Upfront Stereotactic Radiosurgery Research Articles

Stereotactic radiosurgery for asymptomatic petroclival region meningiomas: a focused analysis from the IMPASSE study.

The optimal management of asymptomatic, petroclival meningiomas remains incompletely defined. The purpose of this study was to evaluate the safety and efficacy of upfront stereotactic radiosurgery (SRS) for patients with asymptomatic, petroclival region meningiomas. This retrospective, international, multicenter study involved patients treated with SRS for an asymptomatic, petroclival region meningioma. Study endpoints included local tumor control rate, procedural complications, and the emergence of new neurological deficits. There were 72 patients (22 males, mean age 59.53years (SD ± 11.9)) with an asymptomatic meningioma located in the petroclival region who were treated with upfront SRS. Mean margin dose and maximum dose were 13.26 (SD ± 2.72) Gy and 26.14 (SD ± 6.75) Gy respectively. Median radiological and clinical follow-up periods post-SRS were 52.5 (IQR 61.75) and 47.5months (IQR 69.75) respectively. At last follow-up, tumor control was achieved in all patients. SRS-related complications occurred in 6 (8.33%) patients, with 3 of them (4.17%) exhibiting new neurological deficits. Upfront SRS for asymptomatic, petroclival region meningiomas affords excellent local tumor control and does so with a relatively low risk of SRS-related complications. SRS can be considered at diagnosis of an asymptomatic petroclival region meningioma. If active surveillance is initially chosen, SRS should be recommended when growth is noted during radiological follow-up.

The role of single-fraction stereotactic radiosurgery for atypical meningiomas (WHO grade II): treatment results based on a 25-year experience.

To clarify the role of stereotactic radiosurgery (SRS) for atypical meningiomas (AM). A retrospective analysis of 68 patients with AM having SRS from 1995 until 2019. Nineteen patients (28%) had undergone prior external beam radiation therapy (EBRT) (median dose, 54Gy). The median follow-up period was 52months. Eighteen (26%), 17 (25%), and 33 (49%) patients received SRS as an upfront adjuvant (≤ 6months), early salvage (7-18months), or late salvage treatment (> 18months), respectively. The 3-, 5-, and 10-year progression-free survivals (PFSs) were 52%, 35%, and 25%, respectively. The 3-, 5-, and 10-year disease-specific survivals were 85%, 78%, and 61%, respectively. Adverse radiation events (AREs) were observed in 12 patients (18%), with increased or new seizures being the most frequent complication (n = 7). Prior EBRT was associated with reduced PFS (HR 5.92, P < 0.01), reduced DSS (HR 5.84, P < 0.01), and an increased risk of ARE (HR 3.31, P = 0.04). Timing of SRS was correlated with reduced PFS for patients having early salvage treatment compared to upfront adjuvant (HR 3.17, P = 0.01) or late salvage treatment (HR 4.39, P < 0.01). PFS for patients with residual/recurrent AM remains poor despite SRS. Prior EBRT was associated with worse tumor control, higher tumor-related mortality, and an increased risk of ARE. Further study on the timing of SRS is needed to determine if upfront adjunctive SRS improves tumor control compared to salvage SRS.

Brain Metastases in Metastatic Cutaneous Melanoma: Patterns of Care and Clinical Outcomes in the Era of Immunotherapy and Targeted Therapy

Immune checkpoint inhibitors (CPIs) and BRAF inhibitors (BIs) are standard treatments for metastatic melanoma and have intracranial activity against melanoma brain metastases (MBMs). However, optimal use of CPI/BI with radiation therapy (RT) is not well established. This study evaluates the current practice pattern of how these systemic therapies are chosen and combined with either whole brain radiation therapy (WBRT) or stereotactic radiosurgery (SRS) for MBMs. The study also examines if upfront SRS+CPI results in superior intracranial control (IC) than upfront SRS without CPI or upfront CPI/BI followed by salvage RT.Patients with MBMs who received their first course of intracranial RT with between 1/2014 and 12/2019 at a tertiary cancer center were retrospectively reviewed. Patients with leptomeningeal disease and MBMs from non-cutaneous melanoma were excluded. Prior exposure before MBM diagnosis and concomitant use of CPIs/BIs within 3 months of RT were evaluated. Binary logistic regression was performed to determine predictors of SRS or CPI use. Cox regression analysis was used to assess the association with IC, which was calculated from the time of MBM diagnosis to the first intracranial progression after upfront MBM treatment.A total of 123 patients with MBMs with a median age of 61 (IQR: 51-69) were identified, and 55% were BRAF-mutant. There were 75 patients (61%) with 1-4 MBMs, 31 patients (25%) with 5-10 MBMs, and 17 (14%) patients with > 10 MBMs. Before MBM diagnosis, 30% had prior CPI and 18% had prior BI. For the upfront MBM treatment, 64% received SRS (66% with CPI and 23% with BI), 27% received WBRT (42% with CPI and 30% with BI), 9% received upfront CPI/BI. The baseline characteristics were balanced between the patients who received upfront SRS and upfront CPI/BI except patients who received upfront CPI/BI were more likely to have a BRAF mutation (82% vs. 49%, P = 0.04). The median follow-up was 8.7 mo (IQR: 2.8-22) for all patients and 32 mo (IQR: 18-45) for living patients. For patients who received upfront CPI/BI, 73% underwent salvage SRS and 27% with salvage WBRT at a median of 5.7 mos [IQR: 3.0-7.7] after MBM diagnosis. Fewer number of MBMs, higher KPS, and craniotomy were significant predictors of SRS use on multivariable logistic regression. For the upfront SRS cohort, treatment after 2016, BRAF-wild type status, and prior CPI exposure were associated with higher likelihood of concomitant CPI use with SRS. After adjusting for the number of MBMs, upfront SRS+CPI was associated with higher IC than upfront SRS without CPI (HR: 0.43, 95% CI: 0.22-0.84, P = 0.02). Upfront SRS+ CPI also trended towards a higher IC than upfront CPI/BI with salvage RT (HR: 0.54, 95% CI: 0.27-1.1, P = 0.07) after adjusting for the number of MBMs.Upfront SRS with concomitant CPI was the most frequently used approach to treat newly diagnosed favorable MBMs and may yield superior IC than upfront SRS without CPI or upfront CPI/BI.R. Chin: None. K. Chen: None. C.D. Abraham: None. C.G. Robinson: Research Grant; Varian. Consultant; Varian, AstraZeneca, EMD Serono. Advisory Board; Radialogica. Stock Options; Radialogica. S.M. Perkins: I serve on the Medical Advisory Committee for Mevion Medical Systems and receive compensation for this role.; Mevion Medical Systems. T.M. Johanns: None. L.F. Hernandez-Aya: None. J.W. Keller: None. J. Dowling: None. K. Rich: None. M. Chicoine: None. A.H. Kim: None. G.P. Dunn: None. G. Ansstas: None. J. Huang: None.

Survival in Patients with ≥5 Brain Metastases From Non-Small Cell Lung Cancer Treated With Upfront Stereotactic Radiosurgery

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.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.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).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.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.

Patterns of Care for Brain Metastasis Radiotherapy (RT) in an Integrated Healthcare System: Does Increasing Utilization of Stereotactic Radiosurgery (SRS) Compared to Whole Brain RT (WBRT) Lead to Excessive Use at the End of Life (EOL)?

Previous study at our institution showed a high rate of WBRT received near the EOL. Growing evidence of improved neurocognitive and quality of life (QOL) outcomes without compromise of local control has led to increased advocacy of SRS for brain metastasis compared to WBRT. We examine our trend in patterns of care for non-small cell lung cancer (NSCLC) patients, including palliative care/hospice enrollment, and whether rate of brain metastasis RT near EOL has changed with evolving practices.Central Cancer Registry identified 4765 patients diagnosed with NSCLC at 2 facilities from 2007-17. Patients with brain metastasis were identified using natural language processing of imaging reports and confirmed by image review. Patient clinical/treatment characteristics were obtained through database linkage and manual chart abstraction. Bivariate and multivariate logistic regression analyses were performed.Of 792 patients with brain metastasis, 537 received at least 1 fraction of RT. SRS as initial treatment increased over time, comprising 10% of cases in 2007-11, 22% in 2012-16, and 52% in 2017. Number of lesions initially treated with SRS also increased: among patients with 1-3 lesions, 15% in 2007-11, 33% in 2012-16, and 68% in 2017 received SRS upfront, while 3%, 13%, and 33% of patients with 4-9 lesions received it in the respective periods. SRS for patients with 10-19 lesions was minimal, though half received SRS upfront in 2017. The proportion of patients receiving WBRT near EOL was substantial and higher than for SRS. Of 244 patients with 1-3 lesions, 64 (26%) died within 30 days of RT, comprising 25% of patients receiving WBRT and 11% receiving SRS. Older age, male sex, increasing number of extracranial metastatic sites, and inpatient consultation were independent predictors of death within 30 days of RT. Patients enrolled in palliative care/hospice were less likely to die within 30 days of RT (P = 0.048) and less likely to die as inpatients (P < 0.01).SRS utilization increased from 2007-17, particularly among patients with 1-9 lesions. Despite this increase, the proportion of patients receiving SRS near EOL was low and much less than the proportion receiving WBRT, suggesting that patients were selected well for SRS but not WBRT. As SRS is associated with shorter treatment time and lower toxicity compared to WBRT, greater SRS utilization in those without poor predictive factors may maintain QOL without risking excessive use at EOL. Early palliative care and expanding indications for upfront SRS may be considerations for decreasing the risk of treatment near the EOL.A.D. Batra: None. S. Yang: None. C. Zheng: None. D. Jiang: None. J. Rahimian: None. M.R. Girvigian: None. M.K. Gould: None. J.J. Ryoo: None.

RADI-18. Survival and disease control after upfront stereotactic radiosurgery for brain metastases from breast cancer

Abstract Background As systemic therapy for metastatic breast cancer (BC) improves, the survival benefit from hormonal and targeted therapy urges treatment of brain metastases (BMs) with minimal toxicity and less systemic therapy interruption. Here we assessed clinical outcomes in BC patients who received upfront stereotactic radiosurgery (SRS). Methods We identified 236 patients who received upfront SRS with/without surgery for BMs from metastatic BC from 06/2007 to 05/2018. Twenty-four patients who received SRS for surgical cavity were excluded for analysis. Overall survival (OS) and salvage radiation-free survival (SRFS) were estimated using Kaplan-Meier analysis. Cox proportional hazard regression was used to identify prognostic factors. Results At a median follow-up time of 15.4 months (range, 0.8–119.6), the estimated median OS was 18.5 mo (95% CI, 14.9–21). Factors associated with OS on multivariate analysis (MVA) were molecular subtypes (12.2 months for triple-negative [n=68], 13.3 months for HR+/HER2- [n=66], 36.4 months for HR+/HER2+ [n=46], and 28.1 months for HER2+ [n=32], p=0.002), KPS &amp;gt;80 (p&amp;lt;0.0001), receipt of chemotherapy (p=0.016) or anti-HER2 therapy (p=0.029) after diagnosis of BM, and type of salvage radiation (p&amp;lt;0.0001). OS was comparable in patients who received upfront SRS to less or more than 4 lesions (19.3 months for &amp;lt;4 [n=162] vs. 17.8 months for &amp;gt;/= 4 [n=50], p=0.36). The 12-month salvage RT rate was 25% for WBRT and 26.4% for SRS. The median SRFS was 7.4 months (95% CI, 6.5‒8.3). Factors associated with SRFS on MVA were subtypes (p=0.002), KPS (p=0.011), and receipt of hormone therapy after diagnosis of BM (p=0.031). Conclusions The median OS for BC patients who developed BM is over 15 months. Molecular subtypes (HER2+ and HR+/HER2+), good KPS, and anti-HER2 or hormone therapy predicted better OS and SRFS. Prospective studies are needed to verify these results and refine the best treatment strategies for these patients.

RADI-17. Outcomes for patients with triple negative breast cancer treated with upfront stereotactic radiosurgery for brain metastases

Abstract Background Triple-negative breast cancer (TNBC) is an aggressive subtype with high propensity of developing brain metastases (BM). Clinical outcomes and prognostic factors after stereotactic radiosurgery (SRS) for BM were not well defined. Methods We identified 57 consecutive TNBC patients (pts) treated with single fraction SRS for BM during 05/2008–04/2018. Overall survival (OS) from BM diagnosis and freedom from BM progression (FFBMP) after initial SRS were evaluated. BM progression was defined as local and/or distant brain failure (LBF, DBF) after SRS. Kaplan-Meier analyses and Cox proportional hazard regression were used to estimate survival outcomes and identify prognostic factors. Results The median time to BM development from TNBC diagnosis was 23.7 months (mo) (range 0.7‒271.1). Median OS was 13.1 mo (95%CI 8.0‒19.5). On univariate analysis, Karnofsky performance score (KPS) &amp;gt;70 (p=0.03), number of BMs &amp;lt;3 (p=0.016), and BM among the first metastatic sites (p=0.04) were associated with longer OS. On multivariate analysis, KPS ≤70 was associated with higher risk of death (HR 3.0, p=0.03). Of 46 pts with adequate imaging follow-up, 29 (63%) had intracranial progression with a median FFBMP of 7.4 mo (95% CI 5.7–12.7). At 12 mo the estimated cumulative DBF rate was 61.1% (95%CI 40.8%–74.4%) and LBF rate was 17.8% (95%CI 2%–31.1%). Number of BMs (≥3 vs &amp;lt;3) was not associated with FFBMP (p=0.7). Of the 29 pts with BM progression, additional radiation therapy (RT) (vs. no RT) was associated with improved survival (21.7 vs. 7.0 mo, p&amp;lt;0.0001). Conclusions TNBC pts with BM treated with SRS had an OS of 13.1 mo and FFBMP of 7.4 mo. Good KPS was an independent prognostic factor for OS. Further studies with more pts or conducted prospectively are needed to better understand and to improve treatment outcomes in this pt population.

Care Patterns for Stereotactic Radiosurgery in Small Cell Lung Cancer Brain Metastases

IntroductionThe historical standard of care for brain metastases (BMs) from small cell lung cancer (SCLC) has been whole-brain radiotherapy (WBRT). However, there is growing interest in upfront stereotactic radiosurgery (SRS) for select SCLC patients. Materials and MethodsWe invited United State-based Radiation Oncologists (ROs) via email to answer an anonymous survey using a branching logic system addressing their use of SRS and WBRT for SCLC BMs. Wilcoxon rank-sum test and Fisher's exact test were used to compare differences in continuous and categorical variables, respectively. Multivariable logistic regression analyses were fitted for outcome variables including covariates with P < .10 obtained on univariable analysis. ResultsIn total, 309 ROs completed the survey and 290 (95.7%) reported that they would consider SRS for SCLC BMs under certain clinical circumstances. Across patient characteristics, the number of BMs was the most heavily weighted factor (mean 4.3/5 in importance), followed by performance status, cognitive function, and response to prior therapy. Fewer BMs were correlated with increased SRS use (55.8% offered SRS “very frequently” [>75% of cases] or “often” [51%-75% of cases] for 1 BM vs. 1.1% for >10 BM, P < .001). In situations where WBRT was preferred, concern for rapid intracranial progression (45.3%) and lack of high-level data (36.9%) were the most important factors. The majority (60.6%) were aware of a large recent international retrospective analysis (the FIRE-SCLC study) reporting similar OS between upfront SRS and WBRT; awareness of this study was the only respondent variable predictive of SRS use for limited BMs (19.2% of those aware of the study preferring SRS for limited [≤4] BMs before vs. 61% preferring SRS after the publication, P < .001). The majority of respondents (88.2%) expressed a willingness to enroll patients on a recently opened recently opened randomized trial, NRG-CC009, comparing SRS versus hippocampal-avoidance WBRT. ConclusionsIn the first survey of SRS for SCLC BMs, we observed a high level of physician openness to upfront SRS in SCLC, particularly for patients with limited numbers of BMs, as well as significant interest in generating prospective randomized data to clarify the role of SRS in this population.

Stereotactic radiosurgery for brain metastases from small cell lung cancer without prior whole-brain radiotherapy: A meta-analysis

ObjectivesAssess upfront Stereotactic radiosurgery (SRS) effectiveness for small cell lung cancer (SCLC) brain metastases (BM). Where possible, a comparison with whole-brain radiotherapy (WBRT) was performed. MethodsFollowing PRISMA and MOOSE guidelines, eligible studies were identified on Medline, Embase, Cochrane Library, and proceedings of annual meetings between inception and July 01, 2020. ResultsNine observational studies with 1638 patients were included. The median overall survival (OS) was 8.3 months (95% CI 7.1–9.5 months, I2 = 0%). OS rate at 12 months was 39% (95% CI 31–44%, I2 = 0%). The relative risk between SRS and WBRT for the OS at 12 months was 1.33 (95% CI 1.13–1.51, P = 0.0001). The projected OS for 6, 12, 18- and 24-months comparing SRS with WBRT was 67% vs. 57%, 39% vs. 29%, 22% vs. 15% and 15% vs 9%, favoring SRS (P < 0.001). The LC rate at 12 months was 93% (95% CI 91–94%, I2 = 0%). The distant brain failure rate (DBFR) at 12 months was 41% (95% CI 33–48%, I2 = 52%, P = 0.08). The SRS or WBRT as salvage treatment after upfront SRS was 32% and 19%, respectively. The freedom from neurologic death at 12 months was 87% (95% CI 84–89%). ConclusionBased on the pooling of a large sample of retrospective studies our meta-analysis suggests that for high selected SCLC patients with limited BM upfront SRS produces favorable lesion control and survival outcomes. These findings support the design of randomized clinical trial to confirm the role of SRS in this clinical scenario.

Upfront stereotactic radiosurgery for brain metastases from triple-negative breast cancer.

e14014 Background: Triple-negative breast cancer (TNBC) is an aggressive subtype with high propensity of brain metastases (BM). Outcomes after upfront stereotactic radiosurgery (SRS) for BM from TNBC patients are not well defined. We evaluated outcomes and identified prognostic factors for such patients. Methods: We reviewed 57 consecutive patients treated with upfront SRS for BM from TNBC in May 2008–April 2018 at a large-volume cancer center. Endpoints were overall survival (OS) from BM diagnosis and freedom from BM progression (FFBMP) after initial SRS. BM progression was defined as local and/or distant brain failure (LBF or DBF) after initial SRS; LBF was radiographic progression of treated lesions, assessed by a neuroradiologist or treating physician excluding post-radiation changes or radiation necrosis. Kaplan-Meier and Cox proportional hazard regression analyses were used to estimate survival outcomes and identify prognostic factors. Results: In this cohort of 57 patients with a median age of 53 y (range 26–82) at BM diagnosis and follow-up time of 12.2 months (mo, range 0.8–97.5), median time to BM development from TNBC diagnosis was 23.7 mo (range 0.7‒271.1). Estimated median OS time from initial BM diagnosis was 13.1 mo (95% CI 8.0‒19.5). In univariate analysis, Karnofsky performance score (KPS) &gt; 70 (p = 0.03), having &lt; 3 BMs (p = 0.016) at BM diagnosis, and BM as first site of metastasis (p = 0.041) were associated with longer OS. On multivariate analysis, KPS ≤70 was associated with higher risk of death (HR 3.0, p = 0.03). Of 46 patients with imaging follow-up for FFBMP assessment, 29 (63%) developed BM progression after initial SRS with an estimated median FFBMP of 7.4 mo (95% CI 5.7–12.7). Median times to LBF and DBF were 10 mo (range 0.3–97) and 5.9 mo (range 0.3–90.8). Estimated cumulative LBF rate was 17.8% (95% CI 2%–31.1%) and DBF 61.1% (95% CI 40.8%–74.4%) at 12 mo. Number of BMs at BM diagnosis (≥3 vs &lt; 3) was not associated with FFBMP (p = 0.7). Of the 29 patients with BM progression, 5 did not receive salvage radiation therapy (RT) and 24 received salvage RT (SRS, whole-brain radiation [WBRT], or both SRS+WBRT). Receipt of salvage RT was associated with longer survival (median 21.7 mo vs. 7.0 mo for no salvage RT, p &lt; 0.0001) and did not differ by type of salvage RT (median OS 18.6 mo for WBRT; 26.2 mo for SRS+WBRT; 35.9 mo for SRS, p = 0.08). Conclusions: We reported a median OS of 13.1 mo and FFBMP of 7.4 mo in TNBC patients with good local control. Good KPS was independent prognostic factor for better OS. FFBMP did not differ by number of SRS-treated brain lesions ( &lt; 3 vs ≥3). Further prospective studies of larger numbers of patients needed for more accurate comparisons of treatment types.

Survival and disease control after upfront stereotactic radiosurgery for brain metastases from breast cancer.

e14013 Background: As systemic therapy for metastatic breast cancer (BC) improves, effective treatment for central nervous system involvement has become a major concern, as 10%‒30% of such patients develop brain metastases (BMs). The survival benefit from hormonal and targeted therapy urges to treat patients with BMs with minimal toxicity and less systemic interruption. Here we assessed survival and disease control in patients who received upfront stereotactic radiosurgery (SRS). Methods: We retrospectively reviewed 236 patients who received upfront SRS with/without surgery for BMs from metastatic BC at a single large-volume cancer center from June 2007 to May 2018. We excluded patients who received SRS for surgical cavity alone. A total of 212 were evaluable, of whom 68 had triple-negative (TN), 66 HR+/HER2-, 46 HR+/HER2+, and 32 HER2+ molecular subtypes. Primary endpoints were overall survival (OS) from BM diagnosis and salvage radiation free survival (SRTFS), which were estimated by Kaplan-Meier survival analysis. Cox proportional hazard regression analysis was used to identify prognostic factors. Results: Median age at BM diagnosis was 52.5 y (range 25.6‒85.4); median Karnofsky Performance Score (KPS) was 90 (range 60‒100); and median number of BMs treated was 2 (range 1‒17). At a median follow-up time of 15.4 months (mo) (range, 0.8–119.6), the estimated median OS was 18.5 mo (95% CI, 14.9–21). Factors associated with OS on multivariate analysis (MVA) were subtype (12.2 mo for TN, 13.3 mo for HR+/HER2-, 36.4 mo for HR+/HER2+, and 28.1 mo for HER2+, p= 0.002), KPS ( p &lt;0.0001), receipt of chemotherapy ( p= 0.016) or anti HER2+ therapy (0.029) after diagnosis of BM, and type of salvage radiation ( p &lt;0.0001). Age, extracranial disease status at BM diagnosis, or receipt of upfront surgery was not associated with OS. OS was also comparable in patients who received upfront SRS to less or more than 4 lesions (19.3 mo for &lt; 4 [n = 162] vs. 17.8 mo for &gt; / = 4 [n = 50], p= 0.36). Of the 106 patients (50%) who received salvage therapy after initial SRS, 42 received salvage SRS, 28 received salvage whole-brain radiation therapy (WBRT), and 36 received both. The 12-month salvage RT rate was 25% for WBRT and 26.4% for SRS. The median SRTFS was 7.4 mo (95% CI, 6.5‒8.3). Factors associated with SRTFS on MVA were subtype ( p= 0.002), KPS ( p= 0.011), and receipt of Hormone therapy after a diagnosis of BM (p = 0.031). Conclusions: Molecular subtypes of HER2+ and HR+/HER2+, good KPS, and receipt of chemotherapy or anti-HER2 therapy predicted better OS for patients who received upfront SRS for BMs from BC. Number of BMs treated by upfront SRS was not associated with OS. Molecular subtype, KPS, and receipt of Hormone therapy were also associated with SRTFS. Prospective studies are needed to clarify the best treatment strategies for the various subgroups of patients with BMs from BC particularly in the era of increasing use of new systemic therapies.

Safety and efficacy of upfront stereotactic radiosurgery for brain metastases with high cumulative intracranial tumor volume (&gt; 7 ml): analysis of 233 consecutive patients

The cumulative intracranial tumor volume (CITV) has recently been suggested to be a more relevant predictive factor for patients with brain metastases (BM) treated with stereotactic radiosurgery (SRS). We aimed to investigate the feasibility of upfront SRS for patients with BM having a high CITV, i.e., exceeding 7ml. Two hundred thirty-three consecutive patients with BM having a CITV > 7ml who underwent SRS as first-line treatment from 2011 to 2019 were retrospectively identified. The overall survival (OS) and intracranial disease control rates were analyzed. Multivariate proportional hazards models were used to identify prognostic factors associated with treatment outcome. Toxicity and salvage therapy were also investigated. The median OS was 8.7months (95% confidence interval: 7.1-10.4), and 6-month and 1-year OS rates were 60 and 40%, respectively. Systemic anticancer therapy (hazard ratio (HR): 0.45, p < 0.001), female sex (HR: 0.61, p = 0.001), synchronous SRS (HR: 0.57, p = 0.003), number of BM (HR: 1.04, p = 0.008), controlled extracranial disease (HR: 0.56, p = 0.009), Karnofsky performance status (HR: 0.87, p = 0.015), and staged SRS (HR: 0.71, p = 0.037) were found to be factors independently associated with OS. Post-SRS toxicities of CTCAE grades 3, 4, and 5 were observed in 14, 5, and 1 patient, respectively. As salvage management, repeat SRS, whole brain radiotherapy, and surgical resection were required for 84, 16, and 10 patients, respectively, CONCLUSIONS: With vigilant surveillance and appropriate salvage management, upfront SRS alone can be considered as a relatively safe and effective treatment strategy even for BM with CITV > 7ml.

RADT-10. SURVIVAL IN PATIENTS FULFILLING CCTG CE.7 ELIGIBILITY CRITERIA: EVALUATING INITIAL STEREOTACTIC RADIOSURGERY FOR 5-15 BRAIN METASTASES

Abstract INTRODUCTION The suitability of stereotactic radiosurgery (SRS) in patients with 5-15 brain metastases (BM) is being evaluated in the ongoing CCTG CE.7 randomized trial testing SRS against HA-WBRT. Our study examines the survival of patients with 5-15 BM treated at initial SRS. METHODS Review of our Gamma Knife registry identified 163 patients who fulfilled CCTG CE.7 eligibility criteria. RESULTS 92 females (56%) and 71 males (44%) with median age of 51.6 years (23-98.9) and primary diagnoses of lung (n = 108, 28 EGFR/ALK mutations), breast (n =14, 1 Her2+), melanoma (n = 27, 9 BRAF+), and 14 other were identified. 145 had active extracranial disease (89%); median KPS was 90 (50-100). Median number of tumors at first SRS was 8.2; 114 patients (70%) had 5-9 and 49 (30%) had 10-15 tumors. 73 patients (45%) had subsequent SRS to a median of 19 (6-84) cumulative subsequent tumors at a median time to 2nd treatment of 3.9 months (0.7-30.3). 32 patients (20%) had a 3rd SRS and 24 patients (15%) had 4 or more treatments. 16 patients (10%) received WBRT after initial SRS. 73 patients (45%) were alive at time of data analysis. Median OS from initial SRS for all patients was 15.5 months and was 15, 17.6, 13.4, and 8.7 months, for breast, lung, melanoma, and other respectively. Median OS with 5-9 metastases vs 10-15 metastases was 17.5 vs. 13.3 months (p=.15). Median OS with vs without subsequent SRS was 21.8 vs 8 months (p=.0013). CONCLUSION Patients with 5-15 BM treated with initial SRS can achieve survivals that compare favorably with or better than those of WBRT. These findings potentially challenge the assumption that such patients may be better candidates for HA-WBRT than upfront SRS. Our experience supports the ongoing efforts to prospectively evaluate upfront SRS in these patients.

PO-0861: Survival outcomes after upfront stereotactic radiosurgery for brain metastases from breast cancer

PO-0861: Survival outcomes after upfront stereotactic radiosurgery for brain metastases from breast cancer

Stereotactic radiosurgery combined with anti-PD1 for the management of melanoma brain metastases: A retrospective study of safety and efficacy

BackgroundBrain metastases can be effectively treated with stereotactic radiosurgery (SRS). Immune checkpoint inhibitors are now pivotal in metastatic melanoma care, but some concerns have emerged regarding the safety of their combination with radiation therapy. MethodsWe present a retrospective analysis of a cohort of patients treated by anti-PD1 and SRS as a sole modality of radiation therapy (no whole brain radiation therapy at any time) in a single institution. We included patients on anti-PD1 at the time of SRS or patients who started anti-PD1 within a maximum period of 3 months following SRS and were treated at least one year before the analysis. Clinical and serial imaging data were reviewed to determine the efficacy and the rate of adverse radiation effectss of the combination. ResultsA total of 50 patients were included. SRS targeted 1, 2 to 3 and >3 brain metastases in 17, 16 and 17 patients, respectively. Two patients died before the first evaluation. Nine patients presented with an increase in peritumoral oedema, three with intracranial haemorrhage and one patient with both oedema and haemorrhage. Median follow-up was 38.89 months (interquartile range 24.43; 45.28). Median overall survival from SRS was 16.62 months with 1-, 2- and 3-year rates of 60%, 40% and 35%, respectively. Median brain-Progression Free Survival was 13.2 months with 1, 2 and 3-year rates of 62.1%, 49.7% and 49.7%, respectively. ConclusionsThis real-world cohort of patients treated with a homogeneous strategy combining upfront stereotactic radiosurgery and anti-PD1 shows remarkable survival rates and does not reveal unexpected toxicity.

Outcomes according to initial and subsequent therapies following intracranial progression in patients with EGFR-mutant lung cancer and brain metastasis.

In patients with epidermal growth factor receptor (EGFR)-mutant non–small-cell lung cancer (NSCLC) with brain metastases, it remains controversial whether the use of EGFR-tyrosine kinase inhibitor (TKI) alone without radiotherapy (RT) is an optimal approach. Here, we investigated the clinical outcomes according to the use of upfront RT as well as the subsequent therapy following intracranial progression. This single-centre retrospective study included a total of 173 patients who were treated with EGFR-TKI alone (TKI alone group) or with upfront whole-brain RT (WBRT) or stereotactic radiosurgery (SRS) followed by EGFR-TKI (RT plus TKI group). Clinical outcomes according to initial and subsequent therapies following intracranial progression were analysed. There was no significant difference in OS according to the use of upfront RT (TKI alone group, 24.5 months vs. WBRT group, 20.0 months vs. SRS group, 17.8 months; P = 0.186). Intracranial progression was found in 35 (32.7%) of 107 patients in the TKI alone group. Among them, 19 patients who received salvage RT had the better prognosis than others [median overall survival (OS); 28.6 vs. 11.2 months; P = 0.041]. In the RT plus TKI group, 12 (18.1%) of the 66 patients experienced intracranial progression and 3 of them received salvage RT (median OS; 37.4 vs. 20.0 months; P = 0.044). In multivariate analysis, upfront WBRT was associated with trends towards a lower probability of intracranial progression, whereas upfront SRS was found to be an independent risk factor for poor OS. In conclusion, using EGFR-TKI alone for brain metastasis in EGFR-mutant lung cancer patients showed outcomes comparable to those using upfront RT followed by EGFR-TKI. Patients who could not receive salvage RT following intracranial progression had the worst survival regardless of the type of initial treatment.

Radiomic analysis of magnetic resonance imaging predicts brain metastases velocity and clinical outcome after upfront radiosurgery.

BackgroundBrain metastasis velocity (BMV) predicts outcomes after initial distant brain failure (DBF) following upfront stereotactic radiosurgery (SRS). We developed an integrated model of clinical predictors and pre-SRS MRI-derived radiomic scores (R-scores) to identify high-BMV (BMV-H) patients upon initial identification of brain metastases (BMs).MethodsIn total, 256 patients with BMs treated with upfront SRS alone were retrospectively included. R-scores were built from 1246 radiomic features in 2 target volumes by using the Extreme Gradient Boosting algorithm to predict BMV-H groups, as defined by BMV at least 4 or leptomeningeal disease at first DBF. Two R-scores and 3 clinical predictors were integrated into a predictive clinico-radiomic (CR) model.ResultsThe related R-scores showed significant differences between BMV-H and low BMV (BMV-L), as defined by BMV less than 4 or no DBF (P < .001). Regression analysis identified BMs number, perilesional edema, and extracranial progression as significant predictors. The CR model using these 5 predictors achieved a bootstrapping corrected C-index of 0.842 and 0.832 in the discovery and test sets, respectively. Overall survival (OS) after first DBF was significantly different between the CR-predicted BMV-L and BMV-H groups (median OS: 26.7 vs 13.0 months, P = .016). Among patients with a diagnosis-specific graded prognostic assessment of 1.5–2 or 2.5–4, the median OS after initial SRS was 33.8 and 67.8 months for CR-predicted BMV-L, compared to 13.5 and 31.0 months for CR-predicted BMV-H (P < .001 and <.001), respectively.ConclusionOur CR model provides a novel approach showing good performance to predict BMV and clinical outcomes.

Treatment Outcomes and Follow-Up Compliance after Less than Total and Total Resection of Vestibular Schwannomas in 294 Patients.

To document the outcomes and quality of follow-up compliance after planned subtotal, near-total and gross-total resection (STR, NTR, and GTR) of vestibular schwannomas (VSs). This is a retrospective study of 294 consecutive patients, who underwent excision of a previously untreated VS, between 2005 and 2015. Outcomes including long-term tumor control, facial nerve outcomes, and compliance with follow-up advice were studied. The mean diameter of the tumors was 4.2 cm (±0.8 cm; range: 2.2-7.5 cm). Less than total excision was performed in 55 cases (18.7%), of which NTR was performed in 65% of the cases (n = 36) and STR in the remaining 35%. In the GTR group, 29.3% of patients had a good facial outcome (House and Brackmann [HB] grades 1-3) whereas 81.8% of patients undergoing NTR/STR had a good facial outcome. Follow-up was available in 94.5% of patients undergoing NTR/STR whereas only 69.5% of patients undergoing GTR could be followed up. Only 61.8% of the patients who had NTR/STR were compliant with our follow-up advice and were on either regular radiological surveillance or underwent stereotactic radiosurgery (SRS) as advised. In this group of patients, those with larger tumors and those who underwent a more extensive resection of their tumor were less likely to be compliant with follow-up advice (P = 0.043 and 0.007, respectively). Among patients who had GTR, nine patients (3.7%) were detected to have tumor recurrence at a mean interval of 5.5 years after surgery. "Incomplete" microsurgical excision followed by SRS is an effective strategy that fulfills the twin objectives of preservation of function and long-term tumor control. Considering follow-up attrition due to various causes, upfront SRS at the first follow-up visit-even for a small residue-may be a prudent strategy in selected patients.

Stereotactic Radiosurgery to More Than 10 Brain Metastases: Evidence to Support the Role of Radiosurgery for Ideal Hippocampal Sparing in the Treatment of Multiple Brain Metastases

Brain metastases are a common occurrence, with literature supporting the treatment of a limited number of brain metastases with stereotactic radiosurgery (SRS), as opposed to whole brain radiotherapy (WBRT). Less well understood is the role of SRS in patients with ≥10 brain metastases. Patients treated with SRS to ≥10 brain metastases without concurrent WBRT between March 1999 and December 2016 were reviewed. Analysis was performed for overall survival, treated lesion freedom from progression (FFP), freedom from new metastases (FFNMs), and adverse radiation effect. Hippocampal volumes were retrospectively generated in patients treated with up-front SRS for evaluation of dose volume metrics. A total of 143 patients were identified with 75 patients having up-front SRS and 68 patients being treated as salvage therapy after prior WBRT. The median number of lesions per patient was 13 (interquartile range [IQR], 11-17). Median total volume of treatment was 4.1 cm3 (IQR, 2.0-9.9 cm3). The median 12-month FFP for up-front and salvage treatment was 96.8% (95% confidence interval [CI], 95.5-98.1) and 83.6% (95% CI, 79.9-87.5), respectively (P < 0.001). Twelve-month FFNMs for up-front and salvage SRS was 18.8% (95% CI, 10.9-32.3) versus 19.2% (95% CI, 9.7-37.8), respectively (P= 0.90). The mean hippocampal dose was 150 cGy (IQR, 100-202 cGy). Excellent rates of local control can be achieved when treating patients with >10 intracranial metastases either in the up-front or salvage setting. Hippocampal sparing is readily achievable with expected high rates of new metastatic lesions in treated patients.

RTHP-24. TRENDS IN THE UP FRONT USE OF STEREOTACTIC RADIOSURGERY FOR GLIOBLASTOMA

Abstract BACKGROUND GBM is typically managed with a combined modality approach including resection followed by adjuvant chemoradiation. Despite aggressive up front treatment local failure occurs in the vast majority of patients. The concept of dose escalation through use of stereotactic radiosurgery (SRS) was tested in RTOG 9305 in the pre-temozolomide era with the hopes of improving control, ultimately showing no benefit. We used the National Cancer Database (NCDB) to examine trends in the use of up-front SRS, to see if it had truly fallen out of favor, and if it had any impact on outcome. METHODS We queried the NCDB from 2004–14 for GBM patients that had radiation and 2 months of follow up. Odds ratios were used to determine predictors of SRS. Univariable and multivariable Cox regressions were used to determine potential predictors of overall survival (OS). Propensity adjusted multivariable analysis was used to account for any indication bias. RESULTS We identified 62,681 patients meeting eligibility criteria, of which 1,046 had SRS. SRS decreased over time from 3% to less than 1%. Predictors of SRS were increased age, government insurance, lower comorbid score, treatment at an academic facility, metropolitan location, increased distance to facility, smaller tumor, lack of surgery, no chemotherapy, and more remote year of treatment. Median overall survival was 13.1 months in the non-SRS group and 12.9 months in the SRS group, p=0.28. On multivariable analysis increased age, lack of chemotherapy, higher comorbidity score, extent of surgery, non-academic facility, decreased education, government insurance, urban location, Caucasian race, male gender, larger tumor, and more remote year of treatment predicted for worse overall survival. CONCLUSIONS Use of up-front SRS in the management of GBM has decreased over time, in concordance with past randomized trials examining its use. Our analysis did not show any benefit in survival with its use.