Molecular classification improves therapeutic options for infants and young children with medulloblastoma
Open accessAbstract
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.
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“Medulloblastoma in the WNT group rarely metastasize and tend to have the best prognosis; SHH and G4 tumors generally have an intermediate prognosis (4, 5); and G3 tumors are associated with greater malignancy and more frequent metastatic dissemination (5, 6).”
Self-citation
- Authors
- Bagchi, A., Dhanda, S. K., Dunphy, P., Sioson, E., & Robinson, G. W.
- Affiliations
- St. Jude Children's Research Hospital (US)
- Venue
- Journal of the National Comprehensive Cancer Network
- Publisher
- Harborside Press, LLC
- Published
- 2023-10
- Volume
- 21
- Issue
- 10
- Pages
- 1097-1105
- ISSN
- 1540-1405 (ISSN-L)
- 1540-1413
- PMC
- PMC10765405
- OpenAlex
- W4386250658
- Cited by
- 28
- References
- 52
- Citations by year
- 2026: 8 · 2025: 14 · 2024: 5 · 2023: 1
- FWCI
- 1.31
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of the National Comprehensive Cancer Network (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- American Lebanese Syrian Associated Charities (P30CA021765)
- National Cancer Institute (P30CA021765)
- Topics
- Health Sciences › Medicine › Genetics › Glioma Diagnosis and Treatment
- Health Sciences › Medicine › Neurology › Neuroblastoma Research and Treatments
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Acute Lymphoblastic Leukemia research
- Keywords
- medulloblastoma, infants and young children, molecular classification, sonic hedgehog medulloblastoma, Group 3 medulloblastoma, craniospinal irradiation, relapse, risk stratification, salvage therapy, treatment toxicity
- MeSH terms
- Adolescent, Cerebellar Neoplasms, Child, Child, Preschool, Humans, Infant, Medulloblastoma, Neoplasm Recurrence, Local, Recurrence, Hedgehog Proteins
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