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BACKGROUND/OBJECTIVE Survival has been poor in several multi-center/national trials since the 1980s, either delaying, avoiding or minimizing brain irradiation in young children with medulloblastoma. The introduction of German regimens incorporating both intravenous high-dose (HD-MTX) and intraventricular (IVENT-MTX) methotrexate, and North American regimens utilizing marrow-ablative chemotherapy with autologous hematopoietic cell rescue (HDCx+AuHCR), have reported encouraging outcomes. We performed a comparative outcomes analysis of these strategies for young children with desmoplastic/extensive nodular medulloblastoma (D/ENMB). DESIGN/METHODS Data from 12 trials reported between 2005 and 2019 for children &amp;lt;six-years-old with D/ENMB were reviewed; event-free (EFS) with standard errors were compared. RESULTS The German HIT-SKK’92 and HIT-SKK’00 trials incorporating HD-MTX and IVENT-MTX reported 85+/-8% and 95+/-5% 5-10-year EFS respectively; a third trial (ACNS1221) incorporating HIT-SKK therapy but without IVENT-MTX reported 49+/-10% EFS. Three trials (Head Start I/II combined and CCG-99703) employing induction chemotherapy without HD-MTX, followed by 1/3 HDCx+AuHCR cycles, reported 3-5-year EFS of 67+/-16% and 79+/-11%. Two trials employing HD-MTX-containing induction chemotherapy (Head Start III and ACNS0334), followed by 1/3 HDCx+AuHCR cycles, reported 3-5-year EFS of 89+/-6% and 100%, respectively. Finally, four trials utilizing neither IVENT-MTX nor HDCx+AuHCR (UK-CNS-9204, CCG-9921, COG-P9934 and SJYC07) reported 2-5-year EFS of 35+/-11%, 77+/-9%, 58+/-8% and 53+/-9%. CONCLUSIONS A trend towards better EFS for young children with D/ENMB is observed in trials including either HD-MTX as well as IVENT-MTX or including HD-MTX-containing induction chemotherapy and HDCx+AuHCR. Trials excluding HD-MTX, IVENT-MTX and HDCx+AuHCR have poorer outcomes.

neuro-oncology

MBCL-19. CHEMOTHERAPY STRATEGIES FOR YOUNG CHILDREN NEWLY DIAGNOSED WITH DESMOPLASTIC/EXTENSIVE NODULAR MEDULLOBLASTOMA UP TO THE ERA OF MOLECULAR PROFILING – A COMPARATIVE OUTCOMES ANALYSIS OF PROSPECTIVE MULTI-CENTER EUROPEAN AND NORTH AMERICAN TRIALS