Melanoma brain metastases harboring BRAF V600K or NRAS mutations are associated with an increased local failure rate following conventional therapy

Melanoma brain metastases harboring BRAF V600K or NRAS mutations are associated with an... Studies on melanoma brain metastases (MBM) with regard to mutational status are lacking. We investigated the outcomes of MBM in molecularly characterized patients for BRAF and NRAS mutations receiving conventional treatment. We investigated associations between outcomes [competing risk of local and distant brain failure (LF, DF) and overall survival (OS)] and clinical/pathological features of patients with known mutation status following initial treatment of MBM. Competing risk analysis was performed using the methods of Fine and Gray. We identified 235 patients with MBM diagnosed from 2005 to 2011. Mutation prevalence was BRAF non-V600K 98 (42%), BRAF V600K 34 (14%), NRAS 43 (18%), and wild-type for both genes (WT) 60 (26%) patients. Six month cumulative incidence LF rates were 3% for combined SRS or surgery with adjuvant radiation, 18% for surgery, 18% for SRS, 60% for WBRT, and 67% for systemic therapy. On multivariate analysis, only mutation status and initial treatment type were found to be independent predictors of local control. As compared to WT, NRAS (HR 2.58, 95% CI 1.18–5.67, p = 0.02) and BRAF V600K (HR 2.83, 95% CI 1.23–6.47, p = 0.01) mutational status were statistically significant while BRAF non-V600K status was not statistically significant (p = 0.23). Mutation status was not associated with DF or OS. BRAF V600K and NRAS mutation status predict increased LF following conventional treatments for MBM. These data can inform the design and interpretation of future MBM trials. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Journal of Neuro-Oncology Springer Journals

Melanoma brain metastases harboring BRAF V600K or NRAS mutations are associated with an increased local failure rate following conventional therapy

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Publisher
Springer US
Copyright
Copyright © 2017 by Springer Science+Business Media, LLC, part of Springer Nature
Subject
Medicine & Public Health; Oncology; Neurology
ISSN
0167-594X
eISSN
1573-7373
D.O.I.
10.1007/s11060-017-2695-2
Publisher site
See Article on Publisher Site

Abstract

Studies on melanoma brain metastases (MBM) with regard to mutational status are lacking. We investigated the outcomes of MBM in molecularly characterized patients for BRAF and NRAS mutations receiving conventional treatment. We investigated associations between outcomes [competing risk of local and distant brain failure (LF, DF) and overall survival (OS)] and clinical/pathological features of patients with known mutation status following initial treatment of MBM. Competing risk analysis was performed using the methods of Fine and Gray. We identified 235 patients with MBM diagnosed from 2005 to 2011. Mutation prevalence was BRAF non-V600K 98 (42%), BRAF V600K 34 (14%), NRAS 43 (18%), and wild-type for both genes (WT) 60 (26%) patients. Six month cumulative incidence LF rates were 3% for combined SRS or surgery with adjuvant radiation, 18% for surgery, 18% for SRS, 60% for WBRT, and 67% for systemic therapy. On multivariate analysis, only mutation status and initial treatment type were found to be independent predictors of local control. As compared to WT, NRAS (HR 2.58, 95% CI 1.18–5.67, p = 0.02) and BRAF V600K (HR 2.83, 95% CI 1.23–6.47, p = 0.01) mutational status were statistically significant while BRAF non-V600K status was not statistically significant (p = 0.23). Mutation status was not associated with DF or OS. BRAF V600K and NRAS mutation status predict increased LF following conventional treatments for MBM. These data can inform the design and interpretation of future MBM trials.

Journal

Journal of Neuro-OncologySpringer Journals

Published: Dec 2, 2017

References

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