Sunday 12 May
Time Westside Ballroom 3&4 Marquis A&B Marquis C
08:00
08:00-10:30
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B01
ISRS EDUCATIONAL COURSE
BASIC PRINCIPLES & GENERAL INDICATIONS OF RADIOSURGERY

ISRS EDUCATIONAL COURSE
BASIC PRINCIPLES & GENERAL INDICATIONS OF RADIOSURGERY

08:00 - 08:05 Welcome and Introduction. Marc LEVIVIER (Chef de Service) (Keynote Speaker, Lausanne, Switzerland)
08:05 - 08:20 Principles of Radiosurgery. Marc LEVIVIER (Chef de Service) (Keynote Speaker, Lausanne, Switzerland)
08:20 - 08:40 Basic Radiosurgery Radiobiology. John SUH (Radiation Oncologist) (Keynote Speaker, Cleveland, USA)
08:40 - 09:00 Quality Assurance in Radiosurgery. Elena DE MARTIN (Medical physicist) (Keynote Speaker, Milan, Italy)
09:00 - 09:20 Radiosurgery for Brain Metastases. Gene BARNETT (neurosurgery) (Keynote Speaker, Cleveland, USA)
09:20 - 09:40 Spinal Radiosurgery. Arjun SAHGAL (Professor) (Keynote Speaker, Toronto, Canada)
09:40 - 10:00 Novelties in Radiosurgery (Molecular Pathways, AI, …). Luke PIKE (Attending) (Keynote Speaker, New York, USA)
10:00 - 10:20 Q&A for Speaker Panel.
10:20 - 10:30 Presentation of the Hands-on Cases & Organization. Marc LEVIVIER (Chef de Service) (Keynote Speaker, Lausanne, Switzerland)

10:30 - 11:00 COFFEE BREAK
11:00
11:00-13:00
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B01.2
ISRS EDUCATIONAL COURSE
INTRACRANIAL

ISRS EDUCATIONAL COURSE
INTRACRANIAL

11:00 - 11:20 Intracranial Benign Lesions. Anne BALOSSIER (Dr) (Keynote Speaker, Marseille, France)
11:20 - 11:40 Vascular Malformations. Constantin TULEASCA (Staff neurosurgeon, senior lecturer) (Keynote Speaker, Lausanne, Switzerland)
11:40 - 12:00 Functional SRS (incl. Tremor, OCD, …). Alessandra GORGULHO (Director) (Keynote Speaker, São Paulo, Brazil)
12:00 - 12:20 Malignant Primary Tumors. Samuel CHAO (Radiation Oncologist) (Keynote Speaker, Cleveland, OH, USA)
12:20 - 12:40 Complications - Radiation Necrosis: Imaging and Management. Samuel CHAO (Radiation Oncologist) (Keynote Speaker, Cleveland, OH, USA)
12:40 - 13:00 Q&A for Speaker Panel.

11:00-13:00
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C01.2
ISRS EDUCATIONAL COURSE
EXTRACRANIAL

ISRS EDUCATIONAL COURSE
EXTRACRANIAL

11:00 - 11:20 On-line and Off line Adaptive Radiation, Principles of MRI-guided RT, …. Thierry GEVAERT (Head of Medical physics) (Keynote Speaker, Brussels, Belgium)
11:20 - 11:40 Lung. Ben SLOTMAN (Professor) (Keynote Speaker, AMSTERDAM, The Netherlands)
11:40 - 12:00 Prostate. Michael ZELEFSKY (Keynote Speaker, New York, USA)
12:00 - 12:20 Pancreas & Liver. Rafi KABARRITI (Keynote Speaker, USA)
12:20 - 12:40 Kidney. Alexander LOUIE (Radiation Oncologist) (Keynote Speaker, Toronto, Canada)
12:40 - 13:00 Q&A for Speaker Panel.

13:00 - 13:45 LUNCH BREAK
13:45
13:45-16:45
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B02
ISRS EDUCATIONAL COURSE
Presentations & Hands-On with the Participation of Leading SRS and SBRT Companies

ISRS EDUCATIONAL COURSE
Presentations & Hands-On with the Participation of Leading SRS and SBRT Companies

Refreshments will be served in between the group rotation
13:45 - 15:15 Session 1 - Group A.
15:15 - 16:45 Session 1 - Group B.

13:45-16:45
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C02
ISRS EDUCATIONAL COURSE
Presentations & Hands-On with the Participation of Leading SRS and SBRT Companies

ISRS EDUCATIONAL COURSE
Presentations & Hands-On with the Participation of Leading SRS and SBRT Companies

Refreshments will be served in between the group rotation
13:45 - 15:15 Session 2 - Group B.
15:15 - 16:45 Session 2 - Group A.

16:45 - 16:46 END OF ISRS EDUCATIONAL COURSE
17:30
17:30-18:00
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A04
OPENING CEREMONY PRESIDENTIAL KICKOFF

OPENING CEREMONY PRESIDENTIAL KICKOFF

17:30 - 18:00 Introduction. Marc LEVIVIER (Chef de Service) (Keynote Speaker, Lausanne, Switzerland)

18:00 - 19:00 OPENING OF EXHIBITION
Monday 13 May
Time Westside Ballroom 3&4 Marquis A&B Marquis C
07:00
07:00-08:00
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A10
BREAKFAST SEMINAR - NEUROSURGERY
Meningiomas - Treatment, Timing, Delivery

BREAKFAST SEMINAR - NEUROSURGERY
Meningiomas - Treatment, Timing, Delivery

Moderators: Peter GERSZTEN (Professor/Neurosurgeon) (Pittsburgh, USA), John SUH (Radiation Oncologist) (Cleveland, USA)
07:00 - 07:20 Update on Gene Expression Profiling from the Raleigh Lab at UCSF. Michael MCDERMOTT (Keynote Speaker, USA)
07:20 - 07:40 Meningioma Radiosurgery: Lessons Learned. Ajay NIRANJAN (neurosurgeon) (Keynote Speaker, Pittsburgh, USA)
07:40 - 08:00 An Analysis of Treatment Failures After Gamma Knife for Meningioma. Koray OZDUMAN (Professor and Chair of Neurosurgery) (Keynote Speaker, Istanbul, Turkey)

07:00-08:00
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B10
BREAKFAST SEMINAR - PHYSICS
Dose Rate

BREAKFAST SEMINAR - PHYSICS
Dose Rate

Moderators: John LEE (Aberdeen, United Kingdom), Constantin TULEASCA (Staff neurosurgeon, senior lecturer) (Lausanne, Switzerland)
07:00 - 07:20 Cobalt-60 Source Age: How Old is Too Old? Dose-Rate Effects with Radiosurgery. Derek TSANG (Radiation Oncologist) (Keynote Speaker, Toronto, Canada)
07:20 - 07:40 FLASH Radiation Therapy- an update from Stanford. Lei WANG (Medical Physicist) (Keynote Speaker, Stanford, USA)
07:40 - 08:00 Gamma Knife dose rate effects and biological models: What are the uncertainties? David SCHLESINGER (Medical Physics) (Keynote Speaker, Charlottesville, VA, USA, USA)

07:00-08:00
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C10
BREAKFAST SEMINAR - RADIATION ONCOLOGY
HyTEC and Normal Tissue Tolerance

BREAKFAST SEMINAR - RADIATION ONCOLOGY
HyTEC and Normal Tissue Tolerance

Moderators: Eric CHANG (Radiation Oncology) (Los Angeles, USA), Jonathan KNISELY (Faculty) (New York, USA)
07:00 - 07:20 HyTEC, Normal Tissue Tolerance and Tumor Control: The Case for Hypofractionated SRS. John P. KIRKPATRICK (Professor - Radiation Oncology & Neurosurgey) (Keynote Speaker, Durham, NC, USA)
07:20 - 07:40 Some lessons from HYTEC – Brain. Michael MILANO (faculty) (Keynote Speaker, Rochester, NY, USA)
07:40 - 08:00 Tumor Control Probability for Brain Metastases. Kristin REDMOND (Keynote Speaker, USA)

08:00
08:00-08:30
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A11
KEYNOTE LECTURE

KEYNOTE LECTURE

08:00 - 08:30 Just Another Day In The Office. Scott HAMILTON (Keynote Speaker, USA)
The most recognized male figure skating star in the world, Scott Hamilton has won 70 titles, awards and honors including an Emmy Award nomination, induction into the United States Olympic Hall of Fame and a privileged member of the World Figure Skating Hall of Fame.
In 1984, Scott captured the attention of the world with his Olympic Gold medal performances in Saravejo and since has shared his love and enthusiasm for the sport as a analyst/commentator, performer, producer and best-selling author (Fritzy Finds a Hat, 2020, Finish First: Winning Changes Everything, 2018; The Great Eight, 2009; Landing It, 1999). He further inspires others as a speaker, humanitarian, and as a cancer and pituitary brain tumor survivor.
After losing his mother to cancer, then becoming survivor himself, Scott turned activist, launching the Scott Hamilton CARES Foundation (Cancer Alliance for Research, Education and Survivorship). He founded several education and survivorship programs including Chemocare.com and the 4th Angel Mentoring Program. Events such as Sk8 to Elimin8 Cancer and An Evening with Scott Hamilton & Friends galas fund research into treatments that treat the cancer and spare the patient harm.
He is also the founder of the Scott Hamilton Skating Academy at the Ford Ice Centers in Antioch, TN and Bellevue, TN, where he may frequently be found coaching Learn to Skate students and sharing his love of skating.
In what little free time remains, Scott can be found on the golf course and enjoys spending time with his wife Tracie and four children – at their home in Nashville, Tennessee.

08:30
08:30-09:30
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A12
PLENARY SESSION
The Role of AI in Radiosurgery

PLENARY SESSION
The Role of AI in Radiosurgery

Moderators: Stephen HOLMES (Imaging Consultant and Conference Organizer) (Honolulu, USA), Erqi POLLOM (Physician) (Palo Alto, USA)
08:30 - 09:30 AI, medical imaging and radiosurgery. Pejman Jabehdar MARALANI (physician) (Keynote Speaker, Toronto, Canada)
08:30 - 09:30 The Potential Roles for Artificial Intelligence in Radiosurgery. Douglas KONDZIOLKA (Neurosurgeon) (Keynote Speaker, New York, USA)
08:30 - 09:30 Generative AI in Medicine and Healthcare: Opportunities and Challenges. Timothy SOLBERG (Senior Advisor for Emerging Technology) (Keynote Speaker, Sonoma Valley, USA)

09:30 - 10:00 COFFEE BREAK AND EXHIBITION
10:00
10:00-11:00
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A14
ORAL PRESENTATIONS
Gliomas and Other Primary Brain Tumors

ORAL PRESENTATIONS
Gliomas and Other Primary Brain Tumors

Moderators: Cecelia GZELL (Radiation Oncologist) (Sydney, Australia), Jing LI (Radiation Oncologist) (Houston, USA)
10:00 - 10:10 #39195 - OR001 Long-term outcomes of stereotactic radiosurgery for papillary tumors of the pineal region: a multicenter retrospective study.
OR001 Long-term outcomes of stereotactic radiosurgery for papillary tumors of the pineal region: a multicenter retrospective study.

Background: Papillary tumors of the pineal region (PTPR) are rare neuroepithelial tumors that are known to be at high risk of local recurrence even after gross total resection. They have been recognized as a distinct entity in recent WHO classifications and can be either grade 2 or 3. The optimal management of PTPR, including the potential role of stereotactic radiosurgery (SRS), remains a matter of debate. Only a few single center retrospective outcome studies have been reported in the literature. This study was designed to provide multi-institutional data to strengthen the evidence related to the use of SRS for PTPR.

 

Methods: Centers participating in the International Radiosurgery Research Foundation were asked to review their database and provide data for patients who had SRS for a histology confirmed PTPR (grade 2 or 3). Clinical and imaging follow-up of at least 6 months was required to be included in the study.

 

Results: We identified 12 patients (8 male and 4 female) who underwent SRS for PTPR. Six patients had primary SRS after biopsy, 4 had adjuvant SRS after partial resection and 2 had SRS for recurrent tumor. One patient had prior fractionated radiotherapy. The median margin dose used was 16 Gy (range 10-18 Gy) and median treatment volume was 2.67 cc (range 0.54-13 cc). Initial local control was achieved in all patients after SRS, with a mean progression-free survival of 140 months. Four patients had local tumor recurrence, managed by repeat SRS in 3 patients and surgical resection in the other. Those 4 patients remained free of recurrence at the last follow-up. One patient had ventricular and leptomeningeal dissemination which led to death. The global mean survival duration was 184 months, with a 5-year and 10-year survival rate of 80%, and an estimated survival rate of 65% after 237 months. Adverse radiation effects were observed in 5 out of 12 cases, 4 of which were symptomatic, but eventually resolved in all patients.

 

Conclusion: Stereotactic radiosurgery for the treatment of PTPR is safe and affords local tumor control in most cases. Local recurrence may be treated safely with repeat SRS.


Andréanne HAMEL, Jean-Nicolas TOURIGNY, Sabrina L. BEGLEY, Michael SCHULDER, Nuria MARTINEZ MORENO, Roberto MARTINEZ ALVAREZ, Gregory N. BOWDEN, Ajay NIRANJAN, L.dade LUNSFORD, Zishuo WEI, Priyanka N. SRINIVASAN, David MATHIEU (Sherbrooke, Canada)
10:10 - 10:20 #39694 - OR002 Re Irradiation with potential utilisation of functional imaging in Recurrent Glioblastoma Multiforme - Old wine in New bottle.
OR002 Re Irradiation with potential utilisation of functional imaging in Recurrent Glioblastoma Multiforme - Old wine in New bottle.

Introduction

Glioblastoma Multiforme (GBM) is an extremely aggressive and lethal primary malignant neoplasm of the brain. Maximal safe resection followed by chemoradiotherapy  and adjuvant Temozolomide has been the standard of care. Even after multimodality treatment, the Median Overall survival is 14.6 months and almost 85 - 90 percent have local recurrence within 2 years.In recurrent GBM, systemic therapy, re-excision and radiotherapy have been tried with no significant proven benefit of one modality over the other.  Despite treatment, Overall survival for such patients is less than a year.

Re irradiation with Stereotactic Body Radiation Therapy (SBRT) is a safe and non-invasive treatment option in recurrent gliomas with comparable outcomes.

Here, we present the survival analysis of 54 patients with recurrent GBM who underwent reirradiation with SBRT technique using Cyberknife.

Materials and methods

54 patients with recurrent Glioblastoma multiforme treated from July 2009 to July 2023 were included in the study. All patients underwent Stereotactic Body Radiotherapy using Cyberknife to a dose of 25 Gy to 35 Gy in 3 to 5 fractions (BED range - 45.82 Gy -59.5 Gy) to the Gross Tumor Volume (GTV) as delineated on DOPA Positron Emission Tomography (PET CT) and Magnetic Resonance Imaging (MRI), along with concurrent Temozolomide. Systemic therapy was started post SBRT in most of the patients. The patients were followed up with clinical assessment and imaging (DOPA PET CT and MRI) at least once in 3 months.

Results

54 patients (M:F = 35:19) with a median age of 40.5 (range - 18 to 84 years) were analysed.  Over 90% patients received adjuvant chemotherapy post SBRT. All the patients tolerated the treatment with negligible side effects. The median Overall survival is 15 months after SBRT with a range of 3 to 105 months. The 1 year, 2 year, 3 year and 5 year survival is 60.4 %, 36.8 %, 24.5 %, 15.3 % respectively.

Conclusion

Re- irradiation with SBRT in recurrent GBM is feasible modality lesser treatment related morbidities, thereby improving the patient compliance. We observed an improved Overall survival compared to existing literature/ historical data.

However, a larger sample size is required to validate the same.

 


Sridhar PAPAIAH SUSHEELA (BANGALORE, India), Anu Radha PINNINTI, Priyasha DAMODARA, Satish RUDRAPPA, Swaroop GOPAL, Madhusushan HV, Monica GUPTA, Hegde SWEEKRUTI, Suresh SWETHA, Taj FAREENA, Naik RADHESHYAM, Kumar KALLUR
10:20 - 10:30 #40171 - OR003 Long-Term Results Following Gamma knife Treatment of Incidental Meningiomas.
OR003 Long-Term Results Following Gamma knife Treatment of Incidental Meningiomas.

Incidental meningiomas are becoming a common finding. They represent a clinically challenging cohort due to the lack of a detailed consensus on their management. The risk of tumor progression and that of intervention must be considered. Long-term prospective data on incidental meningiomas are sparse. We aimed to evaluate the long-term effect of Gamma Knife Radiosurgery (GKRS), surgical resection and continued observation for growing incidental meningiomas in this study.

 

A prospective database of 62 patients (70 tumors) commenced under active surveillance was established in 2009. Radiological and clinical data was obtained until sept 2023. The results of long-term observation (group 1) and intervention with GKRS (group 2) or surgery (group 3) at progression was analyzed.

 

Due to growth, 41 (58.6%) tumors were treated. The mean growth rate was higher prior to GKRS (2.1 cm 3 /y) and surgery (0.4 cm 3 /y) than during long-term active surveillance (0.009 cm 3 /y) (p < 0.001). The meningiomas became in mean 31.3% and 99.1% smaller after GKRS and resection, respectively. In comparison, tumors in the long-term surveillance arm increased in mean 27.2% (p < 0.001). According to the RANO response criteria, the complete, partial, and minimal response versus stable disease rates were higher following intervention, the overall progressive disease rates were similar (Group 1; 20.7%, group 2: 11.4% and group 3: 16.7%) (p = 0.232). Treatment versus no-treatment did not affect overall survival (Group 1; 10.3 y, group 2: 11.8 y and group 3: 13.5 y (p = 0.264), which was comparable to the general population. No symptom development was registered in group 1. In group 2, 2.9% experienced transient (grade 2) adverse events, and in group 3 50% suffered permanent (grade 4) adverse events according to the Common Terminology Criteria for Adverse Events (CTCEAv5) . 

 

Intervention effectively reduces tumor volume; however, the clinical significance remains uncertain and side effects are not negligible. Active surveillance is safe, saves > 40% of patients from unnecessary interventions and does not seem to compromise future treatments. The optimal timing and risk of intervention should be further explored in

prospective randomized trials.


Torbjørn Austveg STRØMSNES, Morten LUND-JOHANSEN, Geir Olve SKEIE, Bente Sandvei SKEIE (Bergen, Norway), Maziar BEHBAHANI
10:30 - 10:40 #40126 - OR004 Phase II trial of multifraction radiosurgery in glioblastoma patients: preliminary results.
OR004 Phase II trial of multifraction radiosurgery in glioblastoma patients: preliminary results.

Glioblastoma (GBM) is the most common primary brain tumor, with survival rates still among the lowest, especially for patients who have not undergone complete resection surgery.

In this preliminary analysis, we aim to evaluate the safety and effectiveness of a multifraction radiosurgery (SRS), a radiotherapy regimen that is different from the standard, in patients with a primary diagnosis of glioblastoma and post-surgical residual tumor. 

From January 2021 to July 2023, 12 adult patients were enrolled. The main inclusion criteria were subtotal resection with a tumor volume ≤60 cc (approximately 5 cm maximum diameter) and a maximum PTV of 150 cm³. 

Target was defined on volumetric MRI as follows: GTV consisted of the tumor resection cavity and residual enhancing tumor; CTV was defined by adding a 3-5 mm margin to the GTV; PTV was the same as the CTV. Patients received multifraction radiosurgery treatment with 30 Gy (6 Gy/fx) over 5 consecutive days, followed by adjuvant temozolomide. Treatment was delivered by CyberKnife (Accuray) technology.

Follow-up consisted of physical examination, MRI, and EORTC-C30 and HADS questionnaire after 45-60 days and then every 2 months. FET-PET and advanced MRI sequences were integrated at progression (PD) in selected cases.

The median follow-up was 10 months (range 4-33). PD occurred in 10 patients (7 marginal, 2 outfield, and 1 both). Median PFS was 5.5 months (range 1-17). At 6 months, the PFS rate was 50%. At time of analysis, 4 patients were alive at 35, 25, 11, and 6 months, 2 without signs of progression. The OS rate at 12 months was 66.7%. 

Events possibly or definitely related to radiation treatment were reported in 7 patients (58.3%): 5 (41.7%) were acute (within 4 months) (2 grade 1, 2 grade 2, 1 grade 3 according to CTCAEv5), and 2 were late (16.7%, both grade 2).  Of these, 4 had regression of the symptoms, and 3 had stabilization. Radiation necrosis was registered in 3 patients (25%): 1 asymptomatic and 2 regressed with bevacizumab.

Current literature does not clearly define the role of SRS in GBM. Our study proposes an SRS protocol in a particularly disadvantaged GBM subpopulation: those patients with post-surgical residual disease and IDH-wild type status. Preliminary results appear promising in terms of PFS and OS with an acceptable level of toxicity risk. Exploring integration with advanced imaging techniques will be analyzed.


Cristiana PEDONE (Milan, Italy), Marcello MARCHETTI, Valentina PINZI, Sara MORLINO, Aurora ROMEO, Fabio Martino DONISELLI, Luca Fiorentino Giuseppe DELLAVEDOVA, Maura SERVIDA, Roberto STEFINI, Laura FARISELLI
10:40 - 10:50 #39574 - OR005 Reirradiation of high-grade gliomas with gyroscopic radiosurgery in combination with modulated electro-hyperthermia: preliminary results of a prospective series.
Reirradiation of high-grade gliomas with gyroscopic radiosurgery in combination with modulated electro-hyperthermia: preliminary results of a prospective series.

Purpose/Objectives: The aim of this study is to describe the potential clinical and dosimetric benefits of the implementation of ZAP-X gyroscopic frameless radiosurgery (GRS) in combination with modulated electro-hyperthermia (mEHT) as a radiosensitizer for the reirradiation of recurrent high grade gliomas by analyzing the first reported series of 8 patients treated in our institutions.

 

Material/Methods: Clinical and treatment information of 8 patients with 14 lesions that received GRS and mEHT between April 2023 and November 2023 were prospectively included in a database and analyzed.

 

Results: Eight patients (5 females and 3 males) with a median age of 48 years (30-62) and a median of 2 lesions (1-3) underwent GRS and mEHT during the study period. All patients had received  Stupp protocol and 3 patients had a previous second course of radiation. The median time from previous radiation was 11 months (6 – 21). The median (2.8cm3), minimum (0.2cm3), and maximum PTV volume (51cm3) were registered. 57% (n = 8) of the lesions were treated in 1 fraction, 29% (n = 4) in 5 fractions and 14% (n = 2) in 3 fractions. Median dose in 1 fraction was 15 Gy (15 - 18 Gy). Lesions treated in 5 fractions received 25 Gy or 30 Gy and in 3 fractions received 24 Gy. Median conformity index was 1.18, median homogeneity index was 1.84 and median gradient index 2.84. Median coverage of the prescribed dose was 95%. Median number of placed isocentres was 7. mEHT was applied using an EHY-2000 device, administered every 48 hours during the radiotherapy treatment. Each mEHT treatment had a 60 minute length with power between 60 and 100W, covering the whole brain, and was administered less than 2 hours apart from GRS. 2-3 mEHT aditional treatments were administered after GRS. Median clinical follow-up was 5 months (2-9). 1 patient died of multicentric spread 5 months after treatment, 2 patients received a second GRS for new lesions and one patient experienced a subependymal spread. Local control of the treated lesions was excellent, with no local relapses reported during follow-up. Actuarial overall survival at 6 months was 67%.  Acute and subacute treatment tolerance was acceptable and all patients needed ambulatory steroid medication adjustment. 

Conclusion: High grade glioma reirradiation with GRS in combination with mEHT showed a favourable impact in local control and overall survival with low toxicity. Longer follow-up and larger series is needed to validate these results.

 


Morena SALLABANDA (Madrid, Spain), Elisabeth ARROJO, Pedro Borja AGUILAR, Vânia DIAS, Enrique PASCUAL, Jose Miguel DELGADO, Kita SALLABANDA
10:50 - 11:00 #39818 - OR006 TTFields and Radiosurgery for the treatment of recurrent Glioblastoma +/- 18f-fluoro-ethylTyrosine PET (TaRrGeT) - a pilot, prospective, externally controlled trial.
OR006 TTFields and Radiosurgery for the treatment of recurrent Glioblastoma +/- 18f-fluoro-ethylTyrosine PET (TaRrGeT) - a pilot, prospective, externally controlled trial.

BACKGROUND

Efficacy of SRS is limited due to the radioresistant and invasive nature of glioblastoma. In preclinical experiments, Tumor Treating Fields (TTFields) have been shown to downregulate important genes for DNA damage response and induce replication stress. Therefore, they have been proposed to increase sensitivity to radiation treatment. The integrated use with 18F- fluoroethyltyrosine (FET) -PET decreases the geographical misses.  We hypothesized that combined SRS based on FET-PET and TTFields will be complementary and improving outcomes with minimal toxicity.

 

 MATERIAL AND METHODS

The TaRrGeT trial is a prospective, pilot, single arm study using historical controls, designed to test effectiveness and safety of TTFields in combination with SRS based on FET-PET for the treatment of recurrent glioblastoma. In this trial, TTFields therapy was initiated before radiosurgery and continued until death or significant decrease of patient’s performance status.

The primary endpoint consisted of the one-year survival rate.

RESULTS

A total of 40 patients with recurrent glioblastoma have been enrolled between March 2021 and July 2023. Thirty percent of patients have been diagnosed in second or third recurrence at the time of enrollment. MGMT unmethylated and IDH wildtype status was found in 52.5% and 87% of patients, respectively.

The study met its primary endpoint with a statistically significant improvement in one-year survival rate compared to EF-11. The one-year overall survival rate from recurrence was 69.5% (vs 20%). Twenty-three patients have been enrolled more than 2 years prior to the analysis, of which 40% are still alive. A case-control comparison with matched patients from the EF-11 trial will be shown during the meeting.

Median survival from recurrence was 14 months. Nineteen patients are still alive at time of analysis with median follow up of 24 months, all but one in intact clinical status at last visit. Median OS from primary diagnosis reached 40 months.

 

The distribution of adverse events of  ≥ grade 3 (common toxicity criteria, CTC) was comparable to that of established recurrent glioblastoma trials. Notably, radiation necrosis was found in 20% of patients, but grade >1 only in 1 case (G2).

 

CONCLUSION

 

The pilot TaRrGeT trial met its primary endpoint indicating that SRS based on FET-PET combined with TTFields is feasible, well tolerated and effective.

Symptomatic radiation necrosis rate was low. The OS, 1- and 2- year survival rates were far above expectations. Patients with long follow up after experimental scheme are able to at least, maintain pre-treatment performance status.


Maciej HARAT (Bydgoszcz, Poland), Maciej BLOK, Magdalena ADAMCZAK-SOBCZAK, Michał MARJAŃSKI, Bogdan MALKOWSKI, Izabela MIECHOWICZ, Marek HARAT

10:00-11:00
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B14
ORAL PRESENTATIONS
Genitourinary Tumors

ORAL PRESENTATIONS
Genitourinary Tumors

Moderators: Rohann CORREA (Radiation Oncologist) (London, Canada), Wee Loon ONG (Radiation Oncologist) (Melbourne, Australia)
10:00 - 10:10 #39676 - OR007 Prostate cancer SBRT with focal boost to the dominant intraprostatic lesions guided by PSMA-PET and mpMRI: dosimetry, treatment and early results from the ARGOS-CLIMBER trial.
OR007 Prostate cancer SBRT with focal boost to the dominant intraprostatic lesions guided by PSMA-PET and mpMRI: dosimetry, treatment and early results from the ARGOS-CLIMBER trial.

Purpose: Stereotactic radiation therapy (SBRT) with dose boosting of dominant intraprostatic lesions (DILs) is a promising treatment for unfavorable-intermediate risk or high-risk prostate cancer. DIL delineation predominantly relies on multi-parametric magnetic resonance imaging (mpMRI); more recently PSMA PET has become available to delineate DILs. The ARGOS-CLIMBER is a phase I/II trial using hybrid PSMA PET/MRI to characterize DILs and involved nodal disease and to escalate radiation dose to these volumes using a simultaneous integrated boost during SBRT treatment. We present dosimetry results, discuss treatment protocols, and report on the trial's progress. 

Methods: Patients had PSMA PET/mpMRI prior to a five-fraction SBRT treatment and adjuvant Androgen Deprivation Therapy (ADT). DIL volumes were defined as the union of mpMRI-defined PIRADs 4-5 lesions with intraprostatic PSMA PET avid lesions of 20%-40% SUVmax. Prescription doses were 35Gy to the prostate, 25Gy to the seminal vesicles and regional pelvic nodes, 50Gy to the DILs, and 35Gy to the positive lymph nodes. Patients were treated using volumetric modulated arc therapy (VMAT) using cone beam computed tomography (CBCT) and implanted fiducials for localization. 

Results: 32 Patients were treated at the London Health Sciences Centre (LHSC) and 18 at Toronto Sunnybrook Regional Cancer Centre (TSRCC). The median DIL volume was 3.9 cm3 (0.2 - 80.9); in one case a DIL could not be identified and the prostate was treated to a uniform dose of 40Gy. The median 99% dose coverage (D99%) for the DILs was only 42.5 Gy (40.0 - 50.5) and only about 10% reached 50Gy. The median D1cc for the rectum and bladder was 36Gy (24.4 - 38.1) and 35.7 (30.9 - 41.4), respectively, and the median Dmax for the urethra was 44.8Gy (35.2 - 51.6). Intrafraction monitoring at LHSC enabled the correction of patient position in 32% of treatment sessions. To date, toxicity has been acceptable: 0 Grade 4/5; 1 Grade 3 GI (diarrhea) related to radiation after a median of 6 months follow-up, minimum of 6-weeks. 

Conclusions: PSMA PET/MRI-guided SBRT boosting of DILs was dosimetrically feasible and early toxicity results are promising. Achieving the target dose for DILs was challenging due to the extensive disease and proximity to the rectum. Intra-fraction monitoring of treatment delivery is recommended to optimize delivery.  An extension of the trial is examining the use of neoadjuvant ADT to reduce DIL volumes and improve dosimetry, thereby increasing the therapeutic ratio.   

Funding: OICR Clinical Translation Pathway. CATA project, P.CTP.624 


Hatim FAKIR (London-Ontario, Canada), Andrew LOBLAW, Aneesh DHAR, Sherif RAMADAN, Lucas MENDEZ, Matt WRONSKI, John CONYNGHAM, Zahra KASSAM, Priscila CRIVELLARO, Aaron WARD, Jonathan THIESSEN, Ting-Yim LEE, David LAIDLEY, Glenn BAUMAN
10:10 - 10:20 #40151 - OR008 Elective SBRT for iliac nodes in high risk prostate cancer.
OR008 Elective SBRT for iliac nodes in high risk prostate cancer.

INTRODUCTION

Five-Fraction SBRT has been widely tried in low and intermediate-risk prostate cancer.

OBJECTIVES

To evaluate gastrointestinal (GI) and genitourinary (GU) acute toxicity (<3 months) and delayed (≥3 months), after prostate and pelvic nodes irradiation with SBRT technique. 

MATERIALS AND METHODS

Forty-two patients underwent Five-Fraction SBRT (alternate days), they were prescribed: prostate =40 Gy (EQD2 108,6 Gy), pelvic nodes=25 Gy (EQD2 46,4 Gy), simultaneously treated volumes with Novalis Tx and TrueBeam (BrainLab-Varian). All patients underwent complete hormone blockage. 

The toxicity of GU was evaluated through IPSS (International Prostate Symptom Score), dysuria (G0-G5), and GI toxicity (G0-G5), according to Common Terminology Criteria for Adverse Events (CTCAE v5.0). Patients were previously evaluated at the beginning and immediately after the treatment with a follow-up at 3, 6, 12, 18, 24, 36 and 48 months post SBRT.

RESULTS

Forty-two patients with a mean follow-up of 37 months were evaluated. [2-62].

Early GU toxicity: 1 patient (2%) presented G3 dysuria and 2 patients (5%) G2 dysuria. 

Late GU toxicity: 1 patient (8%) presented G2 dysuria; ≥G3 dysuria was not observed. 

Mean IPSS was 6 [0-19]; 8 [1-25]; 7 [1-17]; 5 [2-13]; 7 [2-18]; 6 [1-23], 3 [1-6], 4 [0-10] and 5 [1-18] prior to the treatment and 3, 6, 12, 18, 24, 36 and 48 months after the treatment, respectively. 

Early GI toxicity: 5 patients (12%) with G2 toxicity, there was no ≥ G3 toxicity.

Late GI toxicity: 2 patients (5%) with G2 toxicity, there was no ≥ G3 toxicity.

CONCLUSIONS

Patients who underwent SBRT tolerated the treatment well, there was no evidence of late GI or GU ≥ G3 toxicity. Regardless of the low number of patients and short follow-up, elective external and internal iliac nodes irradiation with SBRT in high risk prostate cancer is safe and noticeably feasible.  


Oscar MURIANO (Córdoba, Argentina), Patricia MURINA, Milla GALETTO, Daniela ANGEL, Agostina VILLEGAS FRUGONI, Guillermo FOLONIER, Agustin GIRAUDO, Daniel VENENCIA, Silvia ZUNINO
10:20 - 10:30 #39677 - OR010 Prostate stereotactic body radiotherapy with a MRI defined focal simultaneous integrated boost to the dominant intraprostatic nodule.
OR010 Prostate stereotactic body radiotherapy with a MRI defined focal simultaneous integrated boost to the dominant intraprostatic nodule.

Objectives: Stereotactic body radiotherapy (SBRT) represents an effective curative option for localized prostate cancer. Although localized prostate cancer is multifocal, there is a general consensus that dominant intraprostatic nodule (DIN) is mainly responsible for disease progression after radiation therapy. The addition of a focal boost to the DIN is an emerging strategy to potentially improve tumor control in patients with organ-confined prostate cancer.

Patients and Methods: Between May 2020 and June 2023, 44 patients with clinically localized prostate cancer, having a mean age of 72 years (range 56 – 83) and with a mean iPSA of 8.6 ng/ml (range 2.7 – 44.7) underwent Cyberknife stereotactic radiotherapy treatment. According to the D’Amico definition, 10 of them (23%) had low risk, 26 (59%) intermediate and 8 (18%) high risk disease. Most of the patients (52%) had 3+4 or 4+3 Gleason Score. All patients received 37.5 Gy in 5 consecutive fractions to the whole prostate gland, having an average volume of 66 cm³ (range 31 – 138), while an integrated boost up to a total dose of 50 Gy was applied to the DIN detected on the multiparametric MRI, having an average volume of 1.58 cm³ (range 0.28-5.40). 29 patients (66%) had PI-RADS 4 lesions and 10 patients (23%) had PI-RADS 5 lesions. 6 patients (4 high risk and 2 intermediate risk disease) recived concomitant and adjuvant HRT for 12 months mean time (range 4-36). Real time intrafractional motion tracking was used.

Results: The mean IPSS before treatment was 15 (range 1 -22) and no worsening was found during the acute phase. The most common GU complains were urinary urgency and aggravating nocturia, while increased stool frequency was the main GI symptom. Cumulative acute G1-2 GU toxicity rate was 27.3%. In one patient TURP was necessary for acute G3 incontinence. No GI acute toxicity G2 was observed. With a mean follow up of 16 months (range 6 – 36) mean PSA was 0,9 ng/ml (range 0 - 3,5), biochemical failure was observed in 1 intermediate risk disease patients 12 months after the treatment.

Conclusions: Simultaneously integrated boost to the DIN was well tolerated with similar acute GU and GI toxicity rates compared with historical prostate SBRT cohorts, mainly due to the more and more proven ability of current technologies to minimize treatments’ adverse effects. Longer follow-up is required to confirm long term results, both for tumor control and late toxicity.


Isa BOSSI ZANETTI (Milano, Italy), Deliu Victor MATEI, Achille BERGANTIN, Anna Stefania MARTINOTTI, Irene REDAELLI, Chiara SPADAVECCHIA, Giancarlo BELTRAMO
10:30 - 10:40 #39782 - OR011 Quantifying intrafraction motion in prostate SBRT: analysis from initial clinical experience with a 4D transperineal ultrasound real-time monitoring system.
OR011 Quantifying intrafraction motion in prostate SBRT: analysis from initial clinical experience with a 4D transperineal ultrasound real-time monitoring system.

Objectives:

This study aimed to quantify intrafraction motion using a 4D transperineal ultrasound (TPUS) real-time monitoring system in linac-based prostate SBRT.

Methods:

Forty fractions from ten patients with localized prostate cancer treated with 36.25Gy/5fx or 30Gy/3fx since July 2023 were investigated. PTV was obtained by a 3mm isotropic expansion from CTV. Patient setup was achieved through CBCT soft-tissue matching. A TPUS automatic probe fixed to the treatment couch was used for intrafractional monitoring of the prostate volume. The system interrupted the beam delivery when the threshold of 2.5 mm was exceeded for >5 seconds in any of the three spatial directions. Unless the offset was transient, the patient was repositioned by repeating CBCT or using the coordinates recorded in the system, whether the out-of-tolerance movement occurred in the setup or delivery phase, respectively. Couch-relative shifts of the prostate, from the beginning of the setup to the end of treatment delivery, were analyzed for all fractions to capture the real intrafraction motion as a function of time. 

Results:

Intrafractional TPUS tracking was successfully performed in all fractions. Median [range] duration of the whole treatment session was 6.6 minutes [5.1 – 29.3], while the delivery time was less than 2 minutes on average. At least an intervention in the couch position was required in 6 (15%) fractions, while a transient prostate movement outside the 2.5mm threshold was observed in 2 (5%) fractions during the delivery phase. The couch-relative shifts analysis revealed that the mean (SD) shifts of the prostate over all fractions were -0.21 (0.55), 0.53 (0.42), and -1.35 (0.97) in lateral, longitudinal, and vertical directions, respectively. The prostate motion mainly occurred in the posterior direction, while in the longitudinal direction it was likely restricted by the probe pressure towards the perineum. The minimum timeframe for a >3mm prostate shift in any direction over all analyzed fractions was 4.3 minutes. The same time was 9.7 minutes for >5mm shifts. The probability of >3mm movements increased from 5% (2/40) within 5 minutes to 30% (6/20) within 6.6 minutes. There were no fractions with prostate deviations >5mm within 8 minutes, while 40% (4/10) trespassed this margin thereafter. 

Conclusion:

Intrafraction monitoring with TPUS was feasible and effective. The probe pressure limited the prostate motion longitudinally. Keeping treatment time below 8 minutes with standard 5 mm/3 mm posterior margins minimizes the impact of intrafraction motion in prostate SBRT. Tighter margins may require a real-time monitoring device.


Valeria FACCENDA (Monza, Italy), Denis PANIZZA, Giuseppe BONANNO, Chiara CHISSOTTI, Federica FERRARIO, Elena DE PONTI, Stefano ARCANGELI
10:40 - 10:50 #39815 - OR012 Improvement of SBRT Quality in Prostate Cancer in LATAM: The HUG-Working Group Initiative.
OR012 Improvement of SBRT Quality in Prostate Cancer in LATAM: The HUG-Working Group Initiative.

Objectives:

To implement a model of continuous education, improvement, and standardization of SBRT and SRS quality, specifically for prostate-SBRT, in LATAM, through the Halcyon-Users-Group (HUG) virtual platform and its extension, the HUG Working-Group (WG) by Varian.

Materials and Methods:

1. Participant Selection: Call for Halcyon-LATAM users interested in standardizing prostate-SBRT treatment.

2. Curriculum Development: In collaboration with a consortium of prostate-SBRT experts, a continuous education curriculum is designed focused on the pre and post-SBRT process, practice protocolization and standardization, data registration structure, etc. Content is developed according to international standards and adapted to regional needs.

3. Training Strategy: A training program with theoretical and practical modules was established, including interactive sessions (Eclipse-Aria platform) to implement standardized protocols and case management.

4. Virtual Education Platform: A continuous education schedule was programmed, based on a learning curve essential for performing prostate-SBRT, utilizing educational resources previously proven successful in LATAM.

5. Protocol Implementation: Internationally standardized protocols were developed (patient selection, dose prescription, planning, dosimetry, QA, and post-SBRT follow-up).

6. Supervision and Mentoring: Prostate-SBRT experts will provide remote and on-site supervision, ensuring continuous evaluation of the implementation process.

7. Data Collection and Analysis: Two types of analysis will be performed, one based on the practice (prostate-SBRT) pre and post-implementation of the HUG-WG, with the intention of measuring the impact on the improvement of the process quality. The other based on the clinical and technical results, recorded in a structured and protocolized manner, necessary for a scientific report of statistical impact.

8. Results Evaluation: Regular evaluations to monitor improvements in clinical practice quality (treatment precision and protocol adherence). Quality controls will be performed by experts using the ECLIPSE-ARIA platform.

9. Adjustments and Continuous Improvement: The results of the analysis will be used to make adjustments to the program, designed to ensure continuous improvement in the quality of radiotherapy provided in LATAM. 

Results:

The expected results are:

1-Enhancement of prostate-SBRT quality through standardization based on defined international protocols.

2-Acquisition of structured medical information enabling clear evidence of post-training prostate-SBRT practice and the capability to report data with significant statistical impact.

3-Implementation of prospective trials in the region based on achieving an international standard of practice in LATAM. 

Conclusions:

The HUG-WG project has the potential to lay the foundations for advanced radiotherapy practice in LATAM. Through education and standardization, the initiative is expected to positively influence the quality of SBRT and SRS.


Pablo CASTRO PEÑA (Viedma, Argentina), Patrick KUPELIAN, Cleverson LOPES

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C14
ORAL PRESENTATIONS
Organs at Risk and Tolerance / Imaging

ORAL PRESENTATIONS
Organs at Risk and Tolerance / Imaging

Moderators: Caroline CHUNG (Associate Professor, Radiation Oncology) (Houston, USA), John P. KIRKPATRICK (Professor - Radiation Oncology & Neurosurgey) (Durham, NC, USA)
10:00 - 10:10 #39735 - OR014 Impact of the Mean Cochlear Biologically Effective Dose on Hearing Preservation After Stereotactic Radiosurgery for Vestibular Schwannoma: A Retrospective Longitudinal Analysis.
OR014 Impact of the Mean Cochlear Biologically Effective Dose on Hearing Preservation After Stereotactic Radiosurgery for Vestibular Schwannoma: A Retrospective Longitudinal Analysis.

Background and objectives: Stereotactic radiosurgery (SRS) is a useful alternative for small- to medium-sized vestibular schwannoma. To evaluate whether biologically effective dose (BEDGy2.47), calculated for mean (BEDGy2.47 mean) and maximal (BEDGy2.47 max) cochlear dose, is relevant for hearing preservation.

Methods: This is a retrospective longitudinal single-center study. Were analyzed 213 patients with useful baseline hearing. Risk of hearing decline was assessed for Gardner-Robertson classes and pure tone average (PTA) loss. The mean follow-up period was 39 months (median 36, 6-84). The mean BEDGy2.47 corresponding to the mean dose received by the cochlea was 5.8 ± 2.5 (0.71-21.27) Gy2.47. The maximal BEDGy2.47 corresponding to the maximal dose received by the cochlea was 10.6 ± 6 (2.2-46.9) Gy2.47.

Results: Hearing decline (Gardner-Robertson class) 3 years after SRS was associated with higher cochlear BEDGy2.47 mean (odds ratio [OR] 1.39, P = .009). Moreover, BEDGy2.47 mean was more relevant as compared with BEDGy2.47 max (OR 1.13, P = .04). Risk of PTA loss (continuous outcome, follow-up minus baseline) was significantly corelated with BEDGy2.47 mean at 24 (beta coefficient 1.55, P = .002) and 36 (beta coefficient 2.01, P = .004) months after SRS. Risk of PTA loss (>20 dB vs ≤20 dB) was associated with higher BEDGy2.47 mean at 6 (OR 1.36, P = .002), 12 (OR 1.36, P = .007), and 36 (OR 1.37, P = .02) months. Risk of hearing decline at 36 months for the BEDGy2.47 mean of 7-8, 10, and 12 Gy 2.47 was 28%, 57%, and 85%, respectively. The risk of hearing decline at 36 months was for the BEDGy2.47 max of 8, 9, 10, 12, 14, and 15 Gy2.47was 21.3%, 26.6%, 30%, 38.6%, 45.1%, and 46.8%, respectively.

Conclusion: Cochlear BEDGy2.47 mean is relevant for hearing decline after SRS and more relevant as compared with BEDGy2.47 max. Three years after SRS, this was sustained for all hearing decline evaluation modalities. Our data suggest the BEDGy2.47 mean cut-off of ≤8 Gy 2.47 for better hearing preservation rates.


Constantin TULEASCA (Lausanne, Switzerland), Iuliana TOMA-DASU, Sebastien DUROUX, Mercy GEORGE, Raphael MAIRE, Roy Thomas DANIEL, David PATIN, Luis SCHIAPPACASSE, Alexandru DASU, Mohamed FAOUZI, Marc LEVIVIER
10:10 - 10:20 #39751 - OR013 Implementing 3T MRI and new Vantage frame in Gamma Knife SRS: finding the imaging modality for optimal geometrical accuracy.
OR013 Implementing 3T MRI and new Vantage frame in Gamma Knife SRS: finding the imaging modality for optimal geometrical accuracy.

The Gamma Knife (GK) unit at Karolinska University hospital is the first center world-wide to implement the combination of 3T MRI and the new Vantage stereotactic (stx) frame in clinical practice. Compared to 1.5T, 3T MRI has the advantage of faster image acquisition and superior image quality but the disadvantage of being prone to geometrical inaccuracies if not well-calibrated and used with rigorous quality assurance. For this reason, the use of stx 3T MRI only for SRS-treatments may not be recommended in contrary to the well-established practice of using stx 1.5T MRI for both stx coordinate system acquisition and target delineation.

In order to find the optimal radiological modality combination for SRS treatments with 3T MRI, the stx coordinates of the target center were studied in 421 consecutive patients with a total of 592 targets treated with GK Icon and the Vantage frame.  All patients acquired a stx CT, stx MR and pre- and post-treatment stx on-board CBCT. The difference in the Leksell coordinate of the target center was found for (i) stx MR versus MR co-registered with CT and (ii) stx MR versus MR co-registered with pre-treatment CBCT. The center coordinate for the different imaging combinations was found by using the transformation matrix found in source LGP-files. This gives the transformation from CT/CBCT/MR (either stx or co-registered) space to Leksell Space and was used to find the target center Leksell coordinate using the linear algebraic-approach described in Ghazal et al. (2023).

The center target acquired by stx MRI compared to that acquired by co-registration with CT and CBCT, respectively, were all within +-2mm. This difference between stx and co-registered MRI is significant in terms of SRS suggesting that stx 3T MRI only is not warranted in SRS. (i) and (ii) was shown to give similar translations in all three axes: the best agreement between the two were found in x-axis (98% of targets within +-0.5mm difference) and the worst in z-axis (83% of targets within +-0.5mm). The difference in the Euclidean distance of (i) and (ii) was less than +-0.5mm and +-0.75mm in 93% and 99% of the targets, respectively. This work shows that stx 3T MRI only does not guarantee the accuracy required for SRS-treatments. Furthermore, the stx coordinate systems acquired by 3T MR co-registered with CT and CBCT, respectively, can be seen as equivalent within sub-millimeter accuracy with the largest uncertainty in z-axis.


Hamza BENMAKHLOUF (Stockholm, Sweden), Mohammed GHAZAL, Michael GUBANSKI, Amir SAMADI, Marcus FAGER
10:20 - 10:30 #40092 - OR015 Understanding permeability changes in vestibular schwannomas as part of the dynamic stereotactic radiosurgery response.
OR015 Understanding permeability changes in vestibular schwannomas as part of the dynamic stereotactic radiosurgery response.

Introduction

Stereotactic radiosurgery (SRS) is a safe and effective option for patients with vestibular schwannomas. Also after irradiation, the tumors often develop a loss of central contrast uptake on MRI. This is commonly observed 6 months after radiosurgery. Over time, the signal loss begins to fill in, becoming homogeneous on contrast enhanced T1-weighted images. The mechanisms underlying this change are not well understood. In order to better understand this physiologic process, we aimed to measure the vessel permeability changes within the tumor using golden-angle radial sparse parallel (GRASP) dynamic contrast-enhanced (DCE) MRI.

 

Methods

We identified 19 patients with vestibular schwannoma (mean age 58.2 ± 11.9 years) who underwent SRS between 2017 - 2019, had GRASP images acquired before and after SRS, had tumor control at last follow-up, and demonstrated central loss of contrast enhancement and subsequently regained a homogeneous appearance on T1-weighted MRI with contrast. GRASP studies were acquired at 6, 12, and approximately 24 months. Using GRAVIS, an in-house software, we calculated the GRASP time series, normalized to the superior sagittal sinus (SSS), from a region of interest showing contrast loss. Key parameters, the area under the curve (AUC), peak, as well as slopes during the wash-in and wash-out phases of the SSS were extracted. A linear mixed-effects model was used to compare parameters longitudinally, with correction for multiple comparisons. 

 

Results

A change in the GRASP curve was visually recognizable (Figure 1). At 6 months after SRS, the AUC and peak both reduced to 46% of baseline (corrected p < 0.001), and to 67% and 73% respectively of baseline at 12 months (corrected p < 0.05). At 24 months, these values remained significantly decreased. The wash-in phase slope also decreased to 54% at 6 months (corrected p < 0.001) and continued to be reduced at 71% (corrected p < 0.05) and 33% (corrected p < 0.001) of baseline at 12 and 24 months. The wash-out phase slope was reduced at 6 months (corrected p = 0.05), but not significantly different from baseline at 12 or 24 months.

 

Conclusion

Using GRASP, we characterized the changes in vascular permeability within vestibular schwannomas that exhibited loss of enhancement after radiosurgery. We showed that even as contrast enhancing material fills the tumor over time, this slowed dynamic persists, suggesting a different tissue property such as the internal development of scar tissue. 


Ying MENG (New York, USA), Matthew LEE, Wiggins ROY, O'callaghan JAMES, Assaf BERGER, Kenneth BERNSTEIN, Brandon SANTHUMAYOR, Tobias BLOCK, Girish FATTERPEKAR, Douglas KONDZIOLKA
10:30 - 10:40 #39585 - OR016 Both minimum and mean cochlear dose predict hearing outcomes for patients with sporadic vestibular schwannomas treated with radiosurgery.
OR016 Both minimum and mean cochlear dose predict hearing outcomes for patients with sporadic vestibular schwannomas treated with radiosurgery.

It is controversial if cochlear dose impacts hearing after stereotactic radiosurgery (SRS) for sporadic vestibular schwannomas (sVS). This study evaluated the impact of cochlear dose parameters on hearing outcomes for patients with serviceable hearing (SH) at SRS. A total of 205 patients underwent single-session Gamma Knife SRS from 2007 to 2022 for sVS with assessment of ipsilateral Academy of Otolaryngology-Head and Neck Surgery hearing class, pure tone average (PTA), and word recognition score (WRS). Volumetric cochlear dose analysis was performed with computed tomography. Associations with time to non-SH and rates of change in PTA and WRS were evaluated using Cox proportional hazards regression and linear regression models, respectively. Associations of cochlear dose parameters with hearing outcomes were adjusted for select covariates at SRS including age, PTA, WRS, hearing class, tumor location, and linear growth from diagnosis to SRS. At SRS, 54 (26%) tumors were confined to the internal auditory canal and 151 (74%) extended into the cerebellopontine angle. For patients with SH at SRS (i.e., initial class A or B hearing), 132 patients progressed to non-SH at a median of 1.7 years following SRS. Estimated rates of maintaining SH at 1, 2, 5, and 10 years following SRS were 78%, 62%, 37%, and 15%, respectively. Median rates of change in PTA and WRS were 6.0 decibels hearing loss per year and −6.5% per year, respectively. In a multivariable analysis, each 1-Gy increase in minimum cochlear dose was significantly associated with time to non-SH (hazard ratio [HR] 1.5, p=0.001), rate of change in PTA (parameter estimate [PE] 3.4, p=0.02), and rate of change in WRS (PE −6.4, p=0.01). An interaction analysis indicated that the associations of mean cochlear dose with time to non-SH, rate of change in PTA, and rate of change in WRS differed by initial hearing class. When this interaction was included in the multivariable model, the associations between mean cochlear dose and these hearing outcomes were only significant among patients with initial class B hearing (time to non-SH HR 1.3, p=0.001; rate of change in PTA PE 3.6, p=0.003; rate of change in WRS PE −5.7, p=0.006). In conclusion, minimum cochlear dose is consistently associated with time to non-SH and rates of change in PTA and WRS across patients with initial class A or B hearing while mean cochlear dose is associated with these outcomes for patients with initial class B hearing.


Ramin MORSHED (Rochester, USA), Karl KHANDALAVALA, James DORNHOFFER, Eric BABAJANIAN, Ghazal DAHER, John MARINELLI, Paul BROWN, Christine LOHSE, Matthew CARLSON, Michael LINK
10:40 - 10:50 #39808 - OR017 Single Breath Hold Cone Beam CT imaging for guidance of SABR.
OR017 Single Breath Hold Cone Beam CT imaging for guidance of SABR.

Purpose. High quality imaging is critical to the accurate delivery of stereotactic ablative radiation therapy (SABR). An important technique to improve image quality and to achieve precision of treatment delivery is the breath hold (BH) maneuver. However, typical cone beam CT (CBCT) platforms have required approximately one minute for acquisition, thus necessitating multiple breath holds—a requirement that causes inconsistency in projection data that compromises image quality. In this study we examine potential advantages of the new HyperSight CBCT platform (Varian Medical) that allows acquisition in just six seconds, i.e., within a single breath hold.

 

Methods.  Thirty patients were enrolled, where treatment sites included lung (N=9), liver (N=7), breast (N=8), chest wall (N=2), abdomen (N=2), mediastinum (N=1) and pancreas (N=1).  Each patient was imaged during BH using: i) fan beam CT for treatment planning, ii) TrueBeam CBCT (Varian Medical) over multiple BHs, and iii) CBCT on an Ethos unit with HyperSight in six seconds.  On HyperSight, patients were also imaged during free breathing (FB) to isolate the effect of BH. HyperSight images were compared directly with FBCT (representing the “standard” in terms of image quality in the clinic) and TrueBeam (representing the status quo for onboard image guidance). Image quality metrics included artifact index, non-uniformity, contrast, contrast-to-noise ratio (CNR), and Hounsfield Unit (HU) accuracy.

 

Results. All 30 patients were able to undergo HyperSight imaging in a single breath hold. Image artifacts, including those caused by patient motion, gas motion, and beam hardening in HyperSight imaging were comparable in severity to those in FBCT. HyperSight with BH provided significantly improved image uniformity compared to both HyperSight FB and TrueBeam BH. While FBCT provided the best contrast, HyperSight under both BH and FB conditions provided improved CNR compared to TrueBeam. For tissue and fat, HyperSight provided quantitative accuracy within a median of 1 HU, compared to FBCT. For bone and lung, median values were within 12 and 14 HU, respectively.

 

Conclusions. HyperSight provided CBCT imaging within a single breath hold over a broad array of sites relevant to SABR. Artifacts were improved significantly compared to TrueBeam CBCT imaging, and comparable to those in FBCT. BH on the HyperSight improved image quality across all metrics. HyperSight achieved quantitative accuracy within 1 HU for tissue, a capability that may prove useful for SABR sites needing online adaptation.


James ROBAR (Halifax, Canada), Amanda CHERPAK, Robert Lee MACDONALD, Abigail YASHAYAEVA, David MACALONEY, Natasha MCMASTER, Kenny ZHAN, Slawa CWAJNA, Nikhilesh PATIL, Hannah DAHN
10:50 - 11:00 #38933 - OR018 First clinical application of comprehensive motion management on prostate stereotactic body radiotherapy using 1.5 tesla mr-linac.
OR018 First clinical application of comprehensive motion management on prostate stereotactic body radiotherapy using 1.5 tesla mr-linac.

Purpose/Objective

High-field MR-linac allows improved soft-tissue visualization of the tumour and the surroundings tissues. Furthermore, daily MR-imaging allows on-table adapted planning and real-time intra-fraction imaging without additional exposure to radiation. The recent implementation of Comprehensive Motion Management (CMM) guarantees more precise radiation treatments by interrupting the delivery when the target moves outside the defined position and enables radiation oncologist to perform target drift corrections. We report our first clinical experience on prostate adaptive SBRT with true tracking and automatic gating with high-field MR-Linac.

Material/Methods

Between 26th September and 13rd October 2023, we treated 5 male patients affected by low-to-favourable intermediate prostate cancer. For treatment simulation we used a T2-weighted MR sequence that lasts 2 minutes. On this sequence we contour the target and the organs-at-risk. The GTV-to-PTV margins were 5 mm in all directions and 3 mm posteriorly. A 16-fields IMRT plan was prepared and daily adapted with adapt-to-shape workflow during every fraction. The 5-fraction delivered total dose was 35 Gy in low risk and 36.25 Gy in intermediate risk. The motion management was set to deliver the treatment when 100% of the GTV was contained within the PTV. We collected details and times of all treatment phases.

Results

The median on-table time was 34 minutes. The daily 3D T2-weighted sequence acquisition lasted 2 minutes, the registration between daily sequence and reference sequence lasted 1 minute, the daily target and OARs contour definition lasted 4 to 5 minutes and the daily plan adaptation lasted between 7 and 9 minutes.  The median delivery time was 17 minutes (range 15-20 minutes) with a median beam-on time of 14 minutes (range 13.5-17 minutes) and a median gating efficiency of 85% (range 82%-91%). Among the 25 delivered fractions only one drift corrections was needed and the baseline shift replanning lasted 1 minute. The patients performed all the sessions without any clinical issue.

Conclusion

Daily-adaptive MR-guided SBRT to the prostate using Comprehensive Motion Management has been successfully implemented into clinical routine.  The whole process is safe and completely automated even in the case on in-treatment corrections and baseline shift replanning. CMM could allow now a safe reduction of the treatment margins with a guided workflow to manage real tracking and gating.


Michele RIGO (Negrar di Valpolicella, Italy), Niccolo' GIAJ-LEVRA, Rosario MAZZOLA, Luca NICOSIA, Francesco RICCHETTI, Edoardo PASTORELLO, Andrea Gaetano ALLEGRA, Antonio DE SIMONE, Davide GURRERA, Stefania NACCARATO, Gianluisa SICIGNANO, Riccardo BORGESE, Roberto PELLEGRINI, Ruggero RUGGIERI, Filippo ALONGI

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A15
PARALLEL SESSION
Global Radiosurgery Program Development

PARALLEL SESSION
Global Radiosurgery Program Development

Moderators: Andrey GOLANOV (Chief of the Department) (Moscow, Russia), Roberto SPIEGELMANN (Consultant Neurosurgeon) (Tel Aviv, Israel)
11:00 - 12:00 Evolution of Gamma Knife Radiosurgery in Indian context : Past and the Future. Sweta KEDIA (Additional Professor) (Keynote Speaker, New Delhi, India)
11:00 - 12:00 Advancing the Growth of Radiosurgery through ISRS Partner Organizations. Laura FARISELLI (director) (Keynote Speaker, Milan, Italy)
11:00 - 12:00 Radiosurgery in Brazil: current status and challenges for expansion. Alessandra GORGULHO (Director) (Keynote Speaker, São Paulo, Brazil)

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PARALLEL SESSION
Spine Stereotactic Radiosurgery

PARALLEL SESSION
Spine Stereotactic Radiosurgery

Moderators: Peter GERSZTEN (Professor/Neurosurgeon) (Pittsburgh, USA), Samuel RYU (Professor) (Stony Brook, NY, USA)
11:00 - 12:00 The role of spine SRS in metastatic epidural spinal cord compression. Amol GHIA (Associate Professor) (Keynote Speaker, Houston, USA)
11:00 - 12:00 Reirradiation of Spinal Metastases:  The State of the Art. Josh YAMADA (Keynote Speaker, New-York, USA)
11:00 - 12:00 Unanswered Questions in Stereotactic Radiosurgery for Spine Metastases. Scott SOLTYS (ISRS 2023) (Keynote Speaker, Stanford, CA, USA)

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PARALLEL SESSION
Alternative Targeting Strategies - LITT/HIFU/Flash RT

PARALLEL SESSION
Alternative Targeting Strategies - LITT/HIFU/Flash RT

Moderators: Gene BARNETT (neurosurgery) (Cleveland, USA), Steve BRAUNSTEIN (Faculty) (San Francisco, USA)
11:00 - 12:00 Single-energy Bragg-Peak FLASH for Proton SBRT. Jenghwa CHANG (Physicist) (Keynote Speaker, Lake Success, USA)
11:00 - 12:00 The role of Laser Interstitial Thermal Therapy in treatment of Brain metastasis. Alireza MOHAMMADI (zimmer) (Keynote Speaker, Islamic Republic of Iran)
11:00 - 12:00 Finding the ventral intermediate (VIM) nucleus for MR guided focused ultrasound thalamotomy. Michael SCHWARTZ (staff neurosurgeon) (Keynote Speaker, Toronto, Canada)

12:00 - 13:00 SPONSORED LUNCH SYMPOSIA - LUNCH IN THE EXHIBITION
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A17
ORAL PRESENTATION
Vascular - Brain

ORAL PRESENTATION
Vascular - Brain

Moderators: Michael CUSIMANO (Canada), Sweta KEDIA (Additional Professor) (New Delhi, India)
13:00 - 13:10 #39664 - OR019 Quantitative analysis of parenchymal effects and flow of large arteriovenous malformations managed with stereotactic radiosurgery.
OR019 Quantitative analysis of parenchymal effects and flow of large arteriovenous malformations managed with stereotactic radiosurgery.

BACKGROUND : Stereotactic radiosurgery (SRS) of larger arteriovenous malformations (AVM) is associated with an elevated incidence of adverse radiation effects (ARE). To date, volume–response and dose–response models have been used to predict such effects.

OBJECTIVES :To understand radiological outcomes and their hemodynamic effects on the regional brain.

 METHODS: A retrospective analysis was conducted at our institution using a prospective registry of patients managed between 2014 and 2020. We included patients with AVM with a nidus larger than 5 cc who received either single-session or volume-staged Gamma Knife radiosurgery. AVM volume changes, volumes of parenchymal response, and obliteration were analyzed and correlated with transit times and diameters of feeding arteries and draining veins.

 RESULTS: Sixteen patients underwent single-session SRS, and 9 patients underwent volume-staged SRS. The average AVM volume was 12.6 cc (5.5-23). The AVM locations were predominantly lobar (80%) and 17 (68%) were in critical locations. The mean margin dose was 17.2 Gy (15-21), and the median V12Gy was 25.5 cc. Fourteen (56%) AVMs had a transit time shorter than 1 second. The median vein-artery ratio (sum diameter of the veins/sum diameter of feeding arteries) was 1.63 (range, 0.60-4.19). Asymptomatic parenchymal effects were detected in 13 (52%) patients and were symptomatic in 4 (16%) patients. The median time to ARE was 12 months (95% CI 7.6-16.4). On univariate analysis, significant predictors of ARE were lower vein-artery ratio (P = .024), longer transit time (P = .05), higher mean dose (P = .028), and higher D95 (P = .036).

 CONCLUSION: Transittimes and vessel diameters  are valuable predictors of the subsequent parenchymal response after SRS. A more quantitative understanding of blood flow is critical for predicting the effects on the regional brain after AVM radiosurgery.


Juan Diego ALZATE (Cleveland, USA), Elad MASHIACH, Fernando DE NIGRIS VASCONCELLOS, Kenneth BERNSTEIN, Tanxia QU, Joshua SILVERMAN, Howard RIINA, Douglas KONDZIOLKA
13:10 - 13:20 #40143 - OR020 Stereotactic radiosurgery for intracranial dural arteriovenous fistulas: lessons learned over a three-decade single-center experience.
OR020 Stereotactic radiosurgery for intracranial dural arteriovenous fistulas: lessons learned over a three-decade single-center experience.

Introduction: The role of stereotactic radiosurgery (SRS) in the management of intracranial dural arteriovenous fistula (dAVF) is unclear due to their rarity and variability in treatment paradigms. 

Methods: Single institution database search from 1990 to 2022. Two hundred twenty-two patients underwent SRS alone (n=56, 25%) or SRS and embolization (n=166, 75%) depending on severity of symptoms or presence of cortical venous drainage (CVD). Imaging used for targeting initially was angiography alone, then angiography plus magnetic resonance imaging (MRI), and most recently MRI alone. Follow-up after SRS was available for 209 patients (median follow-up, 31 months).

Results: Most patients were female (142/222, 64%); the median patient age was 60 years. Common presenting symptoms were tinnitus (55%), visual change/chemosis (21%), headache (10%), and intracerebral hemorrhage (5%). The most frequent dAVF location was transverse/sigmoid (44%), followed by cavernous sinus (24%), jugular bulb (9%), and torcula (5%). CVD was noted in 28% of cases, with 5% having venous ectasia. Borden grades were I (72%), II (20%), and III (8%). Cognard grades were I (44%), IIa (28%), IIb (4%), IIa+b (15%), III (4%), and IV (5%). The median SRS volume was 5.9 cm3; the median margin/maximum doses were 18/36 Gy. Obliteration was noted in 75% of patients (110/147) with follow-up vascular imaging. Symptoms resolved in 77% of patients (160/209) with clinical follow-up. Fourteen patients (6.3%) had complications related to angiography for SRS planning (n=2, 0.9%), embolization (n=3, 1.4%), post-SRS hemorrhage (n=1, 0.5%), delayed sinus thrombosis (n=1, 0.5%), radiation-induced tumors (n=2, 0.9%), and chronic encapsulated expanding hematoma (n=3, 1.4%).

Conclusion: SRS alone or in conjunction with embolization provided obliteration and symptom relief for the majority of dAVF patients with a low rate of procedure related morbidity. Patients are at risk for late radiation-related complications which may require treatment many years after the SRS procedure.


Pierce PETERS, Ryan NAYLOR, Bruce POLLOCK, Giuseppe LANZINO, Michael LINK (Rochester, USA)
13:20 - 13:30 #39624 - OR021 To treat, or not to treat, that is the question - the radiosurgical versus conservative treatment in cerebral arteriovenous malformations.
OR021 To treat, or not to treat, that is the question - the radiosurgical versus conservative treatment in cerebral arteriovenous malformations.

Background and Objective: Since the publication of the ARUBA trial, many studies have assessed the outcome of different treatment options in ARUBA eligible bAVM patients. Studies on the conservative management of exclusively unruptured ARUBA eligible bAVMs are rather scarce.

Methods: A retrospective observational cohort of 107 patients (out of a total of 897 bAVM patients referred to our institution) with at diagnosis unruptured and conservatively managed bAVMs is presented. In a first step, long-term outcome data of our conservative cohort are compared to the ARUBA study’s medical management arm and in a second step, to our follow-up cohort of 472 radiosurgically treated bAVM patients.

Results: In the conservative observation period, 17% of patients suffered from at least one hemorrhage, resulting in an overall calculated annual hemorrhage risk of 2.7%. Cumulative 1, 5 and 10 year overall hemorrhage rates are 3.0%, 11.3% and 15.3%, respectively. Univariate followed by multivariate Cox regression analyses reveal a temporal and deep seated localization and the presence of seizures as independent risk factors for AVM hemorrhage among the conservative cohort. Of note, the radiosurgical treatment of bAVM leads to a significant improvement in the long-term mortality and hemorrhage risk compared to the conservative treatment.

Conclusion: Our data support the conclusion that even in the post-ARUBA era, tailored active treatment options should be offered to ubAVM patients. For patient counseling, individual risk factors should be weighed against the center’s treatment specific risks.


Philippe DODIER, Anna CHO, Beate KRANAWETTER, Dorian HIRSCHMANN, Josa Maria FRISCHER (Vienna, Austria)
13:30 - 13:40 #39733 - OR022 Stereotactic radiosurgery for arteriovenous malformations of the spinal cord.
OR022 Stereotactic radiosurgery for arteriovenous malformations of the spinal cord.

Objective.

Spinal arteriovenous malformations constitute a group of complex vascular lesions, accounting for 3-4% of all intradural lesions of the spinal cord. Microsurgery and endovascular embolization are the mainstays of treatment for these varied lesions, however, success rates and risks depend on the unique anatomy of each lesion. Stereotactic radiosurgery of intracranial AVMs has proven to be an effective treatment method. There are also many reports of the use of radiosurgery in the treatment of primary spinal tumors and metastatic lesions. However, irradiation of spinal malformations is rarely reported due to technical difficulties in implementing this treatment. In the future, stereotactic radiosurgery may become a promising treatment option for spinal AVMs. 

Material and Method

From 2021 to 2023, at the Burdenko Neurosurgical Institute (National Scientific and Practical Center for Neurosurgery named after academician   N.N. Burdenko) 31 patients with vascular pathologies of the spinal cord received radiosurgery (58% women and 42% men). The average age of patients is 39.2 years (median 7-77 years). 3 patients had a dural fistula and 28 patients had arteriovenous malformations. 15 malformations were at the cervical level, 12 malformations at the thoracic level, and 4 at the lumbar spinal cord level.

Treatment was carried out on TrueBeam STX (6 patients), CyberKnife VSI (10 patients) and CyberKnife M6 (15 patients). For 1 fraction treated in 19 patients (61.3%), Dmean was 15.67-24 Gy; 2 fractions in 7 patients (22.5%)  Dmean was 18.95-22 Gy; 3 fractions - in 4 patients (12.9%) – Dmean was 21.04-27 Gy and 5 fractions in 1 patient (3.3%) Dmean was 30 Gy. Average target volume was 4.37 cm3 (median 0.1-100 cm3). 

Results.

Up to date we have information concerning follow up of 12 patients (38%). The median follow-up was 12.25 months (6-25 months). Complete obliteration was revealed In 2 patients according MRI (16.7%) after 13 and 14 months of follow-up, positive dynamics according to control MRI was noted in 5 patients (41.6%), absence changes  - in 5 patients (41.6%). No increase of neurological deficit was recorded.

Conclusion.

Stereotactic radiosurgery   is safe and effective and may be method of choice and can be considered for patients   with spinal AVM  when surgery or endovascular therapy is not indicated or had no results. Continued follow-up observation is required to assess treatment results.


Arina LESTROVAYA, Andrey GOLANOV (Moscow, Russia), Anastasiya KUZNECOVA, Natalia ANTIPINA, Evgenii VINOGRADOV, Igor PRONIN
13:40 - 13:50 #40113 - OR023 Review of a single centre’s LINAC AVM experience.
OR023 Review of a single centre’s LINAC AVM experience.

INTRODUCTION:

Cerebral arteriovenous malformations (AVM), whilst uncommon, more typically present in patients aged 30-40 years with haemorrhage the most common presenting occurrence. Whilst the annual haemorrhage is only 3%, for younger patients the life-time haemorrhage rate can be greater than 60%. Surgery has definite benefits, however, many factors can define a non-resectable situation. Historically, a stereotactic radiosurgery (SRS) procedure as a day only outpatient event, has involved application of a neurosurgical head-ring with a cerebral angiogram performed on the day, with planning and treatment occurring on the same day. This is a review of the process over a 20 year time-frame.

METHODS:

In this Ethics approved retrospective review (2022/ETH01472), conducted on all adult patients who presented for AVM treatment with SRS in our Centre from January 2000-December 2019. All included patients has minimum follow up of 1-3 years via clinical assessment and 6-12 monthly MRI imaging. When nil flow was evident on the flow sequence, cerebral angiogram was performed. Obliteration rates, time to obliteration (TTO), complications, and predictors associated with obliteration were investigated.

 

RESULTS:

There were 136 included AVMs, 49% (n=67) were male, with mean age 41 years (SD 14.3). Haemorrhage leading to presentation occurred in 32% (n=44), 41% (n=56) had headaches, while 13% (n=17) were asymptomatic. Diameter less than 3cm was evident in 68% (n=92), with 88% (n=119) in eloquent brain. AVM volume was <2cm3 in 26% (n=35), 2-4cm3 in 8% (n=11) and > 4cm3 in 66% (n=90). Radiosurgery dose ≥ 18Gy was given in 81%, and < 18Gy in 50% of patients. Overall obliteration rate was 76% (103/136), with rates of 85% (78/92) in maximum diameter <3cm, 58% (23/40) in 3-6cm, and 50% (2/4) in > 6cm. Obliteration rates were higher with a dose ≥18Gy (81%, 92/114), and this was found to be a predictor of obliteration rate on multivariate analysis, with patients being 4.7 times more likely to achieve this (OR 4.7, 95%CI 1.69-13.25, p=0.003). Mean TTO was 48 months, with no significant predictors found. No complication occurred in 73%, 18% developed a temporary event, permanent in 9%, and necrosis occurred in 8%.

CONCLUSION:

Vascular obliteration rates were high in small (<3cm) AVMs, and where ≥ 18Gy was delivered, rates were comparable to those in published Gamma-knife series. Newer methods enable dispensing with the head-ring.


Robert SMEE (Randwick, Australia), Janet WILLIAMS, Meg SCHNEIDER, Daniel MORRIS, Belinda VANGELOV
13:50 - 14:00 #40153 - OR024 Stereotactic diffusion tensor imaging tractography for brain AVM located in the in deep seated eloquent areas during radiosurgery treatment planning.
OR024 Stereotactic diffusion tensor imaging tractography for brain AVM located in the in deep seated eloquent areas during radiosurgery treatment planning.

OBJECTIVE The integration of modern neuroimaging into treatment planning has increased the therapeutic potential and safety of stereotactic radiosurgery. The authors report their method of integrating stereotactic diffusion tensor imaging (DTI) tractography into treatment planning for CyberKnife radiosurgery (CKRS). The aim of this study was to evaluate whether the use of diffusion-tensor tractography (DTT) of the corticospinal tract could reduce motor complications after radiosurgery. METHODS Between 2013 and 2020, 56 patients with arteriovenous malformation (AVM) in the deep frontal lobe, deep parietal lobe, basal ganglia, and thalamus who had undergone CKRS. DTI were obtained on the day before the localization of head. Data from stereotactic 3D imaging studies were co-registered with the data from DTI tractography. The combined images were transferred to a Cyberknife treatment-planning workstation. During the procedure of creation of treatment planning, the corticospinal tract was clearly visualized on the Multiplan. Results: 56 patients with AVM volume less than 10 cm3 underwent CKRS in Huashan Hosptial. The follow-up time ranged from 36 to 120 months, with median time of 78 months. The prescription dose was 21Gy-22 Gy in 2 fractions or 21Gy – 22.5 Gy in 3 fractions according to AVM volume. A maximum dose to the corticospinal tract of equal to or less than 21 Gy in 3 fractions or 18 Gy in 2 fractions did not cause new neurological deficits. Total obliteration rates were 72% at more than 3 years after one stage or two stage CKRS. One patient had small intracranial hemorrhage 3 years post obliteration. Mild complications were observed in 6 patients because of brain edema, which was required medication.

CONCLUSIONS Integration of stereotactic tractography into CKRS represents a promising tool for preventing radiosurgery complications by reduction in radiation doses to functional organs at risk, including critical cortical areas and subcortical white matter tracts. DTI improved the obliteration of AVM and reduced the motor deficits


Enmin WANG (Shanghai, China), Xiaoxia LIU, Xin WANG, Huaguang ZHU, Xing DI, Wenqian XU

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B17
ORAL PRESENTATIONS
Brain (Benign/Functional)

ORAL PRESENTATIONS
Brain (Benign/Functional)

Moderators: John LEE (Aberdeen, United Kingdom), Daniel M. TRIFILETTI (Professor) (Jacksonville, USA)
13:00 - 13:10 #39864 - OR025 Evaluation of Bilateral VIM Radiosurgery in patients with a severe Essential Tremor : a propsective trial.
OR025 Evaluation of Bilateral VIM Radiosurgery in patients with a severe Essential Tremor : a propsective trial.

Safety efficacy of unilateral VIM Gamma Knife Radiosurgery (VIM GK) has been well demonstrated for Essential tremor (ET). The safety-efficacy of bilateral VIMGK has never been assessed strictly. We conducted a prospective and objective assessed of the changes in cognitive functions (primary criteria), speech, balance in addition to the evaluation of the impact activities of daily living.

Between 03/06/2014 & 09/11/2021 have been treated contralaterally by GKS 33 patients presenting with a severe ET previously treated by VIM GK on the dominant side at least 12 months before (monocentric, prospective, non comparative N° EUDRACT : 2013-A01289-36). Quantitative assessment before, at 6 & 12 months was including neuropsychological testing (MMS, apathy Starkstein scale, Stroop, verbal fluences, similitudes), evaluation of the voice, writing, walk gait (Kinematic gait analysis was performed with the SMART TV image processing system, eMOtion), posture (AMTI force platform), tremor severity (Fahn-Tolosa-Marin rating scale) ADL (Bain Scale) and MRI. Assessment was perform independently from the neurosurgical team. The results were followed and reviewed by an international independent surveillance committee (MH and PK). Patients acted as their own controls.

All the 33 patients have completed the study after the one year follow up (19 male 14 female, 32 right VIM and 1 left). Only one adverse event (expected) was observed (hemi-proprioceptive ataxia & dysarthria due to hyper-response 11 months after VIM GK). The mean age was 71 (55-83). The mean delay between the first and the second GK was 28,7 months. The primary outcome criteria of tolerance on the cognitive functions was altered in none of the patients. The evaluation of speech walk gait and posture (secondary outcome criterion) have shown no worsening. In term of efficacy at 1 year the severity score was improved of 58,5%, the disability score of 84,8% and the functional impact score of 68,6%. Only 4 patients failed to respond but for the 29 remaining the mean improvement was of 74,4% improvement of the tremor on the treated upper limb. No side effect related to the bilaterality of the VIM GKS was found in spite of the independent meticulous prospective assessment.

This is the first prospective trial assessing the safety efficacy of bilateral VIM GK. This trial is demonstrating the excellent safety efficacy of VIM GK of the contralateral side in a subgroup of selected candidates previously treated by VIM GK at least 1 year before with a good response of the first side operated.


Jean REGIS (Marseille), Axel CRETOL, Valentin MIRA, Marwan HARIZ, Paul KRACK, Vaugoyeau MARIANNE, Tatiana WITJAS
13:10 - 13:20 #39837 - OR026 Efficacy and Safety of Frameless Virtual Cone LINAC-Based Stereotactic Radiosurgery in Refractory Tremor: A Phase I/II Prospective Clinical Trial.
OR026 Efficacy and Safety of Frameless Virtual Cone LINAC-Based Stereotactic Radiosurgery in Refractory Tremor: A Phase I/II Prospective Clinical Trial.

Background: Essential and Parkinsonian tremors, prevalent movement disorders, can severely impair patients' daily activities and quality of life. Traditional treatments, including medication and invasive surgical options like deep brain stimulation, have limitations. Traditional gamma knife radiosurgery requires the placement of a stereotactic frame. This study aims to evaluate the safety and efficacy of a novel, frameless linear accelerator (linac)-based stereotactic radiosurgery for refractory tremor.

Methods: This phase I/II prospective clinical trial enrolled 45 patients with medically refractory essential or Parkinsonian tremor, who were either unsuitable or unwilling to undergo deep brain stimulation. The innovative treatment involved a frameless, virtual cone linac-based approach for thalamotomy, negating the need for traditional skull fixation methods and the use of Cobalt-60. The primary endpoint was tremor severity reduction, assessed by standardized scales. Secondary endpoints included quality of life improvements and the incidence of adverse effects, monitored through a combination of clinical evaluations, patient-reported outcomes, and radiological imaging.

Results: Forty out of forty-five participants completed the treatment and follow-up, which ranged from 6 to 18 months, with a median duration of 12 months. The treatment led to a marked reduction in tremor severity, with a significant proportion of participants achieving a clinically meaningful response rate of 87.5%. Median improvement in tremor severity was 54.5% on the Fahn-Tolosa-Marin Tremor scale. The procedure was well-tolerated with minimal acute or peri-procedural toxicity. Thirty-five out of forty patients experienced no toxicity or only transient paresthesias (87.5%). Five out of forty patients (12.5%) experienced bothersome or medically significant adverse effect, which were managed with corticosteroids or bevacizumab.

Conclusion: The findings of this study underscore the potential of frameless linac-based radiosurgery as a pioneering, effective, and patient-friendly intervention for managing medically refractory essential and Parkinsonian tremor. Its non-invasiveness, coupled with a favorable safety profile, positions it as a promising alternative to existing treatment strategies. Further research and long-term follow-up studies are warranted to establish its position in the therapeutic armamentarium for tremor disorders.


Evan THOMAS, Harrison WALKER, Erik MIDDLEBROOKS, Richard POPPLE, John FIVEASH, Sarah BRINKERHOFF, Benjamin MCCULLOUGH, Natalie STOVER, David STANDAERT, Nicole BENTLEY, Marshall HOLLAND, Talene YACOUBIAN, Anthony NICHOLAS, Victor SUNG, Jaime ROPER, Barton GUTHRIE, Markus BREDEL (Birmingham, USA)
13:20 - 13:30 #39682 - OR027 Radiosurgery for refractory, oncological pain.
OR027 Radiosurgery for refractory, oncological pain.

Introduction: Oncological refractory pain, especially at the end of life represents a heavy burden on patients, family, and caregivers as well as any healthcare system as these patients require constant visits to emergency departments or their homes to deal with pain crisis. Radiosurgery since its origins has been used and demonstrated to have some utility in the management of such pain.

Methods: We present our experience in 27  patients that have been treated for oncological pain: 18 patients have been treated with irradiation of the hypophysis alone with typical doses of 140 Gy (90-150), 9 patients have been treated using a triple target strategy consisting of bilateral irradiation to the medial structures and the thalamus and the hypophysis as well with usual doses of 90 Gy to each target, this has been done mainly for mixed oncological pain.

Results: Overall success rate defined by either a visual analogue score or analgesia medicine reduction of 50% or more for irradiation of the hypophysis alone has been reported in 13/18 patients (72%), average time for pain relief is 3.2 days. For the triple target strategy in mixed oncological pain, a 62% success rate for reducing pain 50% or more, time for pain relief was 11.3 days, at one month 70% of patients had a relief of at least 50%, one patient also required bilateral irradiation of the cingulum, median survival for both series was 3.5 months. No clinical or endocrinological manifestations were identified. Most patients experienced various degrees of pain that are more intense days or weeks before they pass away.

Conclusions: Radiosurgery of central targets has proven with modern doses and targeting to be a safe alternative to obtain pain relief in most terminally ill patients. Refractory oncological pain is a complex clinical entity that adds a multidimensional nature to pain, such as suffering and other derived symptoms as depression and anxiety.

Overall success rate of hypophysis alone in mainly somatic pain and triple target for mixed oncological pain hovers around 70% in achieving a pain and medicine reduction.

There is a need for more clinical trial to validate the success rate of radiosurgery in this subgroup of patients, since these are refractory patients, radiosurgery and its noninvasive nature seem to have a high safety profile and appears as a reasonable alternative.


Eduardo LOVO (San Salvador, El Salvador), Alejandro BLANCO, Alejandra MOREIRA, Paola DEL CID
13:30 - 13:40 #39760 - OR028 Gamma knife thalamotomy for pain.
OR028 Gamma knife thalamotomy for pain.

Introduction: One of the methods for pain treatment is thalamotomy using the gamma knife. In this report, we build upon our previous experiences with irradiation of the centromedian – parafascicular (CM/Pf) complex of the thalamus and present a similar group of pain patients after irradiation of the central lateral thalamic nucleus  in whom conservative treatment failed.

Method and Patients: Between 2019 and 2023, we performed the unilateral (contralateral to pain) gamma-thalamotomy  in 31 patients (F:M=20:11; age ranged 53 – 89, mean 80 yrs; VAS ranged 2 – 10, median 8; the history of pain ranged 6-240, median 60 months; follow-up 6 – 34, median 12 months) suffering from various severe pain syndromes. Twenty three  patients underwent another invasive pain treatment before the  gamma-thalamotomy. In 8 patients, the procedure was additionally extended to bilateral by adding the ipsilateral gamma-thalamotomy. The Leksell Stereotactic Frame, GammaPlan Software (Elekta), and T1- and T2-weighted sequences acquired at 1.5 T (Siemens Avanto) were used to localize the targeted central lateral thalamus (CL). The gamma-thalamotomy was performed with an applied dose of 145 Gy in 24 patients and 135 Gy in 7 patients. In 8 cases of additional ipsilateral irradiation, 135 Gy was applied. Neurological examination and pain relief after radiation were evaluated. A decrease in pain intensity to less than 60% of the previous level was considered satisfactory (meaningful). 

Results: Initial meaningful  results were achieved in 13 (43%) of the patients, with  the complete pain relief in 4 patients.  Pain reduction was achieved with a latency of  2 weeks to 6 months (with continued relief up to 12 months after the procedure in 2 patients). Pain reduction was achieved in 9 (39%) patients with 145 Gy and in 4 (57 %) patients with 135 Gy. Additional bilateral intervention did not lead to any further positive effect in our cases. No recurrence of pain and no neurological deficits were observed.

Conclusion: Our results suggest that central lateral  gamma-thalamotomy in patients suffering from severe pain syndromes is a relatively successful and safe method. We did not observe any clinical side effects, no recurrence of pain in our study. Additional irradiation of the ipsilateral thalamus did not lead to further relief in our patients. The higher applied dose  does not evoked better results. Our new results with CL target are practically the same as with CM/Pf complex. Supported by MH CZ – DRO (NHH, 00023884).


Dusan URGOSIK (Prague, Czech Republic), Jaromir MAY, Roman LISCAK
13:40 - 13:50 #39865 - OR074 30 years & 6000 Vestibular Schwannomas Neurosurgically managed: Lessons Learned & Future Considerations about microenvironement.
30 years & 6000 Vestibular Schwannomas Neurosurgically managed: Lessons Learned & Future Considerations about microenvironement.

Background: We propose to analyze the results of 30 years of practice of radiosurgery in vestibular Schwannomas (VS) in order to question basics concepts of knowledge which have been driving our management of these patients during this period of time.

Material and Method: Among 6233 interventions for Vestibular Schwannomas in our group the long term results of the 5328 VS treated by SRS between July 1992 & May 2022 have been reviewed and compared to the literature. These tumors were sporadic VS with no previous therapy in 3487 patients. All these patients were treated with different Gamma Knife models, in a single dose with a marginal dose of 11Gy and 12Gy when the remaining hearing was functional or not respectively.

Results: The tumor control was on the long term 92% with 5 dramatically different patterns of morphological evolution. In 4 of the 5 patterns representing 85% of the patients a pseudo progression with large difference in the delay of onset/ disappearence and amplitude was observed. Depending on the pattern the risk of failure to control the tumor was varying from 0,3% to 29%. A malignant evolution was associated in 0,05%. The rate of facial palsy is 0,3% and trigeminal neuropathy 3,1%. The rate of functional hearing preservation at 1,2,3,5,7,10, 15 and 20 years is respectively 92,4%; 87,9%; 81,8%; 69,7%; 59,3%; 47,3%; 36,2% and 35% whatever the size of the tumor … The best predictors of functional hearing preservation were, early radiosurgery, better hearing class, less hearing disability perception and younger age. The tumor size and tumor increase is found to have no relationship with the clinical presentation but both are turning out to be related to the tumor content of macrophages in operated patients.

Conclusion: A number of these results are leading us to question some of the basic dogma of VS radiosurgery and specially the role of some doseplan principles. Clearly the definition of VS failure have to be revisited. We will discuss how the future practice of VS SRS can be profoundly affected by these findings.


Jean REGIS (Marseille), Anne BALOSSIER, Xavier MURACCIOLE, Jean Marc THOMASSIN, Pierre Hugues ROCHE
13:50 - 14:00 #40180 - OR030 Repeat radiosurgery for sporadic vestibular schwannoma following pirmary radiosurgical failure: An international multi-institutional investigation.
OR030 Repeat radiosurgery for sporadic vestibular schwannoma following pirmary radiosurgical failure: An international multi-institutional investigation.

Objective: To describe outcomes of patients with sporadic vestibular schwannoma (VS) who underwent repeat stereotactic radiosurgery (SRS) following primary SRS failure.

Study Design: Multi-institutional historical cohort study.

Setting: Five tertiary care referral centers.

Patients: Adults ≥18 years old, with sporadic vestibular schwannoma.

Intervention: Primary and repeat treatment with SRS.

Main outcome measure: Microsurgery-free survival following repeat SRS.

Results: Across institutions, 32 patients underwent repeat SRS following primary SRS. Median age at pirmary SRS was 62 years (IQR 49-70 years) and 72% of the patients were women. No patient had prior micorsurgery.  Most patients (74%) had tumors with cerebellopontine angle extension at primary SRS (median size 13.5 mm [IQR 7.5-18.8]). Following primary SRS, patients underwent repeat SRS at a median of 4.8 years (IQR 3.2-5.7). For treatment modality, 30 (94%) patients received Gamma Knife (GK) for primary treatment and 31 (97%) patients received GK as their repeat treatment.  The median marginal dose used was 12 Gy (IQR 12-12.5),  with a maximum dose of 25 Gy (IQR 24-27), with median prescription isodose line of 50% (IQR 49-50). The remaining 2 (6%) patients underwent SRS with CyberKnife® (CK; Accuray, Sunnyvale, CA, USA), both of whom received 3 fractions with a maximum dose of 23 and 24 Gy, respectively, and a marginal dose of 18 Gy. Median tumor volume increased from 0.970 cm3 at primary SRS to 2.200 cm3 at repeat SRS. Facial nerve function worsened in 2 patients after primary SRS and in 2 patients after repeat SRS. In total, 29 patients had audiometric data at primary SRS, and 27 patients had audiometric follow-up prior to repeat SRS. At primary SRS, median PTA and WRS were 39 dB (IQR 23-71) and 87% (IQR 20-100), respectively. At repeat SRS, median PTA worsened to 76 dB (IQR 49-120) and median WRS worsened to 0% (IQR 0-72). The percentage of patients with serviceable hearing (AAO-HNS class A/B) decreased from 59% to 21%.  There were no instances of intracranial complications following repeat SRS. Microsurgery-free survival rates (95% CI; number still at risk) at 1, 3, and 5 years following repeat SRS were 97% (90-100, 24), 84% (71-100, 13), and 68% (48-96, 6), respectively. There was 1 occurrence of malignancy diagnosed after repeat radiosurgery.

Conclusion: Overall, repeat SRS for sporadic VS has comparable risk profile, but lower rates of tumor control, compared to primary SRS.


Michael LINK (Rochester, USA), Karl KHANDALAVALA, Hans HERBERG, Emily KAY-RIVEST, John MARINELLI, Morten LUND-JOHANSENN, Christine LOHSE, Walter KUTZ, Peter SANTA MARIA, John GOLFINOS, Douglas KONDZIOLKA, Oystein TVEITEN, Matthew CARLSON

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C17ok
ORAL PRESENTATIONS
Quality Assurance and dosimetry

ORAL PRESENTATIONS
Quality Assurance and dosimetry

Moderators: David SCHLESINGER (Medical Physics) (Charlottesville, VA, USA, USA), Lei WANG (Medical Physicist) (Stanford, USA)
13:00 - 13:10 #39699 - OR031 Comprehensive multi-institutional results of End-to-End dosimetry audits in cranial Stereotactic Radiosurgery.
OR031 Comprehensive multi-institutional results of End-to-End dosimetry audits in cranial Stereotactic Radiosurgery.

Purpose: The escalating complexity and inherent uncertainties associated with contemporary cranial Stereotactic Radiosurgery (SRS) underscore the necessity for comprehensive audit processes. This study aims to delineate the outcomes derived from a phantom-based End-to-End multi-institutional dosimetry audit in cranial SRS.

Materials & Methods: Results from audits conducted at eleven (11) SRS centers were compiled. Nineteen (19) SRS delivery systems were included, comprising two (2) GammaKnife, two (2) Cyberknife, one (1) Novalis TX, six (6) Varian Truebeam, and eight (8) Elekta VersaHD systems. A commercial head phantom (PRIME phantom, RTsafe, Athens, Greece) was utilized, incorporating film (in all 19 SRS delivery systems), Optically Stimulated Luminescent Dosimeters (OSLDs) (in 7/19 SRS delivery systems), and gel dosimeters (in 8/19 SRS delivery systems). Calibration of film dosimeters and OSLDs was performed at the Secondary Standard Dosimetry of the Greek Atomic Energy Commission, ensuring traceability to BIPM-France. OSLDs were positioned in the coronal plane, while film was placed in both sagittal and coronal orientations. Recommendations from AAPM-TG-191 and AAPM-RSS for SRS-SBRT were adopted for OSL and film dosimetry, respectively. Gel dosimetry primarily assessed the overall 3D spatial accuracy of dose delivery. Users were provided with a multi-target RTstructure set and were tasked with achieving a specific level of accuracy according to the SRS treatment local protocol.

Results:

Film Dosimetry: For both coronal and sagittal configurations, the mean 3D gamma index passing rate for the film plane was approximately 95% for a 5%/1mm global criterion and ~96% for a 3%/2mm local criterion. The lowest passing rates observed were ~71% and 75%, respectively.

OSLDs: Deviations between OSLDs measurements and TPS calculations were generally below 4%, with individual differences reaching up to ~11% in high dose gradient regions.

Gel Dosimetry: The total 3D spatial offset between planned and measured gel distribution was below 0.80 mm for 63% of the study targets, with observed 3D spatial offsets up to ~2 mm.

Conclusions: This multi-institutional cranial SRS auditing study disclosed that the overall performance of audited SRS centers was satisfactory on average. However, there remains significant room for improvement in a significant proportion of these centers. The employed End-to-End auditing process proved efficient, successfully highlighting sources of uncertainties in the treatment workflow. The role of auditing in modern SRS adds value towards ensuring a safer and more effective treatment paradigm.


Kyveli ZOURARI, Vasiliki MARGARONI, Georgios KALAITZAKIS, Emmanouel ZOROS, Evangelos PAPPAS (Athens, Greece)
13:10 - 13:20 #39820 - OR032 Normal tissue sparing by an integrated VMAT planning in single isocenter dynamic conformal arc SRS plan for multiple brain metastases.
OR032 Normal tissue sparing by an integrated VMAT planning in single isocenter dynamic conformal arc SRS plan for multiple brain metastases.

Prior studies showed that single isocenter dynamic conformal arc (SI-DCA) plans provide equivalent normal tissue sparing capability to small, spherical shaped targets compared to volumetric modulated arc therapy (VMAT) plans, while it is much worse for large and/or irregular shaped targets. Recent version of a SI-DCA planning software integrated a VMAT planning on user-specified target while keep other targets planned with DCA technique. The intention is to reduce the local V12Gy around the large mets or cavities with VMAT optimization while keep other smaller mets with simple DCA planning. Three VMAT arc is used on the selected PTV and it shares the same isocenter as the other PTVs. VMAT optimization is run after the SIDCA group PTVs so that its dose distribution is taken into account during optimization.

In this study, 40 cases (266 targets) were included, in which at least one large mets or cavity exists (8.1 ± 3.6 cc in volume and 3.4 ± 0.6 cm in largest dimension). The majority of small mets were prescribed to 21 or 24 Gy, while the large ones at 15 or 18 Gy, following clinical guideline. For the large targets, its conformity index (CI), percentage isodose line (%IDL) and local V12Gy from both the SI-DCA plan and the VMAT- integrated plan were compared. The total V12Gy for entire plan were also compared.

Results: CIs are 1.32 ± 0.16 and 1.13 ± 0.05 for the large targets in DCA and VMAT plans, respectively. %IDL are 71.6 ± 3.5% and 67.8 ± 2.1% respectively. Local V12Gy are 7.3 ± 2.9 cc and 5.0 ± 2.3 cc in the DCA and VMAT plan, respectively, a reduction of 31 ± 12%. Total V12Gy are 16.9 ± 7.5 cc and 14.8 ± 7.4 cc, a reduction of 14 ± 11%.

Conclusions: An integrated VMAT planning in SI-DCA plan is very useful to reduce local V12Gy for large volume, irregular mets, resection cavities, or a group of adjacent mets. It provided an alternative solution between the simple forward planning SI-DCA and the complex full VMAT solution. However, currently only one PTV is allowed to be selected for VMAT, which limited the use of the technique to some extent. We are expecting vendor can make update to allow more PTVs to be included.


Haisong LIU (Philadelphia, USA), Yan YU, Yingxuan CHEN, James EVANS, Wenyin SHI
13:20 - 13:30 #39830 - OR033 Point and line profile dosimetry verification for SRS End to End testing using Trueinvivo micro silica bead TLD array (DOSEmapper).
OR033 Point and line profile dosimetry verification for SRS End to End testing using Trueinvivo micro silica bead TLD array (DOSEmapper).

We report on a novel and cost-effective thermoluminescent dosimeter (TLD) system (Trueinvivo DOSEmappers; 1mm micro silica bead TLD arrays) for systematic quality control in 3 distinct roles in separate equipment and institutions. Point, profile and cross-profile configurations are reported from commissioning and validation in end-to-end tests.

Method/Materials:

DOSEmappers were positioned through high-dose volumes to within +/-0.5mm as evaluated from external reference (crosswire projection) or CT-slice resolution for IGRT process. The DOSEmapper arrays included radiopaque markers to help IGRT and subsequent dose data extraction from the treatment planning system. Dose extraction uncertainty assessed at high dose gradient region within TLD volumes. Gamma analysis was performed for calculated and measured dose comparisons.

At centre-1, as part of a commissioning program for a Gamma-knife Icon, results on the Output factors for 2 collimator sizes are given. These compare Monte-Carlo based factors, a MicroLion chamber, DOSEmappers TLD arrays and EBT3 Film at isocentre in a GK specific, spherical solid-water phantom with a customised insert.    

At centre-2, profiles from high into low dose regions in 3 distinct GTVs measured with DOSEmapper TLD array within an RTSafe PseudoPatient® phantom, simulating BrainLab Elements single isocentre multimet treatment on Varian TrueBeam at 6FFF.

At centre-3, DOSEmapper spatial responses for a Gamma-knife Icon are given and include point results for a highly conformal dose volume with TLD profile across high and low dose regions at both Sup-Inf and Ant-Post directions in RTSafe Prime Phantom.

Results

Output factors for 8mm and 4mm collimators measured using DOSEmappers were 0.896 and 0.799, respectively – i.e. differences of 0.6% ±1.8% and -1.8% ±2.3% compared with TPS. Corresponding DOR for the MicroLion chamber were 0.892 and 0.828 (-0.9% and +1.7%); radiochromic film DOR are 0.892 and 0.815 (-1.0% and +0.1% ± 3.3%).

Centre-2, Profile measurements using TLD DOSEmappers yielded a gamma pass rate of 74% within 1%/1mm for the 0.2cc GTV, but more than 92% for the larger GTVs.

Centre-3, cross profile measurements obtained a gamma pass rates of: 88.2% for 1%/1mm, 91.2% for 3%/1mm sup-inf direction, and 82.4% for 1%/1mm, 94.1% for 3%/1mm Ant-post.

Testing precision of dose reporting from a calculated dosecube (0.1mm resolution) within a DOSEmapper element (1.6mm diameter) shows central dose approximates average doses across the bead even in a dose gradient of 17%.

Conclusion

The results indicate this latest generation of TLD is of adequate precision for commissioning and validation of SRS systems to within 1mm and +/-1cGy precision.


Rollo MOORE, Ian PADDICK, Lucy WINCH, Chris STEPANEK, Shakardokht JAFARI (Portsmouth, United Kingdom)
13:30 - 13:40 #40170 - OR034 Evaluation of the HYPERSCINT scintillation dosimetry platform for small-field characterization of a Leksell Gamma Knife.
OR034 Evaluation of the HYPERSCINT scintillation dosimetry platform for small-field characterization of a Leksell Gamma Knife.

The performance of the HYPERSCINT scintillation dosimetry research platform (RP-200, Medscint, Canada) for the characterization of small radiation fields administered using a Leksell Gamma Knife Perfexion radiosurgery device was evaluated.

The HYPERSCINT detector has a cylindrical sensitive volume of 0.5-mm diameter by 0.5-mm length coupled to a 20-m long optical fiber that connect to the hyperspectral reader at the console. Sensitive volume of the detector was chosen to be smaller than the dose plateau for the smallest of radiation fields produced by the Gamma Knife. Hyperspectral calibration of the detector according to manufacturer’s recommendation was performed using a conventional linear accelerator (TrueBeam, Varian, USA) and allowed for complete stem-effect removal (Cerenkov and fluorescence). Inserts for both solid water and ABS spherical phantoms (Elekta,Sweden) were adapted from the blank ones provided with the phantoms and allowed for positioning the scintillator at the center of each spherical phantom.

Output factors of the machine for both solid water and ABS phantoms were obtained by subjecting the detector to consecutive 120-second shots from the 4, 8, and 16 mm collimators, with the sensitive volume positioned at the focal point of the Gamma Knife. Dose profiles of a 4 mm collimator shot were also measured in the X, Y and Z directions. This was performed by irradiating a sequence that moved the phantom using the patient positioning system by increments of 0.2 mm. Results were compared to those obtained using a radiochromic film at the focal point (4 mm collimators, irradiation of 60 seconds).

The measured output factors and the Monte Carlo reference agreed within 0.5% for the ABS phantom and within 0.9% for the solid water one. Measurement of the full width half maximum (FWHM) for the 4 mm shot with the detector and the radiochromic films showed maximum differences of 0.22 mm in all directions and was within 0.03 mm along the z-axis. Overall, our results show that the detector response was in close agreement with Gamma Knife Monte Carlo reference data and film measurements. Slight differences could be explained by the fact that the phantom had to be moved to obtain the profiles for the scintillator, which was not the case for the film measurements.

Based on the obtained results, the plastic scintillation detector shows the potential for rapid validation of output factors and validation of film measurements as well its use in challenging small-field situations encountered with the Gamma Knife.


Mathieu GUILLOT, Patrick DELAGE (Sherbrooke, Canada), Vincent HUBERT-TREMBLAY, Francois THERRIAULT-PROULX, Danahé LEBLANC
13:40 - 13:50 #39722 - OR035 Development and evaluation of end-to-end quality assurance for single-isocenter linac-based stereotactic radiosurgery.
OR035 Development and evaluation of end-to-end quality assurance for single-isocenter linac-based stereotactic radiosurgery.

Objectives

The nature of Stereotactic Radiosurgery (SRS) requires very high accuracy in both treatment planning and delivery. A large body of literature exists on how to test various aspects of the SRS treatment chain. Only regularly performed end-to-end (E2E) quality assurance (QA) offers a comprehensive overview of the accuracy, by identifying possible uncertainties or weaknesses in the whole process. This study aims to report on the institutional development and evaluation of E2E QA for single-isocenter linac-based SRS.

Methods

The design of the E2E test was developed to assess the performance of the Linac system in single-isocenter SRS for both single and multiple brain metastases with regard to geometric and dosimetric accuracy. A commercially available non-anthropomorphic E2E phantom underwent the entire procedure of a standard patient treatment, encompassing imaging (CT and MRI), multi-modality fusion, structure contouring, treatment planning, positioning, and delivery. Specific dedicated inserts were used for each test, e.g. positioning accuracy was evaluated for kV-CBCT systems using a Winston-Lutz-type test. Dosimetric accuracy was measured with an ionization chamber (PTW Pinpoint) for 5 single target treatments and with films (Ahsland Gafchromic) for 5 single-isocenter multiple-target treatments. 

Results

In terms of test efficiency, when used in the configuration with the chamber perpendicular to treatment beams, the phantom allowed for a full E2E to be conducted in approximately 90 minutes. This timeframe encompasses obtaining a CT scan, undergoing the planning process, and delivering two doses, one to the ion chamber and one to the films. Notably, this timeline did not take into account the MRI acquisitions and fusion with the simulation CT. The E2E test was consistently reproducible. CT parameters of the inserts were within the specifications. For MR images, the grid-like insert showed no distortion. The positioning accuracy of the phantom using the kV-CBCT system was < 0.5 mm. Deviation of the measured point dose values from the treatment planning system (TPS) calculated dose was < 3%, while for the multiple target plans gamma (2%, 2mm) passing rates of corresponding films were greater than 95%.

Conclusion

All aspects of the treatment process were taken into account to ensure the proper ongoing performance of the treatment delivery unit, simulation devices, image guidance system, and TPS. Our E2E test has proven to be suitable for testing complex treatment scenarios, such as single-isocenter linac-based SRS for both single and multiple targets. Thus, it has been introduced as an annual QA in our institution.


Denis PANIZZA (Monza, Italy), Valeria FACCENDA, Valeria TREMOLADA, Martina Camilla DANIOTTI, Sara TRIVELLATO, Gianluca MONTANARI, Stefano ARCANGELI, Elena DE PONTI
13:50 - 14:00 #39666 - OR036 Dosimetrical optimization of stereotactic radiosurgery for multiple brain metastases: dual-isocenter outperforms single-isocenter technique.
OR036 Dosimetrical optimization of stereotactic radiosurgery for multiple brain metastases: dual-isocenter outperforms single-isocenter technique.

Purpose: Linac based single-isocenter technique (SIT) for Stereotactic Radiosurgery (SRS) of multiple brain metastases is a well-accepted treatment modality. Automated targeting and planning with a dedicated software allows more planning consistency and robustness. However, challenges may still occur depending on the proximity of the metastases to the isocenter, distance between metastases, or when the contour is irregular. For this reason, this study aims to compare dosimetrical outcomes using a SIT versus dual-isocenter technique (DIT) approaches for treating multiple brain metastases indicated for SRS.

Methods and Materials: Fifteen patients with each having 4-14metastases (total of 97 metastases), treated with a SIT and a prescription dose of 20Gy, were retrospectively selected. For each patient, lesions were separated into two clustered groups based on their locations and replanned using two isocenters (one per cluster group). Elements Multiple Brain Mets SRS v4.0 (Brainlab, Munich, Germany) protocols were predefined with decision making of isocenter placement and automatic geometrical optimization of 4-7table rotations, 2-4arcs per lesion, gantry, and collimator rotations. The following dosimetric parameters were evaluated: prescription dose covering 99% of the lesion, Paddick conformity index (PCI), mean (Dmean) and maximum (Dmax) lesion¢s dose and volume of brain receiving 12Gy, 10Gy, 5 and 3Gy (V12, V10, V5, V3, respectively). Dose to surrounding organs was limited according to their maximal allowed dose. The Wilcoxon signed-rank tests were applied to evaluate statistically significant differences. The alpha significance level was set at 0.01 to correct for multiple testing. Median values were used to evaluate the differences.

Results: Comparing respectively DIT versus SIT, we observed a statistically higher PCI (0.73 vs. 0.69; p<0.001) and statistically lower Dmax and Dmean (26.4Gy vs. 26.8Gy for Dmax; p<0.001 and 23.7Gy vs. 24.1Gy for Dmean; p<0.001). DIT showed a decrease in the volume of irradiated brain tissue for V12 (-0.25cc), V10 (-0.82cc), V5 (-0.39cc) and V3 (-21.65cc) compared to SIT in these 15 patients. Only the observed difference in V3 was considered statistically significant (p=0.007).

Conclusion: Dual-isocenter approach showed an improvement of conformity and dosimetry with normal tissue sparing for the treatment of multiple brain metastases. These differences relative to the SIT might be explained by the fact that the lesions located the furthest from isocenter are located under the thicker multi leaf collimators, which hinders the conformity.


Cristina TEIXEIRA (Jette, Belgium), Thierry GEVAERT, Racell NABHA, Marlies BOUSSAER, Sven VAN LAERE, Mark DE RIDDER

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A19
PLENARY SESSION
Retreatment in SRS/SBRT

PLENARY SESSION
Retreatment in SRS/SBRT

Moderators: Arjun SAHGAL (Professor) (Toronto, Canada), John SUH (Radiation Oncologist) (Cleveland, USA)
14:00 - 15:00 REPEAT local SBRT in oligometastatic cancer patients. Matthias GUCKENBERGER (Chairman) (Keynote Speaker, Zurich, Switzerland)
14:00 - 15:00 Optimizing reirradiation in the chest: the role of SBRT in locoregionally recurrent lung cancers. Charles SIMONE (Chief Medical Officer) (Keynote Speaker, New York, USA)
14:00 - 15:00 Re-Irradiation for Hepatic and Pancreatic Tumors. David HOROWITZ (Associate Professor) (Keynote Speaker, New York, USA)

15:00 - 15:30 COFFEE BREAK AND EXHIBITION
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A19.1
ORAL PRESENTATION
Brain Metastases - I

ORAL PRESENTATION
Brain Metastases - I

Moderators: John SUH (Radiation Oncologist) (Cleveland, USA), Daniel M. TRIFILETTI (Professor) (Jacksonville, USA)
15:30 - 15:40 #39641 - OR037 International collaboration of neoadjuvant stereotactic radiosurgery for brain metastases (INTERNEO): an individual patient data meta-analysis.
OR037 International collaboration of neoadjuvant stereotactic radiosurgery for brain metastases (INTERNEO): an individual patient data meta-analysis.

Background

Neoadjuvant stereotactic radiosurgery (NaSRS) for brain metastases is an evolving treatment approach that is increasingly utilised. The aim of this study was to report outcomes from the INTERNEO cohort (INTERnational collaboration of NEOadjuvant stereotactic radiosurgery for brain metastases).

Methods

This study is an individual patient data meta-analysis of cohorts from nine institutions in five countries. Cohorts included prospective Phase II trials, prospective registries and retrospective series. Eligibility criteria comprised patients with brain metastases from a solid organ malignancy who underwent NaSRS followed by resection. Endpoints included local failure (LF), radionecrosis (RN), symptomatic RN (sRN), leptomeningeal disease (LMD), nodular LMD (nLMD) and overall survival (OS). Cumulative incidences and pre-defined multi-variable analyses assessing the impact of fractionation after adjusting for maximum tumour diameter were reported using Fine-Gray subdistribution hazards models. Kaplan-Meier estimates were calculated for OS.

Results

There were 179 patients with 189 metastases. On a per-patient level, the median age was 64 years (IQR 55-70) and 76% were ECOG 0-1. On a per-metastasis level, the most common primary histologies were non-small cell lung cancer (n=83, 44%), melanoma (n=32, 17%) and breast (n=22, 12%). The median maximum diameter was 29mm (IQR 21-36). Single-fraction (sf-) NaSRS was performed for 100 (53%) metastases and the median dose was 18 Gy (IQR 16-18). Multi-fraction (mf-) NaSRS was performed for 89 (47%) and the most common dose fractionation was 24 Gy/3# (50/89, 56%). The median time from final NaSRS treatment to resection was three days.

The median clinical follow-up for alive patients was 21.0 months. All endpoints are reported at one year. The cumulative incidence of LF was 4.6% (95% CI 1.4-7.6%). The cumulative incidence of RN was 3.6% (95% CI 0.7-6.4%) and sRN was 1.8% (95% CI 0-3.8%). The cumulative incidence of LMD was 7.2% (95% CI 3.2-11.0%) and nLMD was 1.2% (95% CI 0-2.7%). OS was 66.3% (95% CI 59.5-73.8%). There was no significant difference in LF between sf-NaSRS and mf-NaSRS (HR 0.60 for mf-SRS, p= 0.39).

Conclusion

This individual patient data meta-analysis represents a large multi-national cohort with extended follow-up that further supports the efficacy of NaSRS in the management of brain metastases. We report excellent outcomes for LF, RN and nLMD with one-year rates of <5%. We present the largest cohort of mf-NaSRS and found no difference in LF compared to sf-SRS.


Cristian UDOVICICH (Melbourne, Australia), Kendrick KOO, John BRYANT, Alejandro BUGARINI, Michael HUO, Kyung Hwan KIM, Yuping Derek LI, Daniel E. OLIVER, Samir PATEL, Susanne ROGERS, Michael R. CHICOINE, Matthew C. FOOTE, Seon-Hwan KIM, Anand MAHADEVAN, Mark B. PINKHAM, Joseph SIA, Neda HAGHIGHI
15:40 - 15:50 #39645 - OR038 Intact brain metastases: gamma knife compared to linear accelerator stereotactic radiosurgery (the MET GALA cohort).
OR038 Intact brain metastases: gamma knife compared to linear accelerator stereotactic radiosurgery (the MET GALA cohort).

Background

Studies comparing Gamma Knife (GK) and linear accelerator (Linac) stereotactic radiosurgery (SRS) have been limited to only single-fraction (sf-) SRS in the GK cohort due to older GK models or different treatment protocols across the two platforms. Here, we evaluate contemporary data comparing the efficacy and toxicity of GK and Linac SRS for brain metastases (BrMs) undergoing sf-SRS and multi-fraction (mf-) SRS. 

Methods

This was a single-institution retrospective study of patients who underwent SRS for intact BrMs in 2020-2022. SRS was performed using the GK Icon with a 0mm PTV margin or Varian TrueBeam Linac with a 1mm PTV margin. Dose-fractionation was consistent across platforms and based on BrM diameter. Endpoints included 1-year local failure (1y-LF) and symptomatic radionecrosis (1y-sRN) rates. Cumulative incidences were calculated using the Fine-Gray model, and SRS platforms were compared with Gray’s test. 

Results 

Overall, 273 patients (GK: 136 [50%], Linac: 137 [50%]) and 754 BrMs (GK: 488 [65%], Linac: 266 [35%]) were analysed. There was no difference in the GK and Linac cohorts for baseline patient, primary tumour or concurrent systemic therapy characteristics. The GK cohort had a significantly higher median number of BrMs per patient (3 vs. 1 for Linac, p< 0.01) and a significantly increased proportion of <10mm BrMs (60% vs 35% for Linac, p< 0.01). The most common SRS regimens were 20 Gy/1 fraction (n=531 [70%]) and 24 Gy/3 fractions (n=148 [20%]). 

Median follow-up was 13.5 months (IQR 7.0-20.9). Overall, 1y-LF was not different between GK and Linac (GK: 12% vs. Linac: 15%, p=0.18), but 1y-sRN was significantly higher with Linac (GK: 3% vs. Linac: 7%, p= 0.03). When stratified by BrM size, no 1y-LF difference between GK and Linac was seen for BrMs <10mm (GK: 7% vs. Linac: 6%, p=0.70) or ≥10mm (GK: 21% vs. Linac: 19%, p=0.90). However, 1y-sRN was significantly higher with Linac only for BrMs <10mm (GK: 1% vs. Linac: 5%, p<0.01) and not ≥10mm (GK: 8% vs. Linac: 8%, p=0.90). The median time to overall radionecrosis was 8.1 months in the GK cohort and 7.6 months in the Linac cohort.

Conclusion

To our knowledge, this contemporary study with consistent treatment protocols is the first to compare clinical outcomes of sf-SRS and mf-SRS across GK and Linac SRS and is one of the largest cohorts comparing the two platforms. We observed similar 1y-LF but higher 1y-sRN rates in the Linac cohort, driven by BrMs <10mm. 


Cristian UDOVICICH (Melbourne, Australia), Kendrick KOO, Kevin ARMSTRONG, Gabrielle DRUM, Joshua P HOGAN, Dianna LE, Cathy MARKHAM, Robert NIGRO, Ken NGUYEN, Andrew PESKA, Katrina WOODFORD, Rebecca DARE, Andrew DAVIDSON, Michelle LI, Claire PHILLIPS, Nikki PLUMRIDGE, Joseph SIA, Neda HAGHIGHI
15:50 - 16:00 #39673 - OR039 Volumetric tumour response in patients treated with combination stereotactic radiosurgery and immunotherapy for melanoma brain metastases.
OR039 Volumetric tumour response in patients treated with combination stereotactic radiosurgery and immunotherapy for melanoma brain metastases.

Introduction: Stereotactic radiosurgery (SRS) confers excellent local control for melanoma brain metastases (MBM). This study examines the MRI volumetric tumour response over time of melanoma brain metastases following Gamma Knife SRS, and aims to synthesize a predictive model of volumetric change following treatment. 

Methods: A retrospective single-institution analysis was performed of patients who received single-fraction Gamma Knife SRS for melanoma brain metastases. Predictive factors relating to patient characteristics, tumour factors, SRS dose, volume and systemic therapy treatment factors were collected. Treatment volume was delineated on a T1-weighted Gadolinium contrast enhanced MRI at baseline and each follow-up scan. Cubic spline interpolation was used to extrapolate volumetric change with true MRI intervals and normalize these to 3-monthly intervals. A repeated measures ANOVA was used to assess for differences in mean volumetric change between interpolated 3-month intervals with a two-tailed significance of α=0.05.

Results: 101 patients with 425 melanoma BM were treated with SRS in the study period. Median follow-up was 29.2 months (IQR 19.7-39.8). Median dose was 20Gy (IQR 18-20). Median baseline volume and lesion diameter were 0.24cc (IQR 0.06-1.02) and 7.7mm (IQR 4.8-12.4) respectively. 77% of patients received concurrent immunotherapy. 89.7% of treated lesions had durable local control on MRI at last follow-up. There was a statistically significant association between concurrent immunotherapy and SRS with respect to more rapid volumetric regression of treated metastases. Patients receiving concurrent immunotherapy had a significantly greater regression in tumour volume at 3-months (37% superior [95%CI 6.0-68.1%, p=0.02] and 6-months (48% superior [95%CI 7.4-89.5%, p=0.02] compared to those commencing >4 weeks post-SRS. Patients receiving concurrent and ongoing immunotherapy with SRS were more likely to have a sustained local control (p=0.023), compared to patients not receiving concurrent immunotherapy. 5% of patients experienced symptomatic radionecrosis and 19% had any grade 3 or higher toxicity. The pattern of volumetric change over time was indicative of treatment effect vs. progression of disease. Radiological increase in size of treated at 3 months post SRS were more likely to demonstrate long-term PD whereas initial reduction in treatment volume with subsequent increase in treated lesion size at 12-15 months were found to represented non-sinister treatment effect.

Conclusion: This study demonstrates a significantly greater volumetric regression with concurrent immunotherapy and SRS in melanoma brain metastases in the initial 6-months following treatment. The trajectory of volumetric change can be discriminate between genuine progression or treatment effect in absence of; or inability to obtain, histological confirmation.


Mihir SHANKER (Brisbane, Australia), Heath FOLEY, Samuel CROWLEY, Ryan LUSK, Kendall MUSCAT, Emma LE CORNU, Michael HUO, Matthew FOOTE, Mark PINKHAM
16:00 - 16:10 #38768 - OR041 A randomized prospective study comparing two frameless immobilization systems for stereotactic brain HyperArc™.
OR041 A randomized prospective study comparing two frameless immobilization systems for stereotactic brain HyperArc™.

In the context of stereotactic brain radiotherapy, it is crucial to limit patient movement while ensuring patient comfort. For this purpose, the Double Shell Encompass™ Fibreplast System (DS Encompass) by CQ Medical™ is frequently used for frameless immobilization. To address difficulties in closing the double-shell mask, an alternative mask model has been proposed with the rear shell being replaced by a Moldcare® cushion (M Encompass). To validate the use of this method in conjunction with non-coplanar treatment modalities, we performed a prospective randomized study comparing the inter-and intrafractional variations and patient comfort between both masks.

The study was approved by the ethics committee of the hospital.  Sixty patients gave written consent and were stratified by treatment regimen (radiosurgery, fractionated stereotactic radiotherapy (FSRT), and conventional fractionation schedule with stereotactic margins), patients were randomized between DS or M Encompass. All treatment plans were created with HyperArc™ utilizing stereotactic margins. For radiosurgery and FSRT, a cone-beam CT (CBCT) pre-treatment was taken to correct interfractional variations, followed by a verification CBCT to confirm couch parameters. A post-treatment CBCT was acquired to verify for intrafractional variations. For the long conventional fractionation schedules, no post-CBCT was obtained due to radiation safety. At the end of the treatment, patients were asked to complete a Likert-based survey with two questions assessing their overall experience and the ease of remaining still. Unpaired t-tests were used in data-analysis.

Patient and treatment characteristics are depicted in Table 1. For the interfractional translations, no significant differences between the two systems are observed. Variations remain within 3 mm. More noticeable rotational variations are observed, with a significant difference in roll rotation, where DS Encompass allows for smaller deviations. Intrafractional variations are collected from 48 patients. For translations, the mean deviations remain largely under 1 mm for both systems. Regarding rotations, similar deviations are revealed. The mean rotational intrafractional deviations are less than 0.5°. Fifty-one patients completed the comfort questionnaire, reporting similar experiences in both groups with a mean score of 2-3.

In this randomized prospective study, there is no significant difference between the Double Shell Encompass and the Moldcare Encompass for intrafractional deviations. In terms of interfractional variations, we observed slightly larger mean deviations in the roll-axis with the Moldcare Encompass system. However, since these interfractional discrepancies can be corrected through daily CBCT-scans and 6D-couch corrections, they are not clinically relevant. Additionally, there is no difference in patient comfort within both groups.


Dylan CALLENS, Lise STESSENS, Chahrazad BENAZZOUZ, An NULENS, Wout PIOT, Maarten LAMBRECHT (Leuven, Belgium), Patrick BERKOVIC, Jean-François DAISNE
16:10 - 16:20 #39822 - OR042 Reduction of steroid therapy and neurological improvement in patients with large brain metastases treated with Two-Staged Gamma Knife.
OR042 Reduction of steroid therapy and neurological improvement in patients with large brain metastases treated with Two-Staged Gamma Knife.

Stereotactic radiosurgery is the preferred treatment for small and a limited number of brain metastases. However, due to the risk of toxicity, it is not recommended for large-sized metastases. The introduction of new dose fractionation protocols has opened up new perspectives. It is not yet clear whether hypofractionation (3-5 consecutive days) or adaptive staged radiosurgery (two treatments repeated at intervals of 2-4 weeks) is more effective, and the optimal prescription dose is also unknown.

In this study, we report our experience in treating large brain metastases with two-staged fractionations. The inclusion criterion for the study was the presence of metastases with a volume exceeding 7 ml, which are not suitable for surgical intervention due to the metastasis location (deep or eloquent area), the patient's general conditions, or the presence of multiple brain metastases.

Between January 2019 and November 2023, we treated 25 patients with brain metastases using fractionated modalities. Of these, 14 were men and 11 were women. Two patients had three metastases with a volume greater than 7 ml; therefore, a total of 29 tumors were treated.

The average volume of the lesions was 12.1 ml (7.0 - 21.7 ml), the median prescription dose was 12 Gy, and the median interval between stages was 30 days. 25 tumors showed a volume reduction before the second fraction. Three tumors exhibited a volume variation of less than 5% and were considered stable, while one tumor increased by 30% (treated with only 10 Gy due to proximity to the brainstem) and was consequently treated surgically.

The average volume of the tumors at the time of the second fraction was 7.4 ml (0.5-18.4 ml). The mean percentage reduction of the lesion was 39%, with the maximum reduction being 93%.

Eight patients exhibited neurological symptoms before the first fraction, and seven showed improvement by the second fraction. Nineteen patients were taking dexamethasone before the first fraction. Eight patients halved the dose or completely discontinued the steroid before the second treatment due to clinical improvement.

Two-staged Gamma Knife radiosurgery is a safe, non-invasive, and effective treatment for brain metastases. The reduction in volume between the first and second fractions allows the treatment of even large metastases with stereotactic radiosurgery, rapidly alleviating symptoms and the need for steroids.


Alberto FRANZIN (Brescia, Italy), Giorgio SPATOLA, Nicola REDOLFI, Lodoviga GIUDICE, Karol MIGLIORATI, Chiara BASSETTI, Sara DI MAIO, Mario BIGNARDI

15:30-16:30
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B19.1
ORAL PRESENTATION
Chest Radiosurgery

ORAL PRESENTATION
Chest Radiosurgery

Moderators: Alexander LOUIE (Radiation Oncologist) (Toronto, Canada), Ben SLOTMAN (Professor) (AMSTERDAM, The Netherlands)
15:30 - 15:40 #40142 - OR044 Immunotherapy improves local control for large lung cancer brain metastases compared to radiosurgery alone.
OR044 Immunotherapy improves local control for large lung cancer brain metastases compared to radiosurgery alone.

Objective/Introduction: Stereotactic radiosurgery (SRS) is a key pillar of treatment for patients with brain metastases (BM). However, despite advances in SRS, rates of local control are worse for patients with large BMs. Immune checkpoint inhibitors (ICIs) may provide synergistic effects when implemented alongside SRS, which may improve tumor local control. However, clinical outcome data on the effect of SRS provided with ICI (SRS+ICI) compared to SRS only for people with large BM remains limited. We demonstrate our single-center, retrospective experience with SRS with and without ICI for the treatment of patients having lung cancer BM greater than 4cc in volume.

Methods: Patients who received SRS therapy for the treatment of lung cancer BMs greater than 4cc in volume at Northwell Health between January 2017 and June 2023 were retrospectively identified. Local failure events (LF) and utilization of immunotherapy agents were identified and collected. Rate of local control was compared between the subgroup receiving SRS+ICI compared to SRS alone.

Results: A total of 155 large lung BMs (in 120 patients) greater than 4cc were identified. Of these, 17 patients (22 BMs) received SRS+ICI. There was no significant difference in the median BM volume (10.8cc for SRS only, 10.9cc for SRS+ICI; p=0.225). The rate of LF was significantly higher in the SRS only cohort compared to SRS+ICI (HR for SRS+ICI: 0.178, p=0.032). Six- and 12-month for LF rates were 6.1% and 8.7% for SRS only, and there were no LF events for patients receiving SRS+ICI.

Conclusions: We present one of the few studies demonstrating clinical outcomes for SRS+ICI for patients with large lung BMs. ICI provided alongside SRS yields improved rates of local control compared to SRS only. Further investigation will identify optimal timing of ICI therapy relative to SRS and elucidate the molecular mechanisms underlying this synergy.


Akash MISHRA (Manhasset, USA), Sirisha VISWANATHA, Michael SCHULDER, Anuj GOENKA
15:40 - 15:50 #39625 - OR045 Safety and efficacy of stereotactic radiotherapy for recurrent ventricular tachycardias in patients with structural heart disease - the Czech experience.
OR045 Safety and efficacy of stereotactic radiotherapy for recurrent ventricular tachycardias in patients with structural heart disease - the Czech experience.

Background: Stereotactic Arrhythmia Radiotherapy (STAR) has been proposed recently in patients with structural heart disease after failed catheter ablation (CA) for drug-refractory ventricular tachycardia (VT).  To describe the safety of STAR in the Czech Republic.

Methods: A precise strategy of target volume determination and a unified tactic of CA were used in 17 patients treated from December 2018 until June 2022 (EFFICACY cohort). This group, together with earlier series of 19 patients with less defined ablation strategy and less perfect target volume determination, composed the SAFETY cohort (n=36). A dose of 25 Gy was delivered.

Results: In the EFFICACY cohort, all patients experienced some therapy from implantable cardioverter-defibrillator (ICD) during 13.7 ± 11.6 months after STAR, except for two who died 1 and 8 months later. Eight patients (47 %) underwent at least one repeated CA (including one STAR). The burden of ICD therapies decreased, and this drop reached significance for DC shocks (1.9 ± 3.2 vs. 0.1 ± 0.2 per month, P = 0.03). Altogether eight patients (47 %) died. In the SAFETY cohort, acute adverse effects consisted of nausea in 4/39 (10 %) patients. As concerns long-term side effects observed after 32 procedures with a follow-up >6 months, eight patients (25 %) presented with a progression of mitral valve regurgitation, and three (9 %) of them had to undergo mitral valve intervention during the median follow-up of 33.5 months. Two cases of esophagitis (6 %) were seen with one death due to the esophago-pericardial fistula (3 %). Eighteen patients (50 %) died during the median follow-up of 26.9 months.

 

Conclusions: Although STAR may not be very effective in preventing VT recurrences for patients who have already failed CA treatment in an expert center, it can still modify the arrhythmogenic substrate, and when used with additional CA, reduce the number of ICD shocks.


Jakub CVEK (Frýdek-Místek, Czech Republic), Tomáš BLAŽEK, Eva SKÁCELÍKOVÁ, Lukáš KNYBEL, Jana HAŠKOVÁ, Petr PEICHEL, Otakar JIRAVSKÝ, Radek NEUWIRTH, Josef KAUTZNER
15:50 - 16:00 #38893 - OR046 Stereotactic radiosurgery for non-small cell lung cancer brain metastases before and after the start of the targeted therapy era.
OR046 Stereotactic radiosurgery for non-small cell lung cancer brain metastases before and after the start of the targeted therapy era.

Objective: In recent decades, advancements in detecting and treating targetable mutations in non-small cell lung cancer (NSCLC) have necessitated assessing new options for integrating targeted therapies into treatment plans. We evaluated the impact of stereotactic radiosurgery (SRS) and targeted therapies on median overall survival in NSCLC patients with brain metastases (BMs). Our study examined patients before and after routine testing for mutations and the use of mutation-targeting agents to assess the integration of targeted therapies.

 

Methods: We retrospectively reviewed patient charts from 2001 to 2021, focusing on those who received >1 SRS courses for BM from NSCLC. We compared patients with and without targetable mutations and analyzed median overall survival. Radiation dosages were evaluated using biologically effective dose (BED). Statistical tests included Mann-Whitney U and Chi-square tests and multivariate analysis for identifying independent risks of radiation necrosis/pseudoprogression after SRS. Kaplan-Meier regression was used for time-to-event investigations.

 

Results: Among the 235 patients examined, 88 (37.5%) had targetable mutations and 147 (62.5%) did not. Adenocarcinoma was the primary cancer type for both groups (93.2% and 66.0%, respectively). The most common mutations detected were in EGFR (40.4%), KRAS (23.4%), and ALK (16.0%). Patients with targetable mutations were more likely to be female (63.6%, p<0.001) and nonsmokers (59.1%, p<0.001). They also received more systemic therapies (median 3 vs. 2, p<0.001) and SRS courses (mean 1.56 vs. 1.32, p=0.020), with a higher BED (81.6 vs. 61.2, p<0.001). Rates of BM resection did not differ between the two groups (p=0.425). Patients with targetable mutations had lower mortality rates (72.7% vs. 90.5%, p<0.001) and higher median overall survival (23.2 vs. 7.4 months, p<0.001). Patients who received >1 SRS course had longer median overall survival (20.2 vs. 8.4 months, p<0.001), but higher BED (>60.0 Gy10) did not affect overall survival (11.5 vs. 9.6 months, p=0.556). Only the total number of SRS courses completed independently predicted the risk of radiation necrosis/pseudoprogression (OR 1.61, p=0.042).

 

Conclusion: Our findings indicate that patients with NSCLC BM and targetable mutations benefit the most from concurrent SRS and systemic therapy. Higher BED did not significantly affect overall survival, but the total number of SRS courses increased the risk of radiation necrosis/pseudoprogression. These results inform future best practices for managing NSCLC BM patients.


Randy L. JENSEN (Salt Lake City, USA), Lindsay BURT, Don CANNON, Kyril COLE
16:00 - 16:10 #39219 - OR047 SABR for medically inoperable early stage NSCLC - do we need a nomogram for survival?
OR047 SABR for medically inoperable early stage NSCLC - do we need a nomogram for survival?

Aim

Stereotactic ablative radiotherapy (SABR) for medically inoperable early stage non-small cell lung cancer (ES-NSCLC) is the standard treatment, but controversy persists whether or not all such patients benefit from SABR. The aim of this study is to compare prognostic factors for short and long term overall survival.

Methods

From August 2010 to 2022, 617 patients were treated, and to analyze prognostic factors, data were retrospectively collected and evaluated in 172 patients (median age 78 years) with peripheral or central ES-NSCLC treated between 2018 and 2020. The majority of patients were treated with 60 Gy in 3-5 fractions, and 30-33 Gy per fraction if the lesion diameter was less than 1 cm.  Kaplan-Meier curves were used to show differences in overall survival (OS) between groups. Variables with p < 0.25 from univariate analysis were entered into a multivariate Cox proportional hazards model.

Results

The median OS was 36 months. Median BED was 150 Gy10. The multivariate model showed that male sex (HR 1.51, 95% CI 1.01-2.28; p=.05) and AACCI > 5 (HR 1.56, 95% CI 1.06-2.31; p=.026) were statistically significant negative prognostic factors for OS. However, analysis of the OS curves shows that the negative effect of AACCI > 5 only becomes apparent at three years after SABR (3y-OS 37% vs. 57%, p=.021), whereas the differences in OS at two years and one year are non-significantly different (60% vs. 72%, p=.12; 86% vs. 83%, p=.58).

Conclusion

Intercurrent disease is a major negative prognostic factor for overall survival, but deaths in the first year after SABR are uncommon. Thus, SABR of ES-NSCLC with precise image guidance is the appropriate strategy for all medically inoperable patients with acceptable performance status.


Jakub CVEK (Frýdek-Místek, Czech Republic), Kamila RESOVÁ, Lukáš KNYBEL, Tereza PARAČKOVÁ
16:10 - 16:20 #40193 - OR048 Personalized pulsed SBRT for primary and secondary lung and liver tumors using AlignRT -OSMS.
OR048 Personalized pulsed SBRT for primary and secondary lung and liver tumors using AlignRT -OSMS.

Introduction:

Conventionally, stereotactic body radiotherapy(SBRT) is delivered over a number of daily fractions to a planning target volume that remains unchanged the therapy. However, allowing for longer periods of time between the fractions, there is a possibility of lesion volume reduction (as presented by Dr. Robert Timmerman at the 15th ISRS Congress in Milan - &rdquo;Radiobiological models and innovative dose-fractionation schedules-PULSAR&rdguo;).This way, adaptive plans can be made for every fraction, i.e. pulse, further reducing the dose to neraby organes at risk(OARs).

Objectives:

Our goal was to assess the reduction of lesion volumes between successive pulses, effects on OAR sparing, and total doses deliverd to PTVs.

Method and Materials:

From September 2022 to January 2023, we treted 7 patients with pulse approach, 6 with single lung lesion (in free brething using 4DCT), and one single liver lesion (in gated inspiratory breth hold).Initial patient setup and intrafraction motion was managed using OSMS-AlignRT and CBCT.

Results:

Six of seven patients has lesion volume reduction after the first pulse, and by the end of the SBRT all of lesion volumen has been reduced >_40%. Reductions in doses to OAR have alsobeen measured.

Conclusion:

Our preliminary results suggest that pulsed SBRT could be a good choice for patients with a large volume and close proximity of OARs.


Marica KESER, Sanja BREZOVEC, Mateja NOZINIC (Sveta Nedelja, Croatia)

15:30-16:30
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C19.1
ORAL PRESENTATION
Radiobiology/Focal Therapies/Radiosensitizers/Targeted Therapies

ORAL PRESENTATION
Radiobiology/Focal Therapies/Radiosensitizers/Targeted Therapies

Moderators: Erin DUNBAR (Director) (Atlanta, USA), Michelle KIM (moderator) (Ann Arbor, USA)
15:30 - 15:40 #39812 - OR049 Radiation enhancement using ultrasound-stimulated microbubbles: clinical trial results.
OR049 Radiation enhancement using ultrasound-stimulated microbubbles: clinical trial results.

Purpose: Preclinical studies have demonstrated that tumour cell death can be enhanced 10- to  40-fold when radiotherapy is combined with focussed ultrasound-stimulated microbubble  treatment. The acoustic exposure of microbubbles (intravascular gas microspheres) within the target volume causes bubble cavitation, which induces perturbation of tumour vasculature and activates endothelial cell apoptotic pathways responsible for the ablative effect of stereotactic body radiotherapy. Subsequent irradiation of a microbubble-sensitized tumour causes rapid increased tumour death. The study here presents the mature safety and efficacy outcomes of magnetic resonance (MR)-guided focussed ultrasound-stimulated microbubble (MRgFUS-MB) treatment, a novel radioenhancement therapy for breast cancer.

Methods/Materials: A single-arm phase 1 clinical trial included patients with stage I-IV breast cancer with in situ tumours for whom breast or chest wall radiotherapy was conducted. Patients were excluded if they had contraindications for contrast-enhanced MR or microbubble administration. Patients underwent 2-3 MRgFUS-MB treatments throughout radiotherapy. An MR-coupled focussed ultrasound device operating at 800 KHz and 540 kPa peak negative pressure was used to sonicate intravenously administrated microbubbles within the MR-guided target volume. The primary endpoint was toxicity per CTCAEv5.0 and tumour response at 3 months. Secondary endpoint was local control (LC).

Results: Eighteen patients with 20 primary breast cancers were included in this analysis. The prescribed radiation doses were 20 Gy/5 fractions (40%, n=8/20), 30-35 Gy/5 fractions (35%, n=7/20), 30-40 Gy/10 fractions (15%, n=3/20), and 66 Gy/33 fractions (10%, n=2/20). The median follow-up was 9 months (range, 0.3-29). Radiation dermatitis was the most common acute toxicity (Grade 1 in 16/20, Grade 2 in 1/20, and Grade 3 in 2/20). One patient developed grade 1 allergic reaction possibly related to microbubbles administration. At 3 months, 18 tumours were assessed for response; 83% (n=15/18) had partial (33%, n=6/18) or complete  (50%, n=9/18) responses, with a single progression. Further follow-up of responses indicated that the 6-, 12-, and 24-month LC rates were 94.4%, 88.5%, and 75.9%, respectively.

Conclusions: MRgFUS-MB was a safe and efficient treatment that provided durable responses.


Gregory CZARNOTA (Toronto, Canada), Danny VESPRINI, Hany SOLIMAN, Daniel PALHARES, Archya DASGUPTA, Ciang Ling HO, Lin LU, Joseph KUNG
15:40 - 15:50 #40129 - OR050 Intracranial hemorrhage in patients with renal cell carcinoma brain metastases treated with stereotactic radiosurgery and concurrent VEGF inhibitors.
OR050 Intracranial hemorrhage in patients with renal cell carcinoma brain metastases treated with stereotactic radiosurgery and concurrent VEGF inhibitors.

Purpose

Approximately 10-15% of patients with renal cell carcinoma (RCC) will develop brain metastases (BM) throughout the course of their disease, which portends a median overall survival of approximately 10 months. Targeted antiangiogenic therapies such as vascular endothelial growth factor inhibitors (VEGFi) remain the preferred first-line systemic regimen for patients with RCC, while stereotactic radiosurgery (SRS) can provide excellent local control of BM. RCC BM have a known risk of intracranial hemorrhage (ICH), and it is feared that the combination of SRS and VEGFi may exacerbate that risk. We thus evaluated the incidence of ICH in a large cohort of patients with RCC BM undergoing SRS with or without concurrent VEGFi.

 

Methodology

90 patients with RCC and with radiographic evidence of BM that were treated at Memorial Sloan Kettering Cancer Center (MSKCC) between 2010-2020 who received LINAC-based SRS were included. Concurrent therapy was defined as receipt of a VEGFi within 60 days either before or after the start of SRS. The primary endpoint was the development of new radiographically defined intracranial hemorrhage post-SRS. Median overall survival (OS), cumulative incidence of ICH, and 95% confidence intervals (CI) were estimated using Kaplan-Meier method. Gray’s test was used to evaluate post-SRS ICH events between groups, with patient death without ICH incorporated as a competing event.

 

Results

The median patient age was 62 years, 66 patients (71%) were male, and 78 patients (87%) had clear cell RCC histology. Median time from RCC primary diagnosis to BM diagnosis was 30.3 months. 32 patients received SRS with concurrent VEGFi (cVEGFi). Median follow-up was 20 months, with a median OS of 23.1 months (95% CI, 14.4-33.2). 

There were 22 total ICH events across the 90-patient cohort, with 9 events occurring post-SRS. At 6-, 12-, and 24-months post-SRS, the cumulative incidence of ICH was 9.4%, 9.4%, and 9.4% (95% CI, 2.3-22.5) at each timepoint for cVEGFi patients and 0%, 1.8% (95% CI, 0.1-8.4), and 9.0% (95% CI, 3.3-18.4) for those without concurrent VEGFi, respectively (p=0.996).

 

Conclusion

We present the first ICH profile of patients with RCC BM treated with SRS and concurrent antiangiogenics. We could not identify a difference in cumulative incidence of ICH post-SRS between the two groups. Future work seeks to explore the mechanism of action and efficacy of SRS and concurrent VEGFi in BM.


Luke DEL BALZO (Atlanta, USA), Andrea KNEZEVIC, Jennifer MA, Ritesh KOTECHA, Robert MOTZER, Kenny YU, Yao YU, Jessica WILCOX, Brandon IMBER, Yoshiya YAMADA, Abraham HAKIMI, Luke PIKE
15:50 - 16:00 #40154 - OR051 5-aminoleuvonic acid (5-ALA) use with concurrent intraoperative radiotherapy: interim analysis of radiation necrosis incidence from the INTRAGO II trial for glioblastoma.
OR051 5-aminoleuvonic acid (5-ALA) use with concurrent intraoperative radiotherapy: interim analysis of radiation necrosis incidence from the INTRAGO II trial for glioblastoma.

Purpose:  While the use of 5-ALA has been used to increase the extent of surgical resection in glioblastoma (GBM), its potential to act as a radiosensitizer has not been widely studied in the CNS.  Whereas typical external beam radiotherapy (EBRT) treatments occur weeks after surgery and 5-ALA administration, intraoperative radiotherapy (IORT) delivers radiation while protoporphyrin IX is still present in residual tumor.  This current study examines the potential for radiation necrosis (RN) development following IORT and subsequent fractionated radiotherapy.           

Methods:  Interim data from the INTRAGO II study for newly diagnosed GBM (NCT02685605) were analyzed for the incidence of radiation necrosis (RN) based on 5-ALA use, IORT treatment vs SOC control (60Gy EBRT), and extent of resection. Statistical analysis was performed via univariate (ANOVA), multivariate (Cox regression), and K-M estimations with significance of p<0.005. 

Results:  234 patients were enrolled in INTRAGO II between 2016 and 2022.  Of these, 185 (79%) had a surgical resection performed with the use of 5-ALA tumor fluorescence visualization.  Following surgical resection with 5-ALA, 94 (51%) received IORT (30Gy to the margin) and an additional 60Gy EBRT (ARM A).  Imaging confirmed RN occurred in 11 (12%) of ARM A patients who had 5-ALA assisted resection, compared to 3 (3.3%) of ARM B patients who received only 60Gy EBRT.  In the 49 patients not receiving 5-ALA, the imaging confirmed the RN rate in ARM A patients was 21% (5/24) compared to 12% in ARM B (3/25).  The median time to development of RN was 236 days post-IORT and 158 days post completion of EBRT.  ANOVA demonstrated a significantly (p=0.025) higher rate of RN in ARM A patients overall, but not with the addition of 5-ALA. Cox regression analysis confirmed that only significant predictor of RN on multivariate analysis was IORT plus EBRT (p=0.033) and KM estimations-Log Rank test of RN incidence were greater in Arm A/IORT patients than SOC/Arm B (p=0.029).

Conclusions:  While patients receiving IORT at the time of surgical resection had a higher rate of RN after SOC 60Gy EBRT, the use of 5-ALA in conjunction with surgical resection did not increase RN incidence.  Further analysis will need to consider local PFS rates and the impact of 5-ALA use with IORT.     


Christopher CIFARELLI (Morgantown, USA), Kevin PETRECCA, Henning KAHL, Oliver GANSLANDT, Stephanie COMBS, Frank GIORDANO
16:00 - 16:10 #40174 - OR052 Sulfasalazine as radiosensitizer in combination with stereotactic radiosurgery for recurrent glioblastoma multiforme – results of a phase 1 trial dose-escalation trial - NCT04205357.
OR052 Sulfasalazine as radiosensitizer in combination with stereotactic radiosurgery for recurrent glioblastoma multiforme – results of a phase 1 trial dose-escalation trial - NCT04205357.

Introduction

Glioblastoma (GBM) is an aggressive, radioresistant type of cancer with a dismal prognosis. Preclinically, Sulfasalazine (SAS) has shown tumor selective radiosensitizing properties by blocking the intratumoral production of the antioxidant glutathione (GSH). We examined the safety of SAS in combination with Gamma Knife Radiosurgery (GKRS) in patients with recurrent GBM (rGBM). The trial was funded by the Norwegian Cancer Society.

Material and Methods

We conducted a phase 1 trial which used a 3+3 design with four dose cohorts (1.5, 3.0, 4.5 or 6.0 g SAS/day). Patients with rGBM underwent GKRS with 12 Gy prescription dose following 3 days of pretreatment with SAS. Primary end-point was safety. Secondary end-points were changes in GSH levels measured with GSH-magnetic resonance spectroscopy prior to and after SAS treatment, altered metabolism measured by 11-C-MET-PET, quality of life (QoL) utilizing the Functional assessment of brain cancer therapy (FACT-Br) questionnaire, freedom from local tumor progression (FFTP) using the RANO criteria, progression-free survival (PFS) and overall survival (OS).

Results

Between May 2020 and September 2022, 12 patients with recurrent GBM were included. Dose-limiting toxicity was not reached. All AE were grade 1 (n = 13) or 2 (n = 6) of which 8 (42 %) were possibly related to SAS. FACT-BR remained stable for 6 months (p= 0.056) thereafter it declined significantly. SAS led to a significant but variable reduction in intratumoral GSH levels. Best radiographic response of the treated lesion was complete control in 3 (27.2 %), partial response in 6 (54.5 %), stable disease in 1 (9.1 %) and immediate tumor progression in 1 (9.1 %) out of 11 patient with follow-up images. Six (67 %) of 9 patients with PET at baseline and follow-up had reduced signal indicative of effect. The median FFTP and PFS were 12.1 months (95 % CI 1.2 – 7.1) and 4.1 months (95% CI 1.2 – 7.1) compared to 1.6 (95 % CI 1.4 – 1.8) and 1.6 (0.9 – 2.3) for historical controls, p < 0.001 and p = 0.006, respectively. The median OS was 11.3 months (95 % CI 5.1 – 17.7).

Conclusion

Novel treatment modalities for rGBM are urgently needed. SAS in combination with GKRS was safe and well tolerated with preliminary evidence of anti-tumor response. We are planning a higher phase multicenter trial with a larger cohort of patients for efficacy testing of SAS as radiosensitizer for rGBM.


Bente Sandvei SKEIE (Bergen, Norway), Sidsel BRAGSTAD, Renate GRUNER, Shahin SAROWAR, Goplen DOROTA, Jan Ingemann HEGGDAL, Per Øyvind ENGER
16:10 - 16:20 #39602 - OR053 Safety and efficacy of cyberknife radiosurgery plus anlotinib hydrochloride in patients with recurrent glioblastoma: a prospective phase II single-arm study (HSCK-002).
OR053 Safety and efficacy of cyberknife radiosurgery plus anlotinib hydrochloride in patients with recurrent glioblastoma: a prospective phase II single-arm study (HSCK-002).

BACKGROUND

Glioblastoma (GBM) is a tumor known for its highly vascular nature and limited treatment options upon disease recurrence. While Bevacizumab which target VEGF-A has gained approval for treating recurrent glioblastoma (rGBM), the multi-target tyrosine kinase inhibitor Anlotinib has the ability to directly target Vascular Endothelial Growth Factor Receptor (VEGFR), Platelet-Derived Growth Factor Receptor (PDGFR), and Fibroblast Growth Factor Receptor (FGFR). Theoretically, its anti-angiogenic effect may exceed that of Bevacizumab, and preliminary studies have shown its therapeutic efficacy in rGBM, indicating promising treatment potential. This study aims to present findings regarding the effectiveness and safety of combining Anlotinib with stereotactic radiosurgery (SRS) in treating patients with rGBM.

 

METHODS

HSCK-002 is a prospective single-arm, single center, phase II study (ClinicalTrials.gov Identifier: NCT04197492). Patients who underwent surgery, standard radiotherapy, and temozolomide chemotherapy and were diagnosed with recurrence based on Response Assessment in Neuro-Oncology (RANO) criteria and/or biopsy were eligible for inclusion. Each patient underwent CyberKnife SRS (25Gy/5fx) in combination with oral administration of Anlotinib (12 mg, daily, days 1–14/3 weeks) until encountering disease progression or experiencing intolerable adverse effects. The primary objective was the investigator-assessed median overall survival (OS) using the RANO criteria.

 

RESULTS

Between December 2019 and July 2023, 22 patients (median age: 55 years; range: 28–70 years) were included. According to RANO criteria, 21 patients exhibited tumor response, with 6 achieving complete response, resulting in an objective response rate of 95.5%. Additionally, one patient maintained stable disease without progression. Median progression-free survival (PFS) was 9.1 months (95% CI, 7.5–24.7), with a 6-month PFS rate of 85.7% (95% CI, 71.9–100.0). Median overall survival was 19.5 months (95% CI, 10.6–46.8). Common adverse events included hand-foot skin reactions (40.9%), hypercholesterolemia (27.3%), and hypertension (22.7%). Four patients experienced grade 3 adverse events, accounting for an 18.2% incidence rate. Therapy discontinuation due to ischemic stroke (grade 3) occurred in one patient. No grade 4 events or treatment-related deaths were reported.

 

CONCLUSIONS

The combination of salvage SRS with Anlotinib demonstrated promising outcomes and manageable toxicity in managing recurrent GBM. Currently, a phase II randomized controlled trial, supported by the Shanghai Municipal Commission of Health, is underway. This trial aims to compare the efficacy of Anlotinib combined with radiosurgery against Bevacizumab combined with radiosurgery for the treatment of rGBM patients, further exploring this therapeutic regimen.

 

 


Yun GUAN (Shanghai, China), Wei ZOU, Li PAN, Enmin WANG, Yang WANG, Xin WANG
16:20 - 16:30 #39783 - OR054 A novel method to prescribe iso-BED treatments using the Gamma Knife.
OR054 A novel method to prescribe iso-BED treatments using the Gamma Knife.

Objectives

A number of studies have demonstrated that variations in the overall treatment time of an SRS treatment affects the Biological Equivalent Dose (BED) delivered for a given prescription dose and hence the potential outcome of an SRS treatment. We investigate the feasibility of using an LGP lightning optimization system that fixes the overall treatment time and hence the BED for a given prescription dose.

 

Materials and methods

A series of 20 consecutive clinical AVM treatment plans, with a volume range of 0.23-8.0cc, were selected for replanning using a modified version of Lightning running on MATLAB. For each of the targets, a hard constraint of beam-on-time was enforced in the optimization algorithm producing plans of 30, 45 and 60 minutes duration. To accommodate cobalt decay, reference dose rates of 1.5Gy/min, 2.5Gy/min and 3.5Gy/min were simulated, resulting in nine plans for each target.

 

For each case the Paddick (PCI) and Gradient Indices (GI) were calculated. The BED, for the dose prescription iso-surface (mean and associated minimum and maximum values) was calculated using the bi-exponential repair equation described by Millar and Hopewell.  

 

Results

For fixed 30 min treatments, and varying the dose-rate between 1.5 Gy/min and 3.5Gy/min, the average PCI increased from 0.63 to 0.81 and the average GI decreased from 3.6 to 2.8.

Increasing the beam on time from 30 to 60 minutes increased the average PCI from 0.79 to 0.85 and decreased the average GI from 2.9 to 2.6. Increasing either dose-rate or treatment time will improve the quality of the plan, but this is an exponential effect with diminishing returns. 

 

Reanalysis of the original manual plans showed a significant variation in BED (between 69% and 84%) relative to the basic LQ derived value assuming no repair. This was significantly reduced by fixing treatment times (range 79-84%, 74-80% and 70-75% for 30-, 45- and 60-minutes respectively).

 

Conclusion

Results indicate that quality plans can be created for 45- and 60-minute treatment times even for low reference dose-rates. This gives clinicians the opportunity to deliver the same BED to every target prescribed to the same dose. This work also demonstrates that BED depends mainly on the overall treatment time (inclusive of any gaps in treatment) and the physical prescription dose and not on isocentre number or the reference dose rate. 


Ian PADDICK (London, United Kingdom), Haken NORDSTROM

Tuesday 14 May
Time Westside Ballroom 3&4 Marquis A&B Marquis C
07:00
07:00-08:00
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A20
BREAKFAST SEMINAR NEUROSURGERY
Challenging Cases in CNS

BREAKFAST SEMINAR NEUROSURGERY
Challenging Cases in CNS

Moderators: Michael CUSIMANO (Canada), John SUH (Radiation Oncologist) (Cleveland, USA)
07:00 - 07:20 Challenging Brain Metastasis Management Cases. Veronica CHIANG (Neurosurgery) (Keynote Speaker, New Haven, USA)
07:20 - 07:40 Tackling Complex CNS Challenges with Radiosurgery. Constantin TULEASCA (Staff neurosurgeon, senior lecturer) (Keynote Speaker, Lausanne, Switzerland)
07:40 - 08:00 Management of Radiation Necrosis.

07:00-08:00
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B20
BREAKFAST SEMINAR PHYSICS
Challenging Cases in Prostate

BREAKFAST SEMINAR PHYSICS
Challenging Cases in Prostate

Moderators: David BYUN (Radiation Oncologist) (New York, USA), Michael ZELEFSKY (New York, USA)
07:00 - 07:20 The march towards 2-fraction prostate SBRT. Wee Loon ONG (Radiation Oncologist) (Keynote Speaker, Melbourne, Australia)
07:20 - 07:40 Advancing MR-guided adaptive therapy for prostate cancer: Limitations and opportunities. Neelam TYAGI (Keynote Speaker, USA)
07:40 - 08:00 Technological advancements in the management of prostate cancer. Thierry GEVAERT (Head of Medical physics) (Keynote Speaker, Brussels, Belgium)

07:00-08:00
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C20
BREAKFAST SEMINAR RADIATION ONCOLOGY
Challenging Cases in Thorax and Abdomen

BREAKFAST SEMINAR RADIATION ONCOLOGY
Challenging Cases in Thorax and Abdomen

Moderators: Charles SIMONE (Chief Medical Officer) (New York, USA), Ben SLOTMAN (Professor) (AMSTERDAM, The Netherlands)
07:00 - 07:20 Clinically and Technically Challenging Cases in Abdominal SBRT. Lauren HENKE (Radiation Oncologist) (Keynote Speaker, St. Louis, USA)
07:20 - 07:40 Challenging cases in Lung SBRT. Alexander LOUIE (Radiation Oncologist) (Keynote Speaker, Toronto, Canada)
07:40 - 08:00 Challenging cases in the Liver and Kidney. Kevin STEPHANS (Keynote Speaker, Cleveland, USA)

08:00
08:00-08:30
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A21ok
LARS LEKSELL LECTURE

LARS LEKSELL LECTURE

08:00 - 08:30 For a conceptual renaissance in Radiosurgery. Jean REGIS (PROFESSEUR) (Keynote Speaker, Marseille, France)

08:30
08:30-09:30
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A22
PLENARY SESSION
Advanced Imaging for SRS/SBRT

PLENARY SESSION
Advanced Imaging for SRS/SBRT

Moderators: Caroline CHUNG (Associate Professor, Radiation Oncology) (Houston, USA), Michelle KIM (moderator) (Ann Arbor, USA)
08:30 - 09:30 Advanced Imaging and Motion Management for SBRT. Lucas VITZTHUM (CLINICAL ASSOCIATE PROFESSOR, RADIATION ONCOLOGY) (Keynote Speaker, Palo Alto, CA, USA)
08:30 - 09:30 AI and Computational Imaging: Opportunities in neuro-oncology. Pallavi TIWARI (Associate Professor) (Keynote Speaker, Madison, WI, USA)

09:30 - 10:00 COFFEE BREAK AND EXHIBITION
10:00
10:00-10:30
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A24
FABRIKANT AWARD & LECTURE

FABRIKANT AWARD & LECTURE

10:00 - 10:30 The Past We Know, How Will Be The Radiosurgery Future? Antonio DE SALLES (Professor - Chief) (Keynote Speaker, Sâo Paulo, Brazil)

10:30
10:30-11:30
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A25
PLENARY SESSION
Systemic Therapy and Radiosurgery

PLENARY SESSION
Systemic Therapy and Radiosurgery

Moderators: Manmeet AHLUWALIA (Healthcare) (Miami, USA), Veronica CHIANG (Neurosurgery) (New Haven, USA)
10:30 - 11:30 Systemic therapy with SRS: Use scenarios & management pearls. Erin DUNBAR (Director) (Keynote Speaker, Atlanta, USA)
10:30 - 11:30 SRS and immunotherapy in brain metastases – the double edged SABR. Rovel COLACO (Speaker and delegate) (Keynote Speaker, Manchester, United Kingdom)
10:30 - 11:30 Management of NSCLC Brain Metastasis with Stereotactic Radiosurgery and Tyrosine Kinase Inhibitors. Luke PIKE (Attending) (Keynote Speaker, New York, USA)

11:30
11:30-12:30
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A26
PARALLEL SESSION
Pediatric Radiosurgery

PARALLEL SESSION
Pediatric Radiosurgery

Moderators: Iris GIBBS (Professor) (Stanford, USA), Kiran KUMAR (Assistant Professor) (Dallas, USA)
11:30 - 12:30 Pediatric Cranial Radiosurgery. Erin MURPHY (Radiation Oncologoy) (Keynote Speaker, Cleveland, USA)
11:30 - 12:30 Radiosurgery or fractionated treatmends - what to do in peds and young adults. Stephanie COMBS (Radation Oncology) (Keynote Speaker, Munich, Germany, Germany)
11:30 - 12:30 Consolidative SBRT for Metastatic Pediatric Sarcoma. Matthew Michael LADRA (Keynote Speaker, USA)

11:30-12:30
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B26
PARALLEL SESSION
Access Disparities in SRS/SBRT

PARALLEL SESSION
Access Disparities in SRS/SBRT

Moderators: Andrew DAVIDSON (Australia), Antonio DE SALLES (Professor - Chief) (Sâo Paulo, Brazil)
11:30 - 12:30 Radiosurgery: The great divide, tales from a small country, south of the border. Eduardo LOVO IGLESIAS (Brain and Spine Radiosurgery Program) (Keynote Speaker, San Salvador, El Salvador)
11:30 - 12:30 Frameless functional Trigeminal Radiosurgery - Long term outcomes. Shankar VANGIPURAPU (Senior Consultant) (Keynote Speaker, Chennai, India)
11:30 - 12:30 Timing and Access Challenges in Definitive/Adjuvant Radiation for CNS Tumors Among Rural Patients. Christopher CIFARELLI (Center Director) (Keynote Speaker, Morgantown, USA)

11:30-12:30
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C26ok
PARALLEL SESSION
Guidelines & Societies

PARALLEL SESSION
Guidelines & Societies

Moderators: Samuel CHAO (Radiation Oncologist) (Cleveland, OH, USA), Michael LEE (Neurosurgeon) (Hong Kong SAR, Hong Kong), Jason SHEEHAN (neurosurgeon) (Charlottesville, USA)
11:30 - 12:30 Radiosurgery Guidelines: Beyond making and following rules. Isabelle GERMANO (Keynote Speaker, Briarcliff Manor, USA)
11:30 - 12:30 RANZCR 2023 update of Guidelines for safe practice of stereotactic body (ablative) radiation therapy and the establishment and growth of Stereotactic Interest Group of Australasia (SIGA). Matthew FOOTE (Deputy Director / Co-Director) (Keynote Speaker, Brisbane, Australia)
11:30 - 12:30 Stereotactic body radiotherapy for primary renal cell carcinoma: a systematic review and practice guideline from the International Society of Stereotactic Radiosurgery (ISRS). Simon LO (N/A) (Keynote Speaker, Seattle, USA)

12:30 - 13:30 SPONSORED LUNCH SYMPOSIA - LUNCH IN THE EXHIBITION
12:31
12:31-13:40
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B29bis
Networking Lunch of the Leksell Gamma Knife Society
ALVIN/CARNEGIE/LYCEUM Room

Networking Lunch of the Leksell Gamma Knife Society
ALVIN/CARNEGIE/LYCEUM Room

Kindly note that this is a dedicated LGK Society meeting for LGK practitioners and LGKS members participating in the Congress of the International Stereotactic Radiosurgery Society (ISRS).

Register here: https://events.elekta.com/Leksell-gamma-knife-ISRS
12:31 - 12:45 Doors Open.
12:45 - 13:40 Networking Lunch Starts.

13:30
13:30-16:00
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A29
ePoster viewing session
In presence of the authors and Scientific Jury

ePoster viewing session
In presence of the authors and Scientific Jury

13:30-16:30
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C29
Parallel Scientific / Clinical Sessions

Parallel Scientific / Clinical Sessions

13:40
13:40-16:30
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B29
Meeting of the Leksell Gamma Knife Society
ALVIN/CARNEGIE/LYCEUM Room

Meeting of the Leksell Gamma Knife Society
ALVIN/CARNEGIE/LYCEUM Room

Kindly note that this is a dedicated LGK Society meeting for LGK practitioners and LGKS members participating in the Congress of the International Stereotactic Radiosurgery Society (ISRS).

Register here: https://events.elekta.com/Leksell-gamma-knife-ISRS
13:40 - 14:00 Welcome Address.
14:00 - 16:30 Meeting.

16:00
Wednesday 15 May
Time Westside Ballroom 3&4 Marquis A&B Marquis C
07:00
07:00-08:00
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A30
BREAKFAST SEMINAR NEUROSURGERY
Re-irradiation in CNS Malignancies

BREAKFAST SEMINAR NEUROSURGERY
Re-irradiation in CNS Malignancies

Moderators: Jason SHEEHAN (neurosurgeon) (Charlottesville, USA), Tony WANG (Professor of Radiation Oncology) (New York, USA)
07:00 - 07:20 Reirradiation for brain tumours. Cecelia GZELL (Radiation Oncologist) (Keynote Speaker, Sydney, Australia)
07:20 - 07:40 When SRS Fails: Salvage Strategies For Recurrent Brain Metastases. Thomas BECKHAM (Assistant Professor) (Keynote Speaker, Houston, USA)
07:40 - 08:00 Repeat Radiosurgery for Malignant Brain Tumors. Douglas KONDZIOLKA (Neurosurgeon) (Keynote Speaker, New York, USA)

07:00-08:00
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B30
BREAKFAST SEMINAR PHYSICS
Treatment Uncertainty and Platform Dependent Margins

BREAKFAST SEMINAR PHYSICS
Treatment Uncertainty and Platform Dependent Margins

Moderators: Ian PADDICK (Consultant Physicist) (London, United Kingdom), Scott SOLTYS (ISRS 2023) (Stanford, CA, USA)
07:00 - 07:20 Uncertainties in imaged guided hypofractionated stereotactic radiosurgery and implications to ensure successful treatment delivery. Benjamin ZIEMER (Medical Physicist) (Keynote Speaker, San Francisco, USA)
07:20 - 07:40 Treatment Uncertainty and Margins in Gamma Knife Radiosurgery. Gennady NEYMAN (Medical Physicist) (Keynote Speaker, Cleveland, USA)
07:40 - 08:00 Treatment Uncertainties in Radiosurgery and Application to Single-Isocenter Multi-Target Treatments. Timothy SOLBERG (Senior Advisor for Emerging Technology) (Keynote Speaker, Sonoma Valley, USA)

07:00-08:00
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C30
BREAKFAST SEMINAR RADIATION ONCOLOGY
Building a SBRT Program

BREAKFAST SEMINAR RADIATION ONCOLOGY
Building a SBRT Program

Moderators: Matthew FOOTE (Deputy Director / Co-Director) (Brisbane, Australia), Simon LO (N/A) (Seattle, USA)
07:00 - 07:20 Building spine radiosurgery program. Samuel RYU (Professor) (Keynote Speaker, Stony Brook, NY, USA)
07:20 - 07:40 Key Components to Building a Successful Radiosurgery Program. Rupesh KOTECHA (Radiation Oncologist) (Keynote Speaker, Miami, USA)
07:40 - 08:00 Building a Radiosurgery Program. Antonio DE SALLES (Professor - Chief) (Keynote Speaker, Sâo Paulo, Brazil)

08:00
08:00-08:30
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A31
ISRS STRATEGIC INITIATIVES

ISRS STRATEGIC INITIATIVES

08:00 - 08:01 Welcome and session introduction. Arjun SAHGAL (Professor) (Keynote Speaker, Toronto, Canada)
08:01 - 08:10 ISRS Guidelines Project. Arjun SAHGAL (Professor) (Keynote Speaker, Toronto, Canada)
08:10 - 08:25 ISRS Certifications Service. Ian PADDICK (Consultant Physicist) (Keynote Speaker, London, United Kingdom)
08:25 - 08:29 ISRS Education Program. Marc LEVIVIER (Chef de Service) (Keynote Speaker, Lausanne, Switzerland)
08:29 - 08:30 Closing words. Marc LEVIVIER (Chef de Service) (Keynote Speaker, Lausanne, Switzerland)

08:30
08:30-09:30
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A32ok
PLENARY SESSION
Oligometastatic Disease Management

PLENARY SESSION
Oligometastatic Disease Management

Moderators: Amol GHIA (Associate Professor) (Houston, USA), Michael MILANO (faculty) (Rochester, NY, USA)
08:30 - 09:30 Integrating metastasis-directed SABR into the multi-disciplinary treatment of metastatic disease:  opportunities for biology to guide management. Rohann CORREA (Radiation Oncologist) (Keynote Speaker, London, Canada)
08:30 - 09:30 Management of Oligometastatic Prostate Cancer. Kevin STEPHANS (Keynote Speaker, Cleveland, USA)
08:30 - 09:30 Updates in Principles of Oligometastatic Disease Management. Rupesh KOTECHA (Radiation Oncologist) (Keynote Speaker, Miami, USA)

09:30 - 10:00 COFFEE BREAK AND EXHIBITION
10:00
10:00-11:00
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A34
ORAL PRESENTATIONS
Targeted & Immuno Therapy for Brain Mets Radiosurgery/Brain Mets II

ORAL PRESENTATIONS
Targeted & Immuno Therapy for Brain Mets Radiosurgery/Brain Mets II

Moderators: Steve BRAUNSTEIN (Faculty) (San Francisco, USA), Luke PIKE (Attending) (New York, USA)
10:00 - 10:10 #39637 - OR056 Factors predicting for local failure following Gamma Knife radiosurgery to small melanoma brain metastases: impact of distance from isocenter, prescription isodose and beam-on time.
OR056 Factors predicting for local failure following Gamma Knife radiosurgery to small melanoma brain metastases: impact of distance from isocenter, prescription isodose and beam-on time.

Introduction: 

Stereotactic radiosurgery (SRS) to small brain metastases (BM) achieves high rates of local control but outcomes can still vary. Magnetic resonance imaging distortion increases with distance from imaging isocentre and may impact SRS accuracy, particularly for small targets. Higher covering isodoses for small BM can be used to improve dose conformality. Finally, biologically effective dose (BED) incorporating treatment time has been associated with outcomes in other conditions, but not BM. We investigated factors associated with local failure after SRS in patients with melanoma BM <1cc.

 

Methods:

A single-institution retrospective review was conducted to identify patients with melanoma BM <1cc treated with Gamma Knife SRS. Data on individual BM volume, BRAF mutation status, distance of each BM from treatment isocentre (approximately co-incident with imaging isocentre), SRS dose, prescription isodose, cobalt-60 dose-rate, beam-on time, selectivity and gradient index, and concurrent immunotherapy administration (within 4 weeks) were analysed. Local failure was categorized into binary outcome variables and odds ratios (OR) were generated for the effect of explanatory variables on local failure. Multivariate analysis (MVA) via backwards-elimination was performed with a p<0.05 for significance. 

 

Results:

A total of 77 patients with 311 melanoma BM <1cc were treated with SRS between January 2015 – June 2019. 48% of patients were BRAF-mutant. Median BM volume was 0.125cc (range 0.002-0.986) and median distance from isocentre was 64.9mm (range 11-108mm). The median prescribed SRS dose, coverage, selectivity and gradient index were 20 Gy, 99%, 0.535 and 3.185 respectively. The mean beam-on time was 15 minutes. SRS was delivered concurrently with immunotherapy in 78% of cases. Median follow-up after SRS was 29.2 months. 

 

The overall local control rate was 88%. On MVA, longer beam-on time (OR 1.144, 95% CI: 1.037-1.238; p<0.0057), BRAF mutation (OR 1.574, 95% CI: 0.146-0.765; p<0.0095), and higher prescription isodose (OR 1.063, 95% CI: 0.715-1.040; p<0.0315) were associated with an increased risk of local failure. BM distance from isocentre was not associated with local failure (OR 1.022, 95% CI: 0.999-1.046; p<0.0562), nor were selectivity (OR 7.598, 95% CI: 0.260-172.408; p<0.2513), gradient index (OR 0.801, 95% CI: 0.443-1.448; p<0.4625) and Cobalt-60 dose-rate (OR 2.941, 95% CI: 0.484-5.200; p<0.4466). 

 

Conclusions: 

Longer beam-on time, presence of a BRAF mutation and higher prescription isodose (and thus lower point maximum dose) are associated with local failure following SRS for melanoma brain metastases measuring <1cc. BM distance from isocentre was not associated with local failure, reflecting robust institutional quality-assurance processes.


Michael HUO (Brisbane, Australia), Mihir SHANKER, Ryan LUSK, Catherine JONES, Prabhakar RAMACHANDRAN, Michael JENKINS, Susannah KING, Trevor WATKINS, Bruce HALL, Sarah OLSON, Mark PINKHAM, Matthew FOOTE
10:10 - 10:20 #39742 - OR057 The power of upfront gamma knife stereotactic radiosurgery with new generation tyrosine kinase inhibitors in treating EGFR-mutant lung adenocarcinoma with brain metastasis.
OR057 The power of upfront gamma knife stereotactic radiosurgery with new generation tyrosine kinase inhibitors in treating EGFR-mutant lung adenocarcinoma with brain metastasis.

Background and objectives: Lung adenocarcinoma with epidermal growth factor receptor mutation (EGFR-mutant) is the most common etiology of brain metastasis in Taiwan, and which is usually treated with tyrosine kinase inhibitors (TKIs) and gamma knife stereotactic radiosurgery (GKRS). As the emerging of second or third generation TKIs which are dominating on penetrating brain blood barrier, there are debates about whether GKRS should be postponed as a salvage management or upfront with TKIs as an initial treatment of newly diagnosed brain metastases. Therefore, this study purposed to find out the prognostic factors of these patients and compare the clinical outcome of upfront GKRS with TKIs to solely 2nd or 3rd generation TKIs in treating patients with EGFR-mutant lung adenocarcinoma brain metastasis.

Methods: We retrospectively collected patients with EGFR-mutant lung adenocarcinoma who received 2nd or 3rd generation TKIs with or without upfront GKRS as initial treatment for their newly diagnosed brain metastasis in two medical centers from Jan 2014 to Dec 2021. Probability of Treatment Weighting (IPTW) was used to match whole potential confounders between these two groups. Furthermore, we use SPSS 23.0 for statistics analysis.

Results: There were 143 patients enrolled in this study, including 98 pts had upfront GKRS with 2nd or 3rd generation TKIs and 45 pts with solely 2nd or 3rd generation TKIs as their initially treatment on newly diagnosed brain metastasis. After multivariate regression analysis, age, Karnofsky performance scale (KPS), extracranial metastasis status, control of primary tumor and number of brain metastases are statistics significant prognostic factors. After IPTW, there is no statistic significant difference in upfront GKRS with TKIs group and solely TKIs group on all confounders. The upfront GKRS with 2nd or 3rdgeneration TKIs group demonstrated significantly prolonged median progression-free survival (40.9 months vs. solely 2nd or 3rd generation TKIs group 12.6 months, P<0.001) and median overall survival (59.5 months vs. solely 2nd or 3rd generation TKIs group 30.8 months, P<0.001).

 Conclusion: Age, KPS, extracranial metastasis status, primary tumor control and number of brain metastasis are prognostic factors in patients with EGFR-mutant lung adenocarcinoma brain metastasis. Upfront GKRS with new generation TKIs not only provide better local control but also improve prognosis.


Andrew Szu-Hao LIU (Kaohsiung, Taiwan), Cheng-Chia LEE, Huai-Che YANG, Wei-Lun HUANG, Yu-Hsien HUANG, Wen-Yuh CHUNG, Chi-Jen CHOU
10:20 - 10:30 #38818 - OR058 Synergistic effects of immune checkpoint inhibitors in combination with stereotactic radiosurgery for lung cancer patients with brain metastases: a propensity score-matched analysis.
OR058 Synergistic effects of immune checkpoint inhibitors in combination with stereotactic radiosurgery for lung cancer patients with brain metastases: a propensity score-matched analysis.

OBJECTIVE
Stereotactic radiosurgery (SRS) is the mainstay for treating brain metastases (BMs) from lung cancer (LC). In recent years, immune checkpoint inhibitors (ICIs) have been applied to metastatic LC and have contributed to improved outcomes. The authors investigated whether SRS with concurrent ICIs for LC BMs prolongs overall survival (OS) and improves intracranial disease control, and whether there are any safety concerns.

METHODS
Patients who underwent SRS for LC BMs in our institution between January 2015 and December 2021 were included. Concurrent use of ICIs was defined as no more than 3 months between SRS and ICI administration. The two treatment groups, which had a similar likelihood of receiving concurrent ICIs, were generated by a propensity score matching (PSM) (match ratio 1:1) based on 11 potential prognostic covariates. Patient survival and intracranial disease control were compared between the groups with and without concurrent ICIs (ICI+SRS vs. SRS) by time-dependent analyses taking into account competing events.

RESULTS
In total, 585 LC BM patients (494 NCSCL and 91 SCLC) were eligible. Of those, 93 patients (16%) received concurrent ICIs. Two groups with 89 patients each (ICI+SRS group and SRS group) were generated by PSM. The 1-year survival rates of the ICI+SRS and SRS groups after the initial SRS were 65% and 50%, the median survival times 16.9 and 12.0 months, respectively (HR: 0.62, 95% CI: 0.44–0.87, p = 0.006). The 2-year cumulative neurological mortality rates were 12% and 16%, respectively (HR: 0.55, 95% CI: 0.28–1.10, p = 0.091). The 1-year intracranial progression-free survival rates were 35% and 26% (HR: 0.73, 95% CI: 0.53–0.99, p = 0.047).The 2-year local failure rates were 12% and 18% (HR: 0.72, 95% CI: 0.32–1.61, p = 0.43) and the 2-year distant recurrence rates were 51% and 60% (HR: 0.82 95% CI: 0.55–1.23, p = 0.34). Severe adverse radiation events (CTCAE grade 4) occurred in one patient in each group and CTCAE grade 3 toxicities were observed in 3 patients in the ICI+SRS group and 5 in the SRS group (OR: 1.53, 95% CI: 0.35–7.7, p = 0.75).

CONCLUSIONS
The present study found that SRS with concurrent ICIs for LC BM patients was associated with longer survival and durable intracranial disease control with no apparent increase in treatment-related adverse events.


Shoji YOMO (Matsumoto, Japan)
10:30 - 10:40 #39803 - OR059 3-staged fractionated adaptive Gamma Knife radiosurgery in the management of patients with large brain metastases yields high local control rates with low toxicity profile.
OR059 3-staged fractionated adaptive Gamma Knife radiosurgery in the management of patients with large brain metastases yields high local control rates with low toxicity profile.

Introduction Single fraction Gamma Knife radiosurgery (GKRS) is a well-accepted treatment modality for small to medium sized brain metastases (BM). For large BM (LBM; >10-15 cm3), single fraction GKRS is associated with suboptimal LC rates and an increased risk of treatment-related toxicity. For LBM, 2-staged or 3-staged fractionated adaptive GKRS (3-GKRS) has been used to enhance LC while limiting adverse radiation effects. We present our experience with 3-GKRS in LBM >15 cm3. 

 

Methods Data of patients with LBM >15 cm3 treated with 3-GKRS between January 2018 and March 2023 at the Gamma Knife Center Tilburg were retrospectively collected. The regimen consisted of 3 fractions of 10 Gy prescribed to the isodoseline covering 100% of the target with 2 weeks interval between the subsequent fractions. For each fraction, a new MRI was performed for target delineation and treatment planning. All patients had follow-up appointments with MRI as long as clinical meaningful. In case of new intracranial disease new treatment was offered if appropriate. Descriptive analyses were used to give an overview of the patient and tumor characteristics. Kaplan-Meier curves were used to analyze overall survival.

 

Results 70 patients (male 51%; median age 68 years (range 40-85 years); 56% non-small cell lung cancer, 17% breast cancer) were treated with 3-GKRS. The median tumor volume of the LBM was 29 cm3 (range 15.2 cm3 - 87.4cm3). The median overall survival was 11 months (95% CI, 9 to 13 months). Six patients (14%) died due to a neurological cause (1 due to the LBM). At the 3rd fraction, reduction in volume of the LBM was observed in 85.7% of the patients (>65% reduction in 8 patients). LC rates of the LBM were 98.2%, 93.3% and 91.9% at 6 weeks and at 3 and 6 months respectively. Neurological improvement or stabilization was observed in 57.4%, 60.4% and 66.7% of the patients and dexamethason dose could be reduced to ≤1.5mg/day in 63.9%, 71.4% and 75.7% at 6 weeks and at 3 and 6 months, respectively. Transient symptomatic adverse effects were observed in 20.7% of the patients between 5 and 46 months after GKRS.  

 

Discussion 3-GKRS is well tolerated and a valuable treatment option in patients with LBM. Larger series are needed in order to evaluate for which patients this regimen is an alternative to resection.


Patrick HANSSENS, Patrick HANSSENS (Tilburg, The Netherlands), Eline VERHAAK, Suan Te LIE, Bram VAN DER POL, Jeroen VERHEUL, Liselotte LAMERS, Hazem AL-KHAWAJA, Diana GROOTENBOERS, Jannie SCHASFOORT - VAN DEN TILLAART, Wim DE JONG
10:40 - 10:50 #38726 - OR060 Repeated HyperArc Radiosurgery for recurrent intracranial metastases and dosimetric analysis of recurrence pattern to account for diffuse dose effect on microscopical disease.
OR060 Repeated HyperArc Radiosurgery for recurrent intracranial metastases and dosimetric analysis of recurrence pattern to account for diffuse dose effect on microscopical disease.

Aims: Stereotactic radiosurgery (SRS) is an established non-invasive therapy for multiple brain metastases (BMs). Mono-isocentric techniques allow the delivery of multiple stereotactic courses, in case of intracranial failure. Nevertheless, limited data on the effectiveness and toxicity have been reported, as well as details on patterns of failure. Aim of this study is to evaluate effectiveness and safety of multiple HyperArc courses and patterns of progression in patients affected by BMs with intracranial progression.

Methods: between June 2017 and January 2022, 56 patients were treated for 702 BMs with 197 (range 2-8) HyperArc courses in case of exclusive intracranial progression. Primary tumor was lung in 26 (46.5%), breast in 18 (32%), melanoma in 8 (14%), and other in 4 (7.5%). BM site was: supratentorial in 529 (75%), infratentorial in 160 (23%), brainstem in 13 (2%). The primary end-point was the overall survival (OS), secondary end-points were intracranial progression-free survival (iPFS), toxicity, local control (LC), neurological death (ND), and WBRT-free survival. Site of progression was evaluated against isodoses levels (0, 1, 2, 3, 5, 7, 8, 10, 13, 15, 20, and 24 Gy.).

Results: median SRS dose was 25 Gy (range 24-27 Gy). The 1-year OS was 70%, and the median was 20.8 months (17-36). At the univariate analysis (UVA) BED>51.3Gy and non-melanoma histology significantly correlated with OS. The median time to iPFS was 4.9 months, and the 1-year iPFS was 15%. Globally, 538 new BMs occurred after the first HA cycle in patients with extracranial disease controlled. 95% of them occurred within the isodoses range 0-7 Gy as follows: 27.5% (0 Gy), 19.5% (1 Gy), 16.7% (2 Gy), 16% (3 Gy), 12.5% (5 Gy), 2.8% (7 Gy) (p=0.00). Clinical toxicity was represented by headache 4 (7.1%), and radionecrosis 2 (0.28% of treated metastases). One- and 2-year LC was 90% and 79%, respectively. At the UVA BED>70 Gy and non-melanoma histology were significant predictors of higher LC. The 2-year WBRT-free survival was 70%. After a median follow-up of 20 months, 12 patients deceased by ND (median time 17.4 months).

Conclusion: Intracranical relapses can be safely and effectively treated with repeated HyperArc, with the aim to postpone or avoid WBRT. Diffuse dose by volumetric RT might reduce microscopic disease also at relatively low levels, potentially acting as a virtual CTV. Neurological death is not the most common cause of death in this population, which highlights the impact of extracranial disease on overall survival


Luca NICOSIA, Andrea Gaetano ALLEGRA, Niccolò GIAJ-LEVRA, Reyhaneh BAYANI, Nima Mousavi DARZIKOLAEE, Rosario MAZZOLA, Edoardo PASTORELLO, Paolo RAVELLI, Francesco RICCHETTI, Michele RIGO (Negrar di Valpolicella, Italy), Ruggero RUGGIERI, Davide GURRERA, Riccardo Filippo BORGESE, Simona GAITO, Giuseppe MINNITI, Pierina NAVARRIA, Marta SCORSETTI, Filippo ALONGI

10:00-11:00
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B34
ORAL PRESENTATIONS
Liver/Pancreas/Kidney/Gyn/Breast

ORAL PRESENTATIONS
Liver/Pancreas/Kidney/Gyn/Breast

Moderators: Muhammad ALI (Specialist) (Melbourne, Australia), Lauren HENKE (Radiation Oncologist) (St. Louis, USA)
10:00 - 10:10 #40190 - OR061 Uncovering the Armpit of SBRT: An Institutional Experience with Stereotactic Radiation of Axillary Metastases.
OR061 Uncovering the Armpit of SBRT: An Institutional Experience with Stereotactic Radiation of Axillary Metastases.

Purpose/Objective(s):  The growing use of stereotactic body radiotherapy (SBRT) in metastatic cancer has led to its use in varying anatomic locations. The objective of this study was to review our institutional SBRT experience for axillary metastases (AM), focusing on outcomes and process.

Materials/Methods:  Patients treated with SBRT to AM from 2014-2022 were reviewed. Cumulative incidence functions were used to estimate the incidence of local failure (LF), with death as competing risk. Kaplan-Meier method was used to estimate progression-free (PFS) and overall survival (OS). Univariate regression analysis examined predictors of LF.

Results: We analyzed 37 patients with 39 AM who received SBRT. Patients were predominantly female (60%) and elderly (median age: 72). Median follow-up was 14.6 months. Common primary cancers included breast (43%), skin (19%), and lung (14%). Treatment indication included oligoprogression (46%), oligometastases (35%) and symptomatic progression (19%). A minority had prior overlapping radiation (18%) or surgery (11%).  Most had prior systemic therapy (70%). 

Significant heterogeneity in planning technique was identified; a minority of patient received 4-D CT scans (46%), MR-simulation (21%), or contrast (10%). Median dose was 40Gy (interquartile range (IQR): 35-40) in 5 fractions, (BED10=72Gy). Seventeen cases (44%) utilized a low-dose elective volume to cover remaining axilla.

At first assessment, 87% had partial or complete response, with a single progression.  Of symptomatic patients (n=14), 57% had complete resolution and 21% had improvement. One and 2-year LF rate were 16% and 20%, respectively. Univariable analysis showed increasing BED reduced risk of LF. Median OS was 21.0 months (95% [Confidence Interval (CI)] 17.3-not reached) and median PFS was 7.0 months (95% [CI] 4.3-11.3). Two grade 3 events were identified, and no grade 4/5. 

Conclusion: Using SBRT for AM demonstrated low rates of toxicity and LF, and respectable symptom improvement. Variation in treatment delivery has prompted development of an institutional protocol to standardize technique and increase efficiency. Limited followup may limit detection of local failure and late toxicity.


Alexander LOUIE (Toronto, Canada), Adam MUTSAERS, George LI, Jason FERNANDES, Saher ALI, Hanbo CHEN, Gregory CZARNOTA, Irene KARAM, Daniel PALHARES, Ian POON, Hany SOLIMAN, Danny VESPRINI, Patrick CHEUNG
10:10 - 10:20 #40145 - OR062 SBRT after neoadjuvant chemotherapy for Locally Advanced Pancreatic Cancer: Preliminary institutional results.
OR062 SBRT after neoadjuvant chemotherapy for Locally Advanced Pancreatic Cancer: Preliminary institutional results.

Background

NAC for tumor downstaging, better local/distal disease control, and higher R0 resection rate, followed by pancreatectomy are the two pillars of the management of LAPC. The potential additional role of  radiotherapy remains controversial.  

Materials and Methods

In our tertiary referral center, patients with LAPC undergo a complete course of NAC (mostly FOLFIRINOX), cross-sectional imaging reevaluation in 2 weeks and exploration for possible resection when the tumor looks resectable, en-block with the involved major vascular structure(s). Recently, when such a resection did not look feasible and there was no disease progression, we initiated a program of SBRT (5fr/8Gy per fraction/40Gy total dose), with no concurrent chemotherapy. A month after SBRT, patients were restaged (CT with pancreatic protocol) for possible resection.

Results

Twenty-six patients (10 males/16 females, median age: 59, ECOG-PS score: 0-1) with LAPC underwent SBRT a median of 27 days following NAC (Aug. 2019 – June 2023). No SBRT-related side effects occurred. Follow-up was complete (Dec. 2023) with a median of 18 months. Twelve patients (46%) were subsequently explored for possible resection, a median of 2 months after SBRT, and in 8 of them (75%, or 31% of the total) a pancreatectomy was performed. R0 resection was achieved in 7 (88%). Five patients are alive and well at 11, 14, 19, 21, and 31 months since diagnosis and three patients died at 13, 22, and 27 months. The 4 patients explored, but not resected, had complete encasement of the common and proper hepatic artery from its origin to its bifurcation (2 patients), or micrometastatic liver, or peritoneal disease (1 patient each). The 13 patients not subjected to pancreatectomy were followed closely and received further chemotherapy when appropriate. They had a median survival of 15 months since diagnosis. Local control was achieved in 9 (69%). Seven patients are alive for a median of 15 months and 6 patients died at a median of 15 months.

Conclusions

Our initial experience shows that SBRT following NAC for LAPC is safe, is associated with a high rate of local control and may render resectable about one third of patients considered unresectable after NAC alone.


Georgios KRITSELIS (Athens, Greece), Grigorios TSIOTOS
10:20 - 10:30 #39792 - OR063 Pancreas SBRT in total endotracheal anesthesia, a feasibility analysis.
OR063 Pancreas SBRT in total endotracheal anesthesia, a feasibility analysis.

It has been demonstrated that BED10 > 100 significantly improves local control and overall survival in patients with locally advanced pancreatic cancer (LAPC).  However, performing SBRT for targets with a pancreas localization can be challenging due to motion of the target (respiratory and peristaltic) and proximity to organs at risk. To deal with OAR proximity and target motion a variety of approaches can be used, from breath hold gating, free breathing ITV, using implanted gold fiducials, Calypso extracranial tracking or using MR guided treatments.

Our institution typically uses Calypso Extracranial system to track pancreas based targets, but with the end of support from Varian we were forced to consider a different approach. From December 2022 we enrolled 23 patients in a feasibility study using forced exhalation breath hold using total endotracheal anesthesia in combination with Calypso extracranial tracking for locally advanced pancreatic cancer (LAPC). CT simulation was performed in total anesthesia, a forced ventilation exhalation phase, and a treatment plan was devised using standard protocols for treating LAPC, albeit all treatment plans were single fraction, with a prescribed dose of 30 Gy, and a mean dose 28.4 Gy (24.1-31.8 Gy). Total anesthesia forced exhalation (TAFE) breath hold patients were compared to a similar sized cohort (23) of patients previously treated using Calypso extracranial system and deep inspiration breath hold (DIBH) in our clinic, and motion patterns of the target between those two cohorts were analyzed.

Comparing TAFE vs DIBH patients, TAFE patients statistically outperformed DIBH patients in geometric residual (0.7 vs 1.6 mm, p < 0.05), average rotation, all axes (3.8 vs 9.5 degrees, p < 0.05), mean time in breath hold (19.5 vs 12.9 s, p < 0.01), breath hold geometric standard deviation (0.7 vs 1.3 mm) while differences in mean time per fraction (30.8 vs 34.5 min, p=0.34)  and mean maximal excursions in LR (2.66 vs 2.93 cm, p=0.15 ) AP (1.33 vs 1.87 cm, p=0.11)  and CC (5.56 vs 6.47 cm, p=0.66) were not statistically significant.TAFE patients suffered no acute toxicity higher then grade 2, and the simulation and treatment was well tolerated. Motion analysis of TAFE patients in comparison to DIBH patients shows superior performance of TAFE patients in regards to reproducibility of motion, and planning CT/CBCT match while being noninferior in other metrics compared to DIBH patients. Treatments in forced exhalation breath hold using total endotracheal anesthesia are feasible for LAPC.


Domagoj KOSMINA (Zagreb, Croatia), Hrvoje KAUCIC, Vanda LEIPOLD, Adlan CEHOBASIC, Mihaela MLINARIĆ, Ivana ALERIĆ, Sofija ANTIĆ, Dragan SCHWARZ
10:30 - 10:40 #39594 - OR065 Multicenter retrospective study of stereotactic radiosurgery for gynecologic cancer brain metastases.
OR065 Multicenter retrospective study of stereotactic radiosurgery for gynecologic cancer brain metastases.

Background. Gynecologic primaries represent 10-15% of cancers in women. Although brain metastases are infrequent, significant number of cases occur in clinical practice. As with other histologies, stereotactic radiosurgery (SRS) is now the first line management option in most patients. However, the literature on this topic is limited to older single-center retrospective series. This study will provide further evidence on the efficacy and safety of SRS for brain metastases from the more common gynecologic cancer types.

 

Methods. Centers participating in the International Radiosurgery Research Foundation (IRRF) provided data for patients who had SRS (1-5 fractions) as part of the management of brain metastases from gynecologic tumors. Patients were required to have histology-confirmed diagnosis of epithelial ovarian, cervix or endometrial cancer. Other inclusion criteria included SRS between 2000 and 2020 and at least one imaging and/or clinical follow-up available. RANO-BM criteria were used to assess local tumor response. Kaplan-Meier estimators were used to evaluate progression-free and overall survival. Cox regression analyses were performed to identify predictors of local control, survival, and adverse radiation effects (ARE).

 

Results. We collected data for 246 patients who had SRS for a total of 856 brain metastases. The median age at SRS was 57 years (range, 23-88). The primary cancer site was ovarian in 112 (45.5%), cervical in 40 (16.3%) and endometrial in 94 patients (38.2%). Median KPS was 80% (range, 40-100%). The systemic disease was active in 112 (45.5%) of patients. A median of 5 metastases were treated (range 1-27) per patient. The individual metastasis volume ranged from 0.003 to 60.074 cc, with a median of 0.244 cc. The majority (95.2%) received single fraction SRS, using a median of 18 Gy (range, 10-24 Gy). Actuarial local control was 94.6% at 6 months, 89.9% at 12 months and 79.7% at 24 months. Prior SRS or WBRT and corticosteroid intake at SRS increased the risk of local failure. New remote brain metastases and leptomeningeal dissemination occurred in 13% and 4% of patients, respectively. Actuarial overall survival was 78.9%, 66.0% and 46.7% at 6, 12 and 24 months, respectively. Predictors of worsened survival included cervical and endometrial primary, prior WBRT, active systemic disease, worsened KPS, and increasing number of treated brain metastases. ARE occurred in 13.4% of cases but were symptomatic in only 3%. The only predictor of ARE was prior management of a metastasis with SRS.

 

Conclusion. SRS is an effective management for brain metastases from gynecologic cancers.


Mathilde BILLAU, Andréanne HAMEL, Jean-Nicolas TOURIGNY, Christian IORIO-MORIN, Ajay NIRANJAN, Zishuo WEI, L.dade LUNSFORD, Diego LUY, Shalini JOSE, Sydney SCANLON, Roman LISCAK, Jaromir HANUSKA, Steve BRAUNSTEIN, Christina PHUONG, Selcuk PEKER, Yavuz SAMANCI, Joshua SILVERMAN, Reed MULLEN, Kenneth BERNSTEIN, Douglas KONDZIOLKA, Jason SHEEHAN, Stylianos PIKIS, Jacob KOSYAKOVSKY, Narine WANDREY, Chad RUSTHOVEN, Eric B. HINTZ, Michael SCHULDER, Anuj GOENKA, Gregory N. BOWDEN, Rodney E. WEGNER, Matthew J. SHEPARD, Jennifer PETERSON, David MATHIEU (Sherbrooke, Canada)
10:40 - 10:50 #39755 - OR066 Response assessment of multi-fraction stereotactic radiosurgery for brain metastasis from renal cell carcinoma.
OR066 Response assessment of multi-fraction stereotactic radiosurgery for brain metastasis from renal cell carcinoma.

Objective:

The objective of the study was to evaluate the efficacy and safety of hypofractionated stereotactic radiotherapy (HFSRT) in treatment of patients with renal cell carcinoma (RCC) brain metastases (BM).

Materials and Methods:

We retrospectively evaluated the results of RCC BM patients treated at a single institution between 2010 and 2023. The primary outcome was overall survival (OS). Patient local progression free survival (LPFS) and radiation necrosis were secondary outcomes. Univariate and multivariate Cox proportional-hazards regression was used to model OS and LPFS. The Kaplan-Meier method with log-rank tests was used to compare survival differences.

Results:

Twenty-nine patients with 49 RCC BM were treated with HFSRT via CyberKnife. Median prescribed total margin dose of HFSRT was 29 Gy, median BED10 was 64.59 Gy. After a median follow-up of 28 months (range, 5 to 162 months), HFSRT yielded an 77.6% lesion local control rate. The 6-month, 1-, 2- and 3-year OS rate was 89.7%, 82.8%, 58.6% and 41.4%, respectively. The 6-month, 1-, 2- and 3-year LRFS rate was 93.1%, 93.1%, 89.7% and 79.3%, respectively. In multivariate analysis, higher HFSRT dose was associated with better OS( BED10 HR =0.883 , CI95% [0.8050.969], p = 0.009). Prior BM surgery, target therapy usage, BM number and BM volume failed to show prognostic value in OS or LRFS. Radiation necrosis occurred in 3.4%(1/29) patient during for HFSRT treated metastases.

Conclusion:

HFSRT is highly effective and safe in patients with brain metastases from RCC.


Peng WENSA, Hua Guang ZHU (Shanghai, China), Xin WANG, Enmin WANG

10:00-11:00
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C34
ORAL PRESENTATIONS
Integration of Multi-Modality Imaging / Radiomics

ORAL PRESENTATIONS
Integration of Multi-Modality Imaging / Radiomics

Moderators: Samuel CHAO (Radiation Oncologist) (Cleveland, OH, USA), Glen STEVENS (Neuro-oncology) (Cleveland, USA)
10:00 - 10:10 #39283 - OR067 Normalization of aberrant pre-therapeutic resting-state functional connectivity involved in pain perception in trigeminal neuralgia patients who underwent Gamma Knife radiosurgery.
OR067 Normalization of aberrant pre-therapeutic resting-state functional connectivity involved in pain perception in trigeminal neuralgia patients who underwent Gamma Knife radiosurgery.

Objective: Growing evidence supports the role of central nervous system in the modulation of pain in trigeminal neuralgia (TN) patients. The aim of this study was to assess brain functional connectivity alterations in patients with TN before and after neurosurgical treatment of affected trigeminal nerve.

Methods: Sixteen patients with idiopathic/classic TN, who underwent Gamma Knife radiosurgery, were followed up for at least 3 months within an ongoing longitudinal project. They performed clinical and resting-state functional MRI (RS-fMRI) evaluation before and 3 months after treatment. Thirty-three age-and sex-matched healthy controls were also recruited.

Results: Before treatment, TN patients relative to healthy controls showed an increased functional connectivity (FC) (i) of the precentral and postcentral gyrus within the sensorimotor network, (ii) of the right supramarginal gyrus, right postcentral gyrus and bilateral precuneus within the posterior salience network, and an increased FC (iii) of the right fronto-orbital cortex and caudate within the basal ganglia network. Furthermore, a decreased FC of the precuneus, posterior cingulate gyri and lateral occipital cortex within the posterior default mode network was found relative to healthy subjects (Figure 1). Three months after surgery, all patients experienced a significant improvement of facial pain (Barrow Neurological Institute pain intensity score less than IIIb). At postoperative fMRI assessment, no more significant FC increase was found in TN patients relative to controls. On the contrary, a decreased FC of the precuneus and lateral occipital cortex within the posterior default mode network relative to healthy subjects persisted.

Conclusions: In patients with idiopathic or classic TN, pattern of increased FC may reflect the involvement of a system that receives chronic nociceptive stimuli. An effective neurosurgical treatment of the trigeminal nerve appears likewise to modulate and thus reshape abnormal pre-surgical brain circuitries. The study provides novel insights into functional brain alterations of TN patients, which might contribute to disease development and pain change after surgical treatment. In the future, it will be interesting to analyze if specific brain areas can predict the response to neurosurgical treatment.


Luigi ALBANO (Milan, Italy), Federica AGOSTA, Silvia BASAIA, Edoardo POMPEO, Elisa SIBILLA, Filippo VALTORTA, Roberta MESSINA, Lina Raffaella BARZAGHI, Antonella CASTELLANO, Sonia CALLONI, Andrea FALINI, Pietro MORTINI, Massimo FILIPPI
10:10 - 10:20 #39814 - OR068 The use of Contrast Clearance Analysis Software to differentiate Brain Tumors from Radionecrosis: A Revolution?
OR068 The use of Contrast Clearance Analysis Software to differentiate Brain Tumors from Radionecrosis: A Revolution?

Objective:  To evaluate the experience of the first center in Brazil, and second in South America, using Contrast Clearance Analysis Software (Brainlab) to differentiate tumor recurrence from radionecrosis in the management of benign and malignant brain lesions after radiation treatments.  

Material and Methods: We analyzed benign and malignant brain lesions (tumors and Arteriovenous malformations) images with Contrast Clearance Analysis (CCA) Software from April 2021 to November 2023 in a Radiation Oncology Center in Brazil. Data from 104 patients and 287 CCA images at our institution were studied. All images were obtained with 3T MRI (Verio, Siemens), and a T1 contrast enhanced volumetric sequence (MPRAGE) was acquired at 5 min and 60 to 105 min. The images were transferred to CCA software. A fusion between the 2 MPRAGE sequences was made and a CCA colored map was calculated. The lesion studied was evaluated according to the color on the map: blue (active tumor) or red (radionecrosis) (Figure 1). The results of CCA software were compared to conventional MRI sequences (diffusion, perfusion and spectroscopy) and in five cases a biopsy was performed.

Results:  Median age was 46.8 years (Range: 4-81) and mean follow up was 29.5 months (Range: 2-57). Patient diagnosis were malignant tumor (89 patients), benign lesions (14) (Figure 5 and 6) and brainstem tumor without biopsy (1). 47,25% patients were treated with single dose radiosurgery, 37,36% with hypofractionation and 15,38% with conventional Radiotherapy. At follow up, 26,3% of patients developed new symptoms and Control MRI with conventional sequences demonstrated disease progression, however, at CCA software was radionecrosis (Figure 2 and 3). 100% had complete symptoms relief after treatment (steroids and vitamin E), and 2 lesions practically disappeared (Figure 4). All biopsied cases were compatible to the CCA software. 

Conclusions:  The CCA software is a new technological approach providing efficient distinction between tumor/ radionecrosis. The methodology provides high resolution and easy to interpret images with high accuracy. The present study is the first to describe the CCA software contribution among benign tumors and AVMs. 

 


Joao Gabriel GOMES (Recife, Brazil), Lucas DELBEM, Ernesto ROESLER
10:20 - 10:30 #39317 - OR069 Machine learning-supported MRI radiomics predicts volumetric response of pituitary adenomas to Gamma Knife radiosurgery.
OR069 Machine learning-supported MRI radiomics predicts volumetric response of pituitary adenomas to Gamma Knife radiosurgery.

Purpose: Gamma Knife stereotactic radiosurgery (GKRS) is a widely used treatment for pituitary adenomas (PAs) due to its high precision and efficacy. However, the volume response of PAs to GKRS varies among patients, underscoring the importance of identifying reliable predictors of treatment outcomes. Radiomics, a quantitative imaging analysis approach, can potentially extract imaging biomarkers that can aid in predicting treatment response. This study aims to pioneer the use of radiomic MRI analysis for predicting pituitary adenoma volumetric response to GKRS.

 

Methods: A comprehensive radiomics analysis was performed to predict the volume response of PA to GKRS. The retrospective cohort consisted of 80 patients who underwent GKRS for 29 functional PA and 51 non-functional PA. Forty-eight patients were treated with a single dose of 12 to 40 Gy to the PA margin, and 32 patients were treated with a hypofractionated regimen of 3-5 fractions with 11-35 Gy single fraction equivalent dose (SFED). After a follow-up period of 40.4 (7 - 106) months, a total of 98.8 % of PAs were controlled. The volumetric tumor change varied widely between 90% regression and 93% progression, with a mean regression of 45.7%. Pre-treatment T1w, T2w, FLAIR, and CE-T1w sequences acquired with 3-Tesla MRI were used to extract 2156 radiomic features that captured the tumors' intensity, shape, and texture characteristics. Radiomic signatures were generated using the least absolute shrinkage and selection operator (LASSO) for feature selection, in conjunction with several classifiers: random forest, naïve Bayes, kNN, logistic regression, neural network, and SVM.

 

Results: The models demonstrated predictive performance in the validation folds with AUC values ranging from 0.759 to 0.928 and R2 values between 0.272 and 0.665. Single-sequence T1w, dual-sequence T1w+CE-T1w, and multi-modality including clinicopathological (CP) characteristics (CP+T1w+CE-T1w) achieved similar prognostic performance in validation folds, with respective AUCs of 0.928, 0.899, and 0.909. All these radiomics models significantly (t-test) outperformed a benchmark model involving only clinicopathological features (AUC=0.846). The single-sequence model, including only CE-T1w features, provided the weakest prognostic performance with an AUC of 0.759.

 

Conclusion: This study is the initial radiomic analysis aimed at predicting the volume response of PAs to GKRS. Notably, the developed MRI-based radiomics models exhibited better classification performance compared to the benchmark model composed only of standard clinicopathological parameters. The clinical significance of this result is based on its potential to enable the individualization of therapeutic strategies, thereby enhancing treatment outcomes.


Herwin SPECKTER (Santo Domingo, Dominican Republic), Marko RADULOVIC, Erwin LAZO, Giancarlo HERNANDEZ, Jose BIDO, Diones RIVERA, Luis SUAZO, Santiago VALENZUELA, Peter STOETER, Velicko VRANES
10:30 - 10:40 #40130 - OR070 Automated brain metastasis detection and gross target volume contouring compared to inter-clinician contouring variability.
OR070 Automated brain metastasis detection and gross target volume contouring compared to inter-clinician contouring variability.

Purpose

Automatic contouring of brain metastatic target volumes may improve the efficiency of stereotactic radiosurgery (SRS) workflows. Generating clinically acceptable contours is necessary to realizing this potential. This work aims to evaluate the accuracy of an AI contouring system for brain metastasis (BM) gross tumors volumes (GTVs) with respect to contours defined by physicians.

 

Methods

Post-contrast T1-weighted MR images and GTVs of BM were retrospectively collected from 2092 patients treated using SRS at seven institutions. Centralized data curation was done by two radiologists to delineate GTVs of uncontoured metastases (present in the brains but not amongst the treated tumors). An automated ‘artificial intelligence’ (AI) system based on nnU-Net with adaptive Dice loss and synthetic data augmentation was trained (N=1907) and evaluated (N=185) on non-overlapping subsets of the data. A second testing subset (N=206) was evaluated after the completion of training. BM detection was assessed by sensitivity and false positive rate (FPR). The operation points of the AI system were selected to achieve the target sensitivity of 0.9. To assess interobserver contouring variability, three clinicians each contoured 163 selected BM GTVs from 20 testing patients; one lesion was excluded due to user error during annotation. Interobserver contouring variability between clinicians was quantified as the average pairwise values of three contouring metrics (Dice similarity coefficient (DSC), 95-percentile Hausdorff distance (HD95) and average HD (AHD)). The AI system contouring agreement was compared by measuring the same metrics between the system and each clinician.

 

Results

The AI system achieved overall BM-level detection sensitivity of 0.904 at an FPR of 0.65±1.17 on the first testing dataset, and sensitivity of 0.907 at an FP rate of 0.57±0.8 on the second dataset. Mean values of DSC, HD95 and AHD were 0.758, 1.45 mm and 0.23 mm, respectively, for the first test set and 0.705, 1.91 mm and 0.33 mm, for the second. On the interobserver variability of 20 patients, clinician-clinician mean DSC, HD95 and AHD were 0.714, 1.32 mm and 0.25 mm, respectively. The AI-clinician mean DSC, HD95 and AHD were 0.739, 1.23 mm and 0.22 mm, respectively.

 

Conclusion

The AI system showed contouring variability from clinician contours on par with interobserver variability. Further evaluation will be carried out to evaluate the AI system’s clinical utility.


Youngjin YOO (Princeton, USA), Eli GIBSON, Gengyan ZHAO, Thomas J. RE, Hemant PARMAR, Jyotipriya DAS, Hesheng WANG, Michelle M. KIM, Colette SHEN, Yueh LEE, Douglas KONDZIOLKA, Mohannad IBRAHIM, Jun LIAN, Rajan JAIN, Tong ZHU, Dorin COMANICIU, James M. BALTER, Yue CAO
10:40 - 10:50 #39706 - OR071 PSMA/PET-guided stereotactic radiosurgery of brain metastases in prostate cancer.
OR071 PSMA/PET-guided stereotactic radiosurgery of brain metastases in prostate cancer.

Introduction: Prostate-specific membrane antigen targeted molecular imaging with positron emission tomography (PSMA/PET) is being increasingly utilized in care of prostate cancer patients, allowing for metastatic directed therapies as well as PSMA targeted radionucleotide therapies with significant survival benefits. We present a case series of patients with intra and extra-axial brain metastasis detected on PSMA/PET imaging treated with brain stereotactic radiosurgery (SRS).

Methods: A prospectively collected database was queried for prostate cancer patients who underwent brain SRS from 1/2020 to 12/2023 in an NCI-designated Comprehensive Cancer Center. The patients who underwent F18-PSMA/PET imaging preceding SRS were identified and their clinical course and imaging findings were reviewed.

Results: Among fourteen prostate cancer patients who had received brain SRS, five had undergone PSMA/PET imaging in biochemical recurrent setting, yielding new diagnosis of brain metastases. Two patients had received Lutetium-177 PSMA therapy (Pluvicto) for metastatic skeletal disease a priori. At the time of PSMA/PET imaging, median age was 64years (range: 49-70). Two patients were asymptomatic, two had headaches and one suffered from blurred vision. Two patients had single brain metastasis and three had multiple, with mean standardized uptake values (SUV) of 13 (range 11-19.5) on PSMA/PET. Three also had calvarium/dural based lesions. Brain MRI was acquired for all patients and showed corresponding findings, although extent of base of skull involvement was better delineated with PSMA/PET. Median time to SRS from PSMA/PET imaging acquisition was 3weeks (range 0-15) and one patient had post-SRS resection. Median dose of 16Gy (range 12-21) in 1 fraction was delivered utilizing frame-less gammaknife radiosurgery. Patients were followed with subsequent PSMA/PET and/or brain MRIs. No in-field recurrences were seen in median follow up of 5months (range 2-15), three required SRS to other brain lesions and one died.

Discussion: Brain metastases from prostate cancer are rare though can be effectively treated with SRS. PSMA/PET imaging combined with brain MRI allows for increased sensitivity and specificity of brain metastasis detection and radiosurgery target delineation. Combination of radionucleotide therapy and brain SRS appears safe.


Fatemeh FEKRMANDI (Buffalo, USA), Victor GOULENKO, Venkatesh SHANKAR MADHUGIRI, Dheerendra PRASAD
10:50 - 11:00 #40178 - OR072 Integrating multimodality imaging into radiation therapy simulation through the implementation of a magnetic resonance imaging safety workflow.
OR072 Integrating multimodality imaging into radiation therapy simulation through the implementation of a magnetic resonance imaging safety workflow.

Purpose/Objectives:

            Magnetic resonance (MR) imaging is increasingly integrated into Radiation Oncology (RO) departments with the development of MR-linacs and MR simulation. MR technology allows for better soft tissue contrast which is important for precise tumor delineation in stereotactic radiosurgery (SRS) and stereotactic body radiotherapy (SBRT). Due to the number of foreign bodies and metal implants in patients with cancer, adoption of a comprehensive patient screening and MR safety workflow in RO is critical. Identifying MR unsafe implants only at the time of MR simulation leads to same-day cancellations, potentially delaying treatment, and can risk MR safety events (SEs).

 

Materials/Methods: 

In an effort to decrease same-day cancellations and improve safety of a 3-Tesla MR simulator, three plan-do-study-act (PDSA) cycles were implemented from 4/18/22 – 1/19/23. PDSA cycle 1 involved implementation of a two-screen functional workflow, adapted from radiology at the same institution. PDSA cycle 2 and 3 involved education for stakeholders. PDSA cycle 3 educational intervention included a visual aide to assist with work queue (WQ) use. Endpoints evaluated included the number of same-day cancellations, patients in the WQ (a measure of the number of patients identified at the initial screen as having an implant), and SEs in each PDSA cycle.

 

Results: 

PDSA cycle 1 spanned 56 workdays during which 91 MR simulations were scheduled with 6 cancellations (6.5%). PDSA cycle 2 spanned 84 days during which 173 MR simulations were scheduled with 18 cancellations (10.4%). PDSA cycle 3 spanned 39 workdays and had 94 MR simulations, with 7 cancellations (7.4%). The cancellation rate during each PDSA cycle was 0.11, 0.21, and 0.17 cancellations/day, respectively. The number of patients in the WQ during each PDSA cycle, representing successfully screened high-risk patients, was 0, 0, and 3, respectively. There were no SEs during the study.

 

Conclusion: 

In this study, an MR safety workflow from radiology was successfully implemented into a RO department. There were no SEs during the study, but the number of patients successfully screened as high-risk and placed in the WQ increased after repeat MR education. Further increases in WQ use would decrease the demand for implant assessment at point of care, which could decrease burden on the MR technologist, reduce same day cancellations, and potentially SEs. As the demand for MR simulation for stereotactic radiation target delineation increases, repeated continued and updated MR specific education is important to increase efficiency of MR simulation appointments and maintain patient safety.


Rachel SABOL (San Francisco, USA), Nicolas PRIONAS, Christina CALVIN, Luis PELAYO, Haley RANDOLPH, Sherman LIM, Craig DEVINCENT, Michael OHLIGER, Javier VILLANUEVA-MEYER, Jessica SCHOLEY, Lisa SINGER

11:00
11:00-12:00
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A35
PARALLEL SESSION
Benign Cranial Tumors

PARALLEL SESSION
Benign Cranial Tumors

Moderators: Jason SHEEHAN (neurosurgeon) (Charlottesville, USA), Tony WANG (Professor of Radiation Oncology) (New York, USA)
11:00 - 12:00 Stereotactic Radiosurgery for the Management of Non-Vestibular Cranial Nerve Schwannomas. David MATHIEU (Professor) (Keynote Speaker, Sherbrooke, Canada)
11:00 - 12:00 Minimizing Toxicity After Radiosurgery for Vestibular Schwannoma. Daniel M. TRIFILETTI (Professor) (Keynote Speaker, Jacksonville, USA)
11:00 - 12:00 PET/MRI based Radiation Therapy for benign tumors: Vestibular schwannoma/Paraganglioma/meningioma. Joshua PALMER (Keynote Speaker, USA)

11:00-12:00
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B35
PARALLEL SESSION
Rationale for Hypofractionation in SBRT

PARALLEL SESSION
Rationale for Hypofractionation in SBRT

Moderators: Kristin REDMOND (USA), Arjun SAHGAL (Professor) (Toronto, Canada)
11:00 - 12:00 Ultra-hypofractionated Radiotherapy (Stereotactic Body Radiotherapy) For Spine Metastases: An Update on Efficacy and Safety. Chia-Lin TSENG (Radiation Oncologist) (Keynote Speaker, Toronto, Canada)
11:00 - 12:00 Theoretical and practical rationales for hypofractionation in SBRT for liver and pancreas malignancies. Karyn GOODMAN (Professor) (Keynote Speaker, New York, USA)

12:00 - 13:00 SPONSORED LUNCH SYMPOSIA - LUNCH IN THE EXHIBITION
13:00
13:00-14:00
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A37
ORAL PRESENTATION
Benign cranial tumors (Pituitary/AN/Glomus/Other)

ORAL PRESENTATION
Benign cranial tumors (Pituitary/AN/Glomus/Other)

Moderators: Ajay NIRANJAN (neurosurgeon) (Pittsburgh, USA), Koray OZDUMAN (Professor and Chair of Neurosurgery) (Istanbul, Turkey)
13:00 - 13:10 #38977 - OR073 Single versus fractionated Gamma Knife radiosurgery for non-functioning pituitary adenomas close to the optic pathway: a multicenter propensity score matched study.
OR073 Single versus fractionated Gamma Knife radiosurgery for non-functioning pituitary adenomas close to the optic pathway: a multicenter propensity score matched study.

Objective: Gamma Knife radiosurgery (GKRS), typically administered in a single-session (S-GKRS), is an effective treatment for non-functioning pituitary adenoma (NFPA). For lesions close to the optic pathway the use of hypofractionated radiosurgery is growing. The present study seeks to compare the results of S-GKRS versus fractionated-GKRS (F-GKRS) for NFPAs adjacent to the optic pathway.

Methods: Two cohorts of patients with residual or recurrent NFPAs in contact to the anterior optic pathway were retrospectively included in the study: i) a group of patients who underwent a three-day course of F-GKRS at Neurosurgery and Gamma Knife radiosurgery Unit, IRCCS San Raffaele Hospital, in Milan, Italy and ii) a group of patients treated with S-GKRS at Center for image guided neurosurgery, University of Pittsburgh Medical Center, in Pittsburgh, USA. A propensity score matching (ratio 1:1) was carried out to obtain and compare two homogeneous groups of NFPA patients.

Results: A total of 84 patients were included for analysis (42 in the S-GKRS cohort and 42 in the F-GKRS group).The two cohorts did not differ in terms of age, sex, number of previous surgical procedure, tumor volume and follow-up (Table 1). The mean follow-up was 60.2±37.0 months and 62.4±37.4 months for F-GKRS and S-GKRS cohort, respectively (p=0.38). The overall tumor control at last follow-up was achieved in 95.2% and 92.9% of patients in F-GKRS and S-GKRS, respectively (p=0.64, Figure 1). The 1-year, 3-year, 5-year and 7-year progression-free survival (PFS) rate after F-GKRS was 100%, 97.1%, 97.1% and 91%, respectively. In the S-GKRS sample, PFS rates were 100%, 100%, 92.5% and 92.5% at 1, 3, 5, and 7 years after treatment. Two patients (4.7%) from the F-GKRS cohort and 2 (4.7%) from the S-GKRS cohort sustained visual worsening after radiosurgery (p=1.0).

Conclusions: In the management of NFPAs adjacent to the optic pathway both F-GKRS and S-GKSRS had comparable outcomes and risks at seven years. Future prospective studies including larger cohorts with longer follow-up are needed to confirm our results.


Luigi ALBANO (Milan, Italy), Marco LOSA, Lina Raffaella BARZAGHI, Elena BARRILE, Shray K. BINDAL, Zhishuo WEI, Edoardo POMPEO, Federico VILLANACCI, Antonella DEL VECCHIO, John C. FLICKINGER, Ajay NIRANJAN, Pietro MORTINI, Lawrence Dade LUNSFORD
13:10 - 13:20 #39660 - OR029 Hypofractionated radiosurgery for optic nerve sheath meningiomas: results from an exploratory, single-arm, prospective trial.
Hypofractionated radiosurgery for optic nerve sheath meningiomas: results from an exploratory, single-arm, prospective trial.

Optic nerve sheath meningiomas (ONSM) are rare benign neoplasms affecting the meninges surrounding the optic nerve. Despite their typically slow growth, the gradual compression of the pial vasculature often results in optic nerve dysfunction and irreversible visual loss. Traditional treatment modalities for ONSM, including observation, surgery, and radiotherapy, have not established a definitive treatment approach.

The objective of this study is to assess the safety and the effectiveness of multisession radiosurgery for ONSM, particularly in terms of preserving visual function.

 

The current study is an exploratory, single-arm prospective trial that focuses on patients with optic nerve sheath meningiomas (ONSM) who have undergone multisession radiosurgery. Inclusion criteria are diagnosis of ONSM, visual impairment at presentation, progression of visual dysfunction during the observation period, and evidence of disease progression. The histological diagnosis was not mandatory.

The primary endpoint of the study is to evaluate the effect of multisesion radiosurgery in terms of preserving visual function. This assessment is based on the analysis of visual acuity and the visual field before and after treatment, within a timeframe of at least 5 years.

 

According to the study protocol, 50 patients underwent multisesion radiosurgery between February 2011 and February 2019. Each patient received a 25 Gy treatment delivered in five fractions over five consecutive days, prescribed to the 77-91% isodose line (median 82%).

The mean age at the time of treatment was 50 years (range 19-78). The mean treatment volume was 2.57 cc (range 0.49-16.42 cc).

The mean dose to chiasma and optic nerve, were 4.7Gy (1.5-11.6) Gy and 22.8Gy (8.3-28.5) respectively; the maximum point dose were 15.4 (2.3-26.6) and 28.6 Gy (20.1-32.5).

 

Following a mean follow-up period of 74 months (range 3-142 months), 1 patient experienced a deterioration in visual function, 3 patients showed improvement, and 41 maintained stable visual function, including both visual acuity and visual field.

No cases of post-actinic retinopathies were observed. None of the treated meningiomas exhibited radiological progression during the follow-up period.

The results from the present trial confirm that multisesion radiosurgery (25Gy/5 fractions) is a safe and effective treatment modality for optic nerve sheath meningiomas (ONSM). This treatment regimen appears capable of tumor control while preserving visual function.


Marcello MARCHETTI, Elena DE MARTIN, Cristiana PEDONE, Sara MORLINO, Valentina PINZI, Aurora ROMEO, Laura FARISELLI (Milan, Italy)
13:20 - 13:30 #39123 - OR075 Dynamics of tumor evolution after Gammaknife radiosurgery for sporadic vestibular schwannomas: defining volumetric patterns characterizing individual trajectories.
OR075 Dynamics of tumor evolution after Gammaknife radiosurgery for sporadic vestibular schwannomas: defining volumetric patterns characterizing individual trajectories.

Background: The definition of tumor control after Gammaknife radiosurgery (GKRS), and more precisely of treatment failure, in terms of delay of follow-up and evolution of the tumor volume, still varies across physicians. The lack of knowledge on the dynamics of tumor evolution after GKRS can lead to misinterpretation and subsequent inappropriate second treatment, with potential consequences for the patient. The aim of this study was to evaluate the post-GKRS dynamics of evolution of the tumor volume, and characterize volumetric patterns associated to specific trajectories.

Methods: Were included in the study patients with sporadic VS treated by GKRS in Marseille with an MRI follow-up of 3 years or more. Were excluded patients with neurofibromatosis, with a history of prior microsurgical resection or SRS before GKRS. A clustering in 2 steps was performed: definition of the patterns of evolution based on a subset of patients with the most comprehensive follow-up, then assignment of the remaining patients on a best fit basis. The minimum length of follow-up was assessed by measuring the consistency of the clusters over time (Adjusted Rand Index and Normalized Mutual Information). An analysis of the discriminant variables was finally performed for each pattern. A p value < 0.05 was considered significant.

Results: 1,607 patients were included with a median follow-up of 67 months. Five patterns were defined with one pattern gathering almost all cases of treatment failure. The clustering at 5 years afforded the highest consistency with long-term follow-up. Discriminant variables for the different clusters were: sex, initial symptoms, delay of diagnosis, tumor size related to the Koos grading, fundus invasion, and number of isocenters.

Conclusions: The definition of these robust distinct patterns is likely to help tremendously the physicians to distinguish tumor control from potential failure on the longer term. We advocate for no retreatment decision before 5 years post-GKRS. To decide if the dynamics of evolution can be predicted either at GKRS or in the early follow-up on an individual basis, further investigations are required.


Anne BALOSSIER (Marseille), Madalina OLTEANU, Christine DELSANTI, Lucas TROUDE, Jean-Marc THOMASSIN, Pierre-Hugues ROCHE, Marie CHAVENT, Jean RÉGIS
13:30 - 13:40 #39784 - OR076 Imaging Predictors of Hydrocephalus Risk After Stereotactic Radiosurgery for Vestibular Schwannoma: Utility of the Evans Index.
OR076 Imaging Predictors of Hydrocephalus Risk After Stereotactic Radiosurgery for Vestibular Schwannoma: Utility of the Evans Index.

Introduction:

Hydrocephalus following Gamma Knife® stereotactic radiosurgery (SRS) for vestibular schwannoma is a rare but manageable occurrence. Most series report post-SRS communicating hydrocephalus in about 1% of patients, thought to be related to a release of inflammatory or proteinaceous substances into the cerebrospinal fluid. While larger tumor size and older patient age have been associated with post-SRS hydrocephalus, the influence of baseline ventricular anatomy on this complication remains poorly defined. 

Methods:

A single-institution retrospective cohort study examining patients who developed symptomatic communicating hydrocephalus after undergoing Gamma Knife® stereotactic radiosurgery (SRS) for unilateral vestibular schwannoma from 2011-2021 was performed. Patients with prior hydrocephalus and shunt placement or prior surgical resection were excluded. Baseline tumor volume, third ventricle width, and Evans Index (EI)–maximum width of the frontal horns of the lateral ventricles/maximum internal diameter of the skull–were measured on axial post-contrast T1-weighted MRI images. 

Results:

378 patients with unilateral vestibular schwannoma met inclusion criteria. 14 patients (3.7%) developed symptomatic communicating hydrocephalus. The median time to hydrocephalus was 9.8 months (range: 3.2 – 32.7 months). The odds of developing symptomatic hydrocephalus were 5.0 and 7.7 times higher in association with a baseline EI > 0.28 (p = 0.024) and tumor volume > 3 cm3 (p = 0.007), respectively, in multivariate analysis. Fourth ventricle distortion was associated with hydrocephalus incidence (p < 0.001). Ten patients (2.6%) underwent shunt placement and four patients (1.1%) were observed with milder symptoms.

Conclusion:

Vestibular schwannoma patients with higher baseline EI, larger tumor volumes, and fourth ventricle deformation are at increased odds of developing post-SRS hydrocephalus. Patients with these baseline imaging features should be carefully monitored after SRS for symptoms of hydrocephalus at more frequent intervals.


Brandon SANTHUMAYOR (New York, USA), Elad MASHIACH, Lauren ROTMAN, Ying MENG, Kenneth BERNSTEIN, Fernando VASCONCELLOS, Danielle GOLUB, Joshua SILVERMAN, David HARTER, John GOLFINOS, Douglas KONDZIOLKA
13:40 - 13:50 #39122 - OR077 Long-term hearing outcome after radiosurgery for sporadic vestibular schwannomas: predicting the individual evolution.
OR077 Long-term hearing outcome after radiosurgery for sporadic vestibular schwannomas: predicting the individual evolution.

Background – Serviceable hearing preservation remains a major issue in the management of vestibular schwannomas (VSs). Authors have postulated that hearing gradually deteriorates following stereotactic radiosurgery. We analyzed data prospectively collected during our 30-year experience with the aim of building a predictive model of individual hearing evolution over time.

Methods – Were included patients with serviceable hearing treated in Marseille by Gammaknife radiosurgery (GKRS) for sporadic VS from July 1992 to December 2017. Hearing status was assessed using the Pure Tone Average (PTA). A mixed linear regression model was used to predict the PTA evolution. Discriminant variables were selected with univariate then multivariate analyses performed on a training data set (70% of the cohort). The accuracy of the resulting model was assessed using a test data set (30% of the cohort).

Results – 1,179 patients were included. Median marginal dose was 11 Gy. Median follow-up was 48 months with 448 patients followed 5+ years, 143 patients followed 10+ years, and some up to 30 years. Along with PTA at GKRS, five variables were selected: hearing complaint, Ohata classification, intracanalicular volume, marginal dose, number of isocenters. The accuracy of the model was 0.73.

Conclusions – This model provides valuable guidance. Out of the 6 predictive variables, the physician may influence up to 4 of them. Early detection and treatment of VSs is required. The marginal dose and number of isocenters may be adapted during treatment planning. Finally, this model can help practitioners to deliver to their patients a more comprehensive information regarding their hearing prognosis.


Anne BALOSSIER (Marseille), Jeremy COHEN, Pierre-Hugues ROCHE, Christine DELSANTI, Lucas TROUDE, Jean-Marc THOMASSIN, Roch GIORGI, Jean RÉGIS
13:50 - 14:00 #40125 - OR078 Long-term radiographic and endocrinologic outcomes of stereotactic radiosurgery for recurrent or residual nonfunctioning pituitary adenomas.
OR078 Long-term radiographic and endocrinologic outcomes of stereotactic radiosurgery for recurrent or residual nonfunctioning pituitary adenomas.

Background: Stereotactic radiosurgery (SRS) is used for residual/recurrent nonfunctional pituitary adenoma (NFPA). Long-term tumor control and hypopituitarism results following SRS are required.

 

Methods: This retrospective, multicenter study included patients with recurrent/residual NFPA treated with single-fraction SRS; they were then divided into two arms. The first arm included patients with at least 5 years of radiographic follow-up and all patients with local tumor progression. The second arm included patients with at least 5 years of endocrinological follow-up and all patients that developed endocrinopathy. Study endpoints were tumor control and new or worsening hypopituitarism after SRS; they were analyzed using Cox regression and Kaplan Meier methodology.

 

Results: Our study included 360 patients in the tumor control arm [Median age 52.7 years (Interquartile range (IQR) 42.9-61), male 193 (53.6%)], and 351 patients in the hypopituitarism arm [Median age 52.5 years (IQR 43-61), male 186 (52.9%)]. The median follow-up in the tumor control evaluation group was 7.9 years (IQR 5.7-10.5). Tumor control at 5, 8, and 10 years was 91.5% (CI 95%:88%-94%), 86.2% (CI 95%: 81.6%- 89.7%), and 82% (CI 95%: 75.7% -86.9%), respectively. The median follow-up in the endocrinopathy evaluation group was 8 years (IQR 5.9-10.7). Pituitary function preservation at 5, 8, 10, and 15 years was 82.5% (CI 95%:78%-86%), 80.7% (CI 95%: 76%- 84.6%), 77.6%% (CI 95%: 71.9% -82.2%), 70.6% (CI 95%: 61.5%- 77.9%), respectively. Margin dose >15 Gy (HR=0.8, 95% CI=0.7-0.9, P < 0.001) and a delay from last resection to SRS >1 year (HR=0.8, 95% CI= 0.7-0.9, P = 0.04) were significant factor related to tumor control in multivariable analysis. Pituitary stalk dose (i.e. Dmax to the pituitary) ≤10 Gy (HR=1.1, 95% CI=1.09-1.2, P <0.001) was related to pituitary function preservation. New visual deficit after SRS in tumor control group and endocrinopathy group were 7 (1.94%) and 8(2.2%) respectively, Other new cranial nerve deficits post-SRS were 4/160 and 3/140 in the 2 respective groups..

 

 

Conclusion: SRS affords favorable and durable tumor control for the vast majority of NFPA.  Post-SRS hypopituitarism occurs in a minority of patients, but this risk increases with time and warrants long-term follow up. 


 


Ahmed SHAABAN (Charlottesville, USA), Chloe DUMOT, Georgios MANTZIARIS, Sam DAYAWANSA, Manjul TRIPATHI, Matthew J. SHEPARD, L. Dade LUNSFORD, Douglas KONDZIOLKA, Amr EL-SHEHABY, Anderson BRITO, David MATHIEU, Jennifer MATSUI, Yavuz SAMANCI, Jason SHEEHAN

13:00-14:00
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B37
ORAL PRESENTATIONS
Radiosurgery for Oligometastatic Disease

ORAL PRESENTATIONS
Radiosurgery for Oligometastatic Disease

Moderators: Stephanie COMBS (Radation Oncology) (Munich, Germany, Germany), Daniel M. TRIFILETTI (Professor) (Jacksonville, USA)
13:00 - 13:10 #40103 - OR079 Stereotactic ablative radiation therapy (SABR) for lung metastases from sarcoma primaries: A systematic review and meta-analysis of safety and efficacy.
OR079 Stereotactic ablative radiation therapy (SABR) for lung metastases from sarcoma primaries: A systematic review and meta-analysis of safety and efficacy.

Purpose: Though promising single institution retrospective and prospective studies have been reported on stereotactic ablative radiation therapy (SABR) for management of lung metastases from sarcoma primaries as an alternative to the historical standard of metastasectomy, larger multi-institutional series are limited that report on both safety and efficacy with this treatment paradigm. Thus, we conducted a systematic review and meta-analysis to characterize local control (LC) and toxicities following SABR for lung metastases from sarcoma primaries.

 

Methodology: We examined the literature for studies reporting on patients with lung metastases from sarcoma primaries managed with SABR. The primary outcomes of interest were 1-year and 2-year LC and Grade 3-5 toxicities following SABR. Secondary outcomes were 1-year overall survival (OS) and 2-year OS. Weighted random effects meta-analyses using the DerSimonian and Laird methods were performed to calculate effect sizes.

 

Results: After applying relevant inclusion and exclusion criteria, a total of 14 studies were identified with 533 patients with 940 lung metastases from sarcoma primaries treated with SABR. The median prescription dose was 50 Gy (range: 48-60 Gy) in 5 fractions (range: 4-10). Following SABR, excellent and durable LC was noted with a pooled 1-year LC rate of 97% (95% CI: 95-98%) and a pooled 2-year LC rate was 91% (95% CI: 88-95%). We also noted favorable OS after treatment with SABR with a pooled 1-year OS rate of 85% (95% CI: 80-90%) and the 2-year pooled OS rate was 68% (95% CI: 57-80%). Estimated incidences of Grade 3-5 toxicities following SABR were quite rare at 0.1% (95% CI: 0-0.5%).

 

Conclusions: In the largest meta-analysis to date on this topic, we noted that SABR for sarcoma pulmonary metastases resulted in excellent and durable LC with minimal significant toxicities. This radiotherapy paradigm presents an excellent non-operative alternative to the historical standard of metastasectomy. Patients also were noted to have favorable OS in the context of metastatic disease. Large prospective trials are warranted to further validate, as well as clarify, the role and timing of SABR in combination with standard of care therapy.

 


Robert SIERRA (Columbus, USA), Sidharth IYER, Casey LEIMBACH, Raj SINGH,
13:10 - 13:20 #39576 - OR080 Tolerability and outcomes of neuroendocrine tumors treated with peptide receptor radionuclide therapy and stereotactic body radiation therapy.
OR080 Tolerability and outcomes of neuroendocrine tumors treated with peptide receptor radionuclide therapy and stereotactic body radiation therapy.

Introduction

Peptide receptor radionuclide therapy (PRRT) and stereotactic body radiation therapy (SBRT) for neuroendocrine tumors (NET) may have a synergistic impact, as PRRT may treat widely metastatic disease and SBRT may target areas of tumor heterogeneity. There is a paucity of data evaluating the potential safety and efficacy of this treatment strategy; this is the first series evaluating patients treated with both PRRT and SBRT for locally advanced/metastatic NET.

 Methods

Retrospective review of NETS patients treated with both SBRT and PRRT between January 2013 and May 2023. Demographics and treatment details were abstracted from the patients’ clinical and radiation records. Toxicity was evaluated using CTCAE v5.0 and RECIST v1.1 or SPINO critiera were utilized for response assessment.  

Kaplan-Meier models used to estimate survival, with the log-rank test used to compare survival rates between groups.

 Outcomes

21 patients with 64 targets treated with SBRT were identified (Table 1).  Median follow-up was 40 months. Median time between SBRT and PRRT was 9.23 months. Median time between PRRT and SBRT was 20.8 months.

Figure 1 illustrates OS and PFS for the entire patient cohort. Median OS in the overall population was 19.6 months, with a median PFS of 12.8 months. Rates of local recurrence at 12 and 24 months were 1.8% and 5.9%. For those who had local recurrence, this occurred at a median of 22.8 months.

Toxicity attributed to SBRT or PRRT are outlined in Table 2.  Specific to SBRT, no pain flare or radiation myelopathy was identified, and no liver toxicity was attributable. One case of chest-wall fibrosis likely related to treatment volume was identified. One patient with extensive bone metastases treated with SBRT post-PRRT failure developed Grade 3 thrombocytopenia.No significant acute toxicities were attributable to PRRT. Late grade 4 hyperbilirubinemia was identified in 2 patients. This may be attributable to PRRT +/- SBRT, however both these patients also had trans-arterial liver embolization and had notable intra-hepatic progression. One patient developed leukemia post-PRRT; SBRT was delivered for local control to progressive neuroendocrine liver metastases after the diagnosis of leukemia was established.

 Conclusion

Sequential SBRT and PRRT is tolerable, with acute and long-term adverse effects in line with prior published toxicity data for both PRRT and SBRT as individual treatment. Excellent control of disease treated with SBRT may be relevant when evaluating the factors that influence disease progression in patients treated with PRRT. This supports further research into this potential combined therapy.


Jose NUNEZ RODRIGUEZ, Sylvia NG, Hanbo CHEN, Arjun SAHGAL, Julie HALLET, Calvin LAW, Sten MYREHAUG (Toronto, Canada)
13:20 - 13:30 #40187 - OR081 Characteristics of exceptional responders to comprehensive involved site radiation therapy for oligometastases.
OR081 Characteristics of exceptional responders to comprehensive involved site radiation therapy for oligometastases.

Introduction: While the National Cancer Institute comprehensively investigated exceptional responders to systemic therapy, there remains a paucity of data on the more frequently seen patients achieving long-term complete remission following involved site radiotherapy to all areas of visible active disease for oligometastases.   This study reports long-term outcomes for patients who remain alive and free of recurrence at more than 2-year follow-up following total metastatic ablation with radiotherapy.     

Materials/Methods: Among 131 consecutive patients with solid tumor oligometastases treated by a single radiation oncologist between 2014 and 2021, exceptional response was defined as patients who remain alive and free of recurrence with a minimum of 2-year follow-up allowing for successful salvage with further involved site radiotherapyThis study describes the patient characteristics, treatment and methods of restaging in patients with exceptional response.     

Results: A total of 38 patients (29%) remain alive and free of recurrence at a median follow-up on 54 months (range 24 to 117 months) Key patient characteristics include median age 66, 84% ECOG 0-1, 34% lung primary, 16% prostate primary, 13% breast primary, median pretreatment albumin 4.2 g/dl, 42% synchronous oligometastasis, 32% metachronous oligometastases, 34% more than 1 metastasis targetedMetastatic sites treated included bone 32%, brain 29%, distant lymph nodes 26% while 42% required treatment of the primary tumor and nodes as part of total ablationThe initial course of comprehensive radiation was accomplished using stereotactic radiotherapy (53% of patients; median dose 27 Gy in 3 fractions) or intensity modulated radiation therapy (61% of patients; median dose 53 Gy in 24 fractions) with a median cumulative GTV volume of 21 cc. Comprehensive salvage radiation was required in 16% of patients with a median dose of 43 Gy in 10 fractionsIn addition to radiation, 79% received systemic therapy with 18% receiving hormonal therapy, 11% chemotherapy alone and 43% receiving immunotherapy and/or biologically targeted therapy either alone or in combination with chemotherapy.  In addition to conventional imaging and applicable tumor markers, 6 patients had cell free ctDNA (Signatera) with all 6 with undetectable ctDNA. Late grade 3 toxicities included 2 patients requiring surgery for symptomatic radionecrosis and 1 patient requiring revision for orthopedic screw fixation fraction following femur radiation.    

Conclusions: Long-term complete responses, including molecular complete responses, are achievable with comprehensive involved site radiotherapy in highly diverse clinical presentationsFavorable outcomes are possible even in historically poor prognosis subgroups.


Rachel RADIGAN (West Islip, USA), Vani GUPTA, Symeon MISSIOS, Ashish SANGAL, Johnny KAO
13:30 - 13:40 #39844 - OR083 Stereotactic radiotherapy for colorectal cancer metastases – review of clinical outcomes.
OR083 Stereotactic radiotherapy for colorectal cancer metastases – review of clinical outcomes.

Background/Methods:

Despite advances in systemic therapy, survival in metastatic colorectal cancer (mCRC) remains poor with fewer than 20% being alive at 5 years from diagnosis (1). The utility of stereotactic body radiotherapy (SBRT) and stereotactic radiosurgery (SRS) allowing dose escalation to achieve improved local control has risen in the treatment of mCRC. Despite the growing body of evidence related to SBRT/SRS in mCRC, local control (LC) and overall survival (OS) varies widely between studies, and prognostic factors are not well defined. In addition, few studies have investigated the influence of tumour mutational status. 

 

We retrospectively assessed LC and OS in patients with mCRC treated with SBRT/SRS between 2014–2022 at a tertiary hospital in Australia. LC and OS were calculated using Kaplan-Meier estimates. Factors associated with these outcomes were explored using Cox proportional hazards models. 

 

Results: 

124 patients with 310 lesions were treated during the study period. Median follow up was 17 months. Median age was 68 years (range 21 – 92 years). Of the treated lesions, 53% were located in the brain, 22% lung, 16% liver, 4% bone, 4% nodal and 1% other. Biologically effective dose (BED10) ranged from 33.6 – 151.2Gy. Oligometastatic disease was the treatment indication for 58%, followed by oligoprogressive disease in 14%. 37% of patients had never received systemic therapy for metastatic disease prior to SBRT/SRS, 35% one line, 28% ≥2 lines. 

 

LC was 75% (95%CI 67-81%) at 1 year, 65% (95%CI 56-73%) 2 years, and 56% (95%CI 45%-66%) at 3 years. On multivariate analysis (MVA), older age (HR 1.04, p=0.001), and tumour volume >2.5cc (HR 3.13, p<0.001) were associated with worse LC. BED and lines of systemic therapy were not found to influence LC.

 

OS from first course of SBRT/SRS was 68% at 1 year (95%CI 58-76%), 48% at 2 years (95%CI 38-58%), and 35% (95% CI 25%-46%) at 3 years. On MVA, ≥2 or more lines of systemic therapy (HR 3.04, p<0.001) and intracranial metastases (HR 4.24, p=0.001) were associated with worse OS, and ≥2 courses of SBRT/SRS (HR 0.20, p = 0.004) better OS. 

 

Due to limited data availability, the influence of mutation status (KRAS, NRAS, EGFR, MMR) was inconclusive.  

 

Conclusion: 

Our study reveals that SBRT/SRS offers effective local control despite varied outcomes, with tumour volume as a key predictor of LC. This underscores the importance for ongoing research, particularly on tumour mutational status, to optimise and enhance treatment strategies.


Beini CHEN, Justin SMITH, Revadhi CHELVARAJAH, Alexandra KNESL, Tao MAI, Mark PINKHAM,