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Eighty\u2010three of the 225 patients (37%) had <jats:italic>BRAF<\/jats:italic>\u2010V600 mutations. At initial diagnosis, <jats:italic>BRAF<\/jats:italic>\u2010V600 mutations were associated with younger age (<jats:italic>p<\/jats:italic>\u2009\u2264\u20090.001), higher proportion of females (<jats:italic>p<\/jats:italic>\u2009=\u20090.0037), higher AJCC stage (<jats:italic>p<\/jats:italic>\u2009=\u20090.030), regional lymph node involvement (<jats:italic>p<\/jats:italic>\u2009=\u20090.047), and family history of cancer (<jats:italic>p<\/jats:italic>\u2009=\u20090.044). Compared to <jats:italic>BRAF<\/jats:italic>\u2010WT, <jats:italic>BRAF<\/jats:italic>\u2010V600 patients had an increased risk of brain metastasis in multivariate analysis (OR\u2009=\u20092.24; 95% CL\u2009=\u20091.10\u20134.58; <jats:italic>p<\/jats:italic>\u2009=\u20090.027). However, <jats:italic>BRAF<\/jats:italic>\u2010V600 patients treated with a selective BRAF inhibitor (BRAFi) had a similar risk of brain metastasis compared to <jats:italic>BRAF<\/jats:italic>\u2010WT patients (OR\u2009=\u20091.00; 95% CL\u2009=\u20090.37\u20132.65; <jats:italic>p<\/jats:italic>\u2009=\u20090.98). Moreover, treatment with BRAFi significantly prolonged the time from initial diagnosis to brain metastasis diagnosis (HR\u2009=\u20090.30; 95% CL\u2009=\u20090.11\u20130.79; <jats:italic>p<\/jats:italic>\u2009=\u20090.015). Compared to other tissues, the brain was the most frequent site of metastasis in <jats:italic>BRAF<\/jats:italic>\u2010V600 patients without BRAFi (42% \n<jats:inline-graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"graphic\/ijc30241-math-0001.png\" xlink:title=\"urn:x-wiley:00207136:media:ijc30241:ijc30241-math-0001\"\/> 7%). The frequency of brain metastasis was lower in <jats:italic>BRAF<\/jats:italic>\u2010WT and <jats:italic>BRAF<\/jats:italic>\u2010V600 patients with BRAFi (25% \n<jats:inline-graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"graphic\/ijc30241-math-0002.png\" xlink:title=\"urn:x-wiley:00207136:media:ijc30241:ijc30241-math-0002\"\/> 4% and 25% \n<jats:inline-graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"graphic\/ijc30241-math-0003.png\" xlink:title=\"urn:x-wiley:00207136:media:ijc30241:ijc30241-math-0003\"\/> 8%, respectively). The proportion of patients with brain metastasis as the only site was 40%, 60%, and 0% in the <jats:italic>BRAF\u2010<\/jats:italic>WT, <jats:italic>BRAF<\/jats:italic>\u2010V600 without BRAFi, and <jats:italic>BRAF<\/jats:italic>\u2010V600 with BRAFi groups, respectively. This study provides evidence on the clinical importance of <jats:italic>BRAF<\/jats:italic>\u2010V600 mutations and BRAF inhibition in the progression to melanoma brain metastasis.<\/jats:p>","DOI":"10.1002\/ijc.30241","type":"journal-article","created":{"date-parts":[[2016,6,25]],"date-time":"2016-06-25T08:12:40Z","timestamp":1466842360000},"page":"2716-2727","source":"Crossref","is-referenced-by-count":30,"title":["<i>BRAF<\/i>\u2010V600 mutational status affects recurrence patterns of melanoma brain metastasis"],"prefix":"10.1002","volume":"140","author":[{"given":"Russell","family":"Maxwell","sequence":"first","affiliation":[{"name":"Department of Neurosurgery Johns Hopkins Medical Institutes Baltimore MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomas","family":"Garzon\u2010Muvdi","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery Johns Hopkins Medical Institutes Baltimore 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