{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T15:58:02Z","timestamp":1792166282693,"version":"4.4.0"},"reference-count":0,"publisher":"Oxford University Press (OUP)","license":[{"start":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T00:00:00Z","timestamp":1792108800000},"content-version":"am","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Hippocampal avoidance whole-brain radiotherapy (HA-WBRT) with memantine reduces, but does not eliminate, cognitive decline. Left hippocampal dose may be more closely associated with cognitive outcomes. We investigated whether unilateral (left) HA-WBRT is equivalent to bilateral HA-WBRT for neurocognitive function.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In this randomized, single-blind, phase 2 equivalence trial, patients with brain metastases were assigned 1:1 to unilateral (left) or bilateral HA-WBRT (30\u2009Gy in 10 fractions) with concurrent memantine. The primary endpoint was relative decline in Hopkins Verbal Learning Test-Revised (HVLT-R) memory score from baseline to 6 months; equivalence required the 90% CI for the between-arm difference to fall within \u00b115 percentage points.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Among 73 patients (unilateral, n\u2009=\u200936; bilateral, n\u2009=\u200937; median follow-up, 13.2 months), mean 6-month relative HVLT-R decline was 4.75% versus 5.05% (difference, -0.31%; 90% CI, -12.02% to 11.40%; TOST P = .02), meeting the equivalence criterion. Brain progression-free survival (10.3 vs 10.8 months; P = .96), overall survival (17.8 vs 12.8 months; P = .94), acute toxicity (\u2265 grade 2, 44.4% vs 35.1%; P = .43), and 6-month neurocognitive failure (61.1% vs 56.8%; Gray test P = .78) were similar. Global health status appeared more stable with unilateral HA-WBRT (interaction, P &amp;lt; .001). Exploratory plasma BDNF trajectories varied by neurocognitive failure status (FDR q = .09).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Unilateral (left) HA-WBRT with memantine met the prespecified equivalence criterion for verbal memory, with comparable oncologic outcomes and safety; non-verbal memory was not assessed. These findings warrant validation, particularly when bilateral avoidance is challenging.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/neuonc\/noag261","type":"journal-article","created":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T11:48:25Z","timestamp":1792151305000},"source":"Crossref","is-referenced-by-count":0,"title":["Unilateral vs Bilateral Hippocampal Avoidance During WBRT With Memantine for Brain Metastases: A Randomized Single-Blind Phase 2 Clinical Trial"],"prefix":"10.1093","author":[{"given":"Wen-Chi","family":"Yang","sequence":"first","affiliation":[{"name":"National Taiwan University Cancer Center Department of Radiation Oncology, , Taipei,","place":["Taiwan"]},{"name":"National Taiwan University Hospital Division of Radiation Oncology, Departments of Oncology, , Taipei,","place":["Taiwan"]},{"name":"National Taiwan University College of Medicine Graduate Institute of Oncology, , Taipei,","place":["Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ya-Fang","family":"Chen","sequence":"additional","affiliation":[{"name":"National Taiwan University Hospital Department of Medical Imaging, , Taipei,","place":["Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chi-Cheng","family":"Yang","sequence":"additional","affiliation":[{"name":"National Chengchi University Department of Psychology, , Taipei,","place":["Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Szu-Huai","family":"Lu","sequence":"additional","affiliation":[{"name":"National Taiwan University Hospital Division of Radiation Oncology, Departments of Oncology, , Taipei,","place":["Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shao-Lun","family":"Lu","sequence":"additional","affiliation":[{"name":"National Taiwan University Cancer Center Department of Radiation Oncology, , Taipei,","place":["Taiwan"]},{"name":"National Taiwan University Hospital Division of Radiation Oncology, Departments of Oncology, , Taipei,","place":["Taiwan"]},{"name":"National Taiwan University College of Medicine Graduate Institute of Oncology, , Taipei,","place":["Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming-Che","family":"Kuo","sequence":"additional","affiliation":[{"name":"National Taiwan University Cancer Center Department of Medicine, , Taipei,","place":["Taiwan"]},{"name":"National Taiwan University Hospital Department of Neurology, , Taipei,","place":["Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chin-Hao","family":"Chang","sequence":"additional","affiliation":[{"name":"National Taiwan University Hospital Integrative Medical Data Center, , Taipei,","place":["Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng-Ming","family":"Hsu","sequence":"additional","affiliation":[{"name":"National Taiwan University Cancer Center Department of Radiation Oncology, , Taipei,","place":["Taiwan"]},{"name":"National Taiwan University Hospital Division of Radiation Oncology, Departments of Oncology, , Taipei,","place":["Taiwan"]},{"name":"National Taiwan University College of Medicine Graduate Institute of Oncology, , Taipei,","place":["Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,10,16]]},"container-title":["Neuro-Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/neuro-oncology\/advance-article-pdf\/doi\/10.1093\/neuonc\/noag261\/72048019\/noag261.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/neuro-oncology\/advance-article-pdf\/doi\/10.1093\/neuonc\/noag261\/72048019\/noag261.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T15:43:00Z","timestamp":1792165380000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/neuro-oncology\/advance-article\/doi\/10.1093\/neuonc\/noag261\/8931607"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,16]]},"references-count":0,"URL":"https:\/\/doi.org\/10.1093\/neuonc\/noag261","relation":{},"ISSN":["1522-8517","1523-5866"],"issn-type":[{"value":"1522-8517","type":"print"},{"value":"1523-5866","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,16]]},"article-number":"noag261"}}