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Neuro Oncol. 2016 Feb;18(2):291-7. doi: 10.1093/neuonc/nou357. Epub 2015 Jan 20.

Medulloblastoma subgroup-specific outcomes in irradiated children: who are the true high-risk patients?

Author information

1
Division of Hematology/Oncology, Hospital for Sick Children, Toronto, Ontario, Canada (V.R., J.A., U.B., U.T., A.H., D.M., N.L., E.B.); Program in Developmental and Stem Cell Biology, Hospital for Sick Children, Toronto, Ontario, Canada (V.R., M.R., X.W., M.D.T.); Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada (V.R., M.R., X.W., A.H., C.H., M.D.T); Division of Neurosurgery, Hospital for Sick Children, Toronto, Ontario, Canada (V.R., M.R., X.W., M.D.T.); Department of Pediatric Laboratory Medicine, Hospital for Sick Children, Toronto, Ontario, Canada (C.H.); Department of Radiation Oncology, Princess Margaret Cancer Center, Toronto, Ontario, Canada (N.L.).

Abstract

BACKGROUND:

The advent of integrated genomics has fundamentally changed our understanding of medulloblastoma. Although survival differences exist among the 4 principal subgroups, this has yet to be elucidated in a North American cohort of irradiated patients.

METHODS:

Ninety-two consecutive patients between the ages of 3 and 17 treated with surgery, craniospinal irradiation, and chemotherapy were identified at the Hospital for Sick Children. Molecular subgrouping was performed using nanoString.

RESULTS:

Two treatment periods were identified: prior to 2006 as per the protocols of the Children's Oncology Group, and after 2006 per the St Jude Medulloblastoma 03 protocol. Five-year progression-free survival (PFS) over the entire cohort was 0.801 (95% CI: 0.692-0.875) with no significant difference between treatment protocols. Strikingly, we found that Group 4 patients had excellent 5-year PFS of 0.959 (95% CI: 0.744-0.994) for average risk and 0.887 (95% CI: 0.727-0.956) across all Group 4 patients. Group 3 patients had 5-year PFS of 0.733 (95% CI: 0.436-0.891). Sonic hedgehog patients did poorly across both treatment protocols, with 5-year PFS of 0.613 (95% CI: 0.333-0.804), likely owing to a high proportion of TP53 mutated patients in this age group.

CONCLUSIONS:

In a cohort of irradiated patients over 3 years of age, PFS for Group 4 patients was significantly improved compared with initial reports. The impact of subgroup affiliation in these children needs to be assessed in large prospectively treated cooperative protocols to determine if more than just WNT patients can be safely selected for de-escalation of therapy.

KEYWORDS:

chemotherapy; medulloblastoma; radiation; subgroups

PMID:
25605817
PMCID:
PMC4724171
DOI:
10.1093/neuonc/nou357
[Indexed for MEDLINE]
Free PMC Article

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