{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T22:13:47Z","timestamp":1778278427160,"version":"3.51.4"},"reference-count":18,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2024,11,18]],"date-time":"2024-11-18T00:00:00Z","timestamp":1731888000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,6,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Effective therapy for medulloblastoma at the time of relapse is limited. The objective of this study is to review outcomes from the Seattle Children\u2019s Hospital (SCH) institutional standard therapy for relapsed medulloblastoma, modified from the published ACNS0821 regimen.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Retrospective review of patients treated for relapsed medulloblastoma from 2012-2024 treated with modified ACNS0821 therapy, including combination bevacizumab, irinotecan, and temozolomide, referred to as \u201cTIB.\u201d Each TIB cycle includes oral temozolomide (200 mg\/m2\/day) for the first 5 days, intravenous (IV) bevacizumab (10 mg\/kg\/dose), and IV irinotecan (125 mg\/m2\/dose or 340 mg\/m2) on days 1 and 15 of each cycle. Patient medical history, prior treatment, therapy toxicity, response, and outcome were collected. The analysis included Kaplan\u2013Meier estimates of 3-year overall survival (OS) and 3-year progression-free survival.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Fifteen patients were treated with TIB for relapsed medulloblastoma at SCH (median age 5.81 (0.21\u201323.6) years, 60% male). Twelve patients completed planned therapy. Therapy was discontinued for toxicity (n\u2005=\u20051) and family preference (n\u2005=\u20051). The most common toxicities were thrombocytopenia (n\u2005=\u20057), neutropenia (n\u2005=\u20054), nausea (n\u2005=\u20055), vomiting (n\u2005=\u20055), and diarrhea (n\u2005=\u20053). Five patients required dose modification of one agent for toxicity. Median follow-up from TIB therapy start was 1.61 (0.47\u20137.66) years. Three-year OS was 48% (95% CI: 18%\u201374%) and 3-year event-free survival was 16% (95% CI: 1%\u201349%).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>TIB was well-tolerated in pediatric patients with relapsed medulloblastoma, and outcomes were similar to those published in clinical trials. TIB therapy should be considered for patients with relapsed medulloblastoma, especially patients with limited access to care due to travel barriers.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/nop\/npae114","type":"journal-article","created":{"date-parts":[[2024,11,18]],"date-time":"2024-11-18T09:04:37Z","timestamp":1731920677000},"page":"489-497","source":"Crossref","is-referenced-by-count":4,"title":["Children with medulloblastoma treated with modified ACNS0821 temozolomide, irinotecan, and bevacizumab: The Seattle Children\u2019s Hospital experience"],"prefix":"10.1093","volume":"12","author":[{"given":"Rebecca","family":"Ronsley","sequence":"first","affiliation":[{"name":"Fred Hutch Cancer Center , Seattle, Washington ,","place":["USA"]},{"name":"Ben Towne Center for Childhood Cancer Research, Seattle Children\u2019s Research Institute , Seattle, Washington ,","place":["USA"]},{"name":"Department of Pediatrics, Seattle Children\u2019s Hospital, University of Washington , Seattle, Washington ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miranda C","family":"Bradford","sequence":"additional","affiliation":[{"name":"Biostatistics Epidemiology and Analytics in Research (BEAR) Core, Seattle Children\u2019s Research Institute , Seattle, Washington ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Erin E","family":"Crotty","sequence":"additional","affiliation":[{"name":"Fred Hutch Cancer Center , Seattle, Washington ,","place":["USA"]},{"name":"Ben Towne Center for Childhood Cancer Research, Seattle Children\u2019s Research Institute , Seattle, Washington ,","place":["USA"]},{"name":"Department of Pediatrics, Seattle Children\u2019s Hospital, University of Washington , Seattle, Washington ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3966-4985","authenticated-orcid":false,"given":"Nicholas A","family":"Vitanza","sequence":"additional","affiliation":[{"name":"Fred Hutch Cancer Center , Seattle, Washington ,","place":["USA"]},{"name":"Ben Towne Center for Childhood Cancer Research, Seattle Children\u2019s Research Institute , Seattle, Washington ,","place":["USA"]},{"name":"Department of Pediatrics, Seattle Children\u2019s Hospital, University of Washington , Seattle, Washington ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel V","family":"Runco","sequence":"additional","affiliation":[{"name":"Fred Hutch Cancer Center , Seattle, Washington ,","place":["USA"]},{"name":"Ben Towne Center for Childhood Cancer Research, Seattle Children\u2019s Research Institute , Seattle, Washington ,","place":["USA"]},{"name":"Department of Pediatrics, Seattle Children\u2019s Hospital, University of Washington , Seattle, Washington ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeffrey","family":"Stevens","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Seattle Children\u2019s Hospital, University of Washington , Seattle, Washington ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Corinne","family":"Hoeppner","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Seattle Children\u2019s Hospital, University of Washington , Seattle, Washington ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susan L","family":"Holtzclaw","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Seattle Children\u2019s Hospital, University of Washington , Seattle, Washington ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amy R","family":"Wein","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Seattle Children\u2019s Hospital, University of Washington , Seattle, Washington ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amy","family":"Lee","sequence":"additional","affiliation":[{"name":"Division of Neurosurgery, Seattle Children\u2019s Hospital and Department of Neurological Surgery, University of Washington , Seattle, Washington ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bonnie L","family":"Cole","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology, University of Washington , Seattle, Washington ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ralph","family":"Ermoian","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, University of Washington , Seattle, Washington ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sarah E S","family":"Leary","sequence":"additional","affiliation":[{"name":"Fred Hutch Cancer Center , Seattle, Washington ,","place":["USA"]},{"name":"Ben Towne Center for Childhood Cancer Research, Seattle Children\u2019s Research Institute , Seattle, Washington ,","place":["USA"]},{"name":"Department of Pediatrics, Seattle Children\u2019s Hospital, University of Washington , Seattle, Washington ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2024,11,18]]},"reference":[{"key":"2025060501014993000_CIT0001","doi-asserted-by":"crossref","first-page":"iv1","DOI":"10.1093\/neuonc\/noad149","article-title":"CBTRUS Statistical Report: Primary brain and other central nervous system tumors diagnosed in the United States in 2016-2020","volume":"25","author":"Ostrom","year":"2023","journal-title":"Neuro Oncol"},{"issue":"6","key":"2025060501014993000_CIT0002","doi-asserted-by":"crossref","first-page":"1733","DOI":"10.1007\/s13311-022-01273-0","article-title":"Medulloblastoma in the Modern Era: Review of contemporary trials, molecular advances, and updates in management","volume":"19","author":"Lazow","year":"2022","journal-title":"Neurotherapeutics"},{"issue":"4","key":"2025060501014993000_CIT0003","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1007\/s11940-006-0022-x","article-title":"Current therapy for medulloblastoma","volume":"8","author":"Gottardo","year":"2006","journal-title":"Curr Treat Options Neurol"},{"issue":"12","key":"2025060501014993000_CIT0004","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1007\/s11910-023-01316-9","article-title":"Recent advances in pediatric medulloblastoma","volume":"23","author":"Jackson","year":"2023","journal-title":"Curr Neurol Neurosci Rep."},{"issue":"3","key":"2025060501014993000_CIT0005","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1002\/pbc.20781","article-title":"Outcome for children &lt;4 years of age with malignant central nervous system tumors treated with high-dose chemotherapy and autologous stem cell rescue","volume":"48","author":"Thorarinsdottir","year":"2007","journal-title":"Pediatr Blood Cancer."},{"issue":"3","key":"2025060501014993000_CIT0006","doi-asserted-by":"crossref","first-page":"837","DOI":"10.3390\/cancers14030837","article-title":"High-dose chemotherapy in children with newly diagnosed medulloblastoma","volume":"14","author":"Lafay-Cousin","year":"2022","journal-title":"Cancers (Basel)"},{"issue":"8","key":"2025060501014993000_CIT0007","doi-asserted-by":"crossref","first-page":"2095","DOI":"10.1007\/s00381-023-05918-z","article-title":"Outcomes of a radiation sparing approach in medulloblastoma by subgroup in young children: An institutional review","volume":"39","author":"Ronsley","year":"2023","journal-title":"Childs Nerv Syst."},{"issue":"24","key":"2025060501014993000_CIT0008","doi-asserted-by":"crossref","first-page":"4881","DOI":"10.1200\/JCO.2004.12.126","article-title":"Feasibility and response to induction chemotherapy intensified with high-dose methotrexate for young children with newly diagnosed high-risk disseminated medulloblastoma","volume":"22","author":"Chi","year":"2004","journal-title":"J Clin Oncol."},{"issue":"8","key":"2025060501014993000_CIT0009","doi-asserted-by":"crossref","first-page":"e29031","DOI":"10.1002\/pbc.29031","article-title":"Temozolomide with irinotecan versus temozolomide, irinotecan plus bevacizumab for recurrent medulloblastoma of childhood: Report of a COG randomized Phase II screening trial","volume":"68","author":"Levy","year":"2021","journal-title":"Pediatr Blood Cancer."},{"issue":"3","key":"2025060501014993000_CIT0010","doi-asserted-by":"crossref","first-page":"e159","DOI":"10.1097\/MPH.0000000000001095","article-title":"Survival following tumor recurrence in children with medulloblastoma","volume":"40","author":"Johnston","year":"2018","journal-title":"J Pediatr Hematol Oncol."},{"issue":"7","key":"2025060501014993000_CIT0011","doi-asserted-by":"crossref","first-page":"807","DOI":"10.1200\/JCO.20.01359","article-title":"Clinical outcomes and patient-matched molecular composition of relapsed medulloblastoma","volume":"39","author":"Kumar","year":"2021","journal-title":"J Clin Oncol."},{"issue":"4","key":"2025060501014993000_CIT0012","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1007\/s00381-012-2013-4","article-title":"Response to bevacizumab, irinotecan, and temozolomide in children with relapsed medulloblastoma: A multi-institutional experience","volume":"29","author":"Aguilera","year":"2013","journal-title":"Childs Nerv Syst."},{"issue":"22","key":"2025060501014993000_CIT0013","doi-asserted-by":"crossref","first-page":"1935","DOI":"10.1200\/JCO.19.00175","article-title":"Impact of travel time on health care costs and resource use by phase of care for older patients with cancer","volume":"37","author":"Rocque","year":"2019","journal-title":"J Clin Oncol."},{"issue":"28","key":"2025060501014993000_CIT0014","doi-asserted-by":"crossref","first-page":"3177","DOI":"10.1200\/JCO.2015.61.1558","article-title":"Association between geographic access to cancer care, insurance, and receipt of chemotherapy: Geographic distribution of oncologists and travel distance","volume":"33","author":"Lin","year":"2015","journal-title":"J Clin Oncol."},{"issue":"1","key":"2025060501014993000_CIT0015","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1111\/j.1748-0361.2011.00371.x","article-title":"Is distance to provider a barrier to care for medicaid patients with breast, colorectal, or lung cancer","volume":"28","author":"Scoggins","year":"2012","journal-title":"J Rural Health."},{"issue":"1","key":"2025060501014993000_CIT0016","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1001\/jama.287.1.111-JMS0102-5-1","article-title":"MSJAMA. Relationship between travel distance and utilization of breast cancer treatment in rural northern Michigan","volume":"287","author":"Meden","year":"2002","journal-title":"JAMA."},{"issue":"1","key":"2025060501014993000_CIT0017","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1093\/neuonc\/nox087","article-title":"Response assessment in medulloblastoma and leptomeningeal seeding tumors: Recommendations from the Response Assessment in Pediatric Neuro-Oncology committee","volume":"20","author":"Warren","year":"2018","journal-title":"Neuro Oncol."},{"issue":"1","key":"2025060501014993000_CIT0018","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1097\/MOP.0b013e32834ec106","article-title":"The molecular classification of medulloblastoma: Driving the next generation clinical trials","volume":"24","author":"Leary","year":"2012","journal-title":"Curr Opin Pediatr."}],"container-title":["Neuro-Oncology Practice"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/nop\/advance-article-pdf\/doi\/10.1093\/nop\/npae114\/60933925\/npae114.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/nop\/article-pdf\/12\/3\/489\/60933925\/npae114.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/nop\/article-pdf\/12\/3\/489\/60933925\/npae114.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,6,5]],"date-time":"2025-06-05T05:01:58Z","timestamp":1749099718000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/nop\/article\/12\/3\/489\/7903091"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11,18]]},"references-count":18,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2024,11,18]]},"published-print":{"date-parts":[[2025,6,4]]}},"URL":"https:\/\/doi.org\/10.1093\/nop\/npae114","relation":{},"ISSN":["2054-2577","2054-2585"],"issn-type":[{"value":"2054-2577","type":"print"},{"value":"2054-2585","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2025,6]]},"published":{"date-parts":[[2024,11,18]]}}}