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Clinical Trial
. 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?

Vijay Ramaswamy  1 , Marc Remke  1 , Jennifer Adamski  1 , Ute Bartels  1 , Uri Tabori  1 , Xin Wang  1 , Annie Huang  1 , Cynthia Hawkins  1 , Donald Mabbott  1 , Normand Laperriere  1 , Michael D Taylor  1 , Eric Bouffet  1
Affiliations
Clinical Trial

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

Vijay Ramaswamy et al. Neuro Oncol. 2016 Feb.

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.

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Figures

Fig. 1.
Fig. 1.
Kaplan–Meier survival analysis comparing PFS across treatment protocols and risk levels across 92 medulloblastomas. (A) Comparison of PFS in patients treated with intensified chemotherapy (“SJMB03”) vs protocols of the COG (“Non-SJMB03”). (B) Comparison of PFS in patients with average-risk disease vs those with high-risk disease. P-values determined using the log-rank method.
Fig. 2.
Fig. 2.
Kaplan–Meier survival analysis comparing PFS in a subgroup-specific manner across (A) the entire cohort of 92 medulloblastomas and (B) average-risk medulloblastoma only. P-values determined using the log-rank method.
Fig. 3.
Fig. 3.
Kaplan–Meier survival analysis comparing PFS for (A) TP53 wild-type (WT) vs TP53 mutant SHH medulloblastomas and (B) M0 vs M+ at diagnosis. P-values determined using the log-rank method.
See this image and copyright information in PMC

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