{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T04:55:25Z","timestamp":1781585725857,"version":"3.54.5"},"reference-count":21,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T00:00:00Z","timestamp":1778716800000},"content-version":"vor","delay-in-days":13,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Brain metastases (BMs) are a major cause of mortality in patients with melanoma. We conducted a retrospective observational study to identify prognostic factors for BM development and to evaluate the impact of first\u2010line systemic therapy on BM occurrence and survival outcomes in patients with advanced melanoma. A total of 258 patients with unresectable Stage III or IV melanoma without BM at diagnosis were included and followed for BM occurrence. During a median follow\u2010up of 8.7\u2009years (95% CI, 7.0\u201310.6), 100 patients (38.8%) developed BM. Patients who developed BM were younger (median age 60.5 vs. 66\u2009years;\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.008) and more frequently harbored a\n                    <jats:italic>BRAF V600E\/K<\/jats:italic>\n                    mutation (51.4% vs. 48.6%;\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.001) compared with patients without BM, whereas ulceration status was similar between groups (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.525). A mitotic rate \u2265\u20091 was more frequently observed in patients with BM (67.7% vs. 31.3%;\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.044). In multivariable logistic regression analyses, a high mitotic rate (\u2265\u20096\/mm\n                    <jats:sup>2<\/jats:sup>\n                    ),\n                    <jats:italic>BRAF V600<\/jats:italic>\n                    mutation, and AJCC stage IV M1b disease were independently associated with an increased risk of BM. The effect of first\u2010line systemic therapy on BM was further assessed using Fine\u2013Gray competing\u2010risk models and cause\u2010specific Cox models with a 12\u2010week landmark analysis. Compared with combination immune checkpoint inhibitors (ICIs), first\u2010line chemotherapy was independently associated with a markedly higher risk of BM, whereas targeted therapy showed a strong but non\u2010significant association. Tumor\u2010related factors, including AJCC stage IV M1b disease, high mitotic rate, and\n                    <jats:italic>BRAF V600<\/jats:italic>\n                    mutation, remained independently associated with BM across competing\u2010risk and cause\u2010specific analyses. In cause\u2010specific Cox models, chemotherapy, advanced disease stage, high mitotic rate, and\n                    <jats:italic>BRAF V600<\/jats:italic>\n                    mutation were associated with poorer BM\u2010free survival. In our study, the\n                    <jats:italic>BRAF V600<\/jats:italic>\n                    mutation appears to be an independent and strong prognostic factor for BM, regardless of systemic treatment received in the metastatic setting. First\u2010line combination ICIs significantly reduce the risk of BM and improve survival outcomes.\n                  <\/jats:p>","DOI":"10.1002\/cam4.71939","type":"journal-article","created":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T05:55:29Z","timestamp":1778824529000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Melanoma Brain Metastasis, Prognostic Factors, and Survival Outcomes After First Metastatic Line Therapy: A Monocentric Retrospective Study"],"prefix":"10.1002","volume":"15","author":[{"given":"Hadi","family":"Srour","sequence":"first","affiliation":[{"name":"Department of Dermatology Universit\u00e9 C\u00f4te d'Azur  Nice France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emmanuel","family":"Chamorey","sequence":"additional","affiliation":[{"name":"Epidemiology and Biostatistics Unit Centre Antoine Lacassagne  Nice France"},{"name":"RETINES Universit\u00e9 C\u00f4te d'Azur  Nice France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aram","family":"Hovhannisyan","sequence":"additional","affiliation":[{"name":"Epidemiology and Biostatistics Unit Centre Antoine Lacassagne  Nice France"},{"name":"RETINES Universit\u00e9 C\u00f4te d'Azur  Nice France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra","family":"Picard\u2010Gauci","sequence":"additional","affiliation":[{"name":"Department of Dermatology Universit\u00e9 C\u00f4te d'Azur  Nice France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Troin","sequence":"additional","affiliation":[{"name":"Department of Dermatology Universit\u00e9 C\u00f4te d'Azur  Nice France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Perrine","family":"Rousset","sequence":"additional","affiliation":[{"name":"Department of Dermatology Universit\u00e9 C\u00f4te d'Azur  Nice 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Universit\u00e9 C\u00f4te d'Azur  Nice 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