title: Duration of the pre-diagnostic interval in medulloblastoma is subgroup dependent.
abstract: BACKGROUND
  Children presenting with medulloblastoma have a wide range of initial presenting symptoms. However, the influence of underlying tumor biology on the initial presentation of medulloblastoma is currently unknown. In light of the recent discovery of distinct medulloblastoma subgroups, we sought to define the initial presentation of childhood medulloblastoma in a subgroup specific manner.
  
  
  METHODS
  We assembled a cohort of 126 medulloblastoma cases at the Hospital for Sick Children between 1994 and 2012 and determined subgroup affiliation using nanoString. Clinical details pertaining to the initial presentation were determined through a retrospective chart review.
  
  
  RESULTS
  The median pre-diagnostic interval across all medulloblastoma cases was 4 weeks (IQR: 4-12 weeks). Strikingly, when the pre-diagnostic interval was then determined in a subgroup specific manner, cases with WNT and Group 4 tumors showed significantly longer median pre-diagnostic intervals of 8 weeks compared to 2 weeks for SHH and 4 weeks for Group 3 (P = 0.0001). Younger age was significantly associated with a prolonged pre-diagnostic interval (P = 0.02 for all). When stratifying by subgroup the association with age was only significant in Group 4 (P = 0.04 for Group 4). Improved survival was significantly associated with a longer pre-diagnostic interval (P = 0.02), however is no longer significant when controlling for subgroup (P = 0.07).
  
  
  CONCLUSIONS
  The duration of the pre-diagnostic interval in childhood medulloblastoma is highly subgroup dependent, further highlighting the clinical heterogeneity and biological relevance of the four principle subgroups of medulloblastoma.
authors.affiliation: Division of Neurosurgery, Arthur and Sonia Labatt Brain Tumour Research Centre, Hospital for Sick Children, Toronto, Ontario, M5G 1X8, Canada; Developmental and Stem Cell Biology, Hospital for Sick Children, Toronto, Ontario, M5G 1X8, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, M5S 1A1, Canada.
authors.forename: Vijay
authors.initials: V
authors.lastname: Ramaswamy
authors.forename: Marc
authors.initials: M
authors.lastname: Remke
authors.forename: David
authors.initials: D
authors.lastname: Shih
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
authors.forename: Paul A
authors.initials: PA
authors.lastname: Northcott
authors.forename: Claudia C
authors.initials: CC
authors.lastname: Faria
authors.forename: Charles
authors.initials: C
authors.lastname: Raybaud
authors.forename: Uri
authors.initials: U
authors.lastname: Tabori
authors.forename: Cynthia
authors.initials: C
authors.lastname: Hawkins
authors.forename: James
authors.initials: J
authors.lastname: Rutka
authors.forename: Michael D
authors.initials: MD
authors.lastname: Taylor
authors.forename: Eric
authors.initials: E
authors.lastname: Bouffet
mesh_terms: D000293:Adolescent; D000367:Age Factors; D002648:Child; D002675:Child, Preschool; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D008527:Medulloblastoma / Q000175:diagnosis* / Q000401:mortality* / Q000628:therapy*; D012189:Retrospective Studies; D015996:Survival Rate; D013997:Time Factors
keywords: genomics; medulloblastoma; pediatric brain tumor; pre-diagnostic interval; subgroups