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Medulloblastoma subgroup-specific outcomes in irradiated children: who are the true high-risk patients?
Vijay Ramaswamy1, Marc Remke1, Jennifer Adamski1
1Division 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.).
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.
Insights
Medulloblastoma subgroup analysis in irradiated North American children reveals Group 4 patients have significantly improved survival. Further research is needed to determine if therapy de-escalation is possible for specific subgroups.
Area of Science:
- Pediatric Oncology
- Neuro-oncology
- Genomics
Background:
- Integrated genomics has transformed medulloblastoma understanding.
- Survival differences exist among medulloblastoma subgroups.
- Elucidation in North American irradiated patients is lacking.
Purpose of the Study:
- To elucidate medulloblastoma subgroup survival in a North American cohort.
- To analyze the impact of treatment protocols on survival.
- To assess the prognostic significance of molecular subgroups.
Main Methods:
- Retrospective analysis of 92 pediatric patients (ages 3-17) treated with surgery, craniospinal irradiation, and chemotherapy.
- Molecular subgrouping performed using nanoString technology.
- Comparison of survival outcomes between two treatment periods (pre- and post-2006).
Main Results:
- Overall 5-year progression-free survival (PFS) was 0.801, with no significant difference between treatment protocols.
- Group 4 medulloblastoma showed excellent 5-year PFS (0.959 for average risk, 0.887 overall).
- Group 3 patients had 5-year PFS of 0.733, while Sonic hedgehog patients had poorer outcomes (0.613 PFS), linked to TP53 mutations.
Conclusions:
- Group 4 medulloblastoma patients in this irradiated cohort demonstrated significantly improved PFS compared to initial reports.
- Subgroup affiliation impacts outcomes in pediatric medulloblastoma.
- Further prospective studies are needed to explore de-escalation of therapy for specific subgroups like WNT.
