title: BRAF-V600 mutational status affects recurrence patterns of melanoma brain metastasis.
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.
authors.affiliation: Department of Neurosurgery, Johns Hopkins Medical Institutes, Baltimore, MD.
authors.forename: Russell
authors.initials: R
authors.lastname: Maxwell
authors.affiliation: Department of Neurosurgery, Johns Hopkins Medical Institutes, Baltimore, MD.
authors.forename: Tomas
authors.initials: T
authors.lastname: Garzon-Muvdi
authors.affiliation: Department of Oncology, Johns Hopkins Medical Institutes, Baltimore, MD.
authors.forename: Evan J
authors.initials: EJ
authors.lastname: Lipson
authors.affiliation: Department of Oncology, Johns Hopkins Medical Institutes, Baltimore, MD.
authors.forename: William H
authors.initials: WH
authors.lastname: Sharfman
authors.affiliation: Department of Neurosurgery, Johns Hopkins Medical Institutes, Baltimore, MD.
authors.forename: Chetan
authors.initials: C
authors.lastname: Bettegowda
authors.affiliation: Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins Medical Institutes, Baltimore, MD.
authors.forename: Kristin J
authors.initials: KJ
authors.lastname: Redmond
authors.affiliation: Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins Medical Institutes, Baltimore, MD.
authors.forename: Lawrence R
authors.initials: LR
authors.lastname: Kleinberg
authors.affiliation: Department of Neurosurgery, Johns Hopkins Medical Institutes, Baltimore, MD.
authors.forename: Xiaobu
authors.initials: X
authors.lastname: Ye
authors.affiliation: Department of Neurosurgery, Johns Hopkins Medical Institutes, Baltimore, MD.
authors.forename: Michael
authors.initials: M
authors.lastname: Lim
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001932:Brain Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000556:secondary; D002648:Child; D005260:Female; D006801:Humans; D008297:Male; D008545:Melanoma / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D008875:Middle Aged; D015999:Multivariate Analysis; D009154:Mutation; D009364:Neoplasm Recurrence, Local; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D048493:Proto-Oncogene Proteins B-raf / Q000037:antagonists & inhibitors / Q000235:genetics*; D012189:Retrospective Studies; D012307:Risk Factors; D012878:Skin Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D055815:Young Adult
chemical_list: D047428:Protein Kinase Inhibitors; D048493:Proto-Oncogene Proteins B-raf
keywords: BRAF-V600; brain metastasis; melanoma