# COG ACNS0331

Source: https://onco.cc/trials/acns0331/  
OnCo record `acns0331` (Trial). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

## Fields

- Kind: Trial
- Status: mixed
- Last checked: 2026-09-10
- Tags: nci-coverage; paediatric; cns; de-escalation
- Registry id: 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
- Enrolled: 549
- 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%).
- Outcomes: 5-year event-free survival: boost volume: Involved-field boost 82.5% vs Posterior fossa boost 80.5%, HR 0.97; 5-year event-free survival: CSI dose (age 3-7): 18 Gy CSI 71.4% vs 23.4 Gy CSI 82.9%, HR 1.67
- 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.

## Sources

- ClinicalTrials.gov NCT00085735: https://clinicaltrials.gov/study/NCT00085735
- Michalski et al., JCO 2021: https://doi.org/10.1200/JCO.20.02730

## Connected records

- cancers: [Group 3 and group 4 medulloblastoma (non-WNT/non-SHH)](https://onco.cc/cancers/medulloblastoma-group-3-4/), [Medulloblastoma](https://onco.cc/cancers/medulloblastoma/), [WNT-activated medulloblastoma](https://onco.cc/cancers/medulloblastoma-wnt/)
- technologies: [IMRT / IGRT (modern external beam)](https://onco.cc/technologies/imrt-igrt/), [Proton therapy](https://onco.cc/technologies/proton-therapy/)
- drugs: [Cisplatin](https://onco.cc/drugs/cisplatin/), [Cyclophosphamide](https://onco.cc/drugs/cyclophosphamide/), [Lomustine (CCNU)](https://onco.cc/drugs/lomustine/), [Vincristine](https://onco.cc/drugs/vincristine/)
- companies: [Children's Oncology Group (COG)](https://onco.cc/companies/childrens-oncology-group/)
- terms: [De-escalation, escalation and response-adapted therapy](https://onco.cc/terms/de-escalation/), [Late effects and survivorship toxicity](https://onco.cc/terms/late-effects/)
- bottlenecks: [Survivorship and late effects are neglected](https://onco.cc/bottlenecks/b-survivorship/), [Toxicity and quality of life are undervalued](https://onco.cc/bottlenecks/b-toxicity-qol/)
- key papers: [ACNS0331: reduced-dose and reduced-volume radiotherapy with chemotherapy for average-risk medulloblastoma](https://onco.cc/key-papers/paper-acns0331-michalski-jco-2021/)
- trials: [Childhood Cancer Survivor Study (CCSS)](https://onco.cc/trials/ccss/)
- roadmaps: [Paediatric oncology roadmap: cooperative-group cures → engineered immunity → drugs developed for children first](https://onco.cc/roadmaps/paediatric-oncology-roadmap/), [Radiotherapy roadmap: X-rays → shaped beams → fewer fractions, particles and FLASH](https://onco.cc/roadmaps/radiation-roadmap/)

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