{"entity":{"id":"acns0331","kind":"trial","name":"COG ACNS0331","aka":[],"tldr":"This trial asked whether children with average-risk medulloblastoma could safely receive less radiation. Shrinking the boost to the tumour bed was safe; cutting the dose to the whole brain and spine in young children was not, so 23.4 Gy remains the floor for most.","summary":"Randomised phase 3 (Michalski et al., JCO 2021). 549 enrolled; 464 evaluable for the boost-volume comparison and 226 for the CSI-dose comparison. Five-year event-free survival was 82.5% with involved-field boost versus 80.5% with posterior fossa boost (HR 0.97; non-inferior), and 71.4% with 18 Gy CSI versus 82.9% with 23.4 Gy (HR 1.67; inferior). Post hoc molecular subgrouping showed the dose reduction harmed group 4 tumours most, while SHH tumours did better with involved-field boost. The trial set the current average-risk standard (23.4 Gy CSI plus tumour-bed boost to 54 Gy) and showed that further de-escalation must be subgroup-directed, which the successor trials (ACNS1422 for WNT, SIOP PNET5) now test.","status":"mixed","asOf":"2026-09-10","links":[{"label":"ClinicalTrials.gov NCT00085735","url":"https://clinicaltrials.gov/study/NCT00085735"},{"label":"Michalski et al., JCO 2021","url":"https://doi.org/10.1200/JCO.20.02730"}],"tags":["nci-coverage","paediatric","cns","de-escalation"],"related":[],"cancers":["medulloblastoma","medulloblastoma-wnt","medulloblastoma-group-3-4"],"sections":[],"technologies":["proton-therapy","imrt-igrt"],"targets":[],"drugs":["cisplatin","vincristine","cyclophosphamide","lomustine"],"companies":["childrens-oncology-group"],"institutions":[],"pathways":[],"terms":["late-effects","de-escalation"],"trials":[],"people":[],"bottlenecks":["b-survivorship","b-toxicity-qol"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT00085735","phase":"3","setting":"Average-risk medulloblastoma, age 3-21: involved-field (tumour bed) vs whole posterior fossa boost; and, in children aged 3-7, 18 Gy vs 23.4 Gy craniospinal irradiation","sponsor":"Children's Oncology Group","result":"Involved-field boost non-inferior (5-year EFS 82.5% vs 80.5%); 18 Gy CSI inferior to 23.4 Gy (71.4% vs 82.9%).","started":"2004-04-30","startedType":"actual","yearReported":2021,"enrolled":549,"enrolledBasis":"registry","outcomes":[{"endpoint":"5-year event-free survival: boost volume","primary":true,"unit":"%","arms":[{"name":"Involved-field boost","value":82.5},{"name":"Posterior fossa boost","value":80.5}],"hr":0.97,"source":"https://doi.org/10.1200/JCO.20.02730"},{"endpoint":"5-year event-free survival: CSI dose (age 3-7)","primary":true,"unit":"%","arms":[{"name":"18 Gy CSI","value":71.4},{"name":"23.4 Gy CSI","value":82.9}],"hr":1.67,"source":"https://doi.org/10.1200/JCO.20.02730"}],"replication":"Consistent with the earlier CCG 9892 and A9961 experience that 23.4 Gy with chemotherapy is safe for average risk; SIOP PNET5 is testing subgroup-directed reduction."},"route":"/trials/acns0331/","neighbours":{"cancer":[{"id":"medulloblastoma-group-3-4","kind":"cancer","name":"Group 3 and group 4 medulloblastoma (non-WNT/non-SHH)","route":"/cancers/medulloblastoma-group-3-4/"},{"id":"medulloblastoma","kind":"cancer","name":"Medulloblastoma","route":"/cancers/medulloblastoma/"},{"id":"medulloblastoma-wnt","kind":"cancer","name":"WNT-activated medulloblastoma","route":"/cancers/medulloblastoma-wnt/"}],"technology":[{"id":"imrt-igrt","kind":"technology","name":"IMRT / IGRT (modern external beam)","route":"/technologies/imrt-igrt/"},{"id":"proton-therapy","kind":"technology","name":"Proton therapy","route":"/technologies/proton-therapy/"}],"drug":[{"id":"cisplatin","kind":"drug","name":"Cisplatin","route":"/drugs/cisplatin/"},{"id":"cyclophosphamide","kind":"drug","name":"Cyclophosphamide","route":"/drugs/cyclophosphamide/"},{"id":"lomustine","kind":"drug","name":"Lomustine (CCNU)","route":"/drugs/lomustine/"},{"id":"vincristine","kind":"drug","name":"Vincristine","route":"/drugs/vincristine/"}],"company":[{"id":"childrens-oncology-group","kind":"company","name":"Children's Oncology Group (COG)","route":"/companies/childrens-oncology-group/"}],"term":[{"id":"de-escalation","kind":"term","name":"De-escalation, escalation and response-adapted therapy","route":"/terms/de-escalation/"},{"id":"late-effects","kind":"term","name":"Late effects and survivorship toxicity","route":"/terms/late-effects/"}],"bottleneck":[{"id":"b-survivorship","kind":"bottleneck","name":"Survivorship and late effects are neglected","route":"/bottlenecks/b-survivorship/"},{"id":"b-toxicity-qol","kind":"bottleneck","name":"Toxicity and quality of life are undervalued","route":"/bottlenecks/b-toxicity-qol/"}],"paper":[{"id":"paper-acns0331-michalski-jco-2021","kind":"paper","name":"ACNS0331: reduced-dose and reduced-volume radiotherapy with chemotherapy for average-risk medulloblastoma","route":"/key-papers/paper-acns0331-michalski-jco-2021/"}],"trial":[{"id":"ccss","kind":"trial","name":"Childhood Cancer Survivor Study (CCSS)","route":"/trials/ccss/"}],"roadmap":[{"id":"paediatric-oncology-roadmap","kind":"roadmap","name":"Paediatric oncology roadmap: cooperative-group cures → engineered immunity → drugs developed for children first","route":"/roadmaps/paediatric-oncology-roadmap/"},{"id":"radiation-roadmap","kind":"roadmap","name":"Radiotherapy roadmap: X-rays → shaped beams → fewer fractions, particles and FLASH","route":"/roadmaps/radiation-roadmap/"}]}}