MBCL-15. IMPACT OF MOLECULAR SUBGROUPS ON OUTCOMES FOLLOWING RADIATION TREATMENT RANDOMIZATIONS FOR AVERAGE RISK MEDULLOBLASTOMA: A PLANNED ANALYSIS OF CHILDREN’S ONCOLOGY GROUP (COG) ACNS0331

Abstract The COG conducted a randomized trial for average-risk medulloblastoma (AR-MB). Patients age 3–21 years were randomized to a radiation boost to the whole posterior fossa (PFRT) or an involved field volume (IFRT) after receiving CSI. Patients age 3–7 years were also randomized to standard dose CSI (23.4Gy, SDCSI) or low dose CSI (18Gy, LDCSI). 464 evaluable patients were available to compare PFRT vs. IFRT and 226 for SDCSI vs. LDCSI. 380 cases had sufficient tissue for DNA methylation-based molecular classification: 362 confirmed medulloblastoma; 6 non-medulloblastoma; 12 inconclusive. Molecular subgrouping confirmed the following representation amongst the evaluable cohort: 156 Group 4 (43.1%), 76 Group 3 (21.0%), 66 SHH (18.2%), 64 WNT (17.7%). Five-year event-free survival (EFS) estimates were 82.5±2.7% and 80.5±2.7% for IFRT and PFRT, respectively (p=0.44). Five-year EFS estimates were 71.4±4.4% and 82.9±3.7% for LDCSI and SDCSI, respectively (p=0.028). EFS distributions differed significantly by subgroup (p<0.0001). Group 3 had the worst outcome, while WNT had the best outcome. There was a significant difference in EFS by RT group among SHH patients; SHH patients receiving IFRT arm had better EFS compared to PFRT (p=0.018). There was a significant difference in EFS distributions by CSI group in Group 4 patients; young Group 4 patients treated with SDCSI had better EFS compared to LDCSI (p=0.047). As previously reported, IFRT is noninferior to PFRT in all patients with AR-MB but LDCSI is worse than SDCSI in younger children. Significant differences in outcome by study randomization and molecular subgroup are observed.