@article{8f93dfb414e246739cb939fae9b221d8,
title = "Stereotactic radiosurgery of early melanoma brain metastases after initiation of anti-CTLA-4 treatment is associated with improved intracranial control",
abstract = "Background Numerous studies suggest that radiation can boost antitumor immune response by stimulating release of tumor-specific antigens. However, the optimal timing between radiotherapy and immune checkpoint blockade to achieve potentially synergistic benefits is unclear. Material and methods Multi-institutional retrospective analysis was conducted of ninety-nine metastatic melanoma patients from 2007 to 2014 treated with ipilimumab who later received stereotactic radiosurgery (SRS) for new brain metastases that developed after starting immunotherapy. All patients had complete blood count acquired before SRS. Primary outcomes were intracranial disease control and overall survival (OS). Results The median follow-up time was 15.5 months. In the MD Anderson cohort, patients who received SRS after 5.5 months (n = 20) of their last dose of ipilimumab had significantly worse intracranial control than patients who received SRS within 5.5 months (n = 51) (median 3.63 vs. 8.09 months; hazard ratio [HR] 2.07, 95% confidence interval [CI] 1.03–4.16, p = 0.041). OS was not different between the two arms. The improvement in intracranial control was confirmed in an independent validation cohort of 28 patients treated at Yale-New Haven Hospital. Circulating absolute lymphocyte count before SRS predicted for treatment response as those with baseline counts >1000/µL had reduced risk of intracranial recurrence compared with those with ≤1000/µL (HR 0.46, 95% CI 0.0.23–0.94, p = 0.03). Conclusions In this multi-institutional study, patients who received SRS for new brain metastases within 5.5 months after ipilimumab therapy had better intracranial disease control than those who received SRS later. Moreover, higher circulating lymphocyte count was associated with improved intracranial disease control.",
keywords = "Brain metastases, Immunotherapy, Melanoma, Radiosurgery",
author = "Yi An and Wen Jiang and Kim, {Betty Y.S.} and Qian, {Jack M.} and Chad Tang and Penny Fang and Jennifer Logan and D'Souza, {Neil M.} and Haydu, {Lauren E.} and Wang, {Xin A.} and Hess, {Kenneth R.} and Harriet Kluger and Glitza, {Isabella C.} and Anita Mahajan and Welsh, {James W.} and Lin, {Steven H.} and Yu, {James B.} and Davies, {Michael A.} and Patrick Hwu and Sulman, {Erik P.} and Brown, {Paul D.} and Chiang, {Veronica L.S.} and Jing Li",
note = "Funding Information: Dr. Welsh reports holding stock options in Healios, Molecular Match, OncoResponse, Reflexion Medical, Checkmate Pharmaceuticals and research support from Bristol-Myers Squibb, Merck, GlaxoSmithKline, Varian Medical Systems, Mirna Therapeutics and Incyte for work outside the scope of this article. Dr. Lin reports grant support from Elekta, STCube Pharmaceuticals and Roche/Genentech, and honorarium from US Oncology and AstraZeneca for work outside the scope of this article. Dr. Davies reports serving on the advisory boards for GlaxoSmithKline, Novartis, Roche/Genentech, and Sanofi-Aventis, as well as receiving research funding from GlaxoSmithKline, Roche/Genentech, AstraZeneca, Sanofi-Aventis, Merck, and Oncothyreon for work outside the scope of this article. No other disclosures are reported. Funding Information: This work was supported in part by Cancer Center Support (Core) Grant CA016672 from the National Cancer Institute, National Institutes of Health to The University of Texas MD Anderson Cancer Center. Dr. Kim would like to acknowledge the James C. and Sara K. Kennedy Award, the Jorge and Leslie Bacardi Award from the Mayo Clinic Center for Regenerative Medicine, and the American Brain Tumor Association Discovery Grant for funding support. Dr. Davies would like to acknowledge funding support from NIH/NCI ( 5R01CA154710-04 ) and the MD Anderson Cancer Center Melanoma Moon Shots Program. The sponsors had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. Publisher Copyright: {\textcopyright} 2017",
year = "2017",
month = oct,
doi = "10.1016/j.radonc.2017.08.009",
language = "English (US)",
volume = "125",
pages = "80--88",
journal = "Radiotherapy and Oncology",
issn = "0167-8140",
publisher = "Elsevier Ireland Ltd",
number = "1",
}