title: Improved time to disease progression in the brain in patients with melanoma brain metastases treated with concurrent delivery of radiosurgery and ipilimumab.
abstract: 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 (TTPCNS), 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 TTPCNSwere 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 TTPCNS(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 TTPCNSwas 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.
authors.affiliation: Department of Radiation Oncology, University of Arizona , Tucson, AZ, USA.
authors.forename: Tijana
authors.initials: T
authors.lastname: Skrepnik
authors.affiliation: Department of Internal Medicine, Division of Medical Oncology, University of Arizona , Tucson AZ, USA.
authors.forename: Srinath
authors.initials: S
authors.lastname: Sundararajan
authors.affiliation: The University of Arizona Cancer Center, Department of Biostatistics, University of Arizona , Tucson AZ, USA.
authors.forename: Haiyan
authors.initials: H
authors.lastname: Cui
authors.affiliation: Department of Radiation Oncology, University of Arizona , Tucson, AZ, USA.
authors.forename: Baldassarre
authors.initials: B
authors.lastname: Stea
keywords: Brain metastases; immunotherapy; melanoma; radiosurgery; timing