Gamma knife radiosurgery for brain metastases in the era of modern systemic therapy: A prospective real-world analysis using disease-specific GPA and RANO-BM.

e14026 Background: Gamma Knife radiosurgery (GKRS) is widely used for local control of brain metastases (BM), yet prospective real-world data incorporating disease-specific prognostic stratification and standardized response assessment in the era of modern systemic therapy remain limited. This study prospectively evaluated intracranial response, survival outcomes, and prognostic factors following GKRS. Methods: This was a prospective, non-randomized, single-institution observational study. Thirty consecutive adult patients (18–70 years; KPS ≥70) with 41 brain metastases treated with GKRS between March 2022 and June 2024 were included. Serial contrast-enhanced MRI at 1, 3, 6, and 12 months assessed treatment response using RANO-BM criteria. Disease-specific Graded Prognostic Assessment (GPA) scores were calculated based on primary tumor histology. Primary endpoint was local intracranial control (CR/PR/SD). Secondary endpoints included progression-free survival (PFS), overall survival (OS), and cause-specific mortality. Descriptive statistics were used; associations between prognostic variables and outcomes were explored using univariate analysis. Results: Median age was 57 years, and 63.3% were female. Lung (46.7%) and breast (33.3%) cancers were the most common primary tumors, and 96.7% of patients had extracranial disease. Most patients had solitary BM (66.7%). The median treated lesion volume was 1.5 cm³ (range, 0.03–15.4 cm³). Single-fraction GKRS was delivered in 95.1% of lesions, with a median marginal dose of 21 Gy. At last follow-up, local control was achieved in 63.3% of patients, with complete or partial response in 46.7%. Median intracranial PFS was 7 months and differed by GPA (6 months for GPA ≤2 vs 12 months for GPA >2). Overall mortality was 53.3%, predominantly due to extracranial disease (40.0%). Median overall survival differed by GPA (10 months for GPA ≤2 vs 24 months for GPA >2). No cases of radiation necrosis were observed. On univariate analysis, age, KPS, dose, treatment volume, primary tumor type, and GPA were not statistically significant predictors of local control. Conclusions: GKRS provides effective intracranial control with low neurological mortality in patients with limited brain metastases. Survival outcomes appear primarily driven by extracranial disease burden rather than intracranial response alone. Disease-specific GPA and RANO-BM offer a robust framework for outcome assessment in real-world GKRS practice. Further evaluation in larger prospective cohorts and real-world datasets may help refine patient selection and risk stratification.