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Patients with complete\/near-total resections (GTR\/NTR) or complete response (CR) to induction therapy were randomized to radiation (RT) alone or RT followed by chemotherapy (RT-CHEMO). Primary outcomes were event-free survival (EFS) and overall survival (OS). Due to anticipated noncompliance with chemotherapy, an \u201cas treated\u201d analysis was planned. Patients with subtotal resection (STR) were non-randomly assigned to RT-CHEMO. Grade 2 supratentorial tumors with GTR or CR to induction therapy were observed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Of 449 eligible patients, 325 with GTR\/NTR or CR were randomized. Five-year EFS was 63.7% (95% CI: 55.1%-71.1%) for RT only (n\u2009=\u2009161) versus 69.2% (60.8%-76.3%) for RT-CHEMO (n\u2009=\u2009164) (1-sided log-rank P\u2009=\u2009.299, HR\u2009=\u20090.866). Five-year OS was 86.9% (79.8%-91.6%) for RT only versus 88.3% (81.8%-92.6%) for RT-CHEMO (1-sided log-rank P-value\u2009=\u2009.172, HR\u2009=\u20090.757). The \u201cas treated\u201d and \u201cas randomized\u201d analysis results were similar. Sixty-three subjects with STR were assigned to RT-CHEMO; 5-year EFS was 33.6% (22.1%-45.5%) and OS 74.0% (60.5%-83.5%). Supratentorial grade 2 tumors with GTR or CR were observed with a 5-year EFS of 66.9% (49.0%-79.7%) and OS of 100%. Molecular classification was provided for 94% (n\u2009=\u2009422) of all subjects.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Primary analysis showed no benefit for maintenance chemotherapy. Further follow-up is important to assess its effect on late relapses. This is the largest cohort of molecularly classified ependymomas treated on a Phase 3 randomized trial.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/neuonc\/noaf285","type":"journal-article","created":{"date-parts":[[2025,12,18]],"date-time":"2025-12-18T12:58:49Z","timestamp":1766062729000},"page":"1286-1297","source":"Crossref","is-referenced-by-count":14,"title":["Phase 3 randomized trial of postirradiation chemotherapy in patients with newly diagnosed ependymoma: A report from the Children\u2019s Oncology Group"],"prefix":"10.1093","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-6432-6198","authenticated-orcid":false,"given":"Amy A","family":"Smith","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Cleveland Clinic Children's (A.A.S.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arzu","family":"Onar-Thomas","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, St Jude Children\u2019s 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