{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T08:20:07Z","timestamp":1790497207280,"version":"4.1.0"},"reference-count":35,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2020,4,14]],"date-time":"2020-04-14T00:00:00Z","timestamp":1586822400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100004328","name":"Genentech","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004328","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pediatric Blood &amp; Cancer"],"published-print":{"date-parts":[[2020,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Purpose<\/jats:title><jats:p>To study the efficacy and tolerability of valproic acid (VPA) and radiation, followed by VPA and bevacizumab in children with newly diagnosed diffuse intrinsic pontine glioma (DIPG) or high\u2010grade glioma (HGG).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Children 3 to 21 years of age received radiation therapy and VPA at 15\u00a0mg\/kg\/day and dose adjusted to maintain a trough range of 85 to 115 \u03bcg\/mL. VPA was continued post\u2010radiation, and bevacizumab was started at 10\u00a0mg\/kg intravenously biweekly, four weeks after completing radiation therapy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>From September 2009 through August 2015, 20 DIPG and 18 HGG patients were enrolled (NCT00879437). During radiation and VPA, grade 3 or higher toxicities requiring discontinuation or modification of VPA dosing included grade 3 thrombocytopenia (1), grade 3 weight gain (1), and grade 3 pancreatitis (1). During VPA and bevacizumab, the most common grade 3 or higher toxicities were grade 3 neutropenia (3), grade 3 thrombocytopenia (3), grade 3 fatigue (3), and grade 3 hypertension (4). Two patients discontinued protocol therapy prior to disease progression (one grade 4 thrombosis and one grade 1 intratumoral hemorrhage). Median event\u2010free survival (EFS) and overall survival (OS) for DIPG were 7.8 (95% CI 5.6\u20108.2) and 10.3 (7.4\u201013.4) months, and estimated one\u2010year EFS was 12% (2%\u201031%). Median EFS and OS for HGG were 9.1 (6.4\u201011) and 12.1 (10\u201022.1) months, and estimated one\u2010year EFS was 24% (7%\u201045%). Four patients with glioblastoma and mismatch\u2010repair deficiency syndrome had EFS of 28.5, 16.7, 10.4, and 9 months.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Addition of VPA and bevacizumab to radiation was well tolerated but did not appear to improve EFS or OS in children with DIPG or HGG.<\/jats:p><\/jats:sec>","DOI":"10.1002\/pbc.28283","type":"journal-article","created":{"date-parts":[[2020,4,14]],"date-time":"2020-04-14T12:25:06Z","timestamp":1586867106000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":54,"title":["A phase 2 study of valproic acid and radiation, followed by maintenance valproic acid and bevacizumab in children with newly diagnosed diffuse intrinsic pontine glioma or high\u2010grade glioma"],"prefix":"10.1002","volume":"67","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2125-3659","authenticated-orcid":false,"given":"Jack 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