{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T16:31:17Z","timestamp":1782405077493,"version":"3.54.5"},"reference-count":40,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2026,2,16]],"date-time":"2026-02-16T00:00:00Z","timestamp":1771200000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,3,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Melanoma brain metastases (BM) carry high morbidity and mortality despite advances in systemic therapy. Combined immune checkpoint inhibition (ICI) with ipilimumab and nivolumab (ipi\/nivo) demonstrates intracranial activity, but the influence of prior systemic therapy exposure is poorly defined. This is the first real-world study evaluating outcomes of melanoma BM treated with stereotactic radiosurgery (SRS) and concurrent ipi\/nivo, focusing on the impact of prior ICI or targeted therapy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Patients and Methods<\/jats:title>\n                    <jats:p>We retrospectively analyzed 68 patients with 413 melanoma BM treated with concurrent SRS and ipi\/nivo from 2015 to 2025. Primary endpoints were overall survival (OS) and intracranial progression-free survival (iPFS). Secondary endpoints included local and distant control, radionecrosis, and leptomeningeal disease. Univariable and multivariable Cox models identified predictors of outcome.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Median OS was 24.0 months (12- and 24-month OS: 64% and 50%). ICI-naive patients had longer OS (50.5 vs. 17.6 months; P\u2009=\u20090.007) and iPFS (15.1 vs. 5.9 months) than those with prior ICI. On multivariable analysis, prior ICI (HR 2.23, 95% confidence interval [CI] 1.13-4.41), prior BRAF\/MEKi (HR 2.26, 95% CI 1.01-5.04), and \u226511 SRS-treated lesions (HR 3.22, 95% CI 1.43-7.21) predicted worse outcomes, while higher graded prognostic assessment (GPA) favored OS (HR 0.46, 95% CI 0.29-0.75). At 24 months, local progression was 11%, distant 49%, radionecrosis 7%, and leptomeningeal disease 4%.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Concurrent SRS with ipi\/nivo provides durable intracranial control with low toxicity. Patients with prior ICI or targeted therapy represent a high-risk subgroup with poorer outcomes, supporting exploration of intensified or novel strategies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/oncolo\/oyag043","type":"journal-article","created":{"date-parts":[[2026,2,12]],"date-time":"2026-02-12T12:45:25Z","timestamp":1770900325000},"source":"Crossref","is-referenced-by-count":1,"title":["Outcomes after SRS and ipilimumab plus nivolumab for melanoma brain metastases following prior immune checkpoint inhibitor or targeted therapy"],"prefix":"10.1093","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2950-9823","authenticated-orcid":false,"given":"Ian","family":"Messing","sequence":"first","affiliation":[{"name":"Department of Radiation Oncology, University of Pennsylvania , Philadelphia, PA 19104,","place":["United 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Pennsylvania , Philadelphia, PA 19104,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahron","family":"Flowers","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Pennsylvania , Philadelphia, PA 19104,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John Y K","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, University of Pennsylvania , Philadelphia, PA 19104,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nduka M","family":"Amankulor","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, University of Pennsylvania , Philadelphia, PA 19104,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina","family":"Jackson","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, University of Pennsylvania 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