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Stereotactic radiosurgery (SRS) for brain metastases results in time-to-local failure (TTLF) that significantly correlates with target volume and prescription dose. For large brain metastases (LBM), defined as ≥ 4 cm3, SRS monotherapy can result in &amp;lt; 40% local control (LC) rates. To overcome the TTLF limitations in the management of LBM, 2-staged SRS (2-SSRS) has demonstrated 6-month LC rates of 85–90%. This international multi-institutional study represents the largest series of patients with LBM managed with 2-SSRS. METHODS 181 patients with 218 LBM treated with 2-SSRS were retrospectively reviewed. Local failure (LF) was defined as ≥ 71.5% volumetric increase (equivalent to ≥ 20% increase in maximum diameter; RECIST criteria) from smallest volume date. Kaplan-Meier and log-rank tests were used to estimate and compare overall survival (OS) and TTLF; multivariable analysis was performed using Cox regression model. RESULTS Median age was 63 years (range: 29‒88), male sex was 50.3% with 34.8% of patients having non-small cell lung cancer. Median follow-up was 13.8 months (range:1.1‒49.4) and median OS was 14.6 months (95%CI: 12.6‒17.0). Median TTLF was 27.9 months (95%CI: 17.9‒NA) with a cumulative 6, 12 and 24-month LC of 91%, 81% and 71%, respectively. Using multivariable analysis, older age (≥ 65 years old; HR 1.58, 95%CI 1.06‒2.35, p=0.02) and larger total volume of concurrent small lesions (&amp;gt; 3 cm3; HR 2.05, 95%CI 1.25‒3.39, p=0.005) negatively impacted OS while younger age (&amp;lt; 65 years old; HR 2.60, 95%CI 1.26‒5.34, p=0.01) and RPA Class 3 (HR 3.10, 95%CI 1.26‒7.65, p=0.01) decreased TTLF. The number of concurrent LBM treated and total volume of the LBM were not significant factors. CONCLUSIONS This large multi-institutional dataset demonstrates excellent efficacy and long-term control of LBMs treated with 2-SSRS, which is independent of number or total volume of concurrent LBM.

neuro-oncology

INNV-03. EFFICACY AND LONG-TERM OUTCOMES IN THE MANAGEMENT OF LARGE BRAIN METASTASIS (≥ 4 CM3) USING 2-STAGED STEREOTACTIC RADIOSURGERY (2-SSRS): AN INTERNATIONAL STUDY