{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,20]],"date-time":"2025-09-20T20:11:00Z","timestamp":1758399060113,"version":"3.41.2"},"reference-count":33,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2024,6,13]],"date-time":"2024-06-13T00:00:00Z","timestamp":1718236800000},"content-version":"vor","delay-in-days":164,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000054","name":"NCI","doi-asserted-by":"publisher","award":["U01 CA62475"],"award-info":[{"award-number":["U01 CA62475"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"name":"New Approaches to Brain Tumor Therapy"}],"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>When arsenic trioxide (ATO) was combined with radiation for treatment of transplanted murine gliomas in the brain, tumor response improved with disrupted tumor blood flow and survival was significantly prolonged.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Total of 31 patients with newly diagnosed glioblastoma were accrued to a multi-institutional, NCI-funded, phase I study to determine the maximum tolerated dose (MTD) of ATO administered with radiation. Secondary objectives were survival and pharmacodynamic changes in perfusion on magnetic resonance imaging (MRI). Patients (unknown MGMT and IDH status) received ATO either once or twice weekly during radiation without concurrent or adjuvant temozolomide.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Median age: 54.9 years, male: 68%, KPS \u2265 90: 77%, debulking surgery: 77%. Treatments were well-tolerated: 81% of patients received all the planned ATO doses. Dose-limiting toxicities included elevated liver function tests, hypokalemia, and edema. The MTD on the weekly schedule was 0.4\u00a0mg\/kg and on the biweekly was 0.3\u00a0mg\/kg. The median survival (mOS) for all patients was 17.7 months. Survival on the biweekly schedule (22.8 months) was longer than on the weekly schedule (12.1 months) (P\u2005=\u2005.039) as was progression-free survival (P\u2005=\u2005.004). Similarly, cerebral blood flow was significantly reduced in patients treated on the biweekly schedule (P\u2005=\u2005.007).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>ATO with standard radiation is well tolerated in patients with newly diagnosed glioblastoma. Even without temozolomide or adjuvant therapy, the overall survival of all patients (17.7 months) and especially patients who received biweekly ATO (22.8 months) is surprising and accompanied by pharmacodynamic changes on MRI. Further studies of this regimen are warranted.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/noajnl\/vdae089","type":"journal-article","created":{"date-parts":[[2024,6,13]],"date-time":"2024-06-13T14:41:49Z","timestamp":1718289709000},"source":"Crossref","is-referenced-by-count":3,"title":["Phase I and pharmacodynamic study of arsenic trioxide plus radiotherapy in patients with newly diagnosed glioblastoma"],"prefix":"10.1093","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1697-0100","authenticated-orcid":false,"given":"Samuel","family":"Ryu","sequence":"first","affiliation":[{"name":"Department of Radiation Oncology, Stony Brook University School of Medicine , Stony Brook, New York , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaobu","family":"Ye","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Johns Hopkins University School of Medicine , Baltimore, Maryland , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeffrey J","family":"Olson","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Emory University School of Medicine , Atlanta, Georgia , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tom","family":"Mikkelsen","sequence":"additional","affiliation":[{"name":"Jeffries Center for Precision Medicine, Henry Ford Health , Detroit, Michigan , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lev","family":"Bangiyev","sequence":"additional","affiliation":[{"name":"Department of Radiology, Stony Brook University School of Medicine , Stony Brook, New York , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Glenn J","family":"Lesser","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Hematology and Oncology, Wake Forest School of Medicine , Winston-Salem, North Carolina , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tracy","family":"Batchelor","sequence":"additional","affiliation":[{"name":"Department of Neurology, Brigham and Women\u2019s Hospital , Boston, Massachusetts , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Burt","family":"Nabors","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of Alabama at Birmingham , Birmingham, Alabama , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Serena","family":"Desideri","sequence":"additional","affiliation":[{"name":"Department of Oncology, Johns Hopkins University School of Medicine , Baltimore, Maryland , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0667-8106","authenticated-orcid":false,"given":"Tobias","family":"Walbert","sequence":"additional","affiliation":[{"name":"Department of Neurology, Henry Ford Health, Wayne State School of Medicine , Detroit, Michigan , USA"},{"name":"Department of Surgery, Michigan State University , Detroit, Michigan , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stuart A","family":"Grossman","sequence":"additional","affiliation":[{"name":"Department of Oncology, Johns Hopkins University School of Medicine , Baltimore, Maryland , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2024,6,13]]},"reference":[{"issue":"9","key":"2024070812204479900_CIT0001","doi-asserted-by":"crossref","first-page":"3354","DOI":"10.1182\/blood.V89.9.3354","article-title":"Use of arsenic trioxide (As2O3) in the treatment of acute promyelocytic leukemia (APL): II. 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