PDCT-01. TOXICITY AND OUTCOME IN ADOLESCENT AND YOUNG ADULTS TREATED FOR MEDULLOBLASTOMA AND PRIMITIVE NEUROECTODERMAL TUMORS ON STUDIES COG-A9961 AND CCG-99701: A REPORT FROM THE CHILDREN’S ONCOLOGY GROUP (COG)

Abstract

Adolescent and young adults (AYA) with cancer have inferior outcomes compared with younger patients. We explored whether treatment-related toxicity and survival were associated with age in patients with medulloblastoma (MB) and primitive neuroectodermal tumor (PNET) enrolled on children’s oncology group (COG) studies COG-A9961 and CCG-99701. A retrospective analysis was conducted to compare the outcomes between AYA (15-21 years) vs. younger patients (3-14 years). On CCG-99701, 161 patients (16 AYA) with high-risk MB/PNET were treated with chemoradiotherapy followed by six cycles of maintenance chemotherapy cyclophosphamide/cisplatin/vincristine). On A9961 study, 379 patients with standard-risk MB (25 AYA) received chemoradiotherapy followed by eight cycles of maintenance chemotherapy (cisplatin/CCNU/vincristine). On CCG-99701, estimated 5-year event-free survival (EFS) and overall survival (OS) rates were lower for AYA patients (EFS: 37.5% versus 60.3%, p=0.05; OS: 50.0% versus 70.8%, p=0.005). On multivariate analysis, the observed difference in EFS was not statistically significant (p=0.12) but was still consistent with poorer outcome in older patients (HR 1.75, 95% CI 0.89-3.45) after adjustment for extent of resection and pathology. This difference was mainly due to poorer survival for AYA patients with PNET compared to patients 3-14 years of age (55.7% versus 9.1%; p=.002) as there was no significant difference in survival for high-risk medulloblastoma patients (p=0.26). Peripheral neuropathy was higher among AYA as well. On A9961, there was no difference in EFS or OS between AYA and younger patients. Interestingly, the AYA group experienced less hearing loss. Future studies examining the age-related differences in pharmacokinetics of chemotherapy and differences in tumor molecular biology are necessary.