Reducing CSI dose in young children with average-risk MB results in inferior outcomes, possibly in a subgroup-dependent manner, but is associated with better neurocognitive outcome. CONCLUSION Reducing the radiation boost volume in average-risk MB is safe and does not compromise survival. Children receiving SDCSI exhibited greater late declines in IQ (estimate = 5.87 P =. Patients with group 4 MB receiving LDCSI exhibited inferior EFS (P =. Improved EFS was observed in patients with Sonic Hedgehog MB who were randomly assigned to the IFRT arm (P =. LDCSI was inferior to SDCSI (hazard ratio, 1.67% 80% upper CI, 2.10). IFRT was not inferior to PFRT (hazard ratio, 0.97 94% upper CI, 1.32). RESULTS Five hundred forty-nine patients were enrolled on study, of which 464 were eligible and evaluable to compare PFRT versus IFRT and 226 for SDCSI versus LDCSI. Neurocognitive changes and ototoxicity were monitored over time. Post hoc molecular classification and mutational analysis contextualized outcomes according to known biologic subgroups (Wingless, Sonic Hedgehog, group 3, and group 4) and genetic biomarkers. Young children (3-7 years) were also randomly assigned to receive standard-dose CSI (SDCSI 23.4 Gy) or low-dose CSI (LDCSI 18 Gy). METHODS ACNS0331 ( identifier: NCT00085735) randomly assigned patients age 3-21 years with average-risk MB to receive posterior fossa radiation therapy (PFRT) or involved field radiation therapy (IFRT) following CSI. Efforts to mitigate these effects include deintensification of craniospinal irradiation (CSI) dose and volume. Molecularly informed patient selection warrants further exploration for children with MB to be considered for late-effect sparing approaches.Ībstract = "PURPOSE Children with average-risk medulloblastoma (MB) experience survival rates of ≥ 80% at the expense of adverse consequences of treatment. PURPOSE Children with average-risk medulloblastoma (MB) experience survival rates of ≥ 80% at the expense of adverse consequences of treatment.
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