Ongoing Progress in Treatment of Medulloblastoma 


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Brain tumors are the second most frequent pediatric malignancy. Medulloblastoma, a primitive cerebellar tumor of neuroectodermal origin, is the second most common brain tumor, accounting for 20% of childhood tumors of the central nervous system. Craniospinal radiotherapy has been the main curative modality, although the addition of chemotherapy has allowed children with standard-risk medulloblastoma to be successfully treated with lower doses of radiotherapy. Historically, children with high-risk medulloblastoma have a poor outcome, although more-recent clinical trials have attempted to improve outcome by intensifying therapy with systemic treatment.

Encouraging Outcomes

Dr. Tarbell and colleagues from the Pediatric Oncology Group reported in the Journal of Clinical Oncology the results of a prospective randomized trial in children with high-risk medulloblastoma testing chemotherapy given before vs after radiation therapy. There was no significant difference between approaches in either 5-year event-free or overall survival. However, the outcomes for both approaches were encouraging.

In this study, high-risk medulloblastoma was defined as M1–M4 disease, meaning positive cerebrospinal fluid, metastatic disease in the brain, spine, or extraneural location, or residual local tumor of greater than 1.5 cm3. While the event-free and overall survival for these high-risk patients was encouraging, new biologic and molecular information is coming to light that can provide additional prognostic information and guide treatment in this setting—as in the settings of many other pediatric and adult malignancies.

Four Subtypes

Molecular studies now classify medulloblastoma into four core subtypes based on gene-expression profiles:

  • Subtype 1 includes tumors with aberrations in the WNT signaling pathway; these tend to occur in older children and adolescents and are associated with a very good outcome.
  • Subtype 2 tumors have aberrations in the sonic hedgehog pathway and tend to occur in children under 3 years of age, a population in which there is a favorable outcome.
  • Subtype 3 tumors are histologically either classic or large cell/anaplastic, have a variety of different genetic mutations including MYC amplification, and have the least favorable outcome compared to other subtypes.
  • Subtype 4 medulloblastomas are classic or large cell/anaplastic tumors with a CDK6 amplification and other cytogenetic abnormalities. Their prognosis appears to be better than subtype 3 tumors.

Further insight into the biology of medulloblastoma, coupled with our knowledge of clinical factors and the results of studies such as this by Dr. Tarbell and colleagues, will allow us to devise and implement strategies for treatment that will continue to improve the outcome for all children with medulloblastoma.■

Dr. Marcus is Division Chief, Pediatric Radiation Oncology, Dana Farber/Boston Children’s Cancer and Blood Disorders Center, Brigham and Women’s Hospital, Harvard Medical School, Boston.

Disclosure: Dr. Marcus reported no potential conflicts of interest. 


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