Improved time to disease progression in the brain in patients with melanoma brain metastases treated with concurrent delivery of radiosurgery and ipilimumab

Background: To identify the optimal sequencing and timing of immunotherapy (IT) and stereotactic radiosurgery (SRS) for melanoma brain metastases (MBMs). Methods: The elapsed days between IT and SRS were correlated with local control (LC), regional brain control (RBC), time to CNS progression (TTP_CNS), overall survival (OS), and radiation necrosis (RN). Logistic regression and Cox proportional models were used for statistical analysis. Results: Twenty-five patients with 58 MBMs underwent SRS and IT. Median follow-up was 22.7 mo (3.1–77.9 mo). A median of 2 SRS treatments of 21 Gy (range 16–24 Gy) and 4 cycles of Ipilimumab were delivered. SRS was delivered Before, After or Concurrently with IT in 9, 5, and 11 patients, respectively; 8/25 received SRS ≤30 d of IT and 17/25 were >30 d of IT. Median OS was 35.8 mo, 1- and 2-y OS was 83% and 64%, respectively, and LC was 94.8%. By timing, RBC and TTP_CNS were significantly improved when SRS was delivered ≤30 d of IT (75% vs 23.5%, p = 0.03 and median not reached vs 5.7 mo, p = 0.02, respectively). By groups, Concurrent delivery improved TTP_CNS (p = 0.04). The rate of RN was 20.7% (12/58 lesions) and RN was associated with improved OS (HR 0.21, p = 0.01). Conclusions: High OS was found for MBM treated with SRS and IT compared to historical reports. A significant association for improved RBC and TTP_CNS was found when SRS was delivered concurrently and within 30 d of IT. Occurrence of RN was higher than SRS alone series but significantly associated with improved OS.