and with or without surgery .Age, gender and PTV volumes are important predictors for tumor control. Proper selection of cases and longer follow up is required for best outcomes.

Sanjay HUNUGUNDMATH (pune, INDIA), Sumit BASU, Bhooshan ZADE, Rahul SHARMA, Ashok BHANAGE, Sathiyanarayanan VATYAM
11:40 - 11:50 #9932 - Multi-fraction stereotactic radiosurgery for trigeminal schwannomas: a retrospective study of 56 patients.
Multi-fraction stereotactic radiosurgery for trigeminal schwannomas: a retrospective study of 56 patients.

Objective: Trigeminal schwannomas (TSs) have traditionally been treated by surgery. This retrospective study illustrates the outcomes of a series of TSs, most of which are large tumors, after multi-fraction stereotactic radiosurgery (MF-SRS).

Methods: A series of 56 TSs were treated using the CyberKnife from June 2007 to June 2015 with the multi-fraction SRS technique in Huashan Hospital, Shanghai, China. The mean age was 50 (range 21-78) years. Microsurgery preceded radiosurgery in 13 patients and Gammaknife SRS in 4 patients. The median tumor volume was 13.3 (range 2.1–48.9) cm³ and 32 of them were larger than 10.0 cm³. The prescription dose was 19.8 (range 13.2-24)Gy, which was delivered in 1-4 sessions.

Result: The follow-up period ranged from 19 to 103 months (median 53.5 months). In all patients MRI follow-up was obtained, the overall tumor control rate was 96.4%. The most frequent symptoms
were hypoesthesia/hyperesthesia in 32 patients, diplopia in 10 patients, facial pain in 8 patients. Neurological follow-up examination showed a stable status in 13 patients, whereas 30 patients noted improvement of at least one of their presenting symptoms after treatment. One patient noted a transient ptosis the next day after the first fraction and recovered in a week. One patients had a symptomatic cyst formation of tumor 6 months after SRS, followed by a second subtotal resection. One patient recieved a VP shunt 8 months after SRS which was due to hydrocephalus.

Conclusions: Cyberknife multi-fraction SRS is an effective and minimally invasive management option for patients with residual or newly diagnosed trigeminal schwannomas with respect to not only long-term local tumor control but also neuro-functional preservation.

Hua Guang ZHU (Shanghai, CHINA), Enmin WANG, Xin WANG
11:50 - 12:00 #9970 - Results of 5-fraction hypofractionated gamma Knife radiosurgery for benign neoplasms close to optic pathways.
Results of 5-fraction hypofractionated gamma Knife radiosurgery for benign neoplasms close to optic pathways.

Introduction:

We evaluate the clinical and radiological outcome of a series of 14 patients treated for a benign tumor using hypofractionation with the Gamma Knife.

Materiel & Methods:

All 14 patients of our series had a benign tumor located close to the optic pathways. There were 11 meningioma, 2 pituitary adenomas and 1 craniopharyngioma. All patients were treated with 5 daily fractions of a 5-Gy margin dose, either with a frameless system Extend (n=9) or with a conventional frame (n=5) repositioned each day.  For frameless procedures, the Extend system was used and provided a submillimetric precision of positioning for all sessions of irradiation.

Results:

All patients were followed prospectively. The median follow-up duration was 3.75 years (range 2.5 - 5.5 y). The visual status remained stable for 13 patients and improved for 1 patient. The tumor volume remained stable for 3 patients, reduced over time for 10 patients, and increased for 1 patient. This patient developed an extension of his initial tumor that necessitates a new radiosurgical irradiation on the cavernous sinus. One patient developed 2 new meningiomas 2.5 years after irradiation in other locations, which could have been radiation-induced. No other morbidity was seen.

Conclusions:

The medium- to long-term clinico-radiological outcomes of this series of 14 patients treated for a benign tumor using 5 fractions with the Gamma Knife showed excellent results with a high rate of tumor control and no worsening of the visual status.

 

Daniel DEVRIENDT (Brussels, BELGIUM), Cecile RENIER, Nicolas MASSAGER
12:00 - 12:10 #10066 - Five fraction Stereotactic Radiosurgery (SRS) for Brain meningiomas.
Five fraction Stereotactic Radiosurgery (SRS) for Brain meningiomas.

Objectives: To describe the efficacy and toxicity of the five fraction stereotactic radiosurgery ( SRS) for brain meningiomas.
 
Background: Effectiveness of conventional adjuvant EBRT, affront single session gamma knife radiosurgery and moderately hypo fractionated radiotherapy for brain meningiomas are wel studied and proven to have good local controls with minimum side effects.

Five fractions hypo-fractionated radiotherapy (multisession SRS) was used for relatively large tumors and for those closely lying with critical organs and not suitable for gamma knife single session radiosurgery. This schedule was considered to be beneficial equivalent to single session in terms of local control rate while good protection of critical organs in terms of fractionated irradiation for the large volume meningiomas. 
 
Methods: From 01.01.10 to 30.06.16, 1220 patients were treated on Synergy-S (Linac based radiosurgery system). 100 patients of intracranial meningiomas (including recurrent) were treated with 5 fractions radiosurgery. 40% were male and 60% were female patients. Mean age was 41.74 years (range: 18-67 years). Patients were followed up at 6 weeks, 3 months and then 6 months till 5 years time. Mean volume (PTV) was 46.87 cc (range: 2.20-90.20cc).Prescription dose 2500 cGy was used in five fractions at 400 to 500 cGy/day( Mean Fraction dose= 4.5 Gy/day) . Mean prescription Isodose line was 80 %(range: 65-100%). Median Maximum Dose was 3119 cGy(range: 2442- 4284 cGy). Median Mean dose was 3070 cGy (range: 2251-3592 cGy). Median Minimum dose was 2321cGy(range:1909-2950 cGy).  Review of literature by using Pubmed, Medscape and Pubmed Central was carried out to establish the safety and efficacy of 5 fractions SRS in brain meningiomas. 

Results: Clinical Improvement was seen in about 88 % of the patients, radiologically most of the tumors were stable around 68 %, 10 % had small residual disease while 10% progressed from original size at about 18 months after SRS. 02% patients were lost to follow-up. 10% patients were dead at median follow-up time of 4.2 years (range:1-5.5 years). 50 % of the dead patients had non tumor related death, while 50% had death due to progressive disease. No acute toxicity was observed, while use of steroids was prolonged in about 10 % of the patients mean duration was 3 months (range 1-6 months).

Conclusion: This retrospective study revealed high local tumor control rate and acceptable toxicity of five fractions radiosurgery for brain meningiomas. Further larger  studies required to establish its future use.

Azhar RASHID (KARACHI, PAKISTAN), Muhammad Ali MEMON, A Sattar M HASHIM, Muhammad Abid SALEEM
12:10 - 12:20 #10375 - Staged radiosurgery for large/critical intracranial meningiomas: a monocentric prospective study.
Staged radiosurgery for large/critical intracranial meningiomas: a monocentric prospective study.

Background.The treatment of choice for intracranial meningiomas is surgical removal. However, the complete resection of meningiomas can be difficult or impossible, because of their extension, their proximity to cranial nerves, vascular structures or eloquent areas. Meanwhile, single and staged radiosurgery, in exclusive, adjuvant or salvage setting represents an alternative or complementary viable treatment to the neurosurgery.

Under these circumstances, the staged radiosurgery treatments have been increasing and several authors published excellent results after staged-SRS with a local control (LC) ranging between 90% and 100% and a low treatment-related toxicity, above all because of the potential to deliver sharply focused high doses per fraction without increasing the risk of toxicity.

We present the early and medium-term results of first 53 patients of our ongoing prospective trial on staged radiosurgery for large and/or critical intracranial meningiomas. Reports of symptom control and neurological status are also evaluated.

Methods. The eligibility criteria were either histologically confirmed or imaging-defined benign meningioma diagnosis; large or medium lesion size and/or in critical area; signed informed consent; age ≥ 18 years; and Karnofsky Performance Status (KPS) ≥ 70. All enrolled patients were prospectively followed with clinical, neurological and radiological examinations. The follow-up evaluations were performed after 4 months from the staged-SRS, afterwards every 6 months during the first 2 years and then annually.

Results.The median follow-up for the entire series was 38 months (range, 4-52 months). The LC was obtained in 46 patients (98%) out of 47 available for MRI volumetric analysis. Nineteen (40%) patients presented a partial response, 27 patients (58%) a stable disease. Among 31 (66%) patients who were symptomatic before s-SRS, neurological follow-up showed an improvement in 15 patients (48.3%), stable clinical course in 12 patients (38.7%) and a persistent deterioration of clinical symptoms in 4 patients (13%). The acute toxicity was registered in 8 patients (23.5%). These new symptoms turned up in the patients within few weeks. The adverse events not correlated with radiotherapy were registered in 4 patients (8.5%).  None late symptoms due to staged-SRS were reported.

Conclusion.Our findings show that staged-SRS using the CyberKnife is a safe and effective option in the treatment of large-volume benign meningiomas. A good tumour control and a low morbidity and toxicity rates were achieved in our series, either as a primary or adjuvant approach. Long-term follow-up is warranted to confirm these results.

Valentina PINZI (Milan, ITALY), Alberto BOSETTI, Marcello MARCHETTI, Francesco GHIELMETTI, Milda CERNIAUSKAITE, Laura FARISELLI
12:20 - 12:30 #10389 - Tumor volume reduction and functional outcomes in radiosurgery and fractionated radiotherapy for cavernous sinus meningiomas.
Tumor volume reduction and functional outcomes in radiosurgery and fractionated radiotherapy for cavernous sinus meningiomas.

Introduction

Radiosurgery (RS) and fractionated radiotherapy (FRT) are part of the therapeutic armamentarium for the management of cavernous sinus meningiomas. We propose a systematic review of the local tumor control and clinical outcomes after monofractionated treatment, including gamma knife (GKRS) and linear accelerator (LinacRS), or fractionated radiotherapy.

Materials and Methods

We performed a search in PubMed based on the following Mesh terms: “cavernous sinus”, “meningioma”, “radiosurgery”, “gamma knife”, “linac”, “cyberknife”, and “radiotherapy”. Among 425 screened studies, 36 matched all selection criteria: 24 for GK, 5 for Linac and 7 for FRT.

 

Results

Were included 2817 patients (GKRS=2047, LinacRS=350, FRT=420). Half of patients benefited from upfront RS or FRT; the other half benefited from adjuvant RS or FRT (combined approach or tumor recurrence).  Mean target volume was smaller for RS as compared to FRT (p=0.07). Median marginal dose was 13.9 Gy (range, 11 to 28) for GKRS and 14 Gy (range, 12.8 to 17.7) for LinacRS. For FRT, patients received a mean dose of 51.2 Gy (25.5 fractions, 1.85 Gy each). Mean follow-up was: 48 months (range, 15 to 89) for GKRS, 69 months (range, 46 to 87) for Linac and 59.5 months (range, 33 to 83) for FRT. PFS at 5 years for GKRS, LinacRS and FRT were respectively: 93.6%, 95.6% and 97.4% (p=0.32, Kruskal-Wallis). Monofractionated treatments (GKRS and LinacRS) induced more tumor volume regression than FRT (p=0.001). Tumor recurrence or progression ranged between 3 and 5.8%, without statistically significant difference between modalities (p>0.05). Trigeminal symptoms improved in approximately 54%, and III-IV-VI CN palsies improved in approximately 45%. After GKRS, visual acuity improved in 21% (not enough data available for other modalities). De novo deficits occurred in 5 to 7.5% and adverse radiation effects in 4.6 to 9.3% (all techniques pooled).

Conclusion

RS achieved a twice-higher rate of tumor volume regression than FRT. GK series reported an improvement in visual acuity in 21% of the cases. GK, Linac and FRT provided similar clinical post therapeutic outcomes for the trigeminal and oculomotor CN. 

Henri-Arthur LEROY (Lille), Constantin TULEASCA, Nicolas REYNS, Marc LEVIVIER
Parallel 2- Queen
12:30

Tuesday 30 May

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lunch6
12:30 - 14:00

Day Adjourned

Wednesday 31 May
07:30

Wednesday 31 May

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BS7
07:30 - 08:30

BREAKFAST SEMINAR
ESTRO Session / Metastases Immunotherapy

Moderators: Caroline CHUNG (Associate Professor, Radiation Oncology) (Houston, USA), Andreas HOTTINGER (Lausanne, SWITZERLAND), Olivier MICHIELIN (SWITZERLAND)
07:30 - 08:30 Immunotherapy for dummies. Olivier MICHIELIN (SWITZERLAND)
07:30 - 08:30 Immunotherapy of tumors. Jean BOURHIS (Lausanne, SWITZERLAND)
07:30 - 08:30 Immunotherapy & Radiosurgery. Jing LI (Radiation Oncologist) (Houston, USA)
Parallel 1- Prince

Wednesday 31 May

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BS8
07:30 - 08:30

BREAKFAST SEMINAR
How to design CRT & Big Data Registry?

Moderators: Patrick HANSSENS (Radiation Oncologist) (Tilburg, THE NETHERLANDS), Douglas KONDZIOLKA (New York, USA), Ian PADDICK (Physicist) (London, UK)
07:30 - 07:45 Why do we need Big Data? Ian PADDICK (Physicist) (London, UK)
07:45 - 08:10 The Elekta registry. Douglas KONDZIOLKA (New York, USA)
08:10 - 08:25 QA issues and legal aspects of Big Data registries. Patrick HANSSENS (Radiation Oncologist) (Tilburg, THE NETHERLANDS)
Parallel 2- Queen

Wednesday 31 May

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BS9
07:30 - 08:30

BREAKFAST SEMINAR
System Geometrical Accuracy & final Clinical Accuracy

Moderators: Thierry GEVAERT (Head of Medical physics) (Brussels, BELGIUM), Stephanie TANADINI-LANG (Zurich, SWITZERLAND)
07:30 - 08:30 With what precision can the different RS devices deposit the dose? John KIRKPATRICK (Professor - Radiation Oncology & Neurosurgey) (Durham, NC, USA)
07:30 - 08:30 How accurate do we hit the clincal target? Stephanie TANADINI-LANG (Zurich, SWITZERLAND)
07:30 - 08:30 What are the consequences of the geometrical & clinical accuracy on the dose distribution? David SCHLESINGER (Medical Physics) (Charlottesville, USA)
Parallel 3- BB King
08:45

Wednesday 31 May

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PS4
08:45 - 10:00

PLENARY SESSION 4

Moderators: Lily ANGELOV (Staff Neurosurgeon) (Cleveland, USA), Jean BOURHIS (Lausanne, SWITZERLAND), Christopher DUMA (Neurosurgeon) (Newport Beach, USA)
08:45 - 08:55 Data Blitz: Updates on Imaging. Antonio DE SALLES (Professor - Chief) (Sao Paulo, BRAZIL)
08:55 - 09:05 Special Lecture: Methods for statistical process control: How they can be applied to SRS process improvement. David SCHLESINGER (Medical Physics) (Charlottesville, USA)
09:05 - 09:15 #10123 - Delta radiomic features from MR images can distinguish radiation necrosis from tumor progression after Gamma knife radiosurgery.
Delta radiomic features from MR images can distinguish radiation necrosis from tumor progression after Gamma knife radiosurgery.

Purpose: To develop a predictive model using changes in radiomic features extracted from MR images to distinguish radiation necrosis from tumor progression in brain metastases after Gamma knife radiosurgery.

Methods: We retrospectively identified 87 patients with pathologically confirmed necrosis (42 lesions) or progression (55 lesions), and calculated 285 radiomic features from 4 MR sequences (T1, T1 post-contrast, T2, and FLAIR) obtained at 2 follow-up time points per lesion per patient. Reproducibility of each feature between the two time points was calculated within each group (necrosis or progression) to identify a subset of features with distinct reproducible values between two groups using concordance correlation coefficients. Delta radiomics, i.e. the changes in radiomic features from one time point to the next, were used to build a model to classify necrosis and progression lesions. The model was evaluated by leave-one-out cross-validation and compared with another model built with radiomic features calculated at the second time point.

Results: 55 radiomic features from T1 post-contrast MR images were selected using distinct concordance correlation coefficients between the necrosis and progression lesions. A heuristic approach was used by testing the possibility of all combinations of the 55 radiomic features for feature modeling, and the useful features were further narrowed down to 21 gray-level co-occurrence matrix features.  Delta radiomic features with a complex decision tree classifier had an overall predictive accuracy of 81.4% and an area under the curve (AUC) value of 0.77 in leave-one-out cross-validation. In contrast, the best predictive model using features calculated at the second time point had 62.9% accuracy and 0.63 AUC.

Conclusion: Delta radiomic features extracted from T1 post-contrast MR images have potential for distinguishing radiation necrosis from tumor progression after radiosurgery for brain metastases.

Jinzhong YANG, Zhang ZIJIAN, Wen JIANG, Xin WANG, Paul BROWN, Nandita GUHA-THAKURTA, Sherise FERGUSON, Xenia FAVE, Lifei ZHANG, Dennis MACKIN, Laurence COURT, Jing LI (Houston, USA)
09:15 - 09:25 Pros & Cons - Spine Radiosurgery and fractionation: Is safety-efficacy of hypofractionation better than single dose in Spine Radiosurgery? Yes. Moon-Jun SOHN (Stererotactic radiosurgery using Dedicated LINAC plateform) (Goyang, KOREA)
09:25 - 09:35 Pros & Cons - Spine Radiosurgery and fractionation: Is safety-efficacy of hypofractionation better than single dose in Spine Radiosurgery? No. Samuel RYU (Professor) (Stony Brookn NY, USA)
09:35 - 09:45 Pros & Cons - Radiosurgery in high-grade gliomas: Is the targetting of the T1 contrast enhancement wrong ? Yes. Christopher DUMA (Neurosurgeon) (Newport Beach, USA)
09:45 - 09:55 Pros & Cons - Radiosurgery in high-grade gliomas: Is the targetting of the T1 contrast enhancement wrong ? No. Lily ANGELOV (Staff Neurosurgeon) (Cleveland, USA)
Stravinski Auditorium
10:00

Wednesday 31 May

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10:00 - 10:30

Coffee Break

10:30

Wednesday 31 May

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PS5
10:30 - 11:30

PLENARY SESSION 5

Moderators: Jonathan KNISELY (Lake Success, USA), Olivier MICHIELIN (SWITZERLAND), Antonio NICOLATO (Neuroradiosurgeon) (Verona, ITALY)
10:30 - 10:45 Special Lecture: SRS & Immunotherapy. Olivier MICHIELIN (SWITZERLAND)
10:45 - 10:55 Special Lecture: Synchrotron-generated microbeams as a therapeutical approach for focal epilepsies. Antoine DEPAULIS (Directeur de recherche INSERM) (LA TRONCHE, FRANCE)
10:55 - 11:05 #10178 - Multicenter study for the treatment of meningioma close to anterior optic-pathways or involving the optic nerve sheath with Gamma Knife: preliminary results with stereotactic hypo-fractionation approach on a series of 180 patients with at least 2-year-FU.
Multicenter study for the treatment of meningioma close to anterior optic-pathways or involving the optic nerve sheath with Gamma Knife: preliminary results with stereotactic hypo-fractionation approach on a series of 180 patients with at least 2-year-FU.

Objective. Gamma Knife Radiosurgery (GKRS) has proved to be an outstanding technique while treating skull base (SB) meningiomas (MNs) inferior to 15-20 mL. However, single session GKRS seems sometimes hazardous in cases of anterior optic pathways (AOP) close-fitting lesions or larger tumors, due to potential risks of radiotoxic effects. In order to lower this risk of damage to AOP and keep treatment efficacy, many Centers adopted hypofractionation protocols using either G-frame or relocatable Extend system. Objective of this multicenter study is to describe results obtained with those techniques evaluating the following end-points: local tumor control, ophtalmological outcome (visual acuity and visual field), permanent adverse radiation effect rate and other radiosurgery-related neurological deficits.

Methods. Our protocol consists of a 3 GKRS daily hypo-fractionating treatments (1 session/24 hours; 5-7 Gy/session). Stereotactic imaging (routinely an 1,5 Tesla MRI) is performed the first day. Indications for stereotactic hypo-fractionation approach were as follows: histopathology or clinical and neuroimaging features consistent with MNs close to the AOP or with direct optic sheath invasion or anterior SBMNs exceeding 15-20 mL. From February 2006 to December 2014, 272 patients underwent stereotactic hypo-fractionation treatment in five Centers and 180 of them were followed-up for at least 2 years. Females were 142 and 38 males (ratio 3.7:1), mean age was 50.02 years (range 10-85). There were 110 (61%) primary lesions and 70 (39%) residual meningiomas (GI/GII, 63/7). Location was classified as close to AOP 159 (88%) or involving the optic nerve sheath 21 (12%). Mean gross target volume (GTV) was 6.29  mL (0.1-30.2 mL). Mean prescription isodose was 50% (47-60%). Mean cumulative prescription dose was 19.49 Gy (15-21 Gy), according to GTV and AOP involvement. Follow-up schedule included complete neuro-ophtalmological assessment and contrast-enhanced MRI every six months for the first year and annually thereafter. 

Results. Mean follow-up was 37.5 months (25.3-114 months). 155 (86%) patients were stable (no pre-GK deficit) or improved; 17 (9.5%) showed an unchanged outcome while 8 (4.5%) worsened. Radiological outcome can be summarized as follows: 11 lesions (6%) showed a >50% shrinkage, 74 (41%) an <50% shrinkage; 87 (48.5%) were unchanged and 8 (4.5%) progressed. 

Conclusion. Our multicenter study suggests that GKRS stereotactic hypo-fractionation approach seems to be a safe and effective therapeutic option in selected patients with AOP close-fitting lesions and with optic nerve sheath MNs and in cases larger than 15-20 mL. Visual preservation seems to be associated with a more favourable clinical-radiological outcome.

Antonio NICOLATO, Piero PICOZZI (ROZZANO, ITALY), Virginia Maria ARIENTI, Chiara ARILLI, Luca ATTUATI, Pierpaolo BERTI, Angelo BOLOGNESI, Paolo BONO, Lorenzo BORDI, Maria Grazia BRAMBILLA , Stefano DALL'OGLIO , Antonella DEL VECCHIO, Isacco DESIDERI, Francesca DUSI, Roberto FORONI, Alberto FRANZIN, Daniela GRETO, Alessandro LA CAMERA, Filippo LEOCATA, Lorenzo LIVI, Michele LONGHI, Hae Song MAINARDI, Angelo Filippo MONTI, Pietro MORTINI, Guido PECCHIOLI, Marco PICANO, Paolo Maria POLLONIATO, Giuseppe Kenneth RICCIARDI, Silvia SCOCCIANTI, Mariano VITELLI, Emanuele ZIVELONGHI
11:05 - 11:15 #10105 - Special Lecture: Stereotactic radiosurgery for benign brain tumours: Results of multi-centre benchmark studies.
Special Lecture: Stereotactic radiosurgery for benign brain tumours: Results of multi-centre benchmark studies.

Objectives: Stereotactic radiosurgery (SRS) is strongly indicated for treatment of surgically inaccessible benign brain tumours. Various treatment platforms are available, but most comparisons have been single centre studies. In 2016, a pre-requisite for all providers selected as SRS/SRT centres in England was to participate in a quality assurance process, informed through collaboration between the national trials QA group and a multidisciplinary expert advisory group. All clinical centres undertook planning benchmark cases, providing a unique dataset of current practice across a large number of providers and a wide range of equipment. This was used to facilitate sharing of best practice and support centres with less experience.

Methods: Four benign cases were provided, with images and structures pre-drawn: intracanalicular vestibular schwannoma (VS), large VS, skull base meningioma and secreting pituitary. No guidance was provided on how to plan these cases. Centres produced plans according to their local practice, and these were reviewed centrally using metrics for target coverage, selectivity, gradient fall-off and normal tissue sparing.

Results: 68 plans were submitted, using 18 different treatment platforms, including Gamma Knife, Cyberknife, Varian (Novalis / Truebeam STx / 2100) and Elekta linacs (Synergy / Versa HD). Linac-based plans used either fixed cone arcs, dynamic conformal arcs, static conformal beams or volumetric modulated arc therapy. 14 plans were subsequently revised following feedback, and review of 5 plans led to a restriction of service in 2 centres. Prescription doses were very consistent for VS and meningioma submissions, but a wide range of doses were used for the pituitary case. All centres prioritised coverage, with the prescription isodose covering ≥95% of 78/82 targets. Selectivity was much more variable, and in some cases this was combined with high gradient index and/or >1mm PTV margin, resulting in large volumes of normal tissue being irradiated. Normal tissue doses were more variable across linac-based plans than GammaKnife or Cyberknife, which may reflect the variety of approaches represented, or the necessary trade-off between different objectives. Conformal plans were possible with all four platforms, however, and improvements were possible by re-planning, even without changing margin size.

Conclusion: These benchmarking exercises give confidence in the safe and consistent delivery of SRS services across multiple centres, but have highlighted areas of different priorities, and potential for service improvement. The data can be used to progress standardisation and quality improvement of national services in the future, and may also provide useful guidance for centres worldwide.

David EATON (London, UK), Jonathan LEE, Rushil PATEL, Antony MILLIN, Ian PADDICK, Christopher WALKER
11:15 - 11:20 Special Lecture: World Health Organization. Gail ROSSEAU (Director) (Glen Ellyn, USA)
Stravinski Auditorium
11:30

Wednesday 31 May

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OSP17
11:30 - 12:30

Parallel Session - ESTRO: Metastases 3

Moderators: David LARSON (San Francisco, USA), Sten MYREHAUG (Radiation Oncologist) (Toronto, CANADA), Susanne ROGERS (Radiation Oncologist) (Aarau, SWITZERLAND), Masaaki YAMAMOTO (Gamma Knife) (Hitachi-naka, JAPAN)
11:30 - 11:40 #8943 - Is upfront stereotactic radiosurgery a rational treatment option for very elderly patients with brain metastases? A retrospective analysis of 106 consecutive patients age 80 years and older.
Is upfront stereotactic radiosurgery a rational treatment option for very elderly patients with brain metastases? A retrospective analysis of 106 consecutive patients age 80 years and older.

Background:

Advanced age has been shown to be a factor predicting poor survival in patients with brain metastases (BM). There have been only a few studies focusing on stereotactic radiosurgery (SRS) for elderly BM patients. The present study aimed to investigate the efficacy and limitations of SRS for very elderly BM patients.

Methods:

This was a retrospective observational study analyzing 106 consecutive patients (69 males / 37 females) age 80 years and older who received upfront Gamma Knife SRS for BM between January 2009 and October2015. The median age was 84 years, and the median Karnofsky performance status (KPS) was 70. Fifty-two patients had a solitary BM, and others multiple BM. The median cumulative tumor volume was 3.9 mL and the median dose prescribed was 20 Gy. Overall survival (OS), neurological death rates and distant and local intracranial tumor control rates were analyzed.

Results:

No patients were lost to follow-up. Six-month and 12-month OS rates were 54% and 32%, respectively. The median OS time was 7.1 months. Competing risks analysis showed that 6-month and 12-month neurological death rates were 8% and 11%, respectively. In total, 245 / 311 tumors (79%) in 82 patients (77%) with sufficient radiological follow-up data were evaluated. Six-month and 12-month distant BM recurrence rates (per patient) after SRS were 17% and 25%, respectively. Six-month and 12-month rates of local tumor control (per lesion) were 94% and 89%, respectively. Repeat SRS, salvage WBRT and surgical resection were subsequently required in 25, 4 and 1 patient, respectively. Proportional hazard regression analysis showed that KPS ≥ 70 (HR: 0.444, P < .001), controlled primary disease/no extracranial metastases (HR: 0.361, P < .001) and female sex (HR: 0.569, P = 0.028) were independent factors predicting better OS. Similarly, tumor volume (> 2 mL) was the only factor predicting a higher rate of local control failure (HR: 12.8, P = 0.003).

Conclusions:

The present study suggested an upfront SRS strategy to offer a feasible and effective treatment option for very elderly patients with limited BM. In the majority of patients, neurological death could be delayed or even prevented. 

Shoji YOMO (Tokyo, JAPAN), Motohiro HAYASHI
11:40 - 11:50 #9846 - Stereotactic radiosurgery for elderly patients with brain metastases.
Stereotactic radiosurgery for elderly patients with brain metastases.

Purpose: Recently, with the aging of the population, an increasing number of elderly brain metastasis (BM) patients have been treated with stereotactic radiosurgery (SRS).

Methods: For this IRB-approved, retrospective cohort study, we used our prospectively accumulated database including 3102 consecutive patients undergoing SRS for BMs during the 1998-2015 period. Among these 3102 patients, 1684 were over age 65 years. The patient numbers for the 65-69, 70-74, 75-79, 80-84 and over 85 (max. 96) years of age groups were 557, 524, 382, 166 and 52, respectively.

Results: There was a significant increase in the proportion of elderly patient undergoing SRS in 2006 or earlier (51.1%) versus in 2007 or later (58.0%, p=0.0001). Median survival times (MSTs, months) of the aforementioned age groups were 7.4, 8.1, 7.2, 5.9 and 4.1, respectively (stratified p<0.0001). Although MST differences between each pair of neighboring age groups failed to reach statistical significance, there was a relatively large MST difference between patients under 79 and those over 80 years of age (HR; 1.439 [95% CI: 1.242-1.657], p<0.0001). Furthermore, MSTs of the age groups 65-69, 70-74, and 75-79 years did not differ significantly from the MST of the under-65-year group (8.4 months). Time-to-event outcome analyses showed that these age groups did not differ significantly in cumulative incidences of neurological death (p=0.47), neurological deterioration (0.42), SRS-related complications (0.42) or local recurrence (0.47).

Conclusions: Our results suggest that patients under 79 years of age are not poor candidates for SRS as compared to those over 80 years old.

Yamamoto MASAAKI (Hitachi-naka, JAPAN), Kawabe TAKUYA, Watanabe SHINYA, Koiso TAKAHI, Sato YASUNORI, Bierta E. BARFOD, Aiyama HITOSHI
11:50 - 12:00 #9997 - Stereotactic radiosurgery for focal leptomeningeal disease in patients with brain metastases.
Stereotactic radiosurgery for focal leptomeningeal disease in patients with brain metastases.

Background: Leptomeningeal disease (LMD) presents symptomatically in approximately 5% of patients with metastatic brain cancer. The presence of LMD is conventionally viewed as an indication for whole brain radiation therapy (WBRT) and not suitable for stereotactic radiosurgery (SRS). The purpose of the study was to evaluate the local control rate and overall survival of patients who underwent SRS to focal LMD.

 

Methods: Thirty-two patients with brain metastases and LMD were identified in our prospective Gamma Knife radiosurgery database, from a total of 465 patients that underwent SRS between 2013 and 2015. For 16 patients, focal LMD was targeted with SRS. The median imaging follow-up time was 7 months.  The median volume of LMD was 372 mm3 and the median margin dose was 16 Gy. Five patients had undergone prior WBRT. Histology included non-small cell lung cancer (8), breast cancer (5), melanoma (1), gastrointestinal cancer (1) and ovarian cancer (1).

 

Results: Follow-up MR imaging was available for 14 patients.  For 13 of the 14 patients, LMD was stable (35.7%) or partially regressed (57.1%) at follow-up. Only one patient had progression of LMD associated with hemorrhage 5 months after SRS. Seven patients developed distant LMD at a median time of 7 months. The median actuarial overall survival from SRS for LMD was 10.0 months. The 6-month and 1-year actuarial overall survival was 60% and 26% respectively. Six patients underwent WBRT after SRS for LMD, at a median time of 6 months, with an overall survival of 3.5 months after WBRT.

 

Conclusion: Focal leptomeningeal metastatic disease may be treated successfully with radiosurgery permitting delay or avoidance of WBRT in some patients.

 

Amparo WOLF, Joshua SILVERMAN (New York, USA), Bernardin DONAHUE, Douglas KONDZIOLKA
12:00 - 12:10 #10015 - Re-irradiation spine stereotactic body radiation therapy (SBRT) for spinal metastases: International Stereotactic Radiosurgery Society (ISRS) Consensus Practice Review.
Re-irradiation spine stereotactic body radiation therapy (SBRT) for spinal metastases: International Stereotactic Radiosurgery Society (ISRS) Consensus Practice Review.

Objective:  Spinal metastases recurrent after conventional palliative radiotherapy have historically been difficult to manage due to concerns of spinal cord toxicity in the retreatment setting.  Spine SBRT, also known as stereotactic radiosurgery, is emerging as an effective and safe means of delivering ablative doses to these recurrent tumors. To determine the clinical efficacy and safety of spine stereotactic body radiation therapy (SBRT), specific to previously irradiated spinal metastases, a systematic review of literature was performed.

Methods:  A systematic literature review was conducted specific to SBRT to the spine using Medline, Embase, Cochrane Evidence Based Medicine Database, National Guideline Clearinghouse and CMAinfobase with further bibliographic review of appropriate articles.

            Research questions:

1.      Is retreatment spine SBRT efficacious with respect to local control and symptom control?

2.      Is retreatment spine SBRT safe?

Results: Initial literature search retrieved 2263 articles; 160 were potentially relevant, 105 selected for in-depth review and 9 studies met all inclusion criteria for analysis. All studies were single institution series: 4 retrospective, 3 retrospective series of prospective databases, 1 prospective, and one phase I/II prospective study (low or very-low quality data). The results indicate that spine SBRT is effective with a median 1-year local control rate of 76% (range, 66-90%).  Improvement in patient pain scores post-SBRT were observed to range from 65-81%. Treatment delivery was safe, with a crude rate of vertebral body fracture of 12% (range, 0-22%) and radiation myelopathy of 1.2%.   

Conclusion:  This systematic literature review suggests that SBRT to previously irradiated spinal metastases is safe and effective with respect to both local control and pain relief. Although the evidence is limited to low quality data, SBRT can be a recommended treatment option for re-irradiation.

Sten MYREHAUG (Toronto, CANADA), Arjun SAHGAL, Motohiro HIYASHI, Marc LEVIVIER, Lijun MA, Roberto MARTINEZ-ALVAREZ, Ian PADDICK, Jean REGIS, Samuel RYU, Ben SLOTMAN, Antonio DE SALLES
12:10 - 12:20 #10303 - Assessing and reducing dose to the hippocampi in stereotactic radiosurgery for four or more brain metastases.
Assessing and reducing dose to the hippocampi in stereotactic radiosurgery for four or more brain metastases.

Background: Stereotactic radiosurgery (SRS) for a few brain metastases (BM) is acknowledged as the optimal method for sparing critical structures, such as the hippocampus.  However, in the setting of 4 or more BM, the ability of SRS to spare the hippocampus and, thus, reduce neurocognitive deficits has been questioned.  This study reports hippocampal dose from single-fraction, multi-target SRS for 4-10 BM and assesses the feasibility of hippocampal-sparing SRS via plan reoptimization.

Materials/Methods:  Patients with four to ten brain metastases receiving single-isocenter, multi-target single-fraction SRS were identified in this IRB-approved study. Hippocampi were contoured using the RTOG 0933 atlas. RTOG 0933 dose constraints were converted to a biologically effective dose using an alpha/beta of 2 (D100 421 cGy, Dmax 665 cGy). Number of metastases, total target volume, prescribed dose, and distance of nearest metastasis [dmin] were analyzed as risk factors for exceeding hippocampal dose constraints. If hippocampal dose exceeded constraints, the SRS plan was reoptimized. Key dosimetric parameters were compared between original and reoptimized plans. To determine if a single target would exceed dose constraints, all targets but the metastasis closest to the hippocampi were removed from the plan and dosimetry was compared.

Results: 40 plans were identified. 15 hippocampi (19%) exceeded constraints in 12 SRS plans. Hippocampal sparing was achieved in 10 of 12 replanned cases (83%). Risk factors associated with exceeding hippocampal constraints were decreasing dmin (24.0 v 8.0mm, p=0.002; OR 1.14, 95% CI 1.04-1.26) and higher total target volume (5.46 cm3 vs 1.98 cm3, p=0.03, OR 1.14, 95% CI 1.00-1.32). There was no difference in exceeding constraints for 4-5 vs 6-10 metastases (27% v. 21%, p=0.409) or prescribed dose (18 Gy, p=0.58). For reoptimized plans, there were no significant differences in PTV coverage (99.6% vs 99.0%, p=0.17) or conformity index (2.03 vs 2.09, p=0.78). Six (50%) plans exceeded dose constraints with a single target.

Conclusion:  A substantial proportion of hippocampi may receive a relatively high radiation dose from SRS when treating 4-10 BM. Decreased distance of the closest metastasis to the hippocampus and higher total target volume are associated with exceeding hippocampal constraints. Reoptimizing these plans spares dose to the hippocampi and still yields acceptable dosimetric characteristics. Prospective evaluation of the impact of hippocampal dose on neurocognition in the setting of SRS to 4 or more BM would be valuable.

Adam OLSON, Sam BIRER, Justus ADAMSON, Rodney HOOD, Matthew SUSEN, Grace KIM, Joseph SALAMA, John KIRKPATRICK (Durham, USA)
12:20 - 12:30 #10601 - Stereotactic radiosurgery in association with immune checkpoint therapy for brain metastases of non-small cell lung cancer: feasibility and results.
Stereotactic radiosurgery in association with immune checkpoint therapy for brain metastases of non-small cell lung cancer: feasibility and results.

Introduction: Recent reports suggest that immune checkpoint therapy (ICT) combined with stereotactic radiosurgery (SRS) have been associated with greater lesion regression of melanoma brain metastases and decreased local failure. When given concurrently (within 4 weeks), combined SRS and ICT may result in improved freedom from additional new brain metastases.

Objective: To investigate the feasibility and efficacy of ICT administered with SRS in patients with brain metastases of non small cell lung cancer (NSCLC) and evaluate if synergistic effect observed for melanoma is also identified in these patients. 

Methods: 101 individual patients with brain metastases from lung cancer, being treated 185 times by SRS between March 2014 and November 2016, and followed in the prospective cohort of the brain metastases clinic at the CHUV where included in this analysis. Systemic treatment use within 6 weeks of SRS was noted. The prescription was 20 Gy in single fraction or 33 Gy in 3 fractions, according to the volume of PTV.

Results: Among the 185 SRS performed, 66 corresponded to single metastases, 48 to 2 - 4 metastases, 27 to 5 - 10, and 10 to > 10 in every single event. The median volume for the PTV was 1,68 ml, the average volume 10,17 ml. Fifty-six patients received only one treatment, 29 of them two and 16 three or more (max. 5).

1-year OS was 56,11% and 72,06% for patients in the chemotherapy and immunotherapy groups, respectively (p=0,26); 1-year brain-DFS was 32,16% (chemotherapy) and 33,84% (immunotherapy; p=0,95). Toxicity was minimal, with 3% grade 2 and no adverse event > grade 2. 

Conclusions: SRS in combination with ICT is feasible, without an increase in toxicity. Even if there was a trend for improvement of OS between patients treated with immunotherapy, the brain-DFS was identical in both groups, suggesting that there was no synergistic effect between ICT and SRS in patients with brain metastases of NSCLC.

S. ALSHELRI, R. JUMEAU, Constantin TULEASCA, F. AHMAD, N. MEDEROS, H. BOUCHAAB, M. CHERIF, Marc LEVIVIER, Jean BOURHIS, Luis SCHIAPPACASSE (Lausanne, SWITZERLAND)
Stravinski Auditorium

Wednesday 31 May

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OSP16
11:30 - 12:30

Parallel Session - Clinical Trials in Progress

Moderators: Michel LEFRANC (MEDECIN) (AMIENS, FRANCE), Xavier MURACCIOLE (Marseille, FRANCE), Jannie SCHASFOORT (Medical Physicist) (Tilburg, THE NETHERLANDS), Shoji YOMO (Director of Gamma Knife Center) (Tokyo, JAPAN)
11:30 - 11:40 Clinical trials at the MD Anderson Center, TX, USA. Caroline CHUNG (Associate Professor, Radiation Oncology) (Houston, USA)
11:40 - 11:50 Clinical trials at the NYU Langone Medical Center, NY, USA. Joshua SILVERMAN (New York, USA)
11:50 - 12:00 Clinical trials at the University Hospital of Verona, Italy. Paolo Maria POLLONIATO (Medical Physicist) (Thiene, ITALY)
12:00 - 12:10 Clinical trials at the Timone Hospital, Aix Marseille University, France. Jean REGIS (PROFESSEUR) (MARSEILLE, FRANCE)
12:10 - 12:20 Clinical trials at Gamma Knife Center, Tilburg, The Netherlands. Patrick HANSSENS (Radiation Oncologist) (Tilburg, THE NETHERLANDS)
12:20 - 12:30 Clinical trials at the Cancer center, university of Toronto, Canada. Sten MYREHAUG (Radiation Oncologist) (Toronto, CANADA)
Parallel 1- Prince

Wednesday 31 May

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OSP29
11:30 - 12:30

Parallel Session - Gliomas

Moderators: Juergen CURSCHMANN (Zurich, SWITZERLAND), Thomas MINDERMANN (Neurosurgeon) (Zürich, SWITZERLAND), Nicolas REYNS (Professor of Neurosurgery) (LILLE, FRANCE)
11:30 - 11:40 #9892 - Treatment results for patients with glioblastoma treated on Leksell Gamma Knife.
Treatment results for patients with glioblastoma treated on Leksell Gamma Knife.

Objectives: Main purposes of this study was to analyze treatment results for a group of glioblastoma patients treated in our center on Leksell Gamma Knife (LGK) over past more than twenty years.

Methods and materials: Altogether 126 patients were treated for glioblastoma during 1992-2014 in our institution and analyzed in this study. There were 69 (55%) male and 57 (45%) female with median age of 56 years (range 17-80 years). From this group 123 (98%) underwent surgery, 126 (100%) radiotherapy and 116 (92%) chemotherapy before the LGK radiosurgery.

Results: Median Karnofsky score before the LGK radiosurgery for patients in this group was 90 (range 50-100), median time from diagnosis of glioblastoma to the LGK radiosurgery was 12 months (range 1- 96 months). Median tumor volume was 3.75 cm3 (range 0.04 – 37.10 cm3) and location: 45 (36%) temporal, 31 (25%) frontal, 21 (17%) parietal, 12 (9%) occipital and 17 (13%) other location. All patients in this study were treated by the LGK radiosurgery performed in one single fraction with median minimal tumor dose of 12 Gy (range 10 – 25 Gy) on median 50 % (range 40 – 86 %) isodose line. Two and more LGK radiosurgeries were performed in 19 (15 %) cases. Median patients’ survival since glioblastoma diagnosis was 20 months (range 6 – 237 months) and median patients’ survival after the LGK radiosurgery was 7 months (range 1 – 223 months).

Conclusion: Treatment on the LGK was well tolerated by all patients. It appears a good final therapeutic option for glioblastoma after previous surgery, radiotherapy and chemotherapy for a small residual volume.

Khumar GUSEYNOVA, Josef NOVOTNY (Prague 5, CZECH REPUBLIC), Gabriela SIMONOVA, Roman LISCAK
11:40 - 11:50 #9938 - A phase I/II trial of 5-fraction stereotactic radiosurgery with 5mm margins with concurrent and adjuvant temozolomide in newly diagnosed glioblastoma: quality of life and updated outcomes.
A phase I/II trial of 5-fraction stereotactic radiosurgery with 5mm margins with concurrent and adjuvant temozolomide in newly diagnosed glioblastoma: quality of life and updated outcomes.

OBJECTIVES: We determined the maximum tolerated dose (MTD) of 5-fraction stereotactic radiosurgery (SRS) with concurrent and adjuvant temozolomide (TMZ) in glioblastoma (GBM).

METHODS AND MATERIALS: Patients received 5 consecutive days of SRS in a 3+3 design with 25, 30, 35 or 40 Gy targeting the GTV with a 5 mm CTV and 0 mm PTV (maximum size 150 cm3).  A dose limiting toxicity (DLT) was Grade 3-5 CNS toxicity within 30 days, with life-long assessment for late SRS-related adverse radiation effect (ARE). Secondary endpoints included progression free survival (PFS), overall survival (OS), and health-related quality of life (HRQOL). Changes from baseline for 9 HRQOL measures were calculated at baseline and in follow-up. 

RESULTS: From 2010 to 2015, 30 patients were enrolled.  Median age was 66 years (range 51-86) with median KPS of 80 (range 50-100).  Median GTV was 26.8 cm3 (range 3.8–81.0) with a PTV of 60.2 cm3 (range 14.7–137.3). DLTs occurred in 2 patients and ARE in 12 patients: 5 developed pseudoprogression at a median of 3.0 months and 7 developed grade 1/2 radionecrosis (RN) at a median of 8.0 months after SRS. RN was not associated with dose (p=0.8) or PTV size (p=0.09). With a median follow-up of 14.0 months, median OS and PFS were 14.9 (95%CI 10.9-21.4; range 1.7 - 62.4) and 8.2 (95%CI 4.6-10.5; range 1.7-55.8) months, respectively. RN was associated with improved median survival (33.0 vs. 11.3 months; p=0.05). HRQOL assessment compliance was 76% at 12 months. Communication deficit worsened over time (-1.7 points/month, p=0.008), with no significant changes in the other 8 HRQOL scales.  While RN was not associated with a significant decline in any HRQOL scale, disease progression was associated with communication deficit (p=0.01). 

CONCLUSION: Five-fraction SRS with 5mm margins with TMZ for newly diagnosed GBM has similar OS and HRQOL compared to conventional fractionation. Patients with radiation necrosis, the primary ‘toxicity’, had longer survival with no decline in HRQOL.

Scott SOLTYS (Stanford, USA), Erqi POLLOM, Melissa AZOULAY, Dylann FUJIMOTO, Jacob WYNNE, Kira SEIGER, Leslie MODLIN, Lisa JACOBS, Rie VON EYBEN, Laurie TUPPER, Iris GIBBS, Steven HANCOCK, Gordon LI, Steven CHANG, John ADLER, Griffith HARSH, Ciara HARRAHER, Seema NAGPAL, Reena THOMAS, Lawrence RECHT, Clara CHOI
11:50 - 12:00 #9941 - Reirradiation in Hight Grade Gliomas, long term followup.
Reirradiation in Hight Grade Gliomas, long term followup.

Treatment of recurrent lhight grade gliomas includes a constellation of options including surgery, radiation therapy, cytotoxic chemotherapy, and white therapies. In the case of reirradiation, it is necessary to have clear the volume to be irradiated, the dose received previously so it is necessary to use a technique that allows to achieve a therapeutic dose and at the same time protect the surrounding brain tissue, the above only Is possible through techniques such as radiosurgery and hypofractionation. Which by means of stereotactic localization allows an accuracy of the target to be treated, presents a high dose gradient and protects normal brain tissue.

Patients were analyzed from May 1992 to November 2014 diagnosed with high-grade, recurrent gliomas (WHO varieties III and IV). A total of 43 patients obtained in this study were evaluated with at least 1 year of follow-up from the radiosurgery treatment, in whom radiosurgery was used as treatment for relapse.

There was symptomatic improvement in 44% and stabilization in 35.2%, the progression was observed in 14 of 43 patients, radiologically the reduction was obtained in 22.66% and stabilization in 40.71%, radionecrosis in 20%.

In conclusion, the rescue of patients with recurrent high-grade gliomas should be taken into account for the use of radiosurgery, however, further studies are needed to define possible subgroups of greater benefit

Kita SALLABANADA DIAZ (Madrid, SPAIN)
12:00 - 12:10 #10000 - Salvage Stereotactic Radiosurgery (SRS) for Glioblastoma: Single Institution Experience from 1997-2016.
Salvage Stereotactic Radiosurgery (SRS) for Glioblastoma: Single Institution Experience from 1997-2016.

Introduction: Glioblastoma (GBM) is the most malignant form of astrocytoma with a dismal outcome.  Despite advances in treatment, the average survival in patients with recurrent GBM remains 6-10 months. In this study we evaluated the role of stereotactic radiosurgery (SRS) in the management of recurrent GBM.

Materials and Methods:  A retrospective review of the Cleveland Clinic brain tumor database (1997-2016) was performed following IRB approval. Overall survival (OS) and progression free survival (PFS) from salvage SRS were the primary and secondary end points, respectively. Molecular analysis was performed using standard techniques. Response to SRS was assessed on T1with contrast and T2-FLAIR MRI images. The log rank test and Cox proportional hazard models were used for analysis.

Results:  Fifty-three patients with 75 lesions underwent salvage SRS. Eleven patients (21%) had multiple lesions and one patient (1.8%) underwent treatment in three stages for a single lesion (12 Gy each). The median age at diagnosis and SRS was 58.9 years and 60.5 years, respectively. Overall, 68% (n=36) of patients were male and the majority (70%, n=34) had good performance status (KPS>80). Most patients (74%, 56/75) had either gross total tumor resection (57%, 43/75) or subtotal resection (17%, 13/75) and all surgery was followed by chemoradiotherapy prior to salvage SRS. Most lesions were treated with at least two additional procedures, following index procedure prior to salvage SRS (56%, 42/75). Majority (85%, n=11/13) of patients had wild type IDH, 53% (n=10/19) had extensive Ki-67 staining (>30%) and 71% (n=10/14) were MGMT unmethylated. Median OS post SRS was estimated to be 11.0 months (95% C.I. 7.1-12.2) and median per-lesion PFS was 4.1 months (95% C.I. 2.6-4.4). Median tumor diameter and volume were 2.55 cm and 3.80 cm3, respectively. Median prescription dose was 18 Gy (12-24 Gy) and homogeneity index was 1.90 (1.11-2.02). KPS>80 was independently associated with longer OS (HR: 4.42, CI: 1.89-10.30, p=0.0006). Small tumor size (<3 cm) was positively correlated with PFS (p=0.03) whereas small tumor volume (<15 cc) was independently associated with both OS and PFS (p=0.02 and 0.04 respectively). Higher homogeneity index (>1.75) was independently associated with longer PFS (HR: 2.38, CI: 1.02-5.56, p=0.04).

Conclusions:  Good performance patients with smaller tumor volumes and treated at higher homogeneity index were associated with longer OS/PFS despite multiple prior treatmentsfor recurrent GBM. SRS for recurrent GBM is reasonable salvage treatment option for these patients.

Mayur SHARMA, Antonio MEOLA, Paul ELSON, Jason SCHROEDER, Gene BARNETT, Michael VOGELBAUM, John SUH, Sam CHAO, Alireza MOHAMMADI , Glen STEVENS, Erin MURPHY, Lilyana ANGELOV (Cleveland, USA)
12:10 - 12:20 #10067 - Hypofractionated stereotactic radiotherapy for the treatment of recurrent high-grade gliomas: radiological response and survival outcomes.
Hypofractionated stereotactic radiotherapy for the treatment of recurrent high-grade gliomas: radiological response and survival outcomes.

Objectives: The study aimed to analyze radiological responses of recurrent high-grade glial tumors treated with hypofractionated stereotactic radiotherapy (HSR) and to estimate patient overall survival (OS) and progression-free survival (PFS) after the treatment.

Methods: We retrospectively analyzed 104 patients managed with HSR for recurrent high-grade gliomas between 2011 and 2016. All patients had experienced progression after a complex treatment with surgery and chemo-radiotherapy. 49% of patients were diagnosed with glioblastoma and 51% with grade III glioma. The indications for HSR were locally progressing tumors in 77% or new distant tumors in 23% of patients. Tumor recurrence was determined and localized with MRI matched against C11-methionine PET/CT. The mean target volume was 36.4 cm3, ranging from 2.8 to 127.2 cm3. The prescription dose was volume-dependent from 18 to 30 Gy delivered in three fractions with interfraction intervals from 2 to 10 days. HSR was performed with Cyber Knife (Accuray, Sunnyvale, CA, USA) and linear accelerator TrueBeam STX (Varian Medical Systems, Palo Alto, CA). After treatment, the patients underwent follow-up imaging examination (contrast-enhanced MRI and/or PET/CT with C11-methionine) every 2 months. Post-treatment MR and PET images were fused with initial pre-treatment images and volumetrically analyzed with Gamma Plan software (Elekta AB, Stockholm, Sweden). Radiological response was evaluated using RANO criteria. PFS and OS were calculated using the Kaplan-Meier method. The median follow-up time was 11 months.

Results: We found that patients with recurrent glioblastoma and grade III glial tumors demonstrated a similar pattern of radiological response to HSR: none of the patients achieved a complete response, 9% of patients with glioblastoma and 11% with grade III glioma showed a partial response, 32% and 42% stable disease, 23% and 19% progressive disease, 36% and 28% pseudo-progression. Median progression-free survival from the date of HSR was 8.6 months for patients with glioblastoma and 13.6 months for patients with grade III glioma (p=0.001). Median overall survival after HSR was 13.3 months for glioblastoma and 32.8 months for grade III glioma patients (p=0.011). The invasion of the tumor into deep brain structures appeared to be a crucial factor affecting OS (HR=6.18, p<0.001).

Conclusion: Recurrence often means a fatal outcome for the patient, as standard treatments are no longer effective. This is why HSR may be considered an effective salvage treatment for patients with recurrent high-grade gliomas. A precise determination of recurrent active parts of the tumor is essential for the success of this approach.

Irina ZUBATKINA (Saint-Petersburg, RUSSIA), Pavel IVANOV, Alexandr KUZMIN, Dmitriy NIKITIN, Georgij ANDREEV
12:20 - 12:30 #10302 - CyberKnife treatment for progressive supratentorial malignant glioma: single institution study.
CyberKnife treatment for progressive supratentorial malignant glioma: single institution study.

Study objective: retrospective analysis of results of CyberKnife radiosurgery and hypofractionated irradiation for small to medium-size progression of supratentorial malignant glioma in 61 selected patients treated in Burdenko Neurosurgical Institute in 2009-2016. 

Patients and methods: 32 men and 29 women was included, mean age was 47,2 years. 39 patients had primary glioblastoma, 5 - secondary glioblastoma, 6 - anaplastic astrocytoma, 7 - anaplastic oligoastrocytoma and 4 had anaplastic oligodendroglioma. 60 patient underwent tumor removal and 1 stereotactic biopsy. 57 patients received postoperative radiotherapy with 58-60 Gy in 29-33 fractions and other 4 had shorter courses (33-45 Gy in 12-18 fractions). Patients with glioblastoma and anaplastic astrocytoma received temozolomide 75 mg/m2 during radiotherapy. After completion of radiotherapy 54 patients received adjuvant chemotherapy (35 had temozolomide-based regimen and 19 - other regimens). Mean time from completion of radiotherapy to first progression was 8,2 months in glioblastoma group (44 patients) and 16,3 months in anaplastic glioma group (17 patients).

First progression as single growing lesion in primary tumor region (local type of "monofocal" progression) was observed 31 of 44 (70%) glioblastoma and 14 of 17 (82%) anaplastic glioma patients. 6 glioblastoma and non of anaplastic glioma patients had distant type of monofocal progression (single new distant lesion with absence of progression in primary tumor region). Other 12 patients had "multifocal" progression (2 had several local growing foci, 2 had several distant foci and 8 had at least 1 growing local lesion and 1 new distant lesion).

Lesions with volume less than 11 cm3 was treated with single median dose of 20 Gy, bigger lesions (up to 58 cm3, median volume - 12,7 cm3) were irradiated with 3 to 7 fractions up to total dose of 21-39,5 Gy (every day or every other day). Mean follow-up was 13,3 months after CyberKnife salvage irradiation.

Results: mean time from salvage irradiation to second progression was 8,2 months in glioblastoma group and 17,2 months in anaplastic glioma group; overall survival after salvage irradiation was 16,5 and 31 month respectively. In 6 of 92 irradiated lesions (6,5%) clinically significant adverse radiation effect developed, all were treated successfully with bevacizumab. In primary glioblastoma group (39 patients) addition of more than 3 infusions of 400 mg bevacizumab to CyberKnife treatment was statistically significant associated with better overall survival (p=0.01).

Conclusion: CyberKnife irradiation with bevacizumab is an effective option for monofocal and multifocal forms of supratentorial glioblastoma progression.

Konstantin NIKITIN (Moscow, RUSSIA), Alexandra BELYASHOVA, Svetlana ZOLOTOVA, Natalia ANTIPINA, Andrey GOLANOV
Parallel 2- Queen
12:30

Wednesday 31 May

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lunch11
12:30 - 14:00

Lunch Break

14:00

Wednesday 31 May

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OSP20
14:00 - 15:00

Parallel Session - ESTRO: Spine

Moderators: Lily ANGELOV (Staff Neurosurgeon) (Cleveland, USA), Stephan BODIS (Aarau, SWITZERLAND), Jean BOURHIS (Lausanne, SWITZERLAND), Mark DE RIDDER (Bruxelles, BELGIUM)
14:00 - 14:10 #9839 - Stereotactic Body Radiotherapy for de novo Spinal Metastases: Systematic Review and International Society of Stereotactic Radiosurgery (ISRS) Practice Guideline.
Stereotactic Body Radiotherapy for de novo Spinal Metastases: Systematic Review and International Society of Stereotactic Radiosurgery (ISRS) Practice Guideline.

Objectives:

The aim of this systematic review is to provide an objective summary of the published literature pertaining to the use of stereotactic body radiation therapy (SBRT) specific to previously untreated spinal metastases.

 

Methods:

A systematic review of the literature using PRISMA guidelines was performed up to March of 2015 from MEDLINE, PubMed, Embase, and the Cochrane Library.  The search strategy was limited to publications in the English language.

 

Results:

            A total of fourteen full-text articles were included in the analysis.  All studies were retrospective, except for two prospective studies.  A total of 1,024 treated spinal lesions were analyzed. The median follow-up ranged from 9-49 months. A range of dose-fractionation schemes were utilized, with the most common ones being 16-24Gy/1fraction (fx), 24Gy/2fx, 24-27Gy/3fx, and 30-35Gy/5fx. For studies reporting crude results regarding in-field local tumor control, 346 out of 407 lesions (85%) remained controlled.  For studies reporting actuarial values, the weighted average result demonstrated a 90% one-year local control rate.  Only three studies reported data on complete pain response, and the weighted average of these results yielded a complete pain response rate of 54%. The most common toxicity was new or progressing vertebral compression fracture, which was observed in 9.4% of cases, and two cases (0.2%) of myelopathy were reported.

 

Conclusion:

            There is a paucity of prospective data specific to SBRT in patients with spinal metastases not otherwise irradiated. This systematic review demonstrates that SBRT is associated with favorable rates of local control of approximately 90% at one year, and rates of complete pain response of approximately 50%, with low rates of serious adverse events. Practice guidelines are summarized based on these data and ISRS consensus.

Zain HUSAIN, Arjun SAHGAL (Toronto, CANADA), Antonio DESALLES, Melissa FUNARO, Janis GLOVER, Motohiro HAYASHI, Masahiro HIRAOKA , Marc LEVIVIER, Lijun MA, Roberto MARTINEZ, Ian PADDICK, Jean REGIS, Ben SLOTMAN, Samuel RYU
14:10 - 14:20 #9921 - Treatment outcomes comparing coventional external beam radiation therapy (cEBRT) and Stereotactic Radiosurgery (SRS) after open surgery for Spine Metastases.
Treatment outcomes comparing coventional external beam radiation therapy (cEBRT) and Stereotactic Radiosurgery (SRS) after open surgery for Spine Metastases.

Purpose/Objective(s):

Surgery followed by conventional external beam radiotherapy (cEBRT) remains the standard of care in treating patients with metastatic epidural spinal cord compression. However, only one series has evaluated the impact of standard fractionated cEBRT vs. stereotactic radiosurgery (SRS) in the post-surgical setting. SRS may lead to suboptimal local control (LC) due to incomplete tumor bed coverage while there is evidence that cEBRT may impair healing and hardware integrity. The purpose of this study was to assess oncologic control, wound complications, and mechanical failure after SRS vs. cEBRT.

Materials/Methods:

An IRB approved retrospective review of patients treated with surgery followed by cEBRT or SRS for spinal metastases was performed. Local failure was defined as failure within the originally involved vertebral level(s). Surgical bed failure was any oncologic failure within the operative bed. Wound complications included post radiation infection or hematoma. Mechanical failure was defined as clinically significant hardware lucency or breakage, dynamic motion on imaging, loosening of bone-graft interface, or new pain not explained by oncologic progression.

Results:

63 patients were treated from 2006-2014: 37 received post-operative SRS; 26 received post-operative cEBRT. Instrumentation was performed in all 37 SRS patients and 18/26 (69%) cEBRT patients. Median follow-up post-SRS and cEBRT was 7.4 (range 1-39) and 4.4 (range 0-73) months, respectively (p=0.29). Karnofsky Performance Status ≥70 post-SRS and cEBRT was 86% vs 44%, respectively (p<0.01). The most common dose schedules were 16 Gy single fraction (SRS) and 30 Gy in 10 fractions (cEBRT). 1-year local failure was 9% vs. 30% (p=0.026) for SRS and cEBRT respectively, with 6/9 cEBRT patients demonstrating multilevel failure within and beyond the originally involved vertebral bodies; surgical bed failure at 1 year was 26.8% versus 30.0% (p=0.61). No mechanical failures were observed. Wound complications occurred in 2 SRS patients and 1 cEBRT patient; projected 1-year cumulative incidence rate of 2.8% and 6.3% respectively (p=0.91).

Conclusion:  

Post-operative SRS provides excellent LC in patients who have undergone surgery for spinal metastases. The 9% LF is less than that for SRS alone for patients with epidural disease, suggesting a benefit to post-operative SRS in carefully selected patients. The absence of significant complications in either group suggests that both SRS and cEBRT are safe approaches in this population.

Camille BERRIOCHOA, E. Emily BENNETT, Jacob MILLER, Eshan BALAGAMWALA, Matthew WARD, Sam CHAO, John SUH, Edward BENZEL, Naichang YU, Lilyana ANGELOV (Cleveland, USA)
14:30 - 14:40 #10056 - Imaging-Based Outcomes for 24 Gy in 2 Daily Fractions for Patients with De Novo Spinal Metastases Treated with Spine Stereotactic Body Radiotherapy (SBRT): An Emerging Standard.
Imaging-Based Outcomes for 24 Gy in 2 Daily Fractions for Patients with De Novo Spinal Metastases Treated with Spine Stereotactic Body Radiotherapy (SBRT): An Emerging Standard.

Objectives: Currently, there is no consensus fractionation scheme for spine SBRT. We report mature outcomes for a cohort of patients with no prior radiation (de novo) treated with 24 Gy in 2 daily fractions, which represents an emerging Canadian standard.

 

Methods: The cohort consisted of 279 de novo spinal metastases in 145 consecutive patients treated with 24 Gy in 2 SBRT fractions, between 2009 and 2015, identified from a prospective database. All vertebral segments were treated with an institutionally standardized linac-based approach using cone-beam CT image guidance and six degrees-of-freedom online setup correction. The endpoints were overall survival (OS), local control (LC), and the rate of vertebral compression fractures (VCF). OS rates were obtained using Kaplan-Meier methods and cumulative incidences of LC and VCF were obtained from competing risk analysis using death as a competing risk event. Evaluation of tumor control was based on serial spine magnetic resonance imaging (MRI) as per the SPIne response assessment in Neuro-Oncology (SPINO) criteria recommendations.

 

Results: The median follow-up was 17.0 months (range, 0.1–71.6 months). The 1-year and 2-year OS rates were 73.1% and 60.7%, respectively. Presence of epidural disease (p < 0.0001), lung (p = 0.0415) and renal cell (p < 0.0001) primary histologies and diffuse spinal metastatic disease as opposed to oligometastatic disease (p = 0.0034) were significant prognostic factors. The 1-year and 2-year LC rates were 90.3% and 82.4%, respectively, and the median time to local failure (LF) was 9.2 month (range, 0.4–31.3 months). Only the presence of epidural disease predicted for LF (p < 0.0001). The cumulative risk of VCF at 1 and 2 years were 8.5% and 13.8%, respectively. Lytic (p = 0.0143) or mixed lytic/blastic (p = 0.0214) lesions, spinal misalignment (p = 0.0121), and the dose to 90% of the planning target volume (PTVD90) (p = 0.0085) were significant predictors of VCF.

 

Conclusion: 24Gy in 2 daily fractions is safe and effective in achieving high tumor control rates for de novo spinal metastases. This fractionation scheme is currently the standard SBRT arm on an ongoing Phase 3 randomized Canadian national trial (CCTG-SC 24) comparing it to a conventional radiation dose of 20 Gy delivered in 5 daily fractions.

Chia-Lin TSENG (Toronto, CANADA), Mikki CAMPBELL, Hany SOLIMAN, Sten MYREHAUG, Mark RUSCHIN, Young K. LEE, Eshetu ATENAFU, Arjun SAHGAL
14:40 - 14:50 #10357 - A retrospective analysis of factors affecting overall survival and outcome in the patients with metastatic spinal cord compression from NSCLCa following Spinal SRS.
A retrospective analysis of factors affecting overall survival and outcome in the patients with metastatic spinal cord compression from NSCLCa following Spinal SRS.

Introduction:

Lung cancer is a leading cause of oncologic death in our country and commonly metastasize to spine which often resulted in spinal cord compression. Although recent advance in systemic therapeutic modalities including chemo- and targeted therapy, the prognosis of these metastatic disease is still poor and overall survival length is often less than 1 year. Recent radiosurgical treatment arm often provide better pain palliation and effectively durable local tumor control. Depending upon the patients’ clinical status, therapeutic strategies should be tailored to improve quality of life for these patients with considering prognostic prediction and overall survival.

 

Method:

Fifty-six patients with metastatic spinal cord compression from NSCLCa were treated with stereotactic radiosurgery between 2005 and 2014. Male to female ratio was 32 to 25. Median age was 66 year-old (range of 43 to 82 year). Pretreatment performance scale over 80 versus less than 70 was 25 versus 29. Cox regression model was utilized to analyze prognostic factors affecting overall survival including sex, age, KPS, No. of bone metastasis, No. of visceral metastasis, grade of metastatic epidural compression, history of prior radiation treatment and interval between initial diagnosis and spinal metastasis. In addition, based on the individual preradiosurgical scoring status and survival length, concordance rate were calculated by applying the three different prognostic systems such as Revised Tokuhashi, Tomita, and Van der Linden. By comparing the factors and outcome prediction of each system, useful relevant prognostic factors were evaluated.  

 

Results:

Average survival length was 8.5 months (range of 1~32 months). Concordance rates of predicting survival length with applying Tokuhashi, Tomita and Van der Linden scoring systems were 73%, 50% and 65% independently. Systemic oncologic statue and performance scale are the important parameters in evaluating tools to anticipate overall survival and outcome. Time to diagnosis of metastatic disease and primary lung cancer also showed significant predicting factor affecting survival length (< 2mos vs > 6mos, HR: 2.115, 95% CI 1.17~3.81, p=0.127).

 

Conclusions:

The significant prognostic factors associated with survival after spinal SRS for metastatic NSCLCa are including pretreatment performance scale, primary disease control, and time between first metastasis and performance status. Relevant outcome factors should be carefully considered and evaluated in order to determine optimal therapeutic strategies including stereotactic radiosurgery.

Moon-Jun SOHN (Goyang, KOREA), Dong Joon LEE, Hye Ran LEE
14:50 - 15:00 #10113 - Radiosurgery of High-Grade Spinal Cord Compression.
Radiosurgery of High-Grade Spinal Cord Compression.

Radiosurgical epidural decompression has been demonstrated with in 80% with complete or significant reduction of epidural tumor volume, indicating that these patients can be treated with non-invasive radiosurgery. In order to help a better communication and unifrom decision-making of treatment, we also developed a dual grading system of spinal cord compression with graces 0 - V radiographic (anatomical), and grades a - e neurological (functional) grades. While open surgery is able to decompress the spinal cord immediately, radiosurgical spinal cord decompression occurs gradually and is suitable for patients with no neurological deficit. However, the current practice is to make such decision based on the MR imaging study rather than the patient’s neurological status, and controversity exists whether high grade spinal cord compression can be safely treated with radiosurgery. Practioners are indeed concerned about the presence of spnal cord compression. Therefore, the current study was performed to demonstrate the role of radiosurgery in patients with high-grade spinal cord compression on MRI imaging with grade IV (significand compression and displacement of spinal cord, T2-weighted CSF signal is still visible, aka partial block) and V (no visible t-2 weighted CSF signal, aka complete block on conventional myelogram). Total 33 patients with 35 lesions with radiographic grades IV-V were inrolled, with minimal or no neurological deficit (grade a-b) except one patient with neurological grade c (nonambulatory). The patients were treated with single dose spine radiosurgery 18-20 Gy, prescribed to the tumor margin. Spinal cord contraint was 10 Gy to the 10% cord volume defined 6 mm above and below the epidural tumor target. Median followup time of 6.4 months with MR imaging study and neurological examination every 2 months. Radiosurgery resulted in 75% spinal cord decompression at 2 months MRI scan post-radiosurgery, and 70% neurological improvement. One patient with neurological grade c became fully ambulatory. Only 2 patients required open surgery due to neurological decline, and 2 patients due to intractable pain. There was no other complication. Progression-free survival was improved in patients who responded to the radiosurgery treatment. Neurological grade was the only prognostic factor. Radiographic high grade did not affect the outcome. The results strongly support the use of radiosurgery for high grade spinal cord compression with no or minimal neurological deficit.

Samuel RYU (Stony Brookn NY, USA), Ian LEE, Jack ROCK, Edward VALENTINE, Arthur ROSIELLO, Raphael DAVIS
Stravinski Auditorium

Wednesday 31 May

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OSP19
14:00 - 15:00

Parallel Session - Ocular tumors

Moderators: Mikhail CHERNOV (Assistant Professor) (Tokyo, JAPAN), Antonio NICOLATO (Neuroradiosurgeon) (Verona, ITALY), Alessia PICA (Villigen, SWITZERLAND)
14:00 - 14:10 #9870 - Linear accelerator stereotactic radiosurgery for intraocular uveal malignant melanoma - experience with 3D printed model of the eye.
Linear accelerator stereotactic radiosurgery for intraocular uveal malignant melanoma - experience with 3D printed model of the eye.

Objectives:

Malignant melanoma is the most frequent intraocular tumor in adults. One day session LINAC based stereotactic radiosurgery (SRS) of intraocular malignant melanoma is a method of "conservative" attitude to treat uveal melanoma.

Experience with 3D printed model of the eye with intraocular tumor used by planning on linear accelerator LINAC based stereotactic radiosurgery.

Methods:

Retrospective clinic-based study - clinical findings of patients with posterior uveal melanoma (choroid) in stage T1/T3 who underwent stereotactic radiosurgery (SRS) at LINAC  in Slovakia. Patients were not randomized either to radical or to “conservative” procedure, but the treatment was determined exclusively on a case-by-case basis. Tumor stage, volume, maximum elevation, localization presence of secondary retinal detachment, general status, age, gender, the functional tests were taken into consideration. The stereotactic frame was fixed to the head and the sutures were tied to the stereotactic frame. We used model Clinac 600 C/D Varian (system Aria, planning system Corvus version 6.2 verification IMRT OmniPro) with 6 MeV X by rigid immobilization of the eye to the Leibinger frame. The patient underwent CT and MRI examination with the fixed eye to the frame. The stereotactic treatment planning after fusion of CT and MRI was optimized according to the critical structures (lens, optic nerve, also lens and optic nerve at the contralateral side, chiasm).

The best plan was applied for therapy at C LINAC accelerator. The planned therapeutic dose was 35.0 Gy by 99 % of DVH (dose volume histogram).

In the software for segmentation (3DSlicer) created virtual 3D model of eye globe with tumorous mass based on tissue density from CT and MRI data. Virtual model was then processed in the slicing software (Simplify3D) and printed on 3D printer using FDM (fused deposition modeling) technology. Material used for printing was polylactic acid.

Results:

In period 2001 - 2015 the group of 150 patients with uveal melanoma (139 choroidal melanoma, 11 ciliary body melanoma) was treated. The median tumor volume was 0.5 cm3 (0.2 - 1.6 cm3). The radiation dose was 35.0 Gy by 99 % of DVH (dose volume histogram). Since 2015 stereotactic planning scheme was optimized with help of 3D printed model of the patient’s eye with intraocular tumor.

Conclusion:

Our 3D printed model of eye with tumor was helpful in planning process to achieve the optimal scheme for irradiation which requires high accuracy of defining the targeted tumor mass and critical structures.

Alena FURDOVA, Miron SRAMKA (Bratislava, SLOVAKIA), Adriana FURDOVA, Andrej THURZO, Gabriel KRALIK, Martin CHORVATH
14:10 - 14:20 #9942 - Radiosurgery for the treatment of choroidal melanoma: follow-up and size patterns of melanomas posterior to radiosurgery.
Radiosurgery for the treatment of choroidal melanoma: follow-up and size patterns of melanomas posterior to radiosurgery.

Objectives: To describe the general follow-up of patients and to analyze the evolution pattern of melanomas choroidal treated with radiosurgery.

Material and methods: A retrospective and descriptive analysis of 8 patients (4 men, 4 women, mean age of 58 years) diagnosed with choroidal melanoma who were treated with radiosurgery, from January 2015 to January 2017, was performed at the Radiosurgery Service of the Hospital Español, Mexico City. All patients were previously assessed with a complete ophthalmologic evaluation and with imaging studies to rule out metastases. A dedicated Novalis 600 N, 6 MV linear accelerator (BrainLab, Heimstetten, Germany) was used to impart doses ranging from 35 to 40 Gy (mean 35.75 Gy). Melanomas were located in the right eye in 87.5% of patients and the mean treated volume was 0.882 cc (0.202-1.819 cc). The main symptoms included a decreased visual acuity and quadrantanopsia. The mean follow-up was 12.8 months (4-22 months). Tumor size (area) was measured using ultrasound imaging during follow-up.

Results: After treatment, the percentage in tumor control, survival and metastasis was 87.5%, 100% and 0%, respectively. The TNM stage for choroidal melanomas of the patients was T2 and T2a. The evolution after radiosurgery was variable: 4 patients showed a progressive decline in tumor size, 3 patients had an initial tendency to increase tumor size followed by a significant reduction three months after treatment. Finally, one patient only had a 50% increase in tumor size and was considered as a disease progression. Visual acuity was reported to decrease 3 months after treatment. Complications: 50% developed retinopathy between 9 and 12 months, one patient had cataract/papillopathy and one patient showed no response to treatment. Follow-up of 7 functional patients continues.

Conclusions: Radiosurgery is a very minimal invasion alternative for the treatment of choroidal melanomas providing good tumor control and health-related quality of life. In our study some patients showed an initial increase in tumor size followed by a significant reduction. Thus, it is important to recognize tumor size changes after the radiosurgery to properly assess its efficacy. A larger number and longer follow-up periods of patients with choroidal melanomas treated with radiosurgery are required to better quantify the treatment success.

Claudia Katiuska GONZÁLEZ-VALDEZ (Mexico City, MEXICO), Emiliano FULDA-GRAUE, Gabriel GALVÁN-SALAZAR, Jazmín ROA-SOLÍS, César DÍAZ-PÉREZ , Ana CANO-AGUILAR, Eric HERNÁNDEZ-FERREIRA, Rebeca GIL-GARCÍA
14:20 - 14:30 #10035 - Preliminar results of fractionated cyberknife radiosurgery for uveal melanoma.
Preliminar results of fractionated cyberknife radiosurgery for uveal melanoma.

Aims: We report our clinical experience of a hypofractionated Cyberknife Radiosurgery schedule for uveal melanoma treatment.

Methods: Between April 2014 and March 2016 14 patients (pts), mean age 65 years (range 36 – 83 years) suffering from uveal melanoma (11 choroidal melanoma and 1 ciliary body melanoma) were treated at Cyberknife Center, Centro Diagnostico Italiano, Milan. All of the pts had received a diagnosis and referral from an ophthalmologist. Cyberknife radiosurgery was performed delivering a total dose of 54 - 60 Gy (mean 60 Gy) given in 3 or 4 fractions (mean 3) of 15 - 20 Gy (mean 20 Gy) prescribed to the 79 - 82% (mean 80%) isodose surface. All pts underwent orbit MRI with gadolinium for coregistration with the planning CT scans. The planning target volume (PTV) included the contrast-enhancing lesion on MRI plus a 2.5 mm margins in all directions. All pts were irradiated eyelids closed, using a contention with a thermoplastic mask. The mean PTV volume was 2037 mm³ (range 701.82 – 5792 mm³), mean tumor base measured ultrasonographically 11.36 mm (range 7-15 mm), mean thickness 4.79 mm (range 2.5 – 10 mm), with a mean distance of 5.25 mm (range 0 – 15 mm) from fovea and 5.55 mm (range 0 – 13 mm) from optic nerve.

Results: After a mean follow-up of 17 months (range 7 – 30) local control was achieved in 100% of pts. No patient underwent enucleation and none developed distant metastases (all pts underwent abdomen ultrasound and liver blood examination once every six months and chest CT once a year). We observed a reduction of 13% in median base and of 44% in median thickness that were respectively 10 mm (range 4.8 – 13 mm) and 2.45 mm (range 0.5 – 5 mm) at last follow-up. Visual acuity was reduced in 64 % of pts, while in the others no change was found. Four pts suffered of radiation maculopathy, associated in one case with atrophy and in three cases with cystoids macular edema. Moreover radiation-induced optic neuropathy and radiation vasculopathy occurred respectively in 3 and 4 cases. 7 pts developed choroidal ischemia and 3 retinal detachment. At the last follow-up none had corneal anomalies.


Conclusions: These initial results of our Cyberknife schedule are consistent with data in literature and show a safe, minimally invasive and well tolerated method for treating uveal melanoma. Further follow-up is necessary.


Isa BOSSI ZANETTI (Milano, ITALY), Pellegrini MARCO, Giancarlo BELTRAMO, Vittoria RAVERA, Achille BERGANTIN, Anna Stefania MARTINOTTI, Irene REDAELLI, Paolo BONFANTI, Andrea BRESOLIN, Livia Corinna BIANCHI, Giovanni STAURENGHI
14:30 - 14:40 #10209 - Retrospective multicenter study on results of gamma knife surgery for uveal melanoma in Europe.
Retrospective multicenter study on results of gamma knife surgery for uveal melanoma in Europe.

The objective of the present study was retrospective evaluation of results of Gamma Knife surgery (GKS) for uveal melanoma performed in 8 European Gamma Knife centers (Bucharest, Florence, Istanbul, Moscow, Prague, Saint Petersburg, Sheffield, and Zurich), which agreed to participate and provided required information. Study design presumed collection of the various data (62 investigated variables) on individual patients with creation of the integrated database for further statistical analysis. Primary end-points were overall survival, local tumor control, eye retention rate, and morbidity during follow-up. Secondary end-points were tumor response, preservation of visual function on the affected eye, and incidence of metastatic disease after GKS. 

In total 349 cases were collected. All patients were treated between July 2001 and October 2015. The stage of treated tumors corresponded to I, IIA, IIB, and IIIA in 26%, 43%, 23% and 7% of cases, respectively. Eye fixation was attained with retrobulbar anesthetic blocking in 65% of cases or suturing of rectus muscles in 24% of cases; in 11% of cases no eye fixation was done. Median marginal dose was 30 Gy (range, 25-30 Gy), median maximal dose was 50 Gy (range, 30-80 Gy), median maximal dose to the ipsilateral optic nerve was 8.7 Gy (range, 0.7 – 61.2 Gy). In 23 patients GKS was done before planned eye-preserving endoresection of the tumor. Follow-up information was available in 314 cases and median length of follow-up was 40 months (range, 1-132 months). 

Actuarial survival rates at 3 and 5 years after GKS were 91% and 89%, respectively. Crude tumor control rate was 98%. Complete response was noted in 19% of cases, partial response in 46% of cases. Crude eye-retention rate was 95.5%. In overall 13 enucleations were done owed to tumor progression (5 cases), complications (2 cases), or unknown reasons (6 cases). Complications were noted in 67% of patients, and exudative retinal detachment (15%), cataract (13%), neovascular glaucoma (11%) and retinopathy (11%) were the most common. The risk of loss of the useful vision on the affected eye during follow-up after GKS was 40%. Suturing of the extraocular muscles for eye fixation during irradiation and two-staged treatment (GKS followed by planned endoresection of the tumor) were associated with significantly lower risk of complications and visual loss on the affected eye. Distant metastases after treatment were disclosed in 10% of patients.

In conclusion, GKS seems effective treatment option for management of uveal melanoma at early stage of disease.

Mikhail CHERNOV (Tokyo, JAPAN), Fery STOICA, Gabriela MURGOI, Rodica STEMPURSZKI, Daniela GRETO, Selcuk PEKER, Meltem YILMAZ, Andrey GOLANOV, Valery KOSTJUCHENKO, Olesya GOLUBEVA, Roman LISCAK, Gabriela SIMONOVA, Ladislav NOVACEK, Pavel IVANOV, Irina ZUBATKINA, Oleg SINYAVSKIY, Matthias RADATZ, Thomas MINDERMANN
14:40 - 14:50 #10220 - Visual outcomes predictors after stereotactic radiosurgery for choroidal melanomas.
Visual outcomes predictors after stereotactic radiosurgery for choroidal melanomas.

Objectives: Visual function preservation is a secondary endpoint of choroidal melanomas (CM) treatment. We aim to identify factors predictable of better visual acuity after radiotherapy treatment.

Methods: A total of 21 patients with unilateral CM were treated in LINAC based with stereotactic radiosurgery since 2014. Sixteen patients, with tumor height ≤8 mm and base ≤16 mm,  and median FU of 20 months were enrolled in this retrospective analysis. SRS was delivered to a dose of 50 Gy in five fractions. An eye monitoring system was applied for the acquisition of planning CT and treatment delivery. Standardized A- and B-scan echography and MRI of the eye were performed at baseline and during follow up. Toxicity was graded using the CTCAE v4.0. Structures at risk in the eye, including the delineation of the macula region, were analyzed in the setting of maximum dose received.

Results: Thirteen patients had severe visual loss at baseline and three had preserved (>20/40) visual acuity. Of these three patients, one remained with 20/25 visual acuity at last FU after 10 months, despite development of radiation induced grade 2 cataract (Macula Dmax 45,3Gy; Optic Nerve Dmax 24,7 Gy). One maintained good visual function (20/40) at last FU after 31 months with no treatment toxicity (Macula Dmax 59,7Gy; Optic Nerve Dmax 31,4 Gy). Another had pre treatment cataract and maintained good visual outcome (≥20/25) until 9 months, but developed blindness at 10 months (Macula Dmax 52,7 Gy; Optic Nerve Dmax 21,6 Gy). At 12 months, this patient underwent enucleation due a residual image on MRI. Histological specimen showed residual CM. Of the 13 patients who had severe visual loss pre treatment, four had improvement in visual acuity from 20/80 to 20/25 at 6 months (Macula Dmax 53,5 Gy; Optic Nerve Dmax 21,5 Gy), 20/60 to 20/40 at 4 months (Macula Dmax 58,2 Gy; Optic Nerve: Dmax 31 Gy), 20/80 to 20/30 at 13 months (Macula Dmax 12,2 Gy; Optic Nerve Dmax 36,1 Gy), and 20/70 to 20/50 at 15 months (Macula Dmax 55,2Gy; Optic Nerve Dmax 46,8 Gy). Two of them had pre treatment cataract. One patient developed radiation induced neuropathy (Macula Dmax 51,5 Gy; Optic Nerve Dmax 51,5 Gy). Six patients developed grade 3/4 radiation induced retinopathy, retinal detachment or cataract.

Conclusion: Optic nerve lower Dmax correlates with good visual outcome. Despite high macula Dmax, patients showed improvement of visual acuity. Cataract does not predict worse results.

Yasmine VIEIRALVES (RIO DE JANEIRO, BRAZIL), Daniel PRZYBYSZ, Maria NEVES, Evandro LUCENA, Denise MAGALHAES, Carlos ARAUJO, Delano BATISTA, Lucia BRADELLA, Felipe ERLICH
14:50 - 15:00 #10399 - Gamma Knife Radiosurgery of uveal melanoma with focus on tumor visualization and eye globe fixation.
Gamma Knife Radiosurgery of uveal melanoma with focus on tumor visualization and eye globe fixation.

Objectives: To estimate the reliability of different techniques of eye globe fixation and to determine the most appropriate MRI sequences for tumor visualization and localization.

Methods: From January 2013 to December 2016, 87 patients with uveal melanoma underwent Gamma Knife radiosurgery. The affected eye was immobilized with different techniques (retrobulbar anesthetic block, fixation of two or three rectus muscles), which were tested in order to determine their reliability. For the verification of eye globe position MRI was performed immediately after the Gamma Knife procedure. The stereotactic images before and after radiosurgery were compared using the Leksell Gamma Plan software in terms of the position of the eye globe and the tumor. For visualization of choroidal melanomas, surrounding eye structures and optic pathways different MRI sequences (T1, T2, CISS and T1 with contrast enhancement) were examined to identify the most appropriate ones.

Results: Gamma Knife radiosurgery of uveal melanoma requires reliable eye immobilization, which can be achieved by complete fixation of at least three rectus muscles. Post-radiosugery MRI revealed that retrobulbar anesthesia could not provide reliable immobilization as significant shift of the eye was observed. MRI visualization of uveal melanoma is a complicated task. The tumor may appear with different signal intensity on T1- and T2-weighted images. In all cases, only the combination of T1, T2 and CISS images allowed us to identify the tumor clearly and to distinguish between the tumor and retinal detachment.  We did not find any advantages in T1 with contrast enhancement for tumor visualization.

Conclusion: Reliable eye globe fixation is extremely crucial for radiosugical treatment; only rigid fixation with suturing of the rectus muscles can give one confidence in precise irradiation. Clear visualization of the tumor can be achieved with T1, T2 and CISS sequences.  A combination of precise stereotactic visualization and complete immobilization of the eye makes it possible to perform conformal high-dose irradiation. 

Irina ZUBATKINA (Saint-Petersburg, RUSSIA), Pavel IVANOV, Oleg SINYAVSKIY, Ernest BOYKO, Roman TROYANOVSKY, Alexey KULIKOV, Matvey ALYABEV, Andrey TIBILOV
Parallel 1- Prince

Wednesday 31 May

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OSP21
14:00 - 15:00

Parallel Session - Radiobiology

Moderators: Abdulhamid CHAIKH (Post-PhD) (Grenoble, FRANCE), Douglas KONDZIOLKA (New York, USA), Jeremy ROWE (Sheffield, UK)
14:10 - 14:20 #10037 - Revisiting the risk of malignancy after gamma knife radiosurgery: with 10 years more experience, are the questions changing with changing practice?
Revisiting the risk of malignancy after gamma knife radiosurgery: with 10 years more experience, are the questions changing with changing practice?

Objectives

            Ten years ago, we reported a retrospective cohort study.[1] National health service numbers cross-referenced patients treated with radiosurgery against the national cancer database. This ascertained how many of our patients developed malignant tumours, and what the predicted background rate was. Then, with 30,000 patient-years of follow-up, no increased risk was identified. A criticism was the lack of long-term follow-up. We therefore revisited this study, with 10 years more data accrual and follow-up; but are aware that our practice and the resultant questions are changing.

 

Methods

            The methodology was unchanged. UK patients were identified, and those with abnormal tumour suppressor genes (mainly type 2 neurofibromatosis) excluded. A vital status check corrected for loss of follow-up due to death. Patients were then stratified for sex, age and the year of follow-up data available. This generates, with national incidence rates, a background risk of developing different malignancies. This is compared with new reported malignancies in our treated patient cohort.

 

Results

            Statistically, with 110,297 patient-years of follow-up, on an age, sex and time matched basis, we would have predicted 11.76 intracranial malignancies, and have identified 11. Eight of these were astro-glial, two were malignant transformations of vestibular schwannomas(VS) 9 and 10 years after the radiosurgery, and one malignant transformation of a meningioma.  In interpreting this, the cohort includes 3012 VS patients, 4489 patients having more than 10 years follow-up, and 1132 more than 20 years.

 

Conclusions

            This study supports the long-term safety of Gamma Knife radiosurgery. Overall there is no statistical increased risk of malignancy with a data set exceeding 100,000 patient years of follow-up. The two malignant VS transformations are of concern. The background risk of malignant nerve sheath tumours of the eighth cranial nerve without irradiation has been estimated at 1 in 1041 VS,[2] so with 3012 VS patients treated, this may reflect the background rate rather than an increased risk related to radiosurgery. The more radiosurgery becomes the main primary treatment for VS, the more likely it is that any VS undergoing malignant transformation will have been irradiated.

 

1. Rowe et al. (2007) Neurosurgery 60:60-66.

2. Carlson et al (2016) J Neurosurg 125:1120-9.

Alison GRAINGER, Lee WALTON, Matthias RADATZ, Dev BHATTACHARYYA, John YIANNI, Jeremy ROWE (Sheffield, UK)
14:10 - 14:20 #9990 - The risk of radiation-associated malignancy after Gamma Knife radiosurgery: a multi-institutional study.
The risk of radiation-associated malignancy after Gamma Knife radiosurgery: a multi-institutional study.

Background

A major concern of patients undergoing Gamma Knife radiosurgery (GKS) for benign tumors is the risk of a separate secondary malignancy or malignant transformation. Long-term follow up studies are lacking and the exact incidence of radiosurgery-associated malignancy is not known. This study quantifies this risk and compares it to estimates of population risk based on the Central Brain Tumor Registry of the United States.

 

Methods

Data on all patients who have undergone radiosurgery for arteriovenous malformations (AVM), trigeminal neuralgia or benign intracranial tumors was collected through the International Gamma Knife Research Foundation (IGKRF). The incidence of malignant transformation and separate radiation-associated intracranial neoplasia was calculated in patient-years. Follow-up duration was defined as the time from radiosurgery to the time of death or last-follow up.

 

Results

To date, we have compiled data on 11 320 patients with a total of 59 200 patient-years of follow-up who under radiosurgery for meningioma (n=3141), AVM (n=2854), trigeminal neuralgia (n=1967), vestibular schwannoma (n=1914), pituitary adenoma (n=1182), other schwannoma (n=184) and hemangioblastoma (n=78). The overall median follow-up time was 3.97 years (0-24 years). Follow-up durations included 3928 patients with 2 to 5 years, 2018 patients with 5 to 10 years, 1462 patients with 10 to 15 years and 508 patients with greater than 15 years of follow-up.

 

Two cases of malignant transformation of vestibular schwannomas were reported at 8.7 and 11.8 years after radiosurgery, pathologically verified as malignant schwannoma. Two cases of presumed WHO grade1 meningioma transformed to an atypical meningioma and malignant meningioma at 3.5 years and 5.3 years respectively. No other cases of malignant transformation were reported.  Three new malignant brain tumors were reported including one AVM patient and one meningioma patient, who developed radiographic features of distant intracranial malignancy at 4.3 and 8.7 years respectively. One patient with a pituitary adenoma developed pathologically verified osteosarcoma locally 12.8 years after radiosurgery.

 

Conclusion

 

The present analysis indicates that the incidence of malignant transformation after radiosurgery for benign tumors is approximately 1 in 14 800 patient-years. The incidence of a new malignancy after radiosurgery, either locally or distant, is 1 in 19 733 patient-years. These risks are not substantially higher than the CBTRUS (2009-2013) derived annual incidence rate of all primary malignant CNS tumors of 7.18 per 100 000.  Patients can safely be counseled that the risk of malignancy after radiosurgery remains extremely low even at long-term follow-up of greater than 10 years.

Amparo WOLF, Moses TAM, Josef NOVOTNY, Roman LISCAK, N MARTINEZ-MORENO, Roberto MARTINEZ-ALVAREZ, N SISTERSON, Hideyuki KANO, L. Dade LUNSFORD , Joshua SILVERMAN, Douglas KONDZIOLKA (New York, USA)
14:20 - 14:30 #10174 - Radiosurgery-Induced Neuroinflammation of the Spinal Cord and Mitigation by Ramipril.
Radiosurgery-Induced Neuroinflammation of the Spinal Cord and Mitigation by Ramipril.

Spinal Cord is the most critical organ in spine radiosurgery. Once the spinal cord has been damaged, it can cause a serious neurological consequence leading to sensory and motor deficit and paralysis. Various mechanisms of radiation tissue reaction have been proposed, but with no therapeutic targets for mitigation of complication. To find a putative target of radiation-induced spinal cord damage, we explored neuroinflammation at the site of radiation to the spinal cord. Fisher 344 rats were irradiated to the spinal cord C4-T2 with a single radiosurgical doses of 23-33 Gy. The rats were randomized to sham treatment and Ramipril, ACE inhibitor, 1.5mg/kg/day until paralysis occurred. The spinal cord was then harvested and tested for neuroinflammation with immunohistochemical studies. There was a sharp curve causing no paralysis at 23 Gy to 100% paralysis above 28 Gy radiation at 125±4 days post-radiation. Ramipril reduced the paralysis rate to 60 % at the high doses, and significantly delayed the onset of paralysis to 135±4 days (p<0.05). The number of microglia (by anti-iba1 stain) on 40X filed by confocal microscopy was 2.5 ± 0.57 in control, 6.9 ± 0.89 in radiation group, and 4.12 ± 1.20 in radiation plus Ramipril-treated group. This was statistically significant (p<0.05) particularly in dorsal funiculus area. VEGF expression were increased in the sham-treated spinal cord, in contrast to the Ramipril-treated group. The finding indicates that Ramipril decreased the paralysis rate and delayed the onset of paralysis. Ramipril reduced the radiation-induced neuroinflammation, and it may be a potential agent of mitigating radiation complication.

 

Samuel RYU (Stony Brookn NY, USA), Mariano CLAUSI, Alex STESSIN, Stella TSIRKA
14:30 - 14:40 #9898 - Dose rate effect on Leksell Gamma Knife – in vitro study on meduloblastoma DAOY cells.
Dose rate effect on Leksell Gamma Knife – in vitro study on meduloblastoma DAOY cells.

Objectives: In principle there are two reasons why dose rate on Leksell Gamma Knife (LGK) is being reduced during patient irradiation: 1) Co-60 sources decay with half-life of 5.26 years and 2) overall irradiation time is being extended by using multiple isocenters and conformal treatment plans (e.g. with blocked beams). It is thus important to study and evaluate effect of dose rate in LGK clinical conditions. This in vitro study is a pilot experimental work performed with meduloblastoma DAOY cells.    

Methods and materials: Multiple experiments were performed with meduloblastoma DAOY cells irradiated on LGK by various dose rate (0.35 – 1.60 Gy/min). Currently, after Co-60 sources reloading in our center, experiments continue with dose rate up to 3.50 Gy/min. Irradiation was performed in a spherical Elekta ABS plastic phantom which was adapted to accommodate micro centrifuge tube (Eppendorf tube) containing cells. Leksell GammaPlan treatment planning software was used to plan cell irradiation. To produce different dose rate, sector blocking (0, 4 or 6 sectors blocked) was used together with 16 mm collimator to ensure cells homogenous irradiation. Plating efficiency and surviving fraction was determined for each experimental cell sample. Nine different doses in the range 0 – 6 Gy were used to have enough experimental points to obtain surviving curve. Linear quadratic model was used to fit experimental data. Surviving curves for different dose rates were plotted and compared.       

Results: This is an initial pilot study with very preliminary data. However, based on so far obtained data it could be observed higher cell survival for dose rates lower than 0.40 Gy/min compare to higher dose rates over 0.75 Gy/min. Currently, experiments continue with dose rates up to 3.50 Gy/min.

Conclusion: Very preliminary data from this study do show different cell survival for studied meduloblastoma DAOY cells based on a dose rate that was used for an irradiation. Higher survival is observed for a lower dose rate. However, to confirm this hypothesis and initial observation, more experimental work is needed.

 

This study was supported by Ministry of Health, Czech Republic - conceptual development of research organization (Nemocnice Na Homolce - NNH, 00023884)

Miroslav DAVID, Marie DAVIDKOVA, Josef NOVOTNY (Prague 5, CZECH REPUBLIC), Jana VACHELOVA, Veronika PASTYKOVA, Marketa HURYCHOVA, Roman LISCAK
14:40 - 14:50 #10252 - Impact of radiobiological models and their parameters on the individualized medical decision of proton vs photon radiotherapy.
Impact of radiobiological models and their parameters on the individualized medical decision of proton vs photon radiotherapy.

Objectives: The use of appropriate radiobiological models to estimate the tumor control probability (TCP) and the normal tissue complication probability NTCP is an important step to rank and compare proton vs photon plans for cost effectiveness. The objectives of this study are to asses and quantify the uncertainties resulting from the choice of radiobiological models on the medical decision and to propose a new approach to estimate the real benefit from proton therapy.

Material and methods: clinical cases of cranio-spinal irradiations for pediatric patients were studied. The treatment plans were generated and calculated with photon and proton dose calculation algorithms to deliver the same prescription dose. The DVH metrics are the base of TCP/NTCP calculation. Two radiobiological models were used for TCP calculations: Poisson and equivalent uniform dose (EUD); and two NTCP models were used: Lyman-Kutcher-Burman (LKB) and EUD.

Results and discussion: proton and photon achieved close TCP values with both models. Regarding NTCP reduction, the choice of the NTCP model can deeply influence the medical decision since NTCP-LKB were higher than NTCP-EUD for most of the organs. Nevertheless, the proton plans offer NTCP reductions for most of the OARs. However, the magnitude of absolute NTCP reduction is sometimes very similar due to high TD50/5 values, initially proposed for grade > 2 and late toxicity from photon treatments. This gives the misleading impression that the proton does not show a real benefit in terms of NTCP reduction. Conversely, if comparing EUD values in Gy, it is obvious that proton offers the best and a significant dose reduction (EUD proton << EUD photon), especially for organs in thorax region as lung, heart, esophagus, with p < 0.05. Thus, our findings suggest, that it would be more consistent to refer and fitting TD50/5 to lower grade toxicity as "grade ≤ 2" to better estimate the NTCP reduction and have relevant reasons to select the optimal plan predicting lower toxicity.

Conclusions: The considerable impact of radiobiological model on the radiotherapy outcomes urges to renew the reference toxicities to tune NTCP parameters’.  The use of the recommended mean doses as TD50/5 in NTCP model could be a realistic approach to estimate low grade NTCP. In addition, EUD values translate the DVH data is a robust indicator be better estimate the dosimetric benefit. Moreover, further improvements of DVH, including secondary electrons, RBE variation and secondary neutrons are necessary.

Abdulhamid CHAIKH (Grenoble), Jacques BALOSSO, Pierre-Yves BONDIAU
14:50 - 15:00 #10372 - Risk of extracranial secondary cancer after radiosurgery: comparison of different treatment platforms.
Risk of extracranial secondary cancer after radiosurgery: comparison of different treatment platforms.

Background

Secondary malignancy is a known complication of any radiation exposure.  Though this risk is highest in the high dose treatment volume, it is clearly established that low dose radiation also results in a lifetime increased risk of cancer.  Intracranial radiosurgery results in a small extracranial dose of radiation which therefore will increase a patient's risk of cancer within the body. Different treatment platforms’ differing physical qualities result in small differences in this body dose delivered. This is of particular importance to young patients treated for benign conditions who have an otherwise normal life expectancy.  The aim of this study is to compare the risk of extracranial secondary cancer after stereotactic radiosurgery (SRS) using different treatment platforms.

 

Methods

For an average sized 5 year old and adult the dose to the body to 14 female and 12 male organs received during treatment with SRS at 12.5Gy was calculated for four different radiosurgical treatment platforms using doses interpolated from literature and measurements.  Lifetime risk of secondary cancer per 100,000 exposed was calculated for males and females exposed aged 5/15/25/35/45 years old utilising the National Cancer Institute RadRAT (v4.1.1) calculator.  Chi squared statistical analysis.

Results

The platforms investigated were Gamma Knife Perfexion (Elekta, Stockholm), Linac (micro-multileaf collimator (mMLC) (Philips SL75-5 (Elekta) and cones (Radionics, Burlington, MA)), and Cyberknife (Accuracy, Sunnyvale).

The estimated excess number of extracranial cancers after treatment was:

Gamma Knife Perfexion 151-22 (0.43-0.06%) female 5-45yr/ 53-11 (0.14-0.03%) male 5-45yr per 100,000;  Linac mMLC 1840-261(5.3-0.78%) female 5-45yr/ 649-139 (1.7-0.36%) male 5-45yr per 100,000; Linac cones 3010-437 (8.6-1.3%) female 5-45yr/ 1080-235 (2.9-0.61%) male 5-45yr per 100,000; Cyberknife 6680-1270 (19.1-3.8%) female 5-45yr/ 2740-837 (7.3-2.2%) male 5-45yr per 100,000.  At all ages/sex there was a statistically significant (p<0.001) difference in risk of secondary malignancy between Gamma Knife Perfexion, Linac and Cyberknife.

Conclusion

The extracranial dose of radiation that the body receives in radiosurgery results in an excess lifetime risk of secondary cancer which can only be estimated from extrapolated data from other ionising radiation exposure data.   However these risks are potentially substantial for younger patients with normal life expectancy, so patients should be offered treatment utilising a radiosurgery platform which minimises this lifelong risk.  Gamma Knife Perfexion results in the lowest estimated lifelong risk of secondary malignancy, with linac mMLC, linac cones and cyberknife progressively increasing risk.

Alison L CAMERON (Bristol, UK), Alex DIMITRIADIS, Ian PADDICK
Parallel 2- Queen
15:00

Wednesday 31 May

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OSP23
15:00 - 16:00

Parallel Session - ESTRO: Metastases 4

Moderators: Jean-François DAISNE (Radiation Oncologist) (NAMUR, BELGIUM), Matthias GUCKENBERGER (Chairman) (Zurich, SWITZERLAND), Xavier MURACCIOLE (Marseille, FRANCE)
15:00 - 15:10 #9601 - Evaluation of dynamic changes large metastases in deep brain structures after hypofractionation stereotactic radiotherapy.
Evaluation of dynamic changes large metastases in deep brain structures after hypofractionation stereotactic radiotherapy.

Purpose: To asses by MRI the dynamic changes of deep brain large metastases after hypofractionation stereotactic radiation therapy.
Methods and Materials: In retrospective analysis, 146 patients (mean age 55 y.o.) with 215 brain metastases, treated by hypofractioning radiotherapy were included (dose 8-10 Gy, mean metastasis volume 1.5 cm3). 1.5 and 3.0T scanners were used with Т13D sequences 1mm before and after contrast enhancing, Т2 WI tra 2mm, flair tra 1-3mm, T2 WI cor 2mm, DWI. In 21 patients SWI was added. In 30 patients СT or MRI PWI and PET with 11C methionine were added. Tumour volume control was performed by GammaPlan 10.1 station. Patients were assessed before treatment, after 1 month, then, every 3 months.
Results: We have detected 6 radiologic patterns: tumour dimensions changes (68%), structural necrosis (28%), metastasis contrasting decreasing (64%), contour changes (83%), perifocal swelling area reduction (97%), intratumour haemorrhage (14%). The most variable were dimensions and volume changes: volume reduction or stabilisation, volume increasing by necrosis or disease progression, volume increasing on 1st control, then decreasing on 2nd control (necrosis), then increasing by haemorrhage. According PET with 11C methionine and PWI continued tumor growth was detected in 4% of cases.
Conclusion: Brain metastases reaction after radiotherapy characterised by heterogeneity. Imaging results (volume and contour changes, haemorrhage) are non-specific and may be signs of local disease progression or postradiation reactions. To process these data in the future and to avoid misinterpretation of the results when pseudo-progression and to determine the optimal dose/volume/fractionation need well-designed prospective, multicenter clinical trials with strict inclusion criteria of patients in the study with a standardized MRI Protocol, timely re-examination as MRI and PET and PWI.

Alina SMIRNOVA (Saint-Petersburg, RUSSIA), Olga LUKINA, Nadezhda PLAKHOTINA, Aleksandr KUZ'MIN
15:10 - 15:20 #9755 - Results of radical local treatment of non-small cell lung cancer patients with synchronous oligo-metastases.
Results of radical local treatment of non-small cell lung cancer patients with synchronous oligo-metastases.

Background

Patients with stage IV non-small cell lung cancer (NSCLC) are considered incurable and mainly treated palliatively.  In contrast, a radical treatment approach is increasingly recommended in patients with oligometastatic stage IV disease. The purpose of this study was to investigate progression free survival (PFS) and overall survival (OS) of NSCLC patients diagnosed with synchronous oligometastatic disease who underwent radical treatment.

 

Methods: Patients with NSCLC and oligometastatic disease at diagnosis, who were treated with radical intent between 2008 and 2016, were included.  Treatment consisted of systemic treatment and radical/stereotactic radiotherapy or resection of the intrathoracic disease. Treatment of the metastases consisted of radical/stereotactic radiotherapy, surgical resection or radiofrequency ablation (RFA).

 

Results: Ninety-one patients (52% men, mean age 60 years), were included with a median follow-up of 35 months.  Almost all patients (98%) were in good condition ( WHO=0-1). The intrathoracic tumor stage, ignoring M-status, was; IA ( (11%)), IB (3%), IIA (12%), IIB (11%), IIIA (36%) and IIIB (26%). Seventy-seven patients (85%) presented with a solitary metastasis, mostly occurring in the brain (32%), bone (25%) or adrenal gland (14%). Fourteen patients presented with 2 or more metastases (9 patients (10%) with 2 metastases, 2 patients (2%) with 3 metastases and 3 patients (3%) with 4 metastases, respectively).

Eighty-one patients (89%) were treated with radiotherapy for the primary tumor of whom 75 patients (93%) received either concurrent (N=9 (12%)) or sequential (N=66 (88%)) systemic therapy. Eight patients (9%) underwent surgery for the primary tumor; 2 patients (2%) received only systemic treatment.

The metastases were treated with ablative/stereotactic radiotherapy (72 (79%)), surgical intervention (5 (6%)), only systemic treatment (6 (6%)), a combination of surgical intervention and radiotherapy (6(6%)), gamma knife (2(2%) and RFA (1(1%))

 

Thirty-eight patients (42%) died during follow-up. The cause of dead was lung cancer in all patients, except one. Sixty-three (69%) patients developed recurrent disease. Eleven recurrences (17%) occurred within the irradiated area. Most recurrences where brain (16(25%)) and pulmonary metastases (13(21%)).

For the whole group, the median PFS was 14 months (range 2-89, 95% CI 12-16) and the median OS was 32 months (range 3-89, 95% CI 25-39). The 1- and 2-year OS rates were 85% and 58% and  the 1- and 2-year PFS rates were 55% and 27%, respectively.

 

Conclusion: Radical local treatment of a selected group of NSCLC patients in good condition presenting with synchronous oligometastatic stage IV disease resulted in favorable long-term PFS and OS.

 

Margriet KWINT (Amsterdam, THE NETHERLANDS), Iris WALRAVEN, Sjaak BURGERS, Koen HARTEMINK, Houke KLOMP, Joost KNEGJENS, José BELDERBOS
15:20 - 15:30 #9794 - Treatment plan quality comparison of Normal Tissue Objective vs. customised Stereotactic Radiosurgery Normal Tissue Objective for multiple target Radiosurgery.
Treatment plan quality comparison of Normal Tissue Objective vs. customised Stereotactic Radiosurgery Normal Tissue Objective for multiple target Radiosurgery.

Purpose or Objective: To evaluate the effects of Normal Tissue Objective (NTO) and Stereotactic Radiosurgery Normal Tissue Objective (SRSNTO) in radiotherapy treatment planning to reduce dose to normal brain and surrounding OARS whilst maintaining PTV coverage.

Materials and methods: Twenty patients, previously treated, for multiple cranial metastases in a single fraction were retrospectively planned using the Eclipse Treatment Planning System [Varian Medical Systems, Palo Alto, CA, USA]. In each case, NTO and SRSNTO were compared as means of controlling dose fall off from the PTV. The cohort of patients included one 4 lesion case, three 3 lesions cases and sixteen 2 lesions cases. PTV volumes varied from 0.5cc to 15.4cc. Plans included 5 non-coplanar arcs with a single isocentre placed at the centre of mass of the total target volume. All plans were optimized using standard objectives with both NTO and SRSNTO. Replans were also done with no upper constraint on target dose. All plans were normalized such that 99% of the target volume received 80% of the prescribed dose. Plan quality was evaluated by; volume of brain receiving 4Gy, volume of brain receiving 12Gy, mean dose to brain, dose to OARS and PTV coverage.

Results: PTV coverage was comparable amongst the techniques. D2% to PTV increased by 1% when planning with SRSNTO compared to NTO. SRSNTO with no upper objectives results in increased D2% by 13% compared to with standard objectives.

V12Gy to brain was not significantly different (p = 0.1) between NTO and SRSNTO but was significantly reduced (p = 0.01) with SRSNTO with no upper objectives. Mean dose to brain was significantly reduced when optimized with SRSNTO (p = 0.01). Plans optimized with SRSNTO and no upper objectives saw a further decrease in mean dose to brain (p=0.01).

V4Gy to brain was reduced by an average of 38cc (range 5cc-259cc) representing an average 28.7% reduction when planning with SRSNTO compared to NTO (p = 0.01). SRSNTO with no upper objectives resulted in a further significant decrease of V4Gy to brain (p=0.01).

OAR doses were not significantly changed when planning with NTO or SRSNTO and were all clinically acceptable.

Conclusion:  Multiple target radiosurgery planning with SRSNTO can result in significantly decreased V4Gy and mean dose to normal brain with no reduction in PTV coverage. SRSNTO optimised with no upper objectives and no OAR constraints offers an uncomplicated planning solution to reduce brain dose further with little optimizer interaction.

Peter HOUSTON (Glasgow, UK), Suzy CURRIE
15:30 - 15:40 #9845 - Salvage whole brain radiothetapy after stereotactic radiosurgery for brain metastases: a prospective study (JLGK0901).
Salvage whole brain radiothetapy after stereotactic radiosurgery for brain metastases: a prospective study (JLGK0901).

Purpose: Little is known about the results of post-stereotactic radiosurgery (SRS) salvage whole brain radiotherapy (WBRT) in brain metastasis (BM) patients.

Methods: Using our prospectively accumulated database including 1194 consecutive patients undergoing SRS alone for initially-diagnosed BMs during the 2009-2012 period (JLGK0901 Study, Lancet Oncol 2014;15: 387-95, UMIN ID; 000001812), we studied the 127 patients (10.6%, 55 females, 72 males, mean age; 62 [range; 36-83] years) who underwent salvage WBRT. Competing risk analysis was applied, as appropriate.

Results: Cumulative incidences of WBRT were 6.3%, 8.8%, 10.2%, 10.8% and 11.0% at the 12th, 24th, 36th, 48th and 60th post-SRS month. Patient age <65 years, SCLC and 2-4 tumors correlated significantly with WBRT. Post-WBRT MST was 4.2 (95% CI; 3.0-5.0, IQR; 2.1-9.5) months. Actuarial survival rates were 34.0%, 17.3%, 6.9%, 2.6%, 1.3% and 1.3% at the 6th, 24th 19th, 24th, 30th and 36th post-WBRT month. The crude incidence of neurological death was 31% (37 patients) and actuarial neurological death rates were 19.8%, 26.5%, 27.4%, 30.0%, 30.0% and 30.0% at the 6th, 24th 19th, 24th, 30th and 36th post-WBRT month. MRI-confirmed leuko-encephalopathy occurred in 11 patients (9%) and WBRT was a significant factor impacting a higher incidence of leuko-encephalopathy (HR; 0.008, 95% CI; 0.001-0.081, p<0.0001). SRS-related complications occurred in 25 patients (18%). Age >65 years, neurological symptoms and WBRT (HR; 0.560, 95% CI; 0.365-0.861, p=0.0081) correlated significantly with higher complication rates.

Conclusions: To our knowledge, this is the first prospective study demonstrating the results of post-SRS salvage WBRT in BM patients.

Yamamoto MASAAKI (Hitachi-naka, JAPAN), Toru SERIZAWA, Higuchi YOSHINORI, Shuto TAKAHI, Akabane ATSUYA, Sato YOSHINORI
15:40 - 15:50 #9999 - Freedom progression, risk of adverse radiation effect, and prognostic variables for repeat SRS for brain metastases.
Freedom progression, risk of adverse radiation effect, and prognostic variables for repeat SRS for brain metastases.

Objectives:  To evaluate freedom from progression (FFP) and risk of adverse radiation effect (ARE) among brain metastases re-treated with stereotactic radiosurgery (SRS) after prior SRS.

Methods:  Brain metastases retreated with SRS were identified within a cohort of 4365 brain metastases with available follow-up imaging treated with single-fraction Gamma Knife SRS at our institution from September 1998-December 2013. FFP and ARE were measured from the date of repeat SRS with censoring at last follow-up imaging.

Results:  A total of 136 brain metastases in 74 patients had repeat SRS at a median of 13.3 months (interquartile range, 7.1-22.4 mo) after prior SRS with or without history of prior whole brain radiotherapy.  The most common primary sites were breast (50), lung (25), and melanoma (42).  The median imaging follow-up after repeat SRS was 16.3 months among these lesions with at least one follow-up scan.  The median quadratic mean diameter (QMD) was 1.4 cm (range, 0.3-4.4 cm; interquartile range, 0.9-1.9 cm) and median target volume 1.1 ml (range, 0.03-26.9 ml; interquartile range, 0.3-2.9 ml).  The median dose was 18.0 Gy (range, 12.0-20.0 Gy; interquartile range, 17.5-18.5 Gy).  Overall, the 1-year FFP probability was 81% (95% confidence interval, 72-87%).  The 1-year probability of ARE by imaging was 31% (24-43%) with a 13% (8-22%) 1-year probability of symptomatic ARE.  The 1-year FFP probabilities were 91% (76-97%), 83% (69-91%), and 58% (36-74%) for QMD ≤1 cm, 1.01-2 cm, and >2 cm, respectively, with corresponding 1-year ARE probabilities of 0%, 18% (9-34%), and 23% (10-48%).  On Cox proportional hazards multivariate analysis, both longer interval from prior SRS to repeat SRS by quartile and smaller QMD (≤1 cm vs. 1.01-2 cm vs. >2 cm) were significantly associated with higher FFP probability (p = 0.003 with HR 0.616 and p < 0.001 with HR = 2.71, respectively).  Only QMD was significantly associated with risk of symptomatic ARE (p = 0.008).

Conclusion:  Repeat SRS for brain metastases with QMD ≤2 cm yielded good local control with acceptable risk of symptomatic ARE.  Longer interval from prior SRS was associated with higher control probability.

Jason W CHAN (San Francisco, USA), Steve E BRAUNSTEIN, Jean L NAKAMURA, Shannon E FOGH, Lijun MA, Philip V THEODOSOPOULOS, Michael W MCDERMOTT, Penny K SNEED
15:50 - 16:00 #10011 - Symptomatic radionecrosis after stereotactic radiosurgery for brain metastases: risk factors identification and development of a predictive model.
Symptomatic radionecrosis after stereotactic radiosurgery for brain metastases: risk factors identification and development of a predictive model.

Purpose / Objective: Symptomatic radionecrosis is the most common side effect of brain metastases stereotactic radiosurgery (SRS), occuring in around 10% of the patients.  Brain volume receiving 12 Gy or more (V12) is the most published identified risk factor.  Different cut-off values are reported but the risk may be modulated by different factors like e.g. smoking history, diabetes, involved lobe, previous whole brain radiotherapy (WBRT),...

Brain metastases SRS is performed since 2008 in CHU-UCL-Namur.  In this retrospective study, we aimed to identify risk factors of symptomatic brain radionecrosis after SRS for metastases and to develop a specific predictive model to calculate prospectively the individual risk probability.

 

Materials and Methods: We identified all patients treated with single-fraction SRS for brain metastases at the CHU-UCL-Namur between 2008 and 2016. All patients eligible for retrospective analysis had to be followed-up by regular clinical examination and imaging for a minimum of six months.  We recorded the following potential variables: V12, history of WBRT, localization of the metastases, post-operative status, DS-GPA index (diagnosis-specific estimate of survival for patients with brain metastases), smoking history and diabetes.  Univariate and multivariate analyses were performed to assess the predictive value of multiple variables.  Logistic regression was used to design a predictive formula of individual risk.

 

Results: 131 eligible patients were identified with a total of 226 different SRS treatments, some patients being treated several times for different metastases.  Symptomatic radionecrosis developed in 21 patients (9.29% of the 226 irradiated targets, 16.03% of the whole population surviving more than 6 months).

Multivariate logistic regression analysis identified V12 as the only risk factor (P = 0.004) and history of previous whole-brain irradiation as a protective factor (P = 0.026). These were the only independent variables that correlated significantly with the occurrence of symptomatic radionecrosis. None of the other tested factors did.

We used logistic regression to design a risk prediction model for symptomatic radionecrosis, integrating V12 and WBRT history. This formula estimates the probability of occurrence : Probability = eß/(1+eß) with ß=-2,50+0,66(V12)-1,2(WBRT).

  

Conclusion: Symptomatic radionecrosis from brain metastases radiosurgery can be individually predicted by a statistical model according to the 12 Gy treatment volume.  The apparent protective effect of previous whole-brain irradiation is a suprise and should be further investigated.

Clémentine DE KETELAERE (Saint-Servais, BELGIUM), Jacques JAMART, Thierry GUSTIN, Micheline MOUCHAMPS, Guus KOERTS, Jean-François DAISNE
Stravinski Auditorium

Wednesday 31 May

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OSP22
15:00 - 16:00

Parallel Session - Body 1

Moderators: Ozer ALGAN (Moderator and Presenter) (Oklahoma City, USA), Laura FARISELLI (director) (milano, ITALY), Leszek MISZCZYK (Head of RT department/ radiation oncologist) (Wilcza, POLAND)
15:00 - 15:10 #9871 - CyberKnife based Stereotactic Ablative Radiotherapy (SABR)of prostate cancer patients – preliminary results of 400 patient irradiation.
CyberKnife based Stereotactic Ablative Radiotherapy (SABR)of prostate cancer patients – preliminary results of 400 patient irradiation.

Objectives:

To evaluate the tolerance and effectiveness of SABR applied in the treatment of Low and Intermediate Risk (LR&IR) Prostate Cancer Patients (PCP).

To provide an evaluation of the level of risk group impact on the treatment results.

To assess Androgen Deprivation Therapy (ADT) usage on PSA decline after SABR.

Material and Methods:

400 PCP (213 LR and 187 IR, including T2c) irradiated with CyberKnife using the fd 7.25 Gy to the TD 36.25 Gy. At the start of treatment, 60.3% of patients used ADT and this percentage gradually decreased to 0% after 38 months. Follow-up median 15.0 months. Patients were monitored on SABR completion and subsequently 1, 4, 8 months later and then every 6 months. GI and GU acute and late adverse effects, PSA and ADT usage were evaluated.

Results:

9 patients (2.25%) failed (5 in LR and 4 in IR group) - 4 relapses and 4 nodal metastases. No G3/4 late adverse effects (EORTC/RTOG) were observed. 0.5% G3 GU and 0.3% G3 GI acute reactions, on SABR completion day and one month later, were noted respectively. The median of PSA declined 1.5 ng/ml during the firs month and 0.6 ng/ml during the next three months. No impact of risk groups on treatment results was found. the only impact og ADT on PSA decline was confirmed for ADT&time points interaction.

Conclusions:

SABR of LR and IR PCP is safe and effective treatment.

The inclusion of T2c patients and the low percentage of IR patient failure permit us to form the assumption that this procedure could be utilized in the treatment of more advanced cases.

The results do not let us define clearly the impact of ADT on radioablation results of LR and IR+T2c prostate cancer patients.

Leszek MISZCZYK (Wilcza, POLAND), Aleksandra NAPIERALSKA, Agnieszka NAMYSŁ-KALETKA, Grzegorz WOŹNIAK, Grzegorz GŁOWACKI, Małgorzata STĄPÓR-FUDZIŃSKA, Andrzej TUKIENDORF
15:10 - 15:20 #9875 - Improvement of Conformal Arc Plans By Using Deformable Margin Delineation Technique for Stereotactic Lung Radiotherapy.
Improvement of Conformal Arc Plans By Using Deformable Margin Delineation Technique for Stereotactic Lung Radiotherapy.

 Purpose: Stereotactic body radiotherapy (SBRT) is an established technique in early stage lung cancer. Both volumetric modulated arc (VMAT) and conformal arc (3DCA) techniques can be used as a treatment method. Previously, we have shown that VMAT is superior to 3DCA technique in terms of plan evaluation parameters.  In this study, we aimed to analyze whether deformable margin delineation technique (DMD) improves the quality of the 3DCA technique and to compare it with VMAT plans.

Methods: Twenty stage I non-small cell lung cancer patients were included. VMAT and 3DCA non-coplanar plans were generated with 6MV FFF photons to conform planning target volume (PTV) according to RTOG 0915. As conventionally 3DCA plans have inferior target coverage compared to VMAT plans, we deformed PTV contour in order to get a better isodose coverage using DMD technique. Briefly, DMD technique is adaptation of isodose levels to the PTV by deforming margins. All techniques were compared in terms of dosimetric parameters; Ratio of prescription isodose volume (IV) to PTV (conformity index - CI), ratio of 50% prescription IV to PTV (Intermediate dose spillage volume - IDSV), maximum dose in % of dose prescribed at 2 cm from PTV (Intermediate dose spillage location - IDSL), and percentage of lung receiving 20 Gy (V20) respectively.

 Results: All plans were acceptable and no deviation was observed according to RTOG criteria’s. CI ranged between 1.00–1.17 (Mean: 1.02); 1.00–1.25 (Mean: 1.06); 1.04–1.29 (Mean 1.15) for 3DCA-DMD-FFF, VMAT-FFF and 3DCA-FFF, respectively. 3DCA-DMD have significantly better CI compared to others (p<0.001, p<0.001). IDSV values ranged between 3.22–4.74 (Mean: 4.00); 3.24–5.92 (Mean: 4.15); 3.27–5.30 (Median: 4.17) for 3DCA-DMD, VMAT-FFF and 3DCA-FFF, respectively. 3DCA-DMD have significantly lower IDSV which indicates superior falloff gradient (p<0.013, p<0.001). IDSL values ranged between 35.7%-67.0% (Mean: 53.2%); 42.1%-79.2% (Mean: 57.8%); 38.8%-75.8% (Median: 57.4%) for 3DCA-DMD, VMAT-FFF and 3DCA-FFF, respectively. 3DCA-DMD have significantly lower IDSL values which shows a better falloff gradient 2 cm away from PTV (p=0.011, p<0.001). V20 for lung ranged between 0.86%–11.9% (Mean: %4.19); 0.80%–14.51% (Mean: 4.31%); %0.80-%10.88 (Mean: %4.06) for 3DCA-DMD, VMAT-FFF and 3DCA-FFF, respectively. No difference was found between 3 techniques for V20 (p=0.881, p=0.079).

Conclusion: Our results have shown that 3DCA plans can be ameliorated by using DMD method and can be even better than VMAT in terms of CI, IDSV and IDSL.  We believe that 3DCA-DMD is a novel, simple and effective technique for a better SBRT  plan.

Gorkem GUNGOR (ISTANBUL, TURKEY), Melek DEMIR, Banu ATALAR, Gokhan AYDIN, Bilgehan SAHIN, Bulent YAPICI, Enis OZYAR
15:20 - 15:30 #10005 - CyberKnife treatment of intraorbital metastases: a single center experience on 24 lesions.
CyberKnife treatment of intraorbital metastases: a single center experience on 24 lesions.

Purpose 

The aim of the study is to evaluate the feasibility, acute toxicity and symptoms control of CyberKnife (Accuray, Sunnyvale, CA)-based stereotactic radiotherapy (CBK-SRT) on intraorbital metastases.

Materials and Methods 

This retrospective analysis included patients (pts) with symptomatic metastases located wholly within the orbit. Palliative radiation treatment was performed using CyberKnife image-guided technology (using skull-tracking technique). Gross tumor volume (GTV) volume was defined on a pre-radiotherapy magnetic resonance imaging (MRI) with Gadolinium. Treated volumes and dose-volume histograms (DVHs) are discussed. Acute toxicity was recorded according to Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer (RTOG/EORTC) Scale.

Results 

Between April 2012 and July 2016, 24 metastases (21 pts, 3 treated bilaterally) underwent CBK-SRT for intraorbital lesions (10 intraocular, 14 periocular) from different primary tumors (breast in 13 pts, lung in 3 pts, kidney in 2 pts, lymphoma in 1 pts, thyroid in 1 pts, trunk leiomyosarcoma in 1 pts). Patients were treated in 2 to 3 fractions (median 3 fractions), individual sessions of CBK-SRT were separated by 24 hours. Treatment dose was prescribed to a median isodose line of 75% (range 73 - 80%) normalized to an median maximum dose of 24 Gy (range 18.75 - 32 Gy). Median volume of GTV was 1.50 cubic centimetre (range 0.14-17.5), median maximal dose to ipsilateral optic nerve was 16.95 Gy (range 1.55-24.00), median mean dose to optic chiasm was 2.1 Gy (range 0.50-18.00), median mean dose to ipsilateral lens 1.35 Gy (range 0.30-9.00). At the end of the treatment, grade 1 toxicity according to RTOG/EORTC score was observed in 8 cases. No change in visual field or loss of vision was documented. 14 lesions of 24 had undergone post-radiotherapy MRI and after median follow-up of 5.5 months (range 2.0-26.5) and no local progression occurred: 6 complete response,  6 partial remission and 2 stabilization of disease were observed. All of these patients reported decreasing pre-radiotherapy symptoms and improvement in quality of life. Longer follow-up (more than 12 months) is available in 4 lesions with complete radiological response in all cases.

Conclusions

In our experience, CyberKnife radiotherapy is a well-tolerated, safe and efficacious technique for palliative treatment of intraocular and periocular metastases.

Giulia RIVA, Matteo AUGUGLIARO, Gaia PIPERNO (Milano, ITALY), Annamaria FERRARI , Elena RONDI, Sabrina VIGORITO , Roberto ORECCHIA , Barbara Alicja JERECZEK-FOSSA
15:30 - 15:40 #10007 - Early stage non-small cell lung cancer in the United States: Patterns of care and survival among elderly patients.
Early stage non-small cell lung cancer in the United States: Patterns of care and survival among elderly patients.

Objective: To analyze the patterns of care of local therapies and their impact on overall survival (OS) among elderly patients with early-stage non-small cell lung cancer (NSCLC) in the United States.

Methods: The National Cancer Database was queried for patients at least age 80 years with NSCLC diagnosed between 2004-2013 with clinical stage T1-3N0M0. Local therapy was analyzed over time and by age. Univariable and multivariable (MVA) models were performed to investigate the impact of prognostic factors on OS.

Results: Among 40,561 patients meeting inclusion criteria, 17,418 (43%), 13,008 (32%), and 10,135 (25%) of patients underwent surgical resection, radiotherapy, and observation, respectively, as their initial mode of local therapy. Overtime, while the utilization of surgical managements generally remained stable, the utilization of conventionally fractionated radiotherapy and observation decreased in favor of stereotactic body radiotherapy (SBRT, p < 0.001). Among operable patients (n = 16,377), after MVA several factors were associated with OS including the choice of local therapy favoring resection over conventionally fractionated radiotherapy and observation (HR compared to lobectomy 1.362, and 2.656, respectively, each p < 0.001). In contrast, there was no statistical difference in OS between resection and SBRT among operable patients (HR for SBRT 1.128, p = 0.156).

Conclusions: The utilization of SBRT as the definitive local therapy in elderly patients with early-stage NSCLC is increasing in the U.S. Given its generally favorable toxicity profile, SBRT should be considered in the substantial proportion of elderly patients still not receiving any definitive local therapy. Among medically operable elderly patients, OS was similar between resection and SBRT.

Daniel TRIFILETTI, Colin HILL, Sonam SHARMA, Charles SIMONE, Timothy SHOWALTER, Surbhi GROVER, James LARNER (Charlottesville, USA)
15:40 - 15:50 #10216 - Exploring the Margin Recipe for Online Adaptive Radiation Therapy for Prostate SBRT: An Intra-fractional Seminal Vesicles Motion Analysis.
Exploring the Margin Recipe for Online Adaptive Radiation Therapy for Prostate SBRT: An Intra-fractional Seminal Vesicles Motion Analysis.

Purpose: To provide a benchmark for seminal vesicle (SV) margin selection to account for intra-fractional motion, and to investigate the effectiveness of two motion surrogates in predicting intra-fractional SV volumetric coverage.
Methods and Materials: 15 prostate Stereotactic Body Radiation Therapy (SBRT) patients were studied. Each patient has five pairs (one patient has four pairs) of pre-treatment and post-treatment cone-beam CTs (CBCTs). Each pair of CBCTs was registered based on fiducial markers in the prostate. All pre-treatment SV volumes were expanded with isotropic margins of 1, 2, 3, 4, 5 and 8 mm to form a series of PTVs, and their corresponding intra-fractional coverage to the post-treatment SV was used to calculate the “ground truth” for exact coverage with different margin recipes. Two commonly used motion surrogates, the center-of-mass (COM) and the border of contour, were evaluated using Pearson product-moment correlation coefficient and exponential fitting for predicting SV underdosage. Action threshold of each surrogate was calculated. For reference, the margin for each surrogate was also calculated based on a traditional margin recipe.
Results: 95% post-treatment SV coverage can be achieved in 9%, 53%, 73%, 86%, 95% and 97% fractions with 1, 2, 3, 4, 5 and 8 mm margin size, respectively. 5 mm margins provided 95% intra-fractional SV coverage in over 90% of the fractions.
The correlation between the COM and border was weak, moderate and strong in the left-right (LR), anterior-posterior (AP) and superior-inferior (SI) directions, respectively. Exponential fitting gave the underdosage threshold of 4.5 and 7.0 mm for the COM and border. The Van Herk’s margin recipe recommended 0, 0.5 and 0.8 mm margins in the LR, AP and SI directions based on the COM. For the border, the corresponding margin was 1.2, 3.9 and 2.5 mm.
Conclusions: 5 mm isotropic margins for the SV is the minimum required to mitigate the intra-fractional SV motion relative to the prostate. Both the COM and border are acceptable predictors for SV underdosage with 4.5 and 7.0 mm action threshold. Traditional margin calculation based on the COM or border underestimates the margin and should be avoided for this application.

Yang SHENG, Taoran LI, W. Robert LEE, Fang-Fang YIN, Q. Jackie WU (Durham, USA)
15:50 - 16:00 #10341 - Stereotactic Body Radiation Therapy in the management of Unresectable Locally Advanced Pancreatic Adenocarcinoma: Outcome and Toxicity from a Phase 2 Study.
Stereotactic Body Radiation Therapy in the management of Unresectable Locally Advanced Pancreatic Adenocarcinoma: Outcome and Toxicity from a Phase 2 Study.

PURPOSE:  Aim of the present study is assess efficacy and toxicity of Stereotactic Body Radiotherapy (SBRT) in patients affected by unresectable locally advanced pancreatic cancer.

MATERIALS AND METHODS: All patients received a prescription dose of 45 Gy in 6 consecutive fractions. Delivery was performed with VMAT and flattening filter free beams (FFFs).  Primary end point of the study was freedom from local progression (FFLP) while secondary end points were overall survival (OS), progression-free survival (PFS), and toxicity. Actuarial survival analysis and univariate or multivariate analysis were investigated. Toxicity was recorded according to the common toxicity criteria version 4.0.

RESULTS:  Forty-five patients were enrolled in a phase 2 trial with a median follow-up of 13.5 months. Two-year FFLP was 90% and both on univariate (P < .03) and multivariate analyses (P < .001), lesion size was statistically significant. Median PFS and OS were 8 and 13 months, respectively. On multivariate analysis, tumor size (P < .001) and FFLP (P < .002) were significantly correlated with OS. Chemotherapy before SBRT were administered in thirty-two (71%) patients with locally advanced pancreatic cancer. Median OS from diagnosis was 19 months. Tumor diameter (P < .002), FFLP (P < .035), and computed tomography SBRT (P < .001) were significantly correlated with OS from diagnosis, at multivariate analysis. No grade 3 or greater toxicity was observed.

CONCLUSION: Stereotactic body radiotherapy is a safe approach for patients with locally advanced pancreatic cancer  and it fits efficiently in a multimodal approach.

Tiziana COMITO (Rozzano, ITALY), Ciro FRANZESE, Luca COZZI, Elena CLERICI, Lucia DI BRINA, Angelo TOZZI, Cristina IFTODE, Fiorenza DE ROSE, Anna Maria ASCOLESE, Pierina NAVARRIA, Giuseppe Roberto D'AGOSTINO, Antonella FOGLIATA, Stefano TOMATIS, Marta SCORSETTI
Parallel 1- Prince

Wednesday 31 May

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OSP24
15:00 - 16:00

Parallel Session - Vascular 2

Moderators: Raphael GUZMAN (Vice Chair) (B‰asel, SWITZERLAND), Enmin WANG (Neurosurgeon) (Shanghai, CHINA)
15:00 - 15:10 #9960 - Enlargement and progression of pediatric cerebral arteriovenous malformations after Gamma Knife Radiosurgery: a report of 5 cases and discussion of treatment strategies.
Enlargement and progression of pediatric cerebral arteriovenous malformations after Gamma Knife Radiosurgery: a report of 5 cases and discussion of treatment strategies.

Introduction: It is believed that arteriovenous malformations(AVMs) are dynamic lesions with ongoing morphological and hemodynamic changes. Enlargement and progression of pediatric cerebral AVMs following Gamma Knife Radiourgery(GKRS) is a rare phenomenon. Herein, we report 5 cases of pediatric AVMs who presented progression of AVM nidus years after GKRS and discuss their treatment strategies.

Methods: We performed a retrospective review of 5 ped