Faculty Bibliography

PURPOSE/OBJECTIVE(S): Multiple brain metastases (BM) from non-small cell lung cancer (NSCLC) historically has a dismal prognosis. Advances in systemic therapy for NSCLC have significantly improved survival, but the effect on prognosis in patients with NSCLC and BM is poorly understood. Stereotactic radiosurgery (SRS) may result in local control even with higher numbers of BM. We report survival outcomes of upfront SRS for >=5 BM from metastatic NSCLC. MATERIALS/METHODS: Review of our registry identified 177 patients treated for >=5 BM from NSCLC between 2012 and 2020, and did not undergo prior intracranial radiation or resection.
RESULT(S): Adenocarcinoma was found in 129 patients (73%). EGFR/ALK mutations were identified in 54 patients (31%). The median number of tumors at initial SRS were 8 (range 5-35). 121 patients (68%) were treated for 5-10 BM, 31 patients (18%) for 11-15 BM, and 25 patients (14%) for > 15 BM. The median overall survival (OS) from initial SRS for all patients was 15.1 months (95% CI 11.5-18.7). Survival at 1, 2, and 3 years was 57%, 39%, and 28% respectively. Adenocarcinoma was associated with improved survival compared to non-adenocarcinoma (P < 0.001), median OS 17.1 months (95% CI 11.4-22.9) and median OS 5.7 months (95% CI 2.8-8.6), respectively. Patients with EGFR/ALK mutations had a significantly greater survival time compared to those without (P=0.008), and median OS of 26.3 months (95% CI 19.1-33.6) versus 10.4 months (95% 6.2-14.6). Treatment of 5-10, 11-15, or > 15 tumors at initial GK were not associated with differences in survival (P=0.48). On multivariate analysis, survival benefit remained significant in patients with adenocarcinoma (HR 0.42, 95% CI 0.24-0.72, P=0.002), and patients with EGFR/ALK mutations (HR 0.58, 95% CI 0.37-0.91, P=0.02).
CONCLUSION(S): Patients treated with initial SRS for multiple BM from NSCLC in the modern era demonstrate longer survival as compared with historical reports. Adenocarcinoma subtype, particularly in the setting of EGFR/ALK mutation is associated with improved prognosis, even in patients with higher number of metastases. AUTHOR DISCLOSURE: J. Gurewitz: None. D. Patel: None. C. Benjamin: None. B.R. Donahue: None. J. Silverman: None. M. Mureb: None. K. Bernstein: None. D. Kondziolka: None.
Copyright

OBJECTIVE:To evaluate outcomes following salvage microsurgery (MS) and salvage stereotactic radiosurgery (SRS) after failure of primary treatment for vestibular schwannomas (VS). STUDY DESIGN/METHODS:Retrospective chart review. SETTING/METHODS:Tertiary referral center. METHODS:Patients with more than 1 intervention for their VS were divided into 4 groups: MS followed by SRS (n = 61), MS followed by MS (n = 9), SRS followed by MS (n = 7), and SRS followed by SRS (n = 7), and outcomes were evaluated. RESULTS:A total of 77 patients were included (84 procedures). In group 1 (MS then SRS), 3% developed a decline in facial function, 3% developed trigeminal sensory loss, and 13% patients had gradual improvement of facial nerve function following SRS. Group 2 (MS then MS) had the highest rates of facial nerve deterioration, although all but 1 patient achieved a House-Brackmann score of II or III. Gross-total resection (GTR) was achieved in 56% of patients. When a different approach was used for salvage resection, GTR occurred more commonly, and facial nerve outcomes were similar. In group 3 (SRS then MS), GTR occurred in 43% of cases, and 2 of 7 patients developed worsened facial function. In group 4 (SRS then SRS), no patient developed facial weakness after reirradiation, and 1 developed a trigeminal nerve deficit. CONCLUSIONS:For MS recurrences/residuals, SRS is the mainstay of treatment and does not preclude facial function recovery. If salvage microsurgery is required, an alternate approach should be considered. For SRS failures, when MS is required, less-than GTR may be preferable, and reirradiation is a potential safe alternative.

OBJECTIVE:Cranial nerve (CN) schwannomas are intracranial tumors that are commonly managed by stereotactic radiosurgery (SRS). There is a large body of literature supporting the use of SRS for vestibular schwannomas. Schwannomas of the oculomotor nerves (CNs III, IV, and VI) are rare skull base tumors, occurring close to the brainstem and often involving the cavernous sinus. Resection can cause significant morbidity, including loss of nerve function. As for other schwannomas, SRS can be used to manage these tumors, but only a handful of cases have been published so far, often among reports of other uncommon schwannoma locations. METHODS:The goal of this study was to collect retrospective multicenter data on tumor control, clinical evolution, and morbidity after SRS. This study was performed through the International Radiosurgery Research Foundation. Patients managed with single-session SRS for an oculomotor cranial nerve schwannoma (CN III, IV, or VI) were included. The diagnosis was based on diplopia or ptosis as the main presenting symptom and anatomical location on the trajectory of the presumed cranial nerve of origin, or prior resection confirming diagnosis. Demographic, SRS dose planning, clinical, and imaging data were collected from chart review of the treated patients. Chi-square and Kaplan-Meier analyses were performed. RESULTS:Seven institutions submitted data for a total of 25 patients. The median follow-up time was 41 months. The median age at the time of treatment was 52 years. There were 11 CN III schwannomas, 11 CN IV schwannomas, and 3 CN VI schwannomas. The median target volume was 0.74 cm3, and the median marginal dose delivered was 12.5 Gy. After SRS, only 2 patients (including the only patient with neurofibromatosis type 2) had continued tumor growth. Crude local control was 92% (23/25), and the 10-year actuarial control was 86%. Diplopia improved in the majority of patients (11/21), and only 3 had worsening following SRS, 2 of whom also had worsened ptosis, both in the context of tumor progression. CONCLUSIONS:SRS for schwannomas of the oculomotor, trochlear, and abducens nerves is effective and provides tumor control rates similar to those for other cranial nerve schwannomas. SRS allows improvement of diplopia in the majority of patients. SRS should therefore be considered as a first-line treatment option for oculomotor nerve schwannomas.

OBJECTIVE:Isocitrate dehydrogenase (IDH) mutation status is recommended used for diagnosis and prognostication of glioblastoma patients. We studied efficacy and safety of stereotactic radiosurgery (SRS) for patients with recurrent IDH-wt glioblastoma. METHODS:Consecutive patients treated with SRS for IDH-wt glioblastoma were pooled for this retrospective observational international multi-institutional study from institutions participating in the International Radiosurgery Research Foundation. RESULTS:) for IDH-wt glioblastoma. All patients had histories of surgery and chemotherapy with temozolomide, and 98% underwent fractionated radiation therapy. MGMT status was available for 42 patients, of which half of patients had MGMT mutant glioblastomas. During median post-SRS imaging follow-up of 6 months, 52% of patients experienced tumor progression. Median post-SRS progression free survival was 4 months. SRS prescription dose of > 14 Gy predicted longer progression free survival [HR 0.357 95% (0.164-0.777) p = 0.009]. Fifty-percent of patients died during post-SRS clinical follow-up that ranged from 1 to 33 months. SRS treatment volume of > 5 cc emerged as an independent predictor of shorter post-SRS overall survival [HR 2.802 95% CI (1.219-6.444) p = 0.02]. Adverse radiation events (ARE) suggestive of radiation necrosis were diagnosed in 6/55 (10%) patients and were managed conservatively in the majority of patients. CONCLUSIONS:SRS prescription dose of > 14 Gy is associated with longer progression free survival while tumor volume of > 5 cc is associated with shorter overall survival after SRS for IDH-wt glioblastomas. AREs are rare and are typically managed conservatively.

OBJECTIVE:Molecular profiles, such as isocitrate dehydrogenase (IDH) mutation and O6-methylguanine-DNA methyltransferase (MGMT) methylation status, have important prognostic roles for glioblastoma patients. The authors studied the efficacy and safety of stereotactic radiosurgery (SRS) for glioblastoma patients with consideration of molecular tumor profiles. METHODS:For this retrospective observational multiinstitutional study, the authors pooled consecutive patients who were treated using SRS for glioblastoma at eight institutions participating in the International Radiosurgery Research Foundation. They evaluated predictors of overall and progression-free survival with consideration of IDH mutation and MGMT methylation status. RESULTS:Ninety-six patients (median age 56 years) underwent SRS (median dose 15 Gy and median treatment volume 5.53 cm3) at 147 tumor sites (range 1 to 7). The majority of patients underwent prior fractionated radiation therapy (92%) and temozolomide chemotherapy (98%). Most patients were treated at recurrence (85%), and boost SRS was used for 12% of patients. The majority of patients harbored IDH wild-type (82%) and MGMT-methylated (62%) tumors. Molecular data were unavailable for 33 patients. Median survival durations after SRS were similar between patients harboring IDH wild-type tumors and those with IDH mutant tumors (9.0 months vs 11 months, respectively), as well as between those with MGMT-methylated tumors and those with MGMT-unmethylated tumors (9.8 vs. 9.0 months, respectively). Prescription dose > 15 Gy (OR 0.367, 95% CI 0.190-0.709, p = 0.003) and treatment volume > 5 cm3 (OR 1.036, 95% CI 1.007-1.065, p = 0.014) predicted overall survival after controlling for age and IDH status. Treatment volume > 5 cm3 (OR 2.215, 95% CI 1.159-4.234, p = 0.02) and absence of gross-total resection (OR 0.403, 95% CI 0.208-0.781, p = 0.007) were associated with inferior local control of SRS-treated lesions in multivariate models. Nine patients experienced adverse radiation events after SRS, and 7 patients developed radiation necrosis at 59 to 395 days after SRS. CONCLUSIONS:Post-SRS survival was similar as a function of IDH mutation and MGMT promoter methylation status, suggesting that molecular profiles of glioblastoma should be considered when selecting candidates for SRS. SRS prescription dose > 15 Gy and treatment volume ≤ 5 cm3 were associated with longer survival, independent of age and IDH status. Prior gross-total resection and smaller treatment volume were associated with superior local control.

BACKGROUND:Pediatric brain arteriovenous malformations (AVMs) are a significant cause of morbidity but the role of multimodal therapy in the treatment of these lesions is not well understood. OBJECTIVE:To compare the outcomes of stereotactic radiosurgery (SRS) with and without prior embolization for pediatric AVMs. METHODS:We retrospectively evaluated the International Radiosurgery Research Foundation pediatric AVM database. AVMs were categorized, based on use of pre-embolization (E + SRS) or lack thereof (SRS-only). Outcomes were compared in unadjusted and inverse probability weight (IPW)-adjusted models. Favorable outcome was defined as obliteration without post-SRS hemorrhage or permanent radiation-induced changes (RIC). RESULTS:The E + SRS and SRS-only cohorts comprised 91 and 448 patients, respectively. In unadjusted models, the SRS-only cohort had higher rates of obliteration (68.5% vs 43.3%,  < .001) and favorable outcome (61.2% vs 36.3%, P < .001) but a lower rate of symptomatic RIC (9.0% vs 16.7%, P = .031). The IPW-adjusted rates of every outcome were similar between the 2 cohorts. However, cumulative obliteration rates at 3, 5, 8, and 10 yr remained higher in the absence of prior embolization (46.3%, 64.6%, 72.6%, and 77.4% for SRS-only vs 24.4%, 37.2%, 44.1%, and 48.7% for E + SRS cohorts, respectively; SHR = 0.449 [0.238-0.846], P = .013). CONCLUSION:Embolization appears to decrease cumulative obliteration rates after SRS for pediatric AVMs without affecting the risk of post-treatment hemorrhage or adverse radiation effects arguing against the routine use of pre-SRS embolization. While endovascular therapy can be considered for occlusion of high-risk angioarchitectural features prior to SRS, future studies are necessary to clarify its role.

PURPOSE/OBJECTIVE:Stereotactic radiosurgery (SRS) has become an important modality in the treatment of brain metastases. The purpose of this study is to investigate the potential of radiomic features from planning magnetic resonance (MR) images and dose maps to predict local failure after SRS for brain metastases. MATERIALS/METHODS/METHODS:Twenty-eight patients who received Gamma Knife (GK) radiosurgery for brain metastases were retrospectively reviewed in this IRB-approved study. 179 irradiated tumors included 42 that locally failed within one-year follow-up. Using SRS tumor volumes, radiomic features were calculated on T1-weighted contrast-enhanced MR images acquired for treatment planning and planned dose maps. 125 radiomic features regarding tumor shape, dose distribution, MR intensities and textures were extracted for each tumor. Logistic regression with automatic feature selection was built to predict tumor progression from local control after SRS. Feature selection and model evaluation using receiver operating characteristic (ROC) curves were performed in a nested cross validation (CV) scheme. The associations between selected radiomic features and treatment outcomes were statistically assessed by univariate analysis. RESULTS:The logistic model with feature selection achieved ROC AUC of 0.82 ± 0.09 on 5-fold CV, providing 83% sensitivity and 70% specificity for predicting local failure. A total of 10 radiomic features including 1 shape feature, 6 MR images and 3 dose distribution features were selected. These features were significantly associated with treatment outcomes (p < 0.05). The model was validated on independent holdout data with an AUC of 0.78. CONCLUSIONS:Radiomic features from planning MR images and dose maps provided prognostic information in SRS for brain metastases. A model built on the radiomic features shows promise for early prediction of tumor local failure after treatment, potentially aiding in personalized care for brain metastases.

PURPOSE/OBJECTIVES/OBJECTIVE:To report our dosimetric analysis of the hippocampi (HC) and the incidence of perihippocampal tumor location in patients with≥25 brain metastases who received stereotactic radiosurgery (SRS) in single or multiple sessions. Materials/Methods Analysis of our prospective registry identified 89 patients treated with SRS for ≥ 25 brain metastases. HC avoidance regions (HA-region) were created on treatment planning MRIs by 5mm expansion of HC. Doses from each session were summed to calculate HC dose. The distribution of metastases relative to the HA-region and the HC was analyzed. RESULTS:Median number of tumors irradiated per patient was 33 (range 25-116) in a median of 3 (range1-12) sessions. Median bilateral HC Dmin (D100), D40, D50, Dmax, and Dmean (Gy) was 1.88, 3.94, 3.62, 16.6, and 3.97 for all patients, and 1.43, 2.99, 2.88, 5.64, and 3.07 for patients with tumors outside the HA-region. Multivariate linear regression showed that the median HC D40, D50, and Dmin were significantly correlated with the tumor number and tumor volume (p <0.001). Of the total3059 treated tumors,83 (2.7%) were located in the HA-region in 57% evaluable patients; 38 tumors (1.2%) abutted or involved the HC itself. CONCLUSIONS:Hippocampal dose, is higher in patients with tumors in the HA-region; however, even for patients with a high burden of intracranial disease and tumors located in the HA-regions, SRS affords hippocampal sparing. This is particularly relevant in light of our finding of eventual perihippocampal metastases in more than half of our patients.