Staged Gamma Knife radiosurgery for large brain metastases: local control and the influence of systemic treatment

Background and purpose: Staged Gamma Knife radiosurgery (SGKRS) delivers high-dose radiotherapy to large brain metastases (BM) in two or three fractions with a time interval of several weeks. Various systemic treatments have also demonstrated favorable intracranial responses. Therefore, the outcome of patients undergoing radiosurgery and systemic treatment for large BM is of high interest but unknown. Materials and methods: A retrospective cohort study was conducted on patients with large BM treated with SGKRS without previous local treatment directed to the brain. The primary outcome measure was the probability of intracranial local control at 12 months, calculated by the Kaplan-Meier method. Univariable and multivariable Cox regression analyses were performed to identify variables associated with intracranial local control. Results: 295 patients were included. Intracranial local control probability at 12 months was 83 % and overall survival at 12 months was 39 %. In the multivariable Cox regression analysis, receiving any type of concurrent or adjuvant systemic treatment (adjusted hazard ratio [aHR] 0.30, 95 % confidence interval [CI] 0.15–0.61) and volume reduction between the first and second fraction (aHR 0.99, 95 % CI 0.98–0.998) were significantly associated with better intracranial local control. Larger total volume of all treated BM (aHR 1.02, 95 % CI 1.01–1.04) was significantly associated with worse intracranial local control. The probability of symptomatic cerebral radiation necrosis at 12 months was 26 %. Conclusion: SGKRS results in high local control, with further improvement when systemic treatment is administered. However, overall survival remains limited, highlighting the importance of adequate patient selection.