{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,21]],"date-time":"2026-03-21T09:18:09Z","timestamp":1774084689594,"version":"3.50.1"},"reference-count":42,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2024,3,14]],"date-time":"2024-03-14T00:00:00Z","timestamp":1710374400000},"content-version":"vor","delay-in-days":73,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006321","name":"National Institutes of Natural Sciences","doi-asserted-by":"publisher","award":["P30CA047904"],"award-info":[{"award-number":["P30CA047904"]}],"id":[{"id":"10.13039\/501100006321","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Outcomes for children with high-grade gliomas (HGG) remain poor. This multicenter phase II trial evaluated whether concurrent use of vorinostat or bevacizumab with focal radiotherapy (RT) improved 1-year event-free survival (EFS) compared to temozolomide in children with newly diagnosed HGG who received maintenance temozolomide and bevacizumab.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Patients\u2005\u2265\u20053 and\u2005&amp;lt;\u200522 years with localized, non-brainstem HGG were randomized to receive RT (dose 54\u201359.4Gy) with vorinostat, temozolomide, or bevacizumab followed by 12 cycles of bevacizumab and temozolomide maintenance therapy.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Among 90 patients randomized, the 1-year EFS for concurrent bevacizumab, vorinostat, or temozolomide with RT was 43.8% (\u00b18.8%), 41.4% (\u00b19.2%), and 59.3% (\u00b19.5%), respectively, with no significant difference among treatment arms. Three- and five-year EFS for the entire cohort was 14.8% and 13.4%, respectively, with no significant EFS difference among the chemoradiotherapy arms. IDH mutations were associated with more favorable EFS (P\u2005=\u2005.03), whereas H3.3 K27M mutations (P\u2005=\u2005.0045) and alterations in PIK3CA or PTEN (P\u2005=\u2005.025) were associated with worse outcomes. Patients with telomerase- and alternative lengthening of telomeres (ALT)-negative tumors (n\u2005=\u20054) had an EFS of 100%, significantly greater than those with ALT or telomerase, or both (P\u2005=\u2005.002). While there was no difference in outcomes based on TERT expression, high TERC expression was associated with inferior survival independent of the telomere maintenance mechanism (P\u2005=\u2005.0012).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Chemoradiotherapy with vorinostat or bevacizumab is not superior to temozolomide in children with newly diagnosed HGG. Patients with telomerase- and ALT-negative tumors had higher EFS suggesting that, if reproduced, mechanism of telomere maintenance should be considered in molecular-risk stratification in future studies.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/noajnl\/vdae035","type":"journal-article","created":{"date-parts":[[2024,3,13]],"date-time":"2024-03-13T18:36:43Z","timestamp":1710355003000},"source":"Crossref","is-referenced-by-count":7,"title":["Vorinostat, temozolomide or bevacizumab with irradiation and maintenance BEV\/TMZ in pediatric high-grade glioma: A Children\u2019s Oncology Group Study"],"prefix":"10.1093","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4109-2207","authenticated-orcid":false,"given":"Rishi R","family":"Lulla","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Hasbro Children\u2019s Hospital, The Warren Alpert Medical School of Brown University , Providence, Rhode Island , 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Senthil","family":"Kumar","sequence":"additional","affiliation":[{"name":"Center for Childhood Cancer Research, Nationwide Children\u2019s Hospital , Columbus, Ohio , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marina N","family":"Nikiforova","sequence":"additional","affiliation":[{"name":"Division of Molecular & Genomic Pathology, University of Pittsburgh Medical Center , Pittsburgh, Pennsylvania , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Uma","family":"Chandran","sequence":"additional","affiliation":[{"name":"Department of Biomedical Informatics, University of Pittsburgh , Pittsburgh, Pennsylvania , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sachin S","family":"Jogal","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Medical College of Wisconsin , Milwaukee, Wisconsin , 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