Salvage Stereotactic Radiosurgery Research Articles

Gross Tumor and Intracranial Control Benefits with Fractionated Radiotherapy Compared with Stereotactic Radiosurgery for Patients with WHO Grade 2 Meningioma

ObjectiveSurgical resection is the mainstay of treatment for WHO grade 2 meningioma. Fractionated radiation therapy (RT) is frequently employed following surgery, though many centers utilize stereotactic radiosurgery (SRS) for recurrence or progression. Herein, we report disease control outcomes from an institutional cohort with adjuvant fractionated RT versus salvage SRS. MethodsWe identified 32 patients from an institutional database with WHO grade 2 meningioma and residual/recurrent tumor treated with either SRS or fractionated RT. Patients were treated between 2007 and 2021 and had at least 1 year of follow-up. Kaplan-Meier estimators were used to determine gross tumor control (GTC) and intracranial control (IC). Univariate Cox proportional hazards models using biologically effective dose (BED) as a continuous parameter were used to assess for dose responses. ResultsWith a median follow-up of 5.5 years, 13 patients (41%) received SRS to a recurrent or progressive nodule, 2 (6%) fractionated radiation to a recurrent or progressive nodule, and 17 (53%) adjuvant fractionated radiation following subtotal resection. 5-year GTC was higher with fractionated RT versus SRS (82% vs. 38%, p=0.03). 5-year IC was also better with fractionated RT versus SRS (82% vs. 11%, p<0.001). On univariate analysis, increasing BED10 was significantly associated with better GTC (p=0.039); increasing BED3 was not (p=0.82). ConclusionsIn this patient cohort, GTC and IC were significantly higher in patients treated with adjuvant fractionated RT compared to salvage SRS. Increasing BED10 was associated with better GTC. Fractionated RT may provide a better therapeutic ratio than SRS for grade 2 meningiomas.

Salvage Stereotactic Radiosurgery for Recurrent WHO Grade 2 and 3 Meningiomas: A Multicenter Study (STORM)

PurposeThe role of stereotactic radiosurgery (SRS) in the management of grade 2 and 3 meningiomas is not well elucidated. Unfortunately, local recurrence rates are high, and guidelines for management of recurrent disease are lacking. To address this knowledge gap, we conducted STORM, a multicenter retrospective cohort study of patients treated with primary SRS for recurrent grade 2 and 3 meningiomas. Methods and MaterialsData on patients with recurrent grade 2 and 3 meningioma treated with SRS at first recurrence were retrospectively collected from eight academic centers in the United States. Patients with multiple lesions at the time of initial diagnosis or more than two lesions at the time of first recurrence were excluded from this analysis. Patient demographics and treatment parameters were extracted at time of diagnosis, first recurrence, and second recurrence. Oncologic outcomes including progression-free survival (PFS) and overall survival (OS) as well as toxicity outcomes were reported at the patient level. ResultsFrom 2000-2022, 108 patients were identified (94% grade 2, 6.0% grade 3). 106 patients (98%) had upfront surgical resection (60% gross-total resection) with 18% receiving adjuvant radiotherapy (RT). Median time to first progression was 2.5 years (IQR 1.34-4.30). At first recurrence, patients were treated with single or fractionated SRS to a median marginal dose of 16 Gy to a maximum of two lesions (87% received single fraction SRS). Median follow-up time after SRS was 2.6 years. 1-, 2-, and 3-year PFS was 90%, 75%, and 57%, respectively after treatment with SRS. 1-, 2-, and 3-year OS was 97%, 94%, and 92%, respectively. On multivariable analysis, grade 3 disease (HR 6.80; 95% CI 1.61-28.6), male sex (HR 3.48; 95% CI 1.47-8.26), and receipt of prior RT (HR 2.69; 95% CI 1.23-5.86) were associated with worse PFS. SRS dose and tumor volume were not correlated with progression. Treatment was well-tolerated, with a 3.0% incidence of grade 2+ radiation necrosis. ConclusionsThis is the largest multi-center study to evaluate salvage SRS in recurrent grade 2 and 3 meningiomas. In this select cohort of patients with primarily grade 2 meningioma with potentially more favorable natural history of delayed, localized first recurrence amenable to salvage SRS, local control rates and toxicity profiles were favorable, warranting further prospective validation.

Gamma knife radiosurgery following whole-brain radiation

In this study, we aimed to determine outcomes for patients requiring salvage stereotactic radiosurgery (SRS) who have progression of brain metastatic disease after initial treatment with whole-brain radiation (WBRT). This is a retrospective analysis of a prospective database of 112 patients who were treated with salvage SRS after experiencing failure following WBRT treatment with salvage SRS. Collectively, the patients had a median overall survival of 7 months after salvage SRS. Patients who had more than two brain metastases had a significantly shorter median survival but were not subjected to increased risk for distant brain failure. We also found that a short intervening time between WBRT and central nervous system (CNS) failure did not seem to worsen the nervous system control or reduce patient survival. Small cell lung cancer (SCLC) was associated with decreased overall survival and CNS control. In conclusion, SRS use following WBRT is safe and effective in the majority of patients. Patients with rapid failure after WBRT can be successfully salvaged with SRS. The findings also shed light on the overall poor outcomes, coupled with low median survival and high rates of CNS failure, in patients suffering multiple metastases stemming from SCLC.

Automated Detection, Segmentation, and Tracking of Brain Metastases in Repeated Courses of Stereotactic Radiosurgery Using Integrated Artificial Intelligence.

Salvage stereotactic radiosurgery (SRS) for distant brain metastases has been demonstrated as a safe and effective approach for intracranial recurrences after initial SRS. However, accurate tumor detection and segmentation among responding tumors within the irradiated parenchyma can be challenging. The requirement for the registration and reference to the previous course of SRS is very time-consuming and suffers significant inter and intra-reader variability. Artificial intelligence (AI)-assisted system has been proven to improve the accuracy and efficiency in the clinical flow of de-novo SRS. We hypothesize that an integrated AI system can facilitate an automated tumor contouring process for repeated SRS. Three patients who underwent their third course of SRS to brain metastases were selected for the pioneering works. They have had two sessions of SRS with a mean lesion number of 4 and 3.7, respectively. VBrain, an FDA-approved brain tumor management AI platform, was used to co-registered serial MR scans and automatically identify, track, and contour brain metastases for each course of SRS. The AI also indicated new lesions and treated lesions for each course. Three radiation oncologists experienced in brain SRS contoured the gross tumor volumes (GTVs) of the third course of SRS in two reader modes (assisted then unassisted) with a memory washout period of one week between each section. The segmentation ground truth was established through consensus among the three experts. Lesion-wise sensitivity, contouring accuracy, and consuming time were compared between the two contouring modes. In each patient, there were 15, 11, and 9 metastases, with a median diameter of 4.72 (95% CI: 4.05, 6.91) mm. The mean lesion-wise sensitivity was 96.96±2.47% with AI assistance and 76.90 ± 7.10% without assistance. There were two false-positive lesions in the assisted read, resulting in a low average false-positive rate of 0.67 per patient, while no false positive for the unassisted mode. AI assistance improved contouring accuracy. The median Dice similarity coefficient (DSC) was 0.71 (95% CI: 0.55, 0.87) for assisted contouring and 0.65 (95% CI: 0.46, 0.85) for unassisted contouring. We also use average Hausdorff distance (HD) to measure segmentation results. The mean HD was 0.72± 0.13 mm versus 0.73±0.08 mm for the two contouring modes (p = 0.02) Furthermore, the median contouring time per case was significantly shorter with AI assistance than without assistance (20.8 minutes vs. 29.8 minutes; p < 0.001), corresponding to a 43.2% time-saving. Our results suggest that the integration of an AI-based system into repeated brain SRS can significantly improve the accuracy and efficiency of tumor detection and segmentation. This approach has the potential to streamline the treatment planning process for salvage SRS.

FOCAL MANAGEMENT OF BRAIN METASTASES IN SMALL CELL LUNG CANCER: A SYSTEMATIC REVIEW

Abstract AIMS Small cell lung cancer (SCLC) brain metastases (BM) are common at both presentation and relapse. Historically, BM are managed with whole brain radiotherapy (WBRT) +/- chemotherapy. However, WBRT is associated with significant cognitive impairment, and so interest in the focal management of BM (encompassing stereotactic radiosurgery (SRS) and surgery) is increasing. We systematically reviewed the current literature regarding focal BM management. METHOD A systematic literature search of PubMed, Embase, and CENTRAL databases and clinicaltrials.gov was conducted to obtain published articles, abstracts, and ongoing studies regarding focal management of SCLC BM. Exclusion criteria included publication before 2005 and publication in a non-English language. Additional papers were added by reviewing citations of relevant papers. RESULTS Following initial review of 15,420 records, we identified 67 articles eligible for inclusion. 24 were published before 2015 and 44 published 2015-2023. 8 related to surgical BM treatment: case studies (n=6), retrospective cohort studies (n=2). 60 articles were identified regarding SRS: abstracts (n=13), case studies (n=5), retrospective cohort studies (n=14), retrospective case series (n=20), prospective trials (n=8). These papers have been further divided by topic: upfront SRS (n=23), salvage SRS (n=19) and WBRT with SRS boost (n=3). There are several ongoing trials (n=8) investigating outcomes in SRS for SCLC BM, both alone and when compared with WBRT. CONCLUSIONS Focal treatments for SCLC BM are being used more frequently. However, randomised trial evidence for their safety and effectiveness are still pending.

P11.74.A EXPERIENCE OF PREOPERATIVE GAMMA KNIFE RADIOSURGERY FOR RECURRENT BRAIN METASTASES

Abstract BACKGROUND Resection of brain metastases (BM) without additional radiation therapy yields a high local failure rate. Surgical resection of newly diagnosed BM combined with post-operative stereotactic radiosurgery (SRS) to reduce the risk of a local recurrence is an accepted and effective treatment option. Drawbacks of postoperative SRS include uncertainty in target delineation, potential delay in the administration of SRS and intraoperative risk of tumor spillage. Preoperative SRS might address these potential drawbacks. We present our experience with preoperative Gamma Knife radiosurgery (GKRS) for recurrent BM. MATERIAL AND METHODS Data of patients with recurrent BM treated with GKRS followed by surgical resection between June 2019 and June 2021 at the Elisabeth-TweeSteden Hospital Tilburg were retrospectively collected. Surgery was necessary according to the multidisciplinary team because of mass effect, a symptomatic lesion or a large tumor volume not eligible for salvage stereotactic radiosurgery. Pre-operative SRS was performed with GKRS followed by surgery within 24 hours. All patients had follow-up appointments with MRI scan 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 characteristics. Kaplan-Meier curves were used to analyze overall survival. RESULTS 25 patients (male 8, female 17; median age 64 years (range 20-79 years)) underwent preoperative GKRS for recurrent brain metastases. Most patients were previously treated with GKRS (76%) or SRS (24%). Most patients had non-small cell lung cancer (44%), followed by breast (12%), small cell lung cancer (12%), and melanoma (12%). The median overall survival was 18.5 months (95% CI, 4.9 to 32.1 months). Eight patients (32%) had (multiple) surgical complications, three of these patients died due to the postoperative complications. Twelve patients (48%) developed a local recurrence. The median time to local recurrence was 6.9 months (95% CI, 4.7 to 9.1months). Of the 16 patients with a subtotal resection, 10 patients developed a local recurrence, with 6 recurrences at the site of the macroscopic residual tumor. Two patients (8%) developed leptomeningeal disease at 2.8 months and 3.9 months. Two patients (8%) developed new brain metastases (distant failure) at 5.4 months and 23.8 months. CONCLUSION Pre-operative radiosurgery was well tolerated in a group of patients with recurrent BM who were eligible for surgery. Larger series are needed to perform multivariate analyses on predictors of local recurrence in order to evaluate for which patients this treatment option is best suited.

Does Adjuvant Gamma Knife Stereotactic Radiosurgery Have a Role in Treating Optic Nerve Sheath Meningiomas?

Meningiomas arising from or adjacent to the optic nerve sheath meningioma (ONSM) are management challenges because of their risk of visual loss. Stereotactic radiosurgery (SRS) is a minimally invasive modality that can be added as adjuvant treatment for patients whose tumor has progressed or recurred after initial resection. The authors retrospectively reviewed 2,030 meningioma patients who underwent SRS between 1987 and 2022. In total, 7 patients (4 females; median age = 49) were found with tumors originating from the optic nerve sheath. None of the patients had tumors that engulfed the optic nerve as such tumors typically undergo fractionated radiation therapy (FRT) to preserve vision. The clinical history, visual function, and radiographic and neurological findings were characterized. Outcome measures included visual status, tumor control, and the need for additional management. All patients underwent either initial gross total (n = 1) or partial surgical resection (n = 6) before SRS. Two patients with progressive tumor growth also had SRS after failing additional fractionated radiation after surgery (54 Gy, 30 fractions for both patients). The median time between the date of surgery and the SRS procedure date was 38 months. The Leksell Gamma Knife was used to deliver a margin dose of 12 Gy (range: 8-14 Gy) to a median cumulative tumor volume of 3.3 cc (range: 1.2-18 cc). The median maximal optic nerve radiation dose was 6.5 Gy (range: 1.9-8.1 Gy). After SRS, the median follow-up time was 130 months (range: 26-169 months). Two patients showed local tumor progression at 20 and 55 months after SRS. Four had stable visual function, 2 experienced improved visual acuity, and 1 patient had visual deterioration. Meningiomas arising from (but not engulfing the optic nerve) represent management quandaries after failed initial surgical removal. In this experience, salvage SRS was associated with tumor control and vision preservation in 5 of 7 patients. Additional experience with this strategy may further define the role of SRS both as a salvage and primary option.

Stereotactic radiosurgery for recurrent skull base polymorphous adenocarcinoma invading the cavernous sinus: illustrative case.

Polymorphous adenocarcinomas (PACs) are rare tumors arising from the salivary glands. Radical resection and postoperative radiotherapy are the mainstays of treatment. However, complete tumor resection is not always achievable when the tumor invades the skull base. Stereotactic radiosurgery (SRS) could be a less invasive alternative for treating skull base PACs. A 70-year-old male with a history of surgery for a right palatine PAC presented with right visual impairment, diplopia, and ptosis. Imaging studies revealed tumor recurrence invading the right cavernous sinus (CS). SRS using a gamma knife was performed for this recurrence, prescribing a marginal dose of 18 Gy at a 50% isodose line. Five months after SRS, his symptoms were relieved, and the tumor was well-controlled for 55 months without any adverse events. To the best of the authors' knowledge, this is the world's first case of recurrent skull base PAC invading the CS that was successfully treated with salvage SRS. Thus, SRS may be an applicable treatment option for skull base PACs.

Radiosurgery outcomes in infratentorial juvenile pilocytic astrocytomas.

To assess survival and neurological outcomes for patients who underwent primary or salvage stereotactic radiosurgery (SRS) for infratentorial juvenile pilocytic astrocytomas (JPA). Between 1987 and 2022, 44 patients underwent SRS for infratentorial JPA. Twelve patients underwent primary SRS and 32 patients underwent salvage SRS. The median patient age at SRS was 11.6years (range, 2-84years). Prior to SRS, 32 patients had symptomatic neurological deficits, with ataxia as the most common symptom in 16 patients. The median tumor volume was 3.22cc (range, 0.16-26.6cc) and the median margin dose was 14Gy (range, 9.6-20Gy). The median follow-up was 10.9years (range, 0.42-26.58years). Overall survival (OS) after SRS was 97.7% at 1-year, and 92.5% at 5- and 10-years. Progression free survival (PFS) after SRS was 95.4% at 1-year, 79.0% at 5-years, and 61.4% at 10-years. There is not a significant difference in PFS between primary and salvage SRS patients (p = 0.79). Younger age correlated with improved PFS (HR 0.28, 95% CI 0.063-1.29, p = 0.021). Sixteen patients (50%) had symptomatic improvements while 4 patients (15.6%) had delayed onset of new symptoms related to tumor progression (n = 2) or treatment related complications (n = 2). Tumor volumetric regression or disappearance after radiosurgery was found in 24 patients (54.4%). Twelve patients (27.3%) had delayed tumor progression after SRS. Additional management of tumor progression included repeat surgery, repeat SRS, and chemotherapy. SRS was a valuable alternative to initial or repeat resection for deep seated infratentorial JPA patients. We found no survival differences between patients who had primary and salvage SRS.

Stereotactic Radiosurgery for Primary Central Nervous System Lymphoma.

Background Primary central nervous system lymphoma (PCNSL) is rare, with a treatment backbone that typically includes high-dose methotrexate-based chemotherapy, with radiation often reserved for persistent or progressive disease. In this study, we report the outcomes of stereotactic radiosurgery (SRS) in patients with PCNSL to potentially defer whole brain radiotherapy (WBRT) or as salvage after WBRT. Methodology We performed a single-institution, retrospective review of 20 patients with PCNSL who received single-fraction or fractionated SRS to 32 lesions between September 1992 and July 2019. Results The median age at SRS was 67 years (interquartile range (IQR) = 56-74 years). The median Karnofsky Performance Status (KPS) at SRS was 80 (IQR = 50-80). In total, 18 (90%) patients received methotrexate-based chemotherapy prior to SRS, with a median of eight cycles (IQR = 5-10). A total of 10 patients received SRS for recurrent disease after chemotherapy and/or WBRT, nine patients received SRS for the persistent disease after chemotherapy alone, and one patient received up-front SRS. Overall, five patients received SRS following WBRT. The median SRS dose was 16 Gy (IQR = 14-22.5 Gy) in one fraction (IQR = 1-5 fractions). Eight patients (40%) were treated with consolidative pomalidomide or lenalidomide following SRS. The local control rate was 100% (32/32 lesions at a median follow-up of 15 months). In total, 13 of 16 (81%) patients with available follow-up experienced distant brain recurrence. The median time to distant failure following SRS was 10 months (IQR = 1-16 months). Three patients received salvage SRS, and three patients received salvage WBRT. The median overall survival from diagnosis was 39 months (95% confidence interval = 24-54 months). KPS at the time of SRS was significantly correlated with time to progression (p = 0.002). The use of lenalidomide or pomalidomide after SRS was associated with improved overall survival after SRS (three vs. 14 months, p = 0.035). Consolidative etoposide and cytarabine after initial methotrexate-based chemotherapy was also associated with improved survival following SRS (eight vs. 47 months, p = 0.028). Conclusions SRS offers effective local tumor control for patients with PCNSL; however, the majority of patients experience distant progression. SRS may have a role in the salvage setting for patients with recurrence after WBRT, or allow deferral of WBRT in select patients, although systemic therapy appears to strongly influence outcomes in this cohort.

CNS Downstaging: An Emerging Treatment Paradigm for Extensive Brain Metastases in Oncogene-Addicted Lung Cancer

IntroductionFor extensive brain metastases (BrM) presentations arising from oncogene-addicted lung cancer, tyrosine kinase inhibitors (TKIs) with high response rates in the central nervous system (CNS) could potentially downstage the CNS disease burden, allowing for the avoidance of upfront whole-brain radiotherapy (WBRT) and the conversion of some patients into candidates for focal stereotactic radiosurgery (SRS). MethodsWe describe the outcomes of patients with ALK, EGFR, and ROS1-driven NSCLC with extensive BrM presentations (defined as > 10 BrMs or leptomeningeal disease) treated with upfront newer generation CNS-active TKIs alone, including osimertinib, alectinib, brigatinib, lorlatinib, and entrectinib, from 2012 to 2021 at our institution. All BrMs were contoured at study entry, best CNS response (nadir), and first CNS progression. ResultsTwelve patients met criteria including 6 with ALK, 3 with EGFR, and 3 with ROS1-driven NSCLC. The median number and volume of BrMs at presentation were 49 and 19.6 cm3, respectively. Eleven patients (91.7 %) achieved a CNS response by modified-RECIST criteria to upfront TKI (10 partial responses, 1 complete response, 1 stable disease) with nadir observed at a median of 5.1 months. At nadir, the median number and volume of BrMs were 5 (median 91.7 % reduction per-patient) and 0.3 cm3(median 96.5 % reduction per-patient), respectively. Eleven patients (91.6 %) developed subsequent CNS progression (7 local failures, 3 local + distant, 1 distant) at a median of 17.9 months. At CNS progression, the median number and volume of BrMs were 7 and 0.7 cm3, respectively. Seven patients (58.3 %) received salvage SRS and no patients received salvage WBRT. The median overall survival from initiation of TKI for the extensive BrM presentation was 43.2 months. ConclusionIn this initial case series, we describe CNS downstaging as a promising multidisciplinary treatment paradigm involving the upfront administration CNS-active systemic therapy and close MRI surveillance for extensive BrMs as a strategy to avoid upfront WBRT and to convert some patients into SRS candidates.

Stereotactic radiosurgery in brain metastasis: treatment outcomes and patterns of failure

Abstract Introduction: Stereotactic radiosurgery (SRS) has become a preferred treatment in the initial management of brain metastases (BM). This study reported treatment outcomes and identified the patient, tumour, and treatment-related factors that predict failure, survival, and brain necrosis (BN). Methods: We retrospectively reviewed the electronic medical records of all BM patients treated with SRS. Patient, tumour characteristics and treatment details data were collected. All recurrences and BN were defined in the neurooncological tumour board. Results: From December 2016 to April 2020, 148 patients were analysed. The median follow-up was 14·8 months (range 6–51). At the time of analyses, 72·3% of the patients were alive. Presence of initial neurological deficit (HR; 2·71 (1·07–6·9); p = 0·036) and prior RT (HR; 2·55 (1·28–5·09); p = 0·008) is associated with worse overall survival. The local recurrence rate was 11·5 %. The distant brain metastasis rate was 53·4 %. Leptomeningeal metastasis was seen in 11 patients (7·4%). Symptomatic BN was seen in 19 patients (12·8 %). Bigger lesions (13 versus 23 mm diameter; p = 0·034) and cavity radiosurgery are associated with more BN (63·2 % versus 36·8%; p: 0·004). Conclusions: Distant BM is the leading cause of CNS recurrences and, salvage SRS is possible. Due to the increasing risk of developing BN routine metastasectomy should be made with caution.

Adverse radiation effect and freedom from progression following repeat stereotactic radiosurgery for brain metastases.

The authors previously evaluated risk and time course of adverse radiation effects (AREs) following stereotactic radiosurgery (SRS) for brain metastases, excluding lesions treated after prior SRS. In the present analysis they focus specifically on single-fraction salvage SRS to brain metastases previously treated with SRS or hypofractionated SRS (HFSRS), evaluating freedom from progression (FFP) and the risk and time course of AREs. Brain metastases treated from September 1998 to May 2019 with single-fraction SRS after prior SRS or HFSRS were analyzed. Serial follow-up magnetic resonance imaging (MRI) and surgical pathology reports were reviewed to score local treatment failure and AREs. The Kaplan-Meier method was used to estimate FFP and risk of ARE measured from the date of repeat SRS with censoring at the last brain MRI. A total of 229 retreated brain metastases in 124 patients were evaluable. The most common primary cancers were breast, lung, and melanoma. The median interval from prior SRS/HFSRS to repeat SRS was 15.4 months, the median prescription dose was 18 Gy, and the median duration of follow-up imaging was 14.5 months. At 1 year after repeat SRS, FFP was 80% and the risk of symptomatic ARE was 11%. The 1-year risk of imaging changes, including asymptomatic RE and symptomatic ARE, was 30%. Among lesions that demonstrated RE, the median time to onset was 6.7 months (IQR 4.7-9.9 months) and the median time to peak imaging changes was 10.1 months (IQR 5.6-13.6 months). Lesion size by quadratic mean diameter (QMD) showed similar results for QMDs ranging from 0.75 to 2.0 cm (1-year FFP 82%, 1-year risk of symptomatic ARE 11%). For QMD < 0.75 cm, the 1-year FFP was 86% and the 1-year risk of symptomatic ARE was only 2%. Outcomes were worse for QMDs 2.01-3.0 cm (1-year FFP 65%, 1-year risk of symptomatic ARE 24%). The risk of symptomatic ARE was not increased with tyrosine kinase inhibitors or immunotherapy before or after repeat SRS. RE on imaging was common after repeat SRS (30% at 1 year), but the risk of a symptomatic ARE was much less (11% at 1 year). The results of repeat single-fraction SRS were good for brain metastases ≤ 2 cm. The authors recommend an interval ≥ 6 months from prior SRS and a prescription dose ≥ 18 Gy. Alternatives such as HFSRS, laser interstitial thermal therapy, or resection with adjuvant radiation should be considered for recurrent brain metastases > 2 cm.

MET-14 OUTCOME OF METASTATIC CEREBELLAR TUMOR: A SINGLE-CENTER STUDY

Abstract Background Brain metastases (BM) to the cerebellum account for approximately 20% of all of BM. From the results of JCOG0504 clinical trial, observation with salvage SRS (stereotactic radiosurgery) has been established as a standard therapy for a patient after complete resection of BM. However, we often experience early local recurrence after resection of cerebellar BM, therefore, we retrospectively analyzed them to consider the appropriate timing of SRS. Methods We extracted surgical cases with cerebellar BM from January 2015 to March 2022 and analyzed the patient characteristics, treatment content, postoperative intracranial progression-free survival (IC-PFS) and postoperative overall survival (OS). Results A total of 57 cases were enrolled (male: female = 43.9%: 56.1%) in this study. The median age was 61.9 years (51.9-68.2). The common primary lesions were NSCLC (31.6%), colorectal cancer (19.3%), and breast cancer (17.5%). The IC-PFS was 4.5 months (2.6-5.7) and the OS was 11.6 months (9.1-21.8), but the local recurrent rate within 3 months was 43.4%. The rate of patients with leptomeningeal metastases (LMM) at the first recurrence was 26.3%, significantly higher than 7.7% in JCOG0504 (p=0.000224). In the postoperative observation group (no SRS within a month), the OS was 25.3 months (11.6-NA), which was longer than the 15.6 months (11.4-20.8) of JCOG0504. RT was performed in 18 patients at the recurrence (SRS: 15, WBRT (whole-brain radiotherapy): 9). SRS was the only factor that prolonged the OS (25.2 vs. 6.1 months (p=0.0212)). Furthermore, in the patients who underwent radiotherapy within 1 month after surgery, postoperative SRS (10.2 vs. 3.1 months, p=0.00437), and postoperative SRS to the resection cavity (11.0 vs. 3.7mo, p=0.0012) significantly prolonged the OS. Conclusion Since cerebellar BM has high recurrence and frequent LMM, early SRS for a resected cavity after surgery might lead to more favorable outcomes in cerebellar BM patients.

Local Control of Brain Metastases with Osimertinib Alone in Patients with EGFR-Mutant Non-Small Cell Lung Cancer

<h3>Purpose/Objective(s)</h3> Osimertinib has emerged as a new standard of care in the treatment of EGFR-mutant metastatic non-small cell lung cancer (NSCLC). However, data on lesion-level control and durability of intracranial response to osimertinib is limited. We aim here to describe longitudinal lesion-level outcomes of brain metastases treated with osimertinib alone. <h3>Materials/Methods</h3> We retrospectively reviewed charts of patients with EGFR-mutant NSCLC with at least one untreated brain metastasis at the time of initiation of osimertinib at our institution from 2006-2021. An FDA-approved brain tumor segmentation tool, VBrain, was used to identify, track, and measure brain metastases larger than 5 mm on serial MRI brain scans. Patients with leptomeningeal disease were excluded. Cumulative incidence of local failure (LF) was calculated with competing risk analysis with death as a competing risk and censored at the last brain MRI follow up. LF was defined as a ≥20% increase in the maximum diameter of a brain lesion using linear measurements on serial imaging. LF was calculated on a per-lesion basis, and univariable and multivariable analysis was conducted with competing risks regression used to identify predictors for LF. Overall survival (OS) was analyzed using Kaplan-Meier. <h3>Results</h3> A total of 73 patients with 284 untreated brain metastases larger than 5 mm were identified. Median follow-up time was 17 months (range 1.3-50.6 months). Median age at brain metastases diagnosis was 60 years old (range 30-90); 68.5% were female. Median number of prior systemic therapies received was 0 (range 0-6), with 32.9%, 27.4%, and 15.1% of patients receiving prior tyrosine kinase inhibitors, chemotherapy, and immunotherapy, respectively. The median size of brain metastases was 6.9 mm (range 5.0-33.6 mm) and the median number of brain metastases larger than 5 mm per patient was 1 (range 0-43). Median OS was 24.4 months (95% confidence interval [CI] 17.6-34.9). The 1-year cumulative incidence of LF was 12.1% (95% CI 8.8-16.1). On univariable analysis, uncontrolled primary tumor (hazard ratio [HR] 3.78, 95% CI 1.87-7.66; <i>p</i><0.001), increasing number of prior systemic therapies before osimertinib (HR 2.12, 95% CI 1.49-3.04; <i>p</i><0.001), and higher ECOG score (HR 7.8, 95% CI 1.99-31.81; <i>p</i>=0.003) was associated with LF. These factors remained significant in multivariable analysis. Median duration on osimertinib was 14.8 months (range 0.2-48.3 months), and 26% of patients experienced toxicities from osimertinib that required either a change in systemic therapy or a dose reduction. 9.6% and 18.6% of patients underwent salvage whole brain radiation therapy and salvage stereotactic radiosurgery, respectively. <h3>Conclusion</h3> Although NSCLC patients have excellent response of untreated intracranial metastases on osimertinib alone, over 10% of metastases will progress locally at 1 year. Further studies are needed to identify the brain metastases at risk for local failure to guide optimal intracranial management in these patients.

Mature Local Control and Radiation Necroses Outcomes Specific to Brain Metastases Treated with Salvage Stereotactic Radiosurgery for Radiosurgical Failures

<h3>Purpose/Objective(s)</h3> The management of locally recurrent brain metastases is a clinical challenge. A second course of radiosurgery may be delivered as the primary salvage treatment or as postoperative radiosurgery to the surgical cavity if the recurrence resected. We report our institutional experience of repeat radiosurgery for locally recurrent brain metastases, with a focus on local control and radionecrosis (RN) outcomes. <h3>Materials/Methods</h3> We report a single institution retrospective cohort study specific to patients with recurrent brain metastases treated with repeat radiosurgery. Clinical and dosimetric details were collected. Overall survival was estimated using the Kaplan Meier method. Local recurrence and RN rates were estimated using the Aalen-Johnson method, with death from any cause as the competing risk for both endpoints. Univariable competing risk regression using Fine and Gray's methods were performed, and subsequent multivariable (MVA) regression based on a priori variable selection generated final adjusted models. <h3>Results</h3> We identified 96 patients and 130 brain metastases re-treated with radiosurgery (either single fraction or hypofractionation between July 2010 to April 2020. The most common primary sites were lung (N = 44, 33.8%), breast, (N = 38, 29.2%), and melanoma (N = 26, 20%). More than half of the retreated lesions were postoperative cavities (N = 68, 52.3%). Re-treatment was most commonly delivered with 25 Gy in 5 fractions (N = 77, 59.2%) followed by 27.5 Gy in 5 fractions (N = 23, 17.7%). The mean BED₁₀ was 39.71 Gy (standard deviation [SD] 6.16) with a mean treatment volume of 14.94 cm³ (SD, 20.15). Nearly half (N = 64, 49.2%) of lesions were treated in the absence of systemic therapy, while 43.8% (N = 57) and 6.9% (N = 9) were treated while receiving targeted therapy/immunotherapy and chemotherapy, respectively. The median time between treatment courses was 13.7 months (IQR 10.88). With a median follow up of 34.9 months (interquartile range [IQR] 25-41.9), the 1 and 2-year overall survival rates were 59.8% (95% confidence interval [95% CI] 50.4-70.9) and 36.2% (95% CI, 27.2-48.2), respectively. The risk of local failure at 1 and 2 years was 26.2% (95%CI, 18.5-34) and 28% (95%CI, 20.1-35.9), respectively. MVA identified increasing target volume (hazard ratio [HR] 1.03; 95% CI, 1.02-1.04), and a shorter time-interval between radiosurgery courses (HR 0.29; 95% CI, 0.19-0.45) to be associated with worse local control. The crude incidence of RN was 18.5% (N = 24), of which 8 events (6.15%) were symptomatic. The 1 and 2-year rates of RN were 17.6% (95% CI, 10.9-34) and 19.3% (95%CI, 12.3-35.9), respectively. <h3>Conclusion</h3> Repeat radiosurgery for locally recurrent brain metastases results in good local control with a moderate risk of RN. Larger target volume and a shorter timeframe between radiosurgery treatments are associated with worse control.

Prospectively Observed Histopathologic Predictors of Progression after Stereotactic Radiosurgery for Recurrent Atypical Meningioma

<h3>Purpose/Objective(s)</h3> Atypical meningiomas (AM) have high rates of progression and recurrence after initial treatment. Optimal management of recurrent AM remains an unresolved issue. In turn, we sought to correlate histopathologic findings of AM at initial resection with survival outcomes after stereotactic radiosurgery (SRS) for treatment of recurrent disease. <h3>Materials/Methods</h3> Prospectively enrolled radiation-naïve patients who were treated with SRS for recurrent AM between 2014 and 2020 were retrospectively reviewed in our institutional review board (IRB) approved database. Kaplan-Meier analysis with log rank testing was used to compare local control and survival in patients with varying histopathological features and Cox regression was used to examine possible prognostic factors for progression after SRS. <h3>Results</h3> Two hundred and seventy-seven patients with meningioma were treated with SRS from 2014 to 2020. Of these, 49 were identified who underwent resection for an atypical meningioma at our institution and then received salvage SRS for first recurrence. Forty-five (92%) patients received salvage radiation after recurrence following a subtotal resection (STR) and four patients (8%) received salvage radiation for recurrent disease after an initial gross total resection (GTR). Patients receiving salvage SRS underwent treatment for recurrent disease at a mean time of 23 months after surgery. Tumor size was not associated with progression after SRS treatment. On univariable analysis, presence of necrosis, presence of brain invasion, and presence of bone invasion predicted for progression. At 2 years, patients treated with SRS had a local control rate of 93%. In the subset of patients found to have necrosis, bone invasion, or brain invasion on surgical pathology, local control at 2 years was 81%. <h3>Conclusion</h3> Histopathologic variables can predict for treatment outcomes of recurrent atypical meningioma treated with radiotherapy and should be considered when deciding on an individual patient's treatment plan in the setting of recurrence. Brain and bone invasion as well as presence of necrosis predict for decreased local control after SRS. Future investigation is warranted to optimize outcomes in this group.

Stereotactic radiosurgery for Rathke's cleft cysts: an international multicenter study.

Rathke's cleft cysts (RCCs) are sellar collections from an incompletely regressed Rathke's pouch. Common symptoms of RCCs can include headaches, visual loss, and endocrinopathy. Surgery is required in some cases of symptomatic or growing RCCs. Recurrence after surgery is common (range 10%-40%). Stereotactic radiosurgery (SRS) has been used in an attempt to control growth and symptoms, but outcomes are not well known. The authors sought to study the outcomes of RCCs following Gamma Knife surgery for both salvage and initial treatment. The outcomes of 25 patients with RCCs who underwent SRS between 2001 and 2020 were reviewed. Four patients received initial SRS and 21 were treated with salvage SRS. Diagnosis was based on imaging or histopathology. Cyst control was defined as stability or regression of the cyst. Kaplan-Meier analysis was used to determine time to recurrence and determine potential factors for recurrence. The respective median clinical follow-up and margin dose were 6.5 years and 12 Gy. Overall control was achieved in 19 (76%) of 25 patients, and 4 recurrences required further intervention. The average time to recurrence was 35.6 months in those RCCs that recurred. Visual recovery occurred in 14 (93.3%) of 15 patients and no new post-SRS visual deficits occurred. The presence of a pretreatment visual deficit was often an indicator of RCC regrowth. All 3 patients with pretreatment hyperprolactinemia experienced resolution after SRS. New endocrinopathy related to SRS was noted in 5 (20%) of 25 patients, all of which were thyroid and/or cortisol axis related. Upfront SRS was used in 4 patients. No new endocrinopathies or visual deficits developed after upfront SRS, and the 1 patient with a pretreatment visual deficit recovered. One of the 4 patients with upfront SRS experienced a recurrence after 7.5 years. SRS produced effective recovery of visual deficits and carries a low risk for new visual deficits. Cyst control was achieved in approximately three-fourths of the patients. Following SRS, patients without pretreatment visual deficits are less likely to have RCC regrowth. Endocrinopathy can occur after SRS, similar to other sellar mass lesions. Initial SRS shows the potential for long-term cyst control, with improvement of symptoms and a low risk for complications.

LOCL-13 SURGICAL RESECTION PLUS STEREOTACTIC RADIOSURGERY (SRS) VERSUS SRS ALONE FOR LARGE POSTERIOR FOSSA BRAIN METASTASES: OUTCOMES AND FACTORS GUIDING THE DECISION OF TREATMENT MODALITY

Abstract INTRODUCTION Approximately 20% of brain metastases (BM) occur in the posterior fossa (PF). However, the criteria to treat large PF BM with surgery (S) followed by stereotactic radiosurgery (SRS) or SRS alone are still unclear. We aim to identify parameters that can help in the decision of treating PF BM with S+SRS or SRS and to compare outcomes between the two groups. METHODOLOGY We reviewed a prospective registry database (2009 to 2020) and identified all patients with PF BM (≥4cc in volume) treated with SRS or S+SRS. Clinical and radiological, parameters were analyzed. We examined two endpoints: Overall Survival (OS) and Local Failure (LF). RESULTS 64 patients were identified; 30 were treated with S+ SRS and 34 with SRS. Gait imbalance and Intracranial pressure symptoms were significantly different between the groups; 97% and 80% for S+SRS vs 47% and 35% for SRS, respectively. Radiologically, there were significant differences in the mean volume of the lesions [6.7 cm3 in SRS vs 29.8cm3 in S+SRS cohort] (p&amp;lt;0.001), compression of the IV ventricle (47% in SRS vs 96% in S+SRS cohort, (p&amp;lt;0.001)) and hydrocephalus (0% in SRS vs 29% in S+SRS cohort, (p&amp;lt;0.001)). One surgical patient required salvage SRS and two SRS patients required salvage S. Patients with S+SRS (HR 0.35, p&amp;lt;0.001) and higher GPA scores (HR 0.62, p=0.007) correlated with better OS. There was no significant difference in rates of LF between the 2 groups. CONCLUSIONS Patients treated with S+SRS were more likely to be symptomatic, have larger tumors, and have compression of the IV ventricle with hydrocephalus. Non-symptomatic patients with moderately sized lesions were safely managed with SRS. S+SRS treatment and higher GPA were associated with improved OS.

Malignant progression of cerebellopontine angle solitary fibrous tumors following radiation: illustrative case.

BACKGROUNDIntracranial solitary fibrous tumors (ISFTs) are rare mesenchymal tumors originating in the meninges and constitute a heterogeneous group of clinical and biological behavior. Benign histotypes, such as hemangiopericytomas are now considered as a cellular phenotypic variant of this heterogenous group of rare spindle-cell tumors. IFSTs are poorly recognized and remain a diagnostic challenge due to rarity and resemblance to other brain tumors. Previously, IFSTs were thought to pursue a slow, indolent, and nonaggressive course, however, a growing body of literature based on longer follow-up demonstrates an unpredictable clinical course and an uncertain diagnosis.OBSERVATIONSA rare case report of malignant transformation of IFST following radiation therapy is reported. In this case a 60-year-old female who underwent gross total resection of the cerebellopontine angle tumor with histopathology consistent with solitary fibrous tumor followed by salvage stereotactic radiosurgery, presented with another recurrence after 2 years of surgery. The authors performed complete removal of the tumor with pathology now consistent with malignant solitary fibrous tumor. A recent follow-up magnetic resonance imaging did not show any recurrence or residual tumor, and the patient reports a generalized well-being.LESSONSThis report will help to understand the natural history and unusual clinical behavior of these intracranial tumors.