{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T15:59:18Z","timestamp":1784735958839,"version":"3.55.0"},"reference-count":40,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2017,10,12]],"date-time":"2017-10-12T00:00:00Z","timestamp":1507766400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000098","name":"NIH Clinical Center","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000098","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancer"],"published-print":{"date-parts":[[2018,1,15]]},"abstract":"<jats:sec><jats:title>BACKGROUND<\/jats:title><jats:p>The development of brain metastases is common for systemic treatment failure in patients with melanoma and has been associated with a poor prognosis. Recent advances with BRAF and immune checkpoint therapies have led to improved patient survival. Herein, the authors evaluated the risk of de novo brain metastases and survival among patients with melanoma brain metastases (MBM) since the introduction of more effective therapies.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS<\/jats:title><jats:p>Patients with unresectable AJCC stage III\/IV melanoma who received first\u2010line systemic therapy at Moffitt Cancer Center between 2000 and 2012 were identified. Data were collected regarding patient characteristics, stage of disease, systemic therapies, MBM status\/management, and overall survival (OS). The risk of de novo MBM was calculated using a generalized estimating equation model and survival comparisons were performed using Kaplan\u2010Meier and Cox proportional analyses.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>A total of 610 patients were included, 243 of whom were diagnosed with MBM (40%). Patients with MBM were younger, with a lower frequency of regional metastasis. No significant differences were noted with regard to sex, <jats:italic>BRAF<\/jats:italic> status, or therapeutic class. The risk of de novo MBM was found to be similar among patients treated with chemotherapy, biochemotherapy, BRAF\u2010targeted therapy, ipilimumab, and anti\u2010programmed cell death protein 1\/programmed death\u2010ligand 1 regimens. The median OS of patients with MBM was significantly shorter when determined from the time of first regional\/distant metastasis but not when determined from the time of first systemic therapy. The median OS from the time of MBM diagnosis was 7.5 months, 8.5 months, and 22.7 months, respectively, for patients diagnosed from 2000 to 2008, 2009 to 2010, and 2011 to the time of last follow\u2010up (<jats:italic>P<\/jats:italic>\u2009=\u2009.002).<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSIONS<\/jats:title><jats:p>Brain metastases remain a common source of systemic treatment failure. The OS for patients with MBM has improved significantly. Further research into MBM prevention is needed. <jats:bold><jats:italic>Cancer<\/jats:italic> 2018;124:297\u2010305.<\/jats:bold> \u00a9 <jats:italic>2017 American Cancer Society<\/jats:italic>.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cncr.30946","type":"journal-article","created":{"date-parts":[[2017,10,12]],"date-time":"2017-10-12T09:46:38Z","timestamp":1507801598000},"page":"297-305","source":"Crossref","is-referenced-by-count":90,"title":["Improved survival of patients with melanoma brain metastases in the era of targeted BRAF and immune checkpoint therapies"],"prefix":"10.1002","volume":"124","author":[{"given":"Sarah","family":"Sloot","sequence":"first","affiliation":[{"name":"Department of General Surgery Groningen University Medical Center Groningen The Netherlands"},{"name":"Department of Cutaneous Oncology Moffitt Cancer Center Tampa Florida"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yian A.","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Biostatistics and Bioinformatics Moffitt Cancer Center Tampa Florida"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiuhua","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Biostatistics and Bioinformatics Moffitt Cancer Center Tampa Florida"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jamie L.","family":"Weber","sequence":"additional","affiliation":[{"name":"Morsani College of Medicine University of South Florida Tampa Florida"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacob J.","family":"Benedict","sequence":"additional","affiliation":[{"name":"Morsani College of Medicine University of South Florida Tampa Florida"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James J.","family":"Mul\u00e9","sequence":"additional","affiliation":[{"name":"Department of Immunology Moffitt Cancer Center Tampa Florida"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keiran S.","family":"Smalley","sequence":"additional","affiliation":[{"name":"Department of Cutaneous Oncology Moffitt Cancer Center Tampa Florida"},{"name":"Department of Tumor Biology Moffitt Cancer Center Tampa Florida"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey S.","family":"Weber","sequence":"additional","affiliation":[{"name":"Laura and Isaac Perlmutter Cancer Center, NYU Langone Medical Center New York New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan S.","family":"Zager","sequence":"additional","affiliation":[{"name":"Department of Cutaneous Oncology Moffitt Cancer Center Tampa Florida"},{"name":"Department of Oncologic Sciences, Morsani College of Medicine University of South Florida Tampa Florida"},{"name":"Department of Surgery, Morsani College of Medicine University of South Florida Tampa Florida"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter A.","family":"Forsyth","sequence":"additional","affiliation":[{"name":"Department of Neurooncology Moffitt Cancer Center Tampa Florida"},{"name":"Department of Neurooncology Southern Alberta Cancer Research Institute Calgary Alberta Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vernon K.","family":"Sondak","sequence":"additional","affiliation":[{"name":"Department of Cutaneous Oncology Moffitt Cancer Center Tampa Florida"},{"name":"Department of Oncologic Sciences, Morsani College of Medicine University of South Florida Tampa Florida"},{"name":"Department of Surgery, Morsani College of Medicine University of South Florida Tampa Florida"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geoffrey T.","family":"Gibney","sequence":"additional","affiliation":[{"name":"Georgetown Lombardi Comprehensive Cancer Center, Medstar Georgetown University Hospital Washington 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