BRAF-V600 mutational status affects recurrence patterns of melanoma brain metastasis

Russell Maxwell, Tomas Garzon-Muvdi, Evan J. Lipson, William H. Sharfman, Chetan Bettegowda, Kristin J. Redmond, Lawrence R. Kleinberg, Xiaobu Ye, Michael Lim

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

Brain metastasis is common and carries a poor prognosis in melanoma. A single institution, retrospective cohort of 225 melanoma patients was analyzed to determine if BRAF-V600 mutational status was associated with brain metastasis. Eighty-three of the 225 patients (37%) had BRAF-V600 mutations. At initial diagnosis, BRAF-V600 mutations were associated with younger age (p ≤ 0.001), higher proportion of females (p = 0.0037), higher AJCC stage (p = 0.030), regional lymph node involvement (p = 0.047), and family history of cancer (p = 0.044). Compared to BRAF-WT, BRAF-V600 patients had an increased risk of brain metastasis in multivariate analysis (OR = 2.24; 95% CL = 1.10–4.58; p = 0.027). However, BRAF-V600 patients treated with a selective BRAF inhibitor (BRAFi) had a similar risk of brain metastasis compared to BRAF-WT patients (OR = 1.00; 95% CL = 0.37–2.65; p = 0.98). Moreover, treatment with BRAFi significantly prolonged the time from initial diagnosis to brain metastasis diagnosis (HR = 0.30; 95% CL = 0.11–0.79; p = 0.015). Compared to other tissues, the brain was the most frequent site of metastasis in BRAF-V600 patients without BRAFi (42% ± 7%). The frequency of brain metastasis was lower in BRAF-WT and BRAF-V600 patients with BRAFi (25% ± 4% and 25% ± 8%, respectively). The proportion of patients with brain metastasis as the only site was 40%, 60%, and 0% in the BRAF-WT, BRAF-V600 without BRAFi, and BRAF-V600 with BRAFi groups, respectively. This study provides evidence on the clinical importance of BRAF-V600 mutations and BRAF inhibition in the progression to melanoma brain metastasis.

Original languageEnglish (US)
Pages (from-to)2716-2727
Number of pages12
JournalInternational Journal of Cancer
Volume140
Issue number12
DOIs
StatePublished - Jun 15 2017
Externally publishedYes

Keywords

  • BRAF-V600
  • brain metastasis
  • melanoma

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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  • Cite this

    Maxwell, R., Garzon-Muvdi, T., Lipson, E. J., Sharfman, W. H., Bettegowda, C., Redmond, K. J., Kleinberg, L. R., Ye, X., & Lim, M. (2017). BRAF-V600 mutational status affects recurrence patterns of melanoma brain metastasis. International Journal of Cancer, 140(12), 2716-2727. https://doi.org/10.1002/ijc.30241