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Background: The management and consequent survival and quality of survival for young children with medulloblastoma have undergone substantial improvement over the last four decades. While many of these changes reflect improvements in pediatric neurosurgical, neuro-imaging and radiation oncologic technology and training, as well as in supportive care experience and expertise, this review will focus particularly upon improvements in chemotherapeutic approaches.

Methods: This review focuses only upon prospective clinical trials conducted in young children with newly-diagnosed medulloblastoma since the 1980s. The upper age limits for these trials varied from under three to up to six years of age at diagnosis.

Results: Certain but not all trials endeavoring to improve outcomes for young children with now-recognized pathological and molecular low-risk characteristics, specifically the Sonic Hedgehog sub-type, representing some 50-60% of young children with medulloblastoma, have reaped substantial gains in event-free and overall survival, irradiation-free survival as well as neuropsychological outcomes. Those successful trials utilized either induction including intravenous high-dose methotrexate and intraventricular (intra-Ommaya) methotrexate without consolidation by marrow-ablative chemotherapy with autologous hematopoietic progenitor cell rescue, or induction with or without intravenous high-dose methotrexate (but not intra-ventricular methotrexate) followed by consolidation with marrow-ablative chemotherapy with autologous hematopoietic progenitor cell rescue. These two approaches have consistently produced superior outcomes compared with other trials. For children with molecularly-characterized Groups 3 or 4 medulloblastoma, representing those at high-risk of relapse, some modest improvements have been made over the years, but much room for improvement remains, especially for those presenting with the highest-risk molecular characteristics (Group 3 medulloblastoma) as well as for children with metastatic disease at initial diagnosis.

Conclusions: Substantial gains in improving outcomes for young children with medulloblastoma have been achieved with acceptable short- and long-term morbidities of treatment. However, the inclusion of intra-ventricular therapies (conventional chemotherapeutic, radio-labeled monoclonal antibody or adaptive cellular immunotherapeutic approaches) as well as the identification of targeted systemic therapies (biological and/or immunological) and their incorporation into prospective multi-center clinical trials, must be investigated prospectively if we are to improve outcomes for those children at high-risk for relapse, even with the inclusion of refined irradiation therapeutic approaches.