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Author Notes:

Correspondence to Mohammad K. Khan, MD, PhD, Department of Radiation Oncology, Emory University, 1365 Clifton Road NE, Room A1312, Atlanta, GA 30322, USA Tel: +1 404 778 3763; fax: +1 404 778 4139; e-mail: drkhurram2000@gmail.com

The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

David Lawson has previously served as a consultant for Bristol Myer Squibb (BMS).

BMS has sponsored clinical trials at our institution.

For the remaining authors there are no conflicts of interest.

Subjects:

Research Funding:

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:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Oncology
  • Dermatology
  • Medicine, Research & Experimental
  • Research & Experimental Medicine
  • BRAF inhibitor
  • brain metastases
  • melanoma
  • radiation necrosis
  • stereotactic radiosurgery
  • METASTATIC MELANOMA
  • DOSE-ESCALATION
  • COMPETING RISK
  • VEMURAFENIB
  • THERAPY
  • RADIOTHERAPY
  • MUTATION
  • TRIAL
  • DABRAFENIB
  • SURVIVAL

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

Tools:

Journal Title:

Melanoma Research

Volume:

Volume 26, Number 4

Publisher:

, Pages 387-394

Type of Work:

Article | Post-print: After Peer Review

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.

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© 2016 Wolters Kluwer Health, Inc. All rights reserved.

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