Molecular Classification Improves Therapeutic Options for Infants and Young Children With Medulloblastoma
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Medulloblastoma in infants and young children is a major challenge to treat because craniospinal irradiation (CSI), a cornerstone of therapy for older children, is disproportionately damaging to very young children. As a result, trials have attempted to delay, omit, and replace this therapy. Although success has been limited, the approach has not been a complete failure. In fact, this approach has cured a significant number of children with medulloblastoma. However, many children have endured intensive regimens of chemotherapy only to experience relapse and undergo salvage treatment with CSI, often at higher doses and with worse morbidity than they would have initially experienced. Recent advancements in molecular diagnostics have proven that response to therapy is biologically driven. Medulloblastoma in infants and young children is divided into 2 molecular groups: Sonic Hedgehog (SHH) and group 3 (G3). Both are chemotherapy-sensitive, but only the SHH medulloblastomas are reliably cured with chemotherapy alone. Moreover, SHH can be molecularly parsed into 2 groups: SHH-1 and SHH-2, with SHH-2 showing higher cure rates with less intensive chemotherapy and SHH-1 requiring more intensive regimens. G3 medulloblastoma, on the other hand, has a near universal relapse rate after chemotherapy-only regimens. This predictability represents a significant breakthrough and affords oncologists the ability to properly risk-stratify therapy in such a way that the most curative and least toxic therapy is selected. This review examines the treatment of medulloblastoma in infants and young children, discusses the molecular advancements, and proposes how to use this information to structure the future management of this disease.
Submitted December 30, 2022; final revision received March 23, 2023; accepted for publication March 24, 2023. Published online August 28, 2023.
Disclosures: The authors have disclosed that they have no financial interests, arrangements, affiliations, or commercial interests with the manufacturers of any products discussed in this article or their competitors.
Funding: Research reported in this publication was supported in part by the National Cancer Institute of the National Institutes of Health under award number P30CA021765, the American Lebanese Syrian Associated Charities, and the St. Jude Comprehensive Cancer Center Developmental Funds.
Disclaimer: The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. None of the funders had any role in the conduct of the study; in the collection, management, analysis, or interpretation of the data; or in the preparation, review, or approval of the manuscript.
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