{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T19:24:24Z","timestamp":1792265064461,"version":"4.4.0"},"reference-count":30,"publisher":"BMJ","issue":"4","license":[{"start":{"date-parts":[[2025,4,28]],"date-time":"2025-04-28T00:00:00Z","timestamp":1745798400000},"content-version":"unspecified","delay-in-days":27,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100005567","name":"H. Lee Moffitt Cancer Center and Research Institute","doi-asserted-by":"publisher","award":["P30-CA076292"],"award-info":[{"award-number":["P30-CA076292"]}],"id":[{"id":"10.13039\/100005567","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100002491","name":"Bristol-Myers Squibb","doi-asserted-by":"publisher","award":["CA209-8NK"],"award-info":[{"award-number":["CA209-8NK"]}],"id":[{"id":"10.13039\/100002491","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Immunother Cancer"],"accepted":{"date-parts":[[2025,3,17]]},"published-print":{"date-parts":[[2025,4]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>We hypothesized treatment with nivolumab and stereotactic radiosurgery (SRS) would be feasible, well tolerated, and may improve intracranial tumor control over SRS alone for breast cancer brain metastases (BCBM).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      The study is a phase Ib trial of nivolumab and SRS for BCBM. Clinical trial information:\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"clintrialgov\" xlink:href=\"NCT03807765\">NCT03807765<\/jats:ext-link>\n                      . Key eligibility criteria include BCBM of all subtypes, age \u226518, Eastern Cooperative Oncology Group Performace Status (ECOG-PS)\u22642 with \u226410 brain metastases. Treatment was initiated with a dose of nivolumab (480\u2009mg intravenously) that was repeated every 4 weeks. The initial dose of nivolumab was followed 1\u2009week later by SRS. Blood was collected at baseline and every 4 weeks for flow cytometry and cell-free DNA (cfDNA) assessment.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>A total of 12 patients received SRS to 17 brain metastases. Breast cancer subtypes included triple negative (50%), hormone receptor (HR)+\/HER2\u2212 (33%), and HR\u2212\/HER2+ (17%). Median follow-up from start of protocol therapy is 56 months. No cases of radionecrosis were noted. Two lesions were noted to undergo local failure, both pathologically confirmed, for a 12-month local control of 94%. Median distant intracranial control was 7.4 months with a 12-month control rate of 33%. Median systemic progression-free survival was 7.7 months with a 12-month rate of 42%. Median overall survival (OS) was 24.7 months with a 12-month OS of 75%. Most patients were noted to have an increase in cfDNA throughout study treatment, at week 5 compared with baseline (83%), week 25 compared with baseline (89%), and 100% at first follow-up. Intracranial control was associated with lower levels of CD4 regulatory T cells (Treg) (p=0.03) and higher levels of CD4 T effector memory (p=0.04).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Nivolumab and SRS is a safe and feasible treatment option in BCBM. Long-term follow-up revealed no cases of radiation necrosis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration number<\/jats:title>\n                    <jats:p>\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"clintrialgov\" xlink:href=\"NCT03807765\">NCT03807765<\/jats:ext-link>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/jitc-2024-011432","type":"journal-article","created":{"date-parts":[[2025,4,28]],"date-time":"2025-04-28T20:05:35Z","timestamp":1745870735000},"page":"e011432","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":11,"title":["Nivolumab and stereotactic radiosurgery for patients with breast cancer brain metastases: long-term results and biomarker analysis from a non-randomized, open-label, phase Ib study"],"prefix":"10.1136","volume":"13","clinical-trial-number":[{"clinical-trial-number":"nct03807765","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct03807765","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct03807765","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3331-1529","authenticated-orcid":false,"given":"Kamran A","family":"Ahmed","sequence":"first","affiliation":[{"name":"Department of Radiation Oncology, Moffitt Cancer Center, Tampa, Florida, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Younchul","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Biostatistics and Bioinformatics, Moffitt Cancer Center, Tampa, Florida, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sungjune","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Mayo Clinic Jacksonville Campus, 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