{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T21:51:56Z","timestamp":1792101116351,"version":"4.4.0"},"reference-count":30,"publisher":"American Medical Association (AMA)","issue":"13","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA"],"published-print":{"date-parts":[[2026,4,7]]},"abstract":"<jats:sec>\n                    <jats:title>Importance<\/jats:title>\n                    <jats:p>Brain metastases are common in patients with cancer, and radiation is often used for management. Among patients with more than 4 brain metastases, the effects of stereotactic radiation targeting only individual tumors, compared with whole brain radiation with hippocampal avoidance, which radiates both tumors and normal brain, remain unknown.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To determine whether stereotactic radiation improves symptom severity and interference with daily functioning, compared with whole brain radiation with hippocampal avoidance.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design, Setting, and Participants<\/jats:title>\n                    <jats:p>Phase 3, open-label, randomized clinical trial conducted at 4 United States\u2013based centers. Eligible patients had 5 to 20 brain metastases and no prior brain-directed radiation. Enrollment occurred between April 11, 2017, and May 17, 2024 (final follow-up, March 18, 2025).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Intervention<\/jats:title>\n                    <jats:p>Stereotactic radiation, compared with whole brain radiation with hippocampal avoidance.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Main Outcomes and Measures<\/jats:title>\n                    <jats:p>Mean weighted patient-reported symptom severity and interference score change over 6 months postbaseline relative to baseline using the MD Anderson Symptom Inventory\u2013Brain Tumor instrument (scale, 0-10; score change range, \u221210 to 10; \u221210\u2009=\u2009best). A clinically meaningful \u0394 was defined as 0.98.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Of 196 randomized patients (mean age, 61 years; 129 [66%] female; 176 [90%] White; median number of brain metastases, 14 [IQR, 11-18]; 49 [25%] with prior neurosurgical resection), 83 (42%) completed the 6-month assessment. For the primary outcome, between baseline and postbaseline assessments through the 6-month follow-up, stereotactic radiation changed the weighted composite MD Anderson Symptom Inventory\u2013Brain Tumor score from 2.69 to 2.37 (mean change, \u22120.32) and hippocampal-avoidance whole brain radiation changed the score from 2.29 to 3.03 (mean change, 0.74) (mean difference, \u22121.06 [95% CI, \u22121.54 to \u22120.58];\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&amp;amp;lt;\u2009.001). Related grade 3-5 adverse events occurred in 12 patients (12%) in the stereotactic radiation group and 13 patients (13%) in the hippocampal-avoidance whole brain radiation group; grade 1-3 fatigue was most frequent (27 [28%] vs 43 [44%], respectively).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions and Relevance<\/jats:title>\n                    <jats:p>In patients with 5 to 20 brain metastases, these findings support stereotactic radiation over hippocampal-avoidance whole brain radiation to improve symptoms and interference with daily functioning, key components of quality of life.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial Registration<\/jats:title>\n                    <jats:p>\n                      ClinicalTrials.gov Identifier:\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/clinicaltrials.gov\/study\/NCT03075072?id=NCT03075072&amp;amp;amp;rank=1\">NCT03075072<\/jats:ext-link>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1001\/jama.2026.0076","type":"journal-article","created":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T16:00:26Z","timestamp":1771516826000},"page":"1127","source":"Crossref","is-referenced-by-count":46,"title":["Treatment for Brain Metastases With Stereotactic Radiation vs Hippocampal-Avoidance Whole Brain Radiation"],"prefix":"10.1001","volume":"335","author":[{"given":"Ayal A.","family":"Aizer","sequence":"first","affiliation":[{"name":"Department of Radiation Oncology, Brigham and Women\u2019s Hospital, Dana-Farber Cancer Institute, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kee-Young","family":"Shin","sequence":"additional","affiliation":[{"name":"Department of Data Science, Dana-Farber Cancer Institute, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul J.","family":"Catalano","sequence":"additional","affiliation":[{"name":"Department of Data Science, Dana-Farber Cancer Institute, Boston, Massachusetts"},{"name":"Department of Biostatistics, Harvard T.H. 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