ID #1040 Relapsed paediatric ependymoma with extraCNS metastases. A Multi-Institutional Serie

Introduction Ependymomas represent the third most common central nervous system (CNS) tumor and the second most frequent malignant CNS neoplasm. Owing to the marked biological and clinical heterogeneity of this disease, 5year overall survival (OS) ranges from 40–70%, while progression-free survival (PFS) rates are 25–40%. These tumors originate from ependymal cells lining the ventricular system, and therefore dissemination or recurrence outside the CNS is considered exceedingly rare (incidence 2-20%), with a few cases reported in the literature. Methods We retrospectively reviewed four patients treated at two institutions in Argentina and Iran who developed extra-CNS metastatic relapse following a diagnosis of intracranial ependymoma. Results All patients initially presented with supratentorial anaplastic ependymomas, with high proliferation indices (Ki67 up to 50%). The cohort included two females and two males, with age at diagnosis ranging from 5 to 15 years. Two of them harbored C11orf95-RELA fusions, while two were assumed ZFTA-fusion-negative based on L1CAM immunohistochemistry. Extra-CNS relapse occurred at a median of 6 years after diagnosis (range 1.2-6.8 years), at sites including parotid gland, lymph nodes, soft tissue, lung, pleura, bone and skin. The two RELA-fusion positive patients experienced late relapses. Treatment for relapse varied: surgery alone (n = 2), surgery plus focal radiotherapy (n = 1), and chemotherapy (n = 1). Despite multimodal therapy, two patients died of disease, while two remain alive without disease at last follow-up (median follow up: 6.2 months). Conclusions Although exceedingly rare, extra-CNS relapses of pediatric ependymoma can occur years after initial diagnosis, involving diverse extracranial sites. Outcomes were heterogeneous, with survival possible following aggressive local therapy in selected cases. These findings underscore the importance of long-term surveillance beyond the CNS and suggest that extra-neural dissemination may be underrecognized. Collaborative international registries are needed to better define risk factors, biology and optimal management strategies for this uncommon but clinically significant pattens of relapse.