{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:51:19Z","timestamp":1786978279459,"version":"build-2736575974"},"reference-count":52,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2021,4,12]],"date-time":"2021-04-12T00:00:00Z","timestamp":1618185600000},"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","award":["provided study medication"],"award-info":[{"award-number":["provided study medication"]}],"id":[{"id":"10.13039\/100004328","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006058","name":"St. Baldrick's Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006058","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["U10CA180899"],"award-info":[{"award-number":["U10CA180899"]}],"id":[{"id":"10.13039\/100000054","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":[[2021,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    <jats:bold>Background<\/jats:bold>\n                    : Approximately 30% of children with medulloblastoma (MB) experience recurrence, which is usually incurable. This study compared the overall survival (OS) of patients receiving temozolomide (TMZ) and irinotecan with that of patients receiving TMZ, irinotecan, and bevacizumab for recurrent MB\/central nervous system (CNS) primitive neuroectodermal tumor (PNET).\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Methods<\/jats:bold>\n                    : Patients with relapsed\/refractory MB or CNS PNET were randomly assigned to receive TMZ (150\u00a0mg\/m\n                    <jats:sup>2<\/jats:sup>\n                    \/day PO on days 1\u20135) and irinotecan (50\u00a0mg\/m\n                    <jats:sup>2<\/jats:sup>\n                    \/day IV on days 1\u20135) with or without bevacizumab (10\u00a0mg\/kg IV on days 1 and 15).\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Results<\/jats:bold>\n                    : One hundred five patients were eligible and treated on study. Median OS was 13\u00a0months in the standard arm and 19\u00a0months with the addition of bevacizumab; median event\u2010free survival (EFS) was 6\u00a0months in the standard arm and 9\u00a0months with the addition of bevacizumab. The hazard ratio for death from the stratified relative\u2010risk regression model is 0.63. Overall, 23 patients completed 12 courses of planned protocol therapy, 23% (12\/52) in the experimental arm with bevacizumab versus 21% (11\/53) in the standard arm. Toxicity profiles were comparable in both treatment arms. The estimate of the incidence of feasibility events associated with the bevacizumab arm is three of 52 (5.8%) (95% CI 1.2\u201316%). Events included myelosuppression, electrolyte abnormalities, diarrhea, and elevated transaminases. One intracranial hemorrhage event was observed in each arm.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Conclusion<\/jats:bold>\n                    : The addition of bevacizumab to TMZ\/irinotecan significantly reduced the risk of death in children with recurrent MB. The combination was relatively well tolerated in this heavily pretreated cohort. The three\u2010drug regimen demonstrated a sufficient risk reduction to warrant further investigation.\n                  <\/jats:p>","DOI":"10.1002\/pbc.29031","type":"journal-article","created":{"date-parts":[[2021,4,12]],"date-time":"2021-04-12T11:49:33Z","timestamp":1618228173000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":67,"title":["Temozolomide with irinotecan versus temozolomide, irinotecan plus bevacizumab for recurrent medulloblastoma of childhood: Report of a COG randomized Phase II screening trial"],"prefix":"10.1002","volume":"68","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1593-8099","authenticated-orcid":false,"given":"Adam S.","family":"Levy","sequence":"first","affiliation":[{"name":"Albert Einstein College of Medicine, Children's Hospital at Montefiore  Bronx New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Krailo","sequence":"additional","affiliation":[{"name":"Department of Preventive Medicine University of Southern California  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan","family":"Chi","sequence":"additional","affiliation":[{"name":"Dana\u2010Farber\/Harvard Cancer Center  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Doojduen","family":"Villaluna","sequence":"additional","affiliation":[{"name":"Children's Oncology Group  Monrovia California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linda","family":"Springer","sequence":"additional","affiliation":[{"name":"Children's Oncology Group  Monrovia California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chris","family":"Williams\u2010Hughes","sequence":"additional","affiliation":[{"name":"Department of Preventive Medicine University of Southern California  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maryam","family":"Fouladi","sequence":"additional","affiliation":[{"name":"Cincinnati Children's Hospital Medical Center  Cincinnati Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5019-0699","authenticated-orcid":false,"given":"Amar","family":"Gajjar","sequence":"additional","affiliation":[{"name":"Saint Jude Children's Research Hospital  Memphis Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,4,12]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-016-1545-1"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-016-1569-6"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2017.72.7842"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2014.59.9217"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1215\/15228517-2008-044"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.24341"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2011.03.004"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11060-016-2202-1"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.2217\/cns.13.30"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.28907"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1097\/MPH.0000000000000547"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1097\/MPH.0000000000001095"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.22961"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/85.4.271"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0889-8588(18)30176-X"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2003.08.175"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1215\/15228517-4-2-102"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2007.11.6103"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1093\/neuonc\/not097"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(94)91280-7"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1179\/016164105X39833"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1215\/15228517-2007-032"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1517\/14712598.3.2.263"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2007.11.9230"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0959-8049(01)00225-8"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.20697"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2006.06.7272"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.4161\/cbt.4.12.2315"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1104819"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-06-4102"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mvr.2007.05.003"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-04-0074"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm0901-987"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-07-0278"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjc.6601005"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2005.01.149"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/92.3.205"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1002\/9781118032985"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.21979"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/0197-2456(96)00075-X"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1097\/MOP.0b013e32834ec106"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-14-0833"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.2174\/1570159X15666171129111324"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(13)70449-2"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature16478"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jocn.2015.10.022"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.28032"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.24006"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1093\/neuonc\/not320"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00381-012-2013-4"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.28343"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.1002\/cam4.1171"}],"container-title":["Pediatric Blood &amp; Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/pbc.29031","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/pbc.29031","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/pbc.29031","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,28]],"date-time":"2023-08-28T04:55:08Z","timestamp":1693198508000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/pbc.29031"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,4,12]]},"references-count":52,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2021,8]]}},"alternative-id":["10.1002\/pbc.29031"],"URL":"https:\/\/doi.org\/10.1002\/pbc.29031","archive":["Portico"],"relation":{},"ISSN":["1545-5009","1545-5017"],"issn-type":[{"value":"1545-5009","type":"print"},{"value":"1545-5017","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,4,12]]},"assertion":[{"value":"2020-12-09","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-03-08","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-04-12","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e29031"}}