PDCT-04. ETMR ONE: AN INTERNATIONAL REGISTRY AND RESEARCH PLATFORM FOR CHILDREN WITH EMBRYONAL TUMOR WITH MULTILAYER ROSETTES

Abstract

Abstract Embryonal tumor with multilayer rosettes (ETMR) is a rare and highly-aggressive CNS neoplasm which occurs almost exclusively in young children and is associated with an extremely poor prognosis. Due to the rare nature of ETMR and its recent classification, no large clinical investigations have been conducted to determine the optimal therapy for these tumors. Historical data suggests that extensive surgical resection, radiotherapy, and high-dose chemotherapy are not sufficient treatment in the vast majority of cases with a reported 1-year EFS of 36% and 1-year OS of 45% using these approaches. New treatment regimens incorporating the known biology of ETMR must be investigated. Pre-clinical drug screens using the ETMR BT183 cell line and its xenograft have demonstrated responses to the chemotherapy agents topotecan, doxorubicin, and actinomycin D. Based on this data, a modified IRS-III chemotherapy regimen incorporating these active agents was developed and a small cohort of four children with ETMR were then treated. Three patients completed therapy without subsequent relapse and have EFS of >30 months. The ETMR One international registry and its associated consensus treatment protocol represent the first prospective evaluation of treatment outcomes for children with ETMR. The consensus regimen involves maximal feasible surgical resection, modified IRS-III chemotherapy, high-dose chemotherapy with autologous stem cell rescue, and radiotherapy (as indicated). Patients enrolled on the registry will have their cases periodically reviewed by a medical advisory board that will offer management recommendations, particularly regarding the use of radiotherapy or the need for additional surgical interventions. Through the procurement of patient tumor samples and development of additional cell lines and xenografts, the registry aims to serve as a platform for translational research. Pre-clinical findings will be used to modify the consensus protocol therapy as indicated or to generate additional biology-based phase I/II trials for ETMR.