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Purpose: Clinical and imaging surveillance of patients with brain metastases is important after stereotactic radiosurgery (SRS) because many will experience intracranial progression (ITCP) requiring multidisciplinary management. The prognostic significance of neurologic symptoms at the time of ITCP is poorly understood. Methods and Materials: This was a multi-institutional, retrospective cohort study from 2015 to 2020, including all patients with brain metastases completing an initial course of SRS. The primary outcome was overall survival (OS) by presence of neurologic symptoms at ITCP. OS, freedom from ITCP (FF-ITCP), and freedom from symptomatic ITCP (FF-SITCP) were assessed via Kaplan-Meier method. Cox proportional hazard models tested parameters impacting FF-ITCP and FF-SITCP. Results: Among 1383 patients, median age was 63.4 years, 55% were female, and common primaries were non-small cell lung (49%), breast (15%), and melanoma (9%). At a median follow-up of 8.72 months, asymptomatic and symptomatic ITCP were observed in 504 (36%) and 194 (14%) patients, respectively. The majority of ITCP were distant ITCP (79.5%). OS was worse with SITCP (median, 10.2 vs 17.9 months, P < .001). SITCP was associated with clinical factors including total treatment volume (P = .012), melanoma histology (P = .001), prior whole brain radiation therapy (P = .003), number of brain metastases (P < .001), interval of 1 to 2 years from primary and brain metastasis diagnosis (P = .012), controlled extracranial disease (P = .042), and receipt of pre-SRS chemotherapy (P = .015). Patients who were younger and received post-SRS chemotherapy (P = .001), immunotherapy (P < .001), and targeted or small-molecule inhibitor therapy (P < .026) had better FF-SITCP. Conclusions: In this cohort study of patients with brain metastases completing SRS, neurologic symptoms at ITCP is prognostic for OS. This data informs post-SRS surveillance in clinical practice as well as future prospective studies needed in the modern management of brain metastases.

Purpose: Existing brain metastasis prognostic models do not identify patients at risk of very poor survival after radiation therapy (RT). Identifying patient and disease risk factors for 30-day mortality (30-DM) after RT may help identify patients who would not benefit from RT. Methods and Materials: All patients who received stereotactic radiosurgery (SRS) or whole-brain RT (WBRT) for brain metastases from January 1, 2017, to September 30, 2020, at a single tertiary care center were included. Variables regarding demographics, systemic and intracranial disease characteristics, symptoms, RT, palliative care, and death were recorded. Thirty-day mortality was defined as death within 30 days of RT completion. The Kaplan-Meier method was used to estimate median overall survival. Univariate and multivariable logistic regression models were used to assess associations between demographic, tumor, and treatment factors and 30-DM. Results: A total of 636 patients with brain metastases were treated with either WBRT (n = 117) or SRS (n = 519). The most common primary disease types were non-small cell lung (46.7%) and breast (19.8%) cancer. Median survival time was 6 months (95% CI, 5-7 months). Of the 636 patients, 75 (11.7%) died within 30 days of RT. On multivariable analysis, progressive intrathoracic disease (hazard ratio [HR], 4.67; 95% CI, 2.06-10.60; P = .002), progressive liver and/or adrenal metastases (HR, 2.20; 95% CI, 1.16-3.68; P = .02), and inpatient status (HR, 4.51; 95% CI, 1.78-11.42; P = .002) were associated with dying within 30 days of RT. A higher Karnofsky Performance Status (KPS) score (HR, 0.95; 95% CI, 0.93-0.97; P < .001), synchronous brain metastases at time of initial diagnosis (HR, 0.45; 95% CI, 0.21-0.96; P = .04), and outpatient palliative care utilization (HR, 0.45; 95% CI, 0.20-1.00; P = .05) were associated with surviving more than 30 days after RT. Conclusions: Multiple factors including a lower KPS, progressive intrathoracic disease, progressive liver and/or adrenal metastases, and inpatient status were associated with 30-DM after RT. A higher KPS, brain metastases at initial diagnosis, and outpatient palliative care utilization were associated with survival beyond 30 days. These data may aid in identifying which patients may benefit from brain metastasis–directed RT.

Purpose: Hypofractionated stereotactic radiosurgery (HF-SRS) with or without surgical resection is potentially a preferred treatment for larger or symptomatic brain metastases (BMs). Herein, we report clinical outcomes and predictive factors following HF-SRS. Methods and Materials: Patients undergoing HF-SRS for intact (iHF-SRS) or resected (rHF-SRS) BMs from 2008 to 2018 were retrospectively identified. Linear accelerator-based image-guided HF-SRS consisted of 5 fractions at 5, 5.5, or 6 Gy per fraction. Time to local progression (LP), time to distant brain progression (DBP), and overall survival (OS) were calculated. Cox models assessed effect of clinical factors on OS. Fine and Gray's cumulative incidence model for competing events examined effect of factors on LP and DBP. The occurrence of leptomeningeal disease (LMD) was determined. Logistic regression examined predictors of LMD. Results: Among 445 patients, median age was 63.5 years; 87% had Karnofsky performance status ≥70. Fifty-three % of patients underwent surgical resection, and 75% received 5 Gy per fraction. Patients with resected BMs had higher Karnofsky performance status (90-100, 41 vs 30%), less extracranial disease (absent, 25 vs 13%), and fewer BMs (multiple, 32 vs 67%). Median diameter of the dominant BM was 3.0 cm (interquartile range, 1.8-3.6 cm) for intact BMs and 4.6 cm (interquartile range, 3.9-5.5 cm) for resected BMs. Median OS was 5.1 months (95% confidence interval [CI], 4.3-6.0) following iHF-SRS and 12.8 months (95% CI, 10.8-16.2) following rHF-SRS (P < .01). Cumulative LP incidence was 14.5% at 18 months (95% CI, 11.4-18.0%), significantly associated with greater total GTV (hazard ratio, 1.12; 95% CI, 1.05-1.20) following iFR-SRS, and with recurrent versus newly diagnosed BMs across all patients (hazard ratio, 2.28; 95% CI, 1.01-5.15). Cumulative DBP incidence was significantly greater following rHF-SRS than iHF-SRS (P = .01), with respective 24-month rates of 50.0 (95% CI, 43.3-56.3) and 35.7% (95% CI, 29.2-42.2). LMD (57 events total; 33% nodular, 67% diffuse) was observed in 17.1% of rHF-SRS and 8.1% of iHF-SRS cases (odds ratio, 2.46; 95% CI, 1.34-4.53). Any radionecrosis and grade 2+ radionecrosis events were observed in 14 and 8% of cases, respectively. Conclusions: HF-SRS demonstrated favorable rates of LC and radionecrosis in postoperative and intact settings. Corresponding LMD and RN rates were comparable to those of other studies.