{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T15:59:11Z","timestamp":1787068751711,"version":"build-2736575974"},"reference-count":20,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2023,12,9]],"date-time":"2023-12-09T00:00:00Z","timestamp":1702080000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["P30CA134274]"],"award-info":[{"award-number":["P30CA134274]"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,5,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Hippocampal avoidant whole brain radiotherapy (HA-WBRT) is the standard of care for patients needing WBRT for brain metastases. This study, using existing data from NRG Oncology CC001 including baseline tumor characteristics and patient-reported MD Anderson Symptom Inventory-Brain Tumor (MDASI-BT) scores, sought to identify subgroups of patients that demonstrate differential neuroprotective treatment response to HA-WBRT.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>An exploratory analysis of NRG CC001, a phase 3 trial in which 518 patients were randomly assigned to WBRT plus memantine or HA-WBRT plus memantine, was performed. Rates of neurocognitive function failure (NCFF) were estimated between subgroups and stratified by arm. Covariate and subgroup interaction with differential treatment response were calculated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The benefit of HA-WBRT on decreasing NCFF was seen in patients living\u2005\u2265\u20054 months (HR 0.75, 95% CI: 0.58\u20130.97, P\u2005=\u2005.03), whereas patients living\u2005&amp;lt;\u20054 months derived no significant neurocognitive benefit. A significant association between baseline MDASI-BT cognitive factor and treatment response (interaction P\u2005=\u2005.03) was identified. Patients with lower MDASI-BT scores (less patient-reported cognitive impairment) derived significantly greater benefit (HR\u2005=\u20050.64, 95% CI: 0.48\u20130.85, P\u2005=\u2005.002) compared to those with highest MDASI-BT scores (HR\u2005=\u20051.24, 95% CI: 0.76\u20132.04, P\u2005=\u2005.39). Tumor histology also had a significant interaction (P\u2005=\u2005.01) with treatment response. Primary lung histology patients derived cognitive failure risk reduction (HR\u2005=\u20050.58, 95% CI: 0.43\u20130.77, P\u2005=\u2005.0007) from HA-WBRT, in contrast to nonlung primary histology patients (HR\u2005=\u20051.15, 95% CI: 0.78\u20131.50, P\u2005=\u2005.48).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Differential neuroprotective response to HA-WBRT was identified in this analysis. Patients surviving\u2005\u2265\u20054 months derived benefit from HA-WBRT. There is evidence of heterogeneity of treatment effect for patients with less severe patient-reported cognitive impairment at baseline and those with primary lung histology.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/neuonc\/noad226","type":"journal-article","created":{"date-parts":[[2023,12,5]],"date-time":"2023-12-05T19:16:04Z","timestamp":1701803764000},"page":"911-921","source":"Crossref","is-referenced-by-count":10,"title":["Evaluating the heterogeneity of hippocampal avoidant whole brain radiotherapy treatment effect: A secondary analysis of NRG CC001"],"prefix":"10.1093","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4817-1007","authenticated-orcid":false,"given":"Hua-Ren R","family":"Cherng","sequence":"first","affiliation":[{"name":"Department of Radiation Oncology, University of Maryland Medical Center , Baltimore, Maryland , 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