BRAF inhibitor and stereotactic radiosurgery is associated with an increased risk of radiation necrosis

• Type of Material: Article
• Authors: Kirtesh R. Patel, Emory University; Mudit Chowdhary, Emory University; Jeffrey Switchenko, Emory University; Ragini Kudchadkar, Emory University; David Lawson, Emory University; Richard J. Cassidy, Emory University; Roshan S. Prabhu, Levine Cancer Institute; Mohammad Khan, Emory University
• Language: English
• Date: 2016-08-01
• Publisher: Lippincott, Williams & Wilkins
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2016 Wolters Kluwer Health, Inc. All rights reserved.
• Final Published Version (URL): http://dx.doi.org/10.1097/CMR.0000000000000268
• Title of Journal or Parent Work: Melanoma Research
• ISSN: 0960-8931
• Volume: 26
• Issue: 4
• Start Page: 387
• End Page: 394
• Grant/Funding Information: Research reported in this publication was supported in part by the Biostatistics and Bioinformatics Shared Resource of Winship Cancer Institute of Emory University and NIH/NCI under award number P30CA138292.
• Keywords: DOSE-ESCALATION; Research & Experimental Medicine; Medicine, Research & Experimental; Dermatology; melanoma; brain metastases; stereotactic radiosurgery; RADIOTHERAPY; THERAPY; BRAF inhibitor; Oncology; SURVIVAL; METASTATIC MELANOMA; Science & Technology; TRIAL; COMPETING RISK; Life Sciences & Biomedicine; radiation necrosis; DABRAFENIB; VEMURAFENIB; MUTATION
• Research Categories: Biology, Biostatistics; Health Sciences, Oncology; Biology, Molecular

Abstract

We retrospectively compared the outcomes and toxicities of melanoma brain metastases (MBM) patients treated with BRAF inhibitors (BRAFi) and stereotactic radiosurgery (SRS) with SRS alone. We identified 87 patients with 157 MBM treated with SRS alone from 2005 to 2013. Of these, 15 (17.2%) patients with 32 MBM (21.4%) received BRAFi therapy: three (20.0%) before SRS, two (13.3%) concurrent, and 10 (66.7%) after SRS. Overall survival (OS) was compared between cohorts using the product limit method. Intracranial outcomes were compared using cumulative incidence with competing risk for death. Baseline patient characteristics were similar between groups, except for the SRS cohort, which had higher rates of chemotherapy and more recent year of diagnosis. Radiation characteristics, including dose per fraction, total dose, gross tumor volume size, and prescription isodose, were also similar between cohorts. One-year outcomes-OS (64.3 vs. 40.4%, P=0.205), local failure (3.3 vs. 9.6%, P=0.423), and distant intracranial failure (63.9 vs. 65.1%, P=0.450) were not statistically different between the SRS+BRAFi and SRS-alone groups, respectively. The SRS+BRAFi group showed higher rates of radiographic radiation necrosis (RN) (22.2 vs. 11.0% at 1 year, P<0.001) and symptomatic radiation necrosis (SRN) (28.2 vs. 11.1% at 1 year, P<0.001). Multivariable analysis showed that BRAFi predicted an increased risk of both radiographic and SRN. SRS and BRAFi predicted for an increased risk of radiographic and SRN compared with SRS alone. Approaches to mitigate RN for patients receiving SRS and BRAFi should be considered until the clinical trial (http//:www.clinicaltrials.gov: NCT01721603) evaluating this treatment regimen is completed.