MB-109: PRELIMINARY RESULTS OF COG ACNS0331: A PHASE III TRIAL OF INVOLVED FIELD RADIOTHERAPY (IFRT) AND LOW DOSE CRANIOSPINAL IRRADIATION (LD-CSI) WITH CHEMOTHERAPY IN AVERAGE RISK MEDULLOBLASTOMA: A REPORT FROM THE CHILDREN'S ONCOLOGY GROUP

Standard therapy for average risk medulloblastoma is standard dose CSI (SD-CSI) to 23.4Gy and posterior fossa radiotherapy (PFRT) to 54Gy accompanied by cisplatin/cyclophosphamide based chemotherapy. This trial tests whether a 5.4Gy reduction in the CSI dose (18Gy, LD-CSI) in children 3-7y and a reduction in boost volume (IFRT) with all children receiving chemotherapy results in non-inferior overall (OS) or event free survival (EFS). Of 549 children enrolled, 464 were eligible and without central review findings of excess disease and were randomized to PFRT (237) or IFRT (227). Of those, 226 were 3-7years and randomized to SD-CSI (110) or LD-CSI (116). With median followup of 6.1 years, the 5 year OS in PFRT and IFRT is 84.8%± 2.8% and 84.7%± 2.8%, respectively. The 5 year EFS in PFRT and IFRT is 80.5%± 3.1% and 82.4%± 3.0%, respectively. The predetermined hazard ratio (HR) limit to determine inferiority was 1.6 and the observed 94% upper confidence limit of HR was 1.3. Therefore, IFRT is deemed non-inferior to PFRT. The 5 year OS in SD-CSI and LD-CSI is 85.3% ± 3.9% and 78.2%± 4.6%, respectively. The 5 year EFS in SD-CSI and LD-CSI is 82.1% ± 4.3% and 71.4% ± 5.1%, respectively. The predetermined hazard ratio (HR) limit to determine inferiority was 1.6 and the observed 80% upper confidence limit of HR was 1.9. Therefore, LD-CSI is inferior to SD-CSI. These data support decreasing radiation volume to the primary site. Decreasing CSI dose to 18Gy may increase risk of recurrence and is not recommended. COG Grants U10CA180886 (NCTN Operations Center Grant), U10CA180899 (NCTN Statistics & Data Center), U10CA098543 (Chair's Grant), and U10CA098413 (Statistics & Data Center Grant).