COG ACNS0331
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.
Overview
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.
- 82.5 vs 80.5 out of 100 free of a major event at 5 years with Involved-field boost compared with Posterior fossa boost; 2 more per 100.
- Roughly one extra person helped for every 50 treated. That is a rough figure taken from the two percentages, not a guarantee for any one person.
- Put another way, the treated group had about 3 percent lower chance of the event at any given time (hazard ratio 0.97).
- 71.4 vs 82.9 out of 100 free of a major event at 5 years with 18 Gy CSI compared with 23.4 Gy CSI; 11.5 fewer per 100.
- On this measure the first group did worse, not better.
- Put another way, the treated group had about 67 percent higher chance of the event at any given time (hazard ratio 1.67).
- This is a surrogate endpoint: it measures the cancer being controlled or absent on scans and tests, which often, but not always, translates into living longer.
- These results apply to the people the trial enrolled: 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. People in a different situation may not see the same effect.
Numbers are from the trial as recorded here; see the source links in the table below. This is orientation, not medical advice: ask your team how closely the trial population matches you.
549 participants enrolled.
| Endpoint | Arm | n | Value | HR (95% CI) | p | Source |
|---|---|---|---|---|---|---|
| 5-year event-free survival: boost volumeprimary | Involved-field boost | — | 82.5% | 0.97 | — | link |
| Posterior fossa boost | — | 80.5% | ||||
| 5-year event-free survival: CSI dose (age 3-7)primary | 18 Gy CSI | — | 71.4% | 1.67 | — | link |
| 23.4 Gy CSI | — | 82.9% |
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