{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T06:10:19Z","timestamp":1789539019016,"version":"build-2803163510"},"reference-count":35,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T00:00:00Z","timestamp":1779667200000},"content-version":"vor","delay-in-days":3,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["UG1CA189824"],"award-info":[{"award-number":["UG1CA189824"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["UG1CA189867"],"award-info":[{"award-number":["UG1CA189867"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["U10CA180868"],"award-info":[{"award-number":["U10CA180868"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["U10CA180822"],"award-info":[{"award-number":["U10CA180822"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,10,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>To examine the feasibility of adding ramipril for prevention of cognitive decline to chemoradiation treatment of glioblastoma (GBM).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This prospective single-arm study (WF-1801) coordinated by the Wake Forest NCI Community Oncology Research Program Research Base (UG1CA189824) assessed feasibility, tolerability, and potential efficacy of ramipril to prevent treatment-induced cognitive decline in patients with GBM. Inclusion criteria and chemoradiotherapeutic paradigms were mirrored to the standard arm of NRG\/RTOG 0825, such that cognitive outcomes could be compared. All patients were treated with ramipril during chemoradiation and for 4 weeks after completion of radiotherapy (RT). Major outcomes were retention and the Clinical Trial Battery Composite (CTB COMP) score of the cognitive tests. Results were compared to the corresponding outcomes from NRG\/RTOG 0825.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>A total of 75 participants were accrued between March 25, 2019 and November 14, 2023: median age was 63 years. The NRG\/RTOG 0825 cohort was younger (median 57 years, P &amp;lt; .0001). Overall retention rate at 1-month post-RT (defined as compliant with 75% of doses and completion of cognitive testing) was 48% (1-sided 95% CI: 38%-100%); 61% of patients completed more than 75% of doses and 57% had a CTB COMP score through week 10. The median (range) change in the CTB COMP score at 1 month after RT completion was 0.01 (\u221282.6, 13.0) versus NRG\/RTOG 0825 median of 0.10 (\u221248.2, 8.6); P = .49.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The ramipril intervention did not meet the prespecified feasibility endpoint, neither did the cognitive scores differ significantly from the NRG\/RTOG 0925 control group. We expect other agents will be the focus of future cytoprotective trials.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/nop\/npag047","type":"journal-article","created":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T11:46:03Z","timestamp":1779363963000},"page":"962-972","source":"Crossref","is-referenced-by-count":0,"title":["WF-1801: Single-arm pilot study of ramipril for prevention of radiation-induced cognitive decline in glioblastoma patients receiving chemoradiotherapy"],"prefix":"10.1093","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7618-3921","authenticated-orcid":false,"given":"Christina K","family":"Cramer","sequence":"first","affiliation":[{"name":"Department of Radiation Oncology, Wake Forest University School of Medicine , Winston-Salem, NC,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1904-3647","authenticated-orcid":false,"given":"Sydney","family":"Smith","sequence":"additional","affiliation":[{"name":"Department of Biostatistics and Data Science, Wake Forest University School of Medicine , Winston-Salem, NC,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6054-7839","authenticated-orcid":false,"given":"Emily V","family":"Dressler","sequence":"additional","affiliation":[{"name":"Department of Biostatistics and Data Science, Wake Forest University School of Medicine , Winston-Salem, NC,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1770-099X","authenticated-orcid":false,"given":"Brandi","family":"Page","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins School of Medicine , Baltimore, MD,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3584-023X","authenticated-orcid":false,"given":"Jeffrey S","family":"Wefel","sequence":"additional","affiliation":[{"name":"Department of Neuro-Oncology, University of Texas MD Anderson Cancer Center , Houston, TX,","place":["USA"]},{"name":"Department of Radiation Oncology, University of Texas MD Anderson Cancer Center , Houston, TX,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9766-3104","authenticated-orcid":false,"given":"Stephen R","family":"Rapp","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Behavioral Medicine, Wake Forest University School of Medicine , Winston-Salem, NC,","place":["USA"]},{"name":"Department of Social Sciences and Health Policy, Wake Forest University School of Medicine , Winston-Salem, NC,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4811-4205","authenticated-orcid":false,"given":"Edward H","family":"Ip","sequence":"additional","affiliation":[{"name":"Department of Biostatistics and Data Science, Wake Forest University School of Medicine , Winston-Salem, NC,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5977-8912","authenticated-orcid":false,"given":"Stephanie L","family":"Pugh","sequence":"additional","affiliation":[{"name":"Department of Statistics, American College of Radiology, NRG Oncology Statistics and Data Management Center , Philadelphia, PA,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2863-203X","authenticated-orcid":false,"given":"Ashley","family":"Sumrall","sequence":"additional","affiliation":[{"name":"Department of Cancer Medicine, Wake Forest University School of Medicine , Charlotte, NC,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6651-5267","authenticated-orcid":false,"given":"Roy E","family":"Strowd","sequence":"additional","affiliation":[{"name":"Department of Neurology, Wake Forest University School of Medicine , Winston-Salem, NC,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-4211-7397","authenticated-orcid":false,"given":"Zachary K","family":"Vaslow","sequence":"additional","affiliation":[{"name":"Cone Health Cancer Center Department of Neuro-Oncology, , Greensboro, NC,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-2232-9822","authenticated-orcid":false,"given":"Gena","family":"Volas-Redd","sequence":"additional","affiliation":[{"name":"Georgia Cancer Specialists, Northside Hospital Cancer Institute , Atlanta, GA,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9006-4064","authenticated-orcid":false,"given":"Kathryn E","family":"Weaver","sequence":"additional","affiliation":[{"name":"Department of Social Sciences and Health Policy, Wake Forest University School of Medicine , Winston-Salem, NC,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-5471-8907","authenticated-orcid":false,"given":"Glenn J","family":"Lesser","sequence":"additional","affiliation":[{"name":"Department of Cancer Medicine, Wake Forest University School of Medicine , Winston-Salem, NC,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5278-6709","authenticated-orcid":false,"given":"Michael D","family":"Chan","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Wake Forest University School of Medicine , Winston-Salem, NC,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,5,22]]},"reference":[{"key":"2026091601514261200_npag047-B1","doi-asserted-by":"publisher","first-page":"iv1","DOI":"10.1093\/neuonc\/nov189","article-title":"CBTRUS statistical report: primary brain and Central nervous system tumors diagnosed in the United States in 2008-2012","volume":"17","author":"Ostrom","year":"2015","journal-title":"Neuro Oncol"},{"key":"2026091601514261200_npag047-B2","doi-asserted-by":"publisher","first-page":"4076","DOI":"10.1200\/jco.2013.49.6067","article-title":"Net clinical benefit analysis of radiation therapy oncology group 0525: a phase III trial comparing conventional adjuvant temozolomide with dose-intensive temozolomide in patients with newly diagnosed glioblastoma","volume":"31","author":"Armstrong","year":"2013","journal-title":"J Clin Oncol"},{"key":"2026091601514261200_npag047-B3","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1007\/s11060-018-03032-8","article-title":"Mild cognitive impairment in long-term brain tumor survivors following brain irradiation","volume":"141","author":"Cramer","year":"2019","journal-title":"J Neurooncol"},{"key":"2026091601514261200_npag047-B4","doi-asserted-by":"publisher","first-page":"73","DOI":"10.3389\/fonc.2012.00073","article-title":"Radiation-induced brain injury: a review","volume":"2","author":"Greene-Schloesser","year":"2012","journal-title":"Front Oncol"},{"key":"2026091601514261200_npag047-B5","doi-asserted-by":"publisher","first-page":"987","DOI":"10.1056\/NEJMoa043330","article-title":"Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma","volume":"352","author":"Stupp","year":"2005","journal-title":"N Engl J Med"},{"key":"2026091601514261200_npag047-B6","doi-asserted-by":"publisher","first-page":"2306","DOI":"10.1001\/jama.2017.18718","article-title":"Effect of tumor-treating fields plus maintenance temozolomide vs maintenance temozolomide alone on survival in patients with glioblastoma: a randomized clinical trial","volume":"318","author":"Stupp","year":"2017","journal-title":"JAMA"},{"key":"2026091601514261200_npag047-B7","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1667\/rr2731.1","article-title":"Chronic administration of the angiotensin-converting enzyme inhibitor, ramipril, prevents fractionated whole-brain irradiation-induced perirhinal cortex-dependent cognitive impairment","volume":"178","author":"Lee","year":"2012","journal-title":"Radiat Res"},{"key":"2026091601514261200_npag047-B8","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1186\/1748-717x-5-6","article-title":"Ramipril mitigates radiation-induced impairment of neurogenesis in the rat dentate gyrus","volume":"5","author":"Jenrow","year":"2010","journal-title":"Radiat Oncol"},{"key":"2026091601514261200_npag047-B9","doi-asserted-by":"publisher","first-page":"499","DOI":"10.1016\/j.ijrobp.2008.09.058","article-title":"The AT1 receptor antagonist, L-158,809, prevents or ameliorates fractionated whole-brain irradiation-induced cognitive impairment","volume":"73","author":"Robbins","year":"2009","journal-title":"Int J Radiat Oncol Biol Phys"},{"key":"2026091601514261200_npag047-B10","doi-asserted-by":"publisher","first-page":"119","DOI":"10.1007\/s11060-006-9256-4","article-title":"Mitigation of radiation-induced optic neuropathy in rats by ACE inhibitor ramipril: importance of ramipril dose and treatment time","volume":"82","author":"Ryu","year":"2007","journal-title":"J Neurooncol"},{"key":"2026091601514261200_npag047-B11","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1097\/00005344-199607000-00008","article-title":"Effects of ramipril and enalapril on cerebral blood flow in elderly patients with asymptomatic carotid artery occlusive disease","volume":"28","author":"Patel","year":"1996","journal-title":"J Cardiovasc Pharmacol"},{"key":"2026091601514261200_npag047-B12","doi-asserted-by":"publisher","first-page":"699","DOI":"10.3233\/jad-2011-110347","article-title":"Associations of anti-hypertensive treatments with Alzheimer\u2019s disease, vascular dementia, and other dementias","volume":"26","author":"Davies","year":"2011","journal-title":"J Alzheimers Dis"},{"key":"2026091601514261200_npag047-B13","doi-asserted-by":"publisher","first-page":"147","DOI":"10.3233\/jad-2012-120763","article-title":"The effects of ramipril in individuals at risk for Alzheimer\u2019s disease: results of a pilot clinical trial","volume":"32","author":"Wharton","year":"2012","journal-title":"J Alzheimers Dis"},{"key":"2026091601514261200_npag047-B14","doi-asserted-by":"publisher","first-page":"699","DOI":"10.1056\/NEJMoa1308573","article-title":"A randomized trial of bevacizumab for newly diagnosed glioblastoma","volume":"370","author":"Gilbert","year":"2014","journal-title":"N Engl J Med"},{"key":"2026091601514261200_npag047-B15","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1076\/clin.12.1.43.1726","article-title":"Hopkins verbal learning test\u2013revised: normative data and analysis of inter-form and test-retest reliability","volume":"12","author":"Benedict","year":"1998","journal-title":"Clin Neuropsychol"},{"key":"2026091601514261200_npag047-B16","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1016\/s0887-6177(03)00039-8","article-title":"Trail making test A and B: normative data stratified by age and education","volume":"19","author":"Tombaugh","year":"2004","journal-title":"Arch Clin Neuropsychol"},{"key":"2026091601514261200_npag047-B17","doi-asserted-by":"publisher","first-page":"329","DOI":"10.1093\/arclin\/11.4.329","article-title":"Benton controlled oral word association test: reliability and updated norms","volume":"11","author":"Ruff","year":"1996","journal-title":"Arch Clin Neuropsychol"},{"key":"2026091601514261200_npag047-B18","doi-asserted-by":"publisher","first-page":"365","DOI":"10.1093\/jnci\/85.5.365","article-title":"The European Organization for Research and Treatment of Cancer QLQ-C30: a quality-of-life instrument for use in international clinical trials in oncology","volume":"85","author":"Aaronson","year":"1993","journal-title":"J Natl Cancer Inst"},{"key":"2026091601514261200_npag047-B19","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1007\/bf00435979","article-title":"The development and psychometric validation of a brain cancer quality-of-life questionnaire for use in combination with general cancer-specific questionnaires","volume":"5","author":"Osoba","year":"1996","journal-title":"Qual Life Res"},{"key":"2026091601514261200_npag047-B20","doi-asserted-by":"publisher","first-page":"1125","DOI":"10.1093\/neuonc\/noab011","article-title":"Neurocognitive, symptom, and health-related quality of life outcomes of a randomized trial of bevacizumab for newly diagnosed glioblastoma (NRG\/RTOG 0825)","volume":"23","author":"Wefel","year":"2021","journal-title":"Neuro Oncol"},{"key":"2026091601514261200_npag047-B21","author":"R: A language and environment for statistical computing","year":"2021"},{"key":"2026091601514261200_npag047-B22","doi-asserted-by":"publisher","first-page":"57","DOI":"10.32614\/RJ-2012-014","article-title":"Rfit: rank-based estimation for linear models","volume":"4","author":"Kloke","year":"2012","journal-title":"R J"},{"key":"2026091601514261200_npag047-B23","doi-asserted-by":"publisher","first-page":"1019","DOI":"10.1200\/jco.19.02767","article-title":"Hippocampal avoidance during WHOLE-BRAIN RADIOTHERAPY plus memantine for patients with brain metastases: phase III trial NRG oncology CC001","volume":"38","author":"Brown","year":"2020","journal-title":"J Clin Oncol"},{"key":"2026091601514261200_npag047-B24","doi-asserted-by":"publisher","first-page":"747","DOI":"10.1212\/WNL.0b013e318283bb0a","article-title":"Neuroanatomical target theory as a predictive model for radiation-induced cognitive decline","volume":"80","author":"Peiffer","year":"2013","journal-title":"Neurology"},{"key":"2026091601514261200_npag047-B25","doi-asserted-by":"publisher","first-page":"1043","DOI":"10.1200\/jco.2015.62.1383","article-title":"Comparing intelligence quotient change after treatment with proton versus photon radiation therapy for pediatric brain tumors","volume":"34","author":"Kahalley","year":"2016","journal-title":"J Clin Oncol"},{"key":"2026091601514261200_npag047-B26","doi-asserted-by":"publisher","first-page":"1429","DOI":"10.1093\/neuonc\/not114","article-title":"Memantine for the prevention of cognitive dysfunction in patients receiving whole-brain radiotherapy: a randomized, double-blind, placebo-controlled trial","volume":"15","author":"Brown","year":"2013","journal-title":"Neuro Oncol"},{"key":"2026091601514261200_npag047-B27","doi-asserted-by":"publisher","first-page":"1653","DOI":"10.1200\/jco.2014.58.4508","article-title":"Donepezil for irradiated brain tumor survivors: a phase III randomized placebo-controlled clinical trial","volume":"33","author":"Rapp","year":"2015","journal-title":"J Clin Oncol"},{"key":"2026091601514261200_npag047-B28","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1007\/s11864-019-0641-6","article-title":"Treatment of radiation-induced cognitive decline in adult brain tumor patients","volume":"20","author":"Cramer","year":"2019","journal-title":"Curr Treat Options Oncol"},{"key":"2026091601514261200_npag047-B29","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1111\/j.1750-3639.1999.tb00212.x","article-title":"Demyelination: the role of reactive oxygen and nitrogen species","volume":"9","author":"Smith","year":"1999","journal-title":"Brain Pathol"},{"key":"2026091601514261200_npag047-B30","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1016\/0022-510x(95)00206-h","article-title":"Cellular management of iron in the brain","volume":"134","author":"Connor","year":"1995","journal-title":"J Neurol Sci"},{"key":"2026091601514261200_npag047-B31","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1056\/nejm200001203420301","article-title":"Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients","volume":"342","author":"Yusuf","year":"2000","journal-title":"N Engl J Med"},{"key":"2026091601514261200_npag047-B32","doi-asserted-by":"publisher","first-page":"1530","DOI":"10.1093\/neuonc\/nou060","article-title":"Hospitalization burden and survival among older glioblastoma patients","volume":"16","author":"Arvold","year":"2014","journal-title":"Neuro Oncol"},{"key":"2026091601514261200_npag047-B33","doi-asserted-by":"publisher","first-page":"32372","DOI":"10.3402\/jchimp.v6.32372","article-title":"Glioblastoma management: challenges in the elderly population","volume":"6","author":"Tachamo","year":"2016","journal-title":"J Community Hosp Intern Med Perspect"},{"key":"2026091601514261200_npag047-B34","doi-asserted-by":"publisher","first-page":"264","DOI":"10.1017\/s0317167100010039","article-title":"Selection bias introduced by neuropsychological assessments","volume":"37","author":"Olson","year":"2010","journal-title":"Can J Neurol Sci"},{"key":"2026091601514261200_npag047-B35","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1097\/COC.0b013e318271ae03","article-title":"Limited margins using modern radiotherapy techniques does not increase marginal failure rate of glioblastoma","volume":"37","author":"Paulsson","year":"2014","journal-title":"Am J Clin Oncol"}],"container-title":["Neuro-Oncology Practice"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/nop\/advance-article-pdf\/doi\/10.1093\/nop\/npag047\/68377344\/npag047.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/nop\/article-pdf\/13\/5\/962\/68377344\/npag047.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/nop\/article-pdf\/13\/5\/962\/68377344\/npag047.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T05:51:47Z","timestamp":1789537907000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/nop\/article\/13\/5\/962\/8691834"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,22]]},"references-count":35,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2026,5,22]]},"published-print":{"date-parts":[[2026,10,1]]}},"URL":"https:\/\/doi.org\/10.1093\/nop\/npag047","relation":{},"ISSN":["2054-2577","2054-2585"],"issn-type":[{"value":"2054-2577","type":"print"},{"value":"2054-2585","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026,10]]},"published":{"date-parts":[[2026,5,22]]}}}