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Importance: Adjuvant stereotactic radiosurgery (SRS) enhances the local control of resected brain metastases (BrM). However, the risks of local failure (LF) and potential for posttreatment adverse radiation effects (PTRE) after early postoperative adjuvant SRS have not yet been established., Objective: To evaluate whether adjuvant SRS delivered within a median of 14 days after surgery is associated with improved LF without a concomitant increase in PTRE., Design, Setting, and Participants: This prospective cohort study examines a clinical workflow (RapidRT) that was implemented from 2019 to 2022 to deliver SRS to surgical patients within a median of 14 days, ensuring all patients were treated within 30 days postoperatively. This prospective cohort was compared with a historical cohort (StanRT) of patients with BrM resected between 2013 and 2019 to assess the association of the RapidRT workflow with LF and PTRE. The 2 cohorts were combined to identify optimal SRS timing, with a median follow-up of 3.3 years for survivors., Exposure: Timing of adjuvant SRS (14, 21, and 30 days postoperatively)., Main Outcomes and Measures: LF and PTRE, according to modified Response Assessment in Neuro-Oncology Brain Metastases criteria., Results: There were 438 patients (265 [60.5%] female patients; 23 [5.3%] Asian, 27 [6.2%] Black, and 364 [83.1%] White patients) with a mean (SD) age of 62 (13) years; 377 were in the StanRT cohort and 61 in the RapidRT cohort. LF and PTRE rates at 1 year were not significantly different between RapidRT and StanRT cohorts. Timing of SRS was associated with radiographic PTRE. Patients receiving radiation within 14 days had the highest 1-year PTRE rate (18.08%; 95% CI, 8.31%-30.86%), and patients receiving radiation between 22 and 30 days had the lowest 1-year PTRE rate (4.10%; 95% CI, 1.52%-8.73%; P = .03). LF rates were highest for patients receiving radiation more than 30 days from surgery (10.65%; 95% CI, 6.90%-15.32%) but comparable for patients receiving radiation within 14 days, between 15 and 21 days, and between 22 and 30 days (≤14 days: 5.12%; 95% CI, 0.86%-15.60%; 15 to ≤21 days: 3.21%; 95% CI, 0.59%-9.99%; 22 to ≤30 days: 6.58%; 95% CI, 3.06%-11.94%; P = .20)., Conclusions and Relevance: In this cohort study of adjuvant SRS timing following surgical resection of BrM, the optimal timing for adjuvant SRS appears to be within 22 to 30 days following surgery. The findings of this study suggest that this timing allows for a balanced approach that minimizes the risks associated with LF and PTRE.

Importance: Brain metastasis (BrM) in gastroesophageal adenocarcinoma (GEA) is a rare and poorly understood phenomenon associated with poor prognosis., Objectives: To examine the clinical and genomic features of patients with BrM from GEA and evaluate factors associated with survival., Design, Setting, and Participants: In this single-institution retrospective cohort study, 68 patients with BrM from GEA diagnosed between January 1, 2008, and December 31, 2020, were identified via review of billing codes and imaging reports from the electronic medical record with follow-up through November 3, 2021. Genomic data were derived from the Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets clinical sequencing platform., Exposures: Treatment with BrM resection and/or radiotherapy., Main Outcomes and Measures: Overall survival after BrM diagnosis., Results: Sixty-eight patients (median age at diagnosis, 57.4 years [IQR, 49.8-66.4 years]; 59 [86.8%] male; 55 [85.9%] White) participated in the study. A total of 57 (83.8%) had primary tumors in the distal esophagus or gastroesophageal junction. Median time from initial diagnosis to BrM diagnosis was 16.9 months (IQR, 8.5-27.7 months). Median survival from BrM diagnosis was 8.7 months (95% CI, 5.5-11.5 months). Overall survival was 35% (95% CI, 25%-48%) at 1 year and 24% (95% CI, 16%-37%) at 2 years. In a multivariable analysis, an Eastern Cooperative Oncology Group performance status of 2 or greater (hazard ratio [HR], 4.66; 95% CI, 1.47-14.70; P = .009) and lack of surgical or radiotherapeutic intervention (HR, 7.71; 95% CI, 2.01-29.60; P = .003) were associated with increased risk of all-cause mortality, whereas 3 or more extracranial sites of disease (HR, 1.85; 95% CI, 0.64-5.29; P = .25) and 4 or more BrMs (HR, 2.15; 95% CI, 0.93-4.98; P = .07) were not statistically significant. A total of 31 patients (45.6%) had ERBB2 (formerly HER2 or HER2/neu)-positive tumors, and alterations in ERBB2 were enriched in BrM relative to primary tumors (8 [47.1%] vs 7 [20.6%], P = .05), as were alterations in PTPRT (7 [41.2%] vs 4 [11.8%], P = .03)., Conclusions and Relevance: This study suggests that that a notable proportion of patients with BrM from GEA achieve survival exceeding 1 and 2 years from BrM diagnosis, a more favorable prognosis than previously reported. Good performance status and treatment with combination surgery and radiotherapy were associated with the best outcomes. ERBB2 positivity and amplification as well as PTPRT alterations were enriched in BrM tissue compared with primary tumors; therefore, further study should be pursued to identify whether these variables represent genomic risk factors for BrM development.