EP-05 * POSTERIOR FOSSA EPENDYMOMA SUBGROUPS HAVE DISTINCT THERAPEUTIC AND PROGNOSTIC IMPLICATIONS

Abstract

BACKGROUND: Recent integrated genomic studies has shown that posterior fossa ependymoma comprise two distinct molecular subgroups, termed EPN-PFA and EPN-PFB, whereby EPN-PFA are typically younger and have a worse prognosis. Current standard of care for all posterior fossa ependymoma include surgery and conformal external beam radiation to the tumour bed, irrespective of extent of resection or subgroup. We sought to delineate the prognostic implications of external beam irradiation in a subgroup specific manner. METHODS: We assembled a cohort of 365 posterior fossa ependymoma's and were subgrouped using genome wide methylation arrays. Clinical details were ascertained through a retrospective chart review. RESULTS: In a primarily pediatric cohort, 10% of cases were EPN-PFB. Five-year progression free survival in EPN-PFA cases was 0.216 +/− 0.03 and EPN-PFB cases was 0.667 +/− 0.082. Five-year overall survival in EPN-PFB cases was 1 suggesting that EPN-PFB cases benefit significantly from salvage therapies. Extent of resection was a significant predictor of poor outcome in EPN-PFA cases (p = 0.012) but not EPN-PFB (p = 0.224). Upfront external beam irradiation conferred a significant survival advantage in EPN-PFA cases, however in EPN-PFB, salvage strategies could be successfully employed in patients not receiving upfront external beam irradiation. Metastatic recurrences were enriched in the EPN-PFA group (p = 0.04). CONCLUSIONS: There are significant clinical and therapeutic differences between the two principle posterior fossa ependymoma subgroups. Extent of resection remains prognostic in EPN-PFA, although gross totally resected EPN-PFA continue to have a poor outcome compared to EPN-PFB. Careful de-escalation of therapy could be considered for older children and adolescents with EPN-PFB tumours.