title: Medulloblastoma subgroup-specific outcomes in irradiated children: who are the true high-risk patients?
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.
authors.affiliation: 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.).
authors.forename: Vijay
authors.initials: V
authors.lastname: Ramaswamy
authors.affiliation: 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.).
authors.forename: Marc
authors.initials: M
authors.lastname: Remke
authors.affiliation: 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.).
authors.forename: Jennifer
authors.initials: J
authors.lastname: Adamski
authors.affiliation: 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.).
authors.forename: Ute
authors.initials: U
authors.lastname: Bartels
authors.affiliation: 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.).
authors.forename: Uri
authors.initials: U
authors.lastname: Tabori
authors.affiliation: 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.).
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
authors.affiliation: 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.).
authors.forename: Annie
authors.initials: A
authors.lastname: Huang
authors.affiliation: 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.).
authors.forename: Cynthia
authors.initials: C
authors.lastname: Hawkins
authors.affiliation: 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.).
authors.forename: Donald
authors.initials: D
authors.lastname: Mabbott
authors.affiliation: 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.).
authors.forename: Normand
authors.initials: N
authors.lastname: Laperriere
authors.affiliation: 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.).
authors.forename: Michael D
authors.initials: MD
authors.lastname: Taylor
authors.affiliation: 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.).
authors.forename: Eric
authors.initials: E
authors.lastname: Bouffet
mesh_terms: D000293:Adolescent; D002528:Cerebellar Neoplasms / Q000145:classification / Q000473:pathology* / Q000532:radiotherapy; D002648:Child; D002675:Child, Preschool; D016371:Cranial Irradiation; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008527:Medulloblastoma / Q000145:classification / Q000473:pathology* / Q000532:radiotherapy; D060787:Neoplasm Grading; D011379:Prognosis; D012307:Risk Factors; D015996:Survival Rate
keywords: chemotherapy; medulloblastoma; radiation; subgroups