Acta Neuropathologica

, Volume 131, Issue 6, pp 821–831 | Cite as

Risk stratification of childhood medulloblastoma in the molecular era: the current consensus

  • Vijay Ramaswamy
  • Marc Remke
  • Eric Bouffet
  • Simon Bailey
  • Steven C. Clifford
  • Francois Doz
  • Marcel Kool
  • Christelle Dufour
  • Gilles Vassal
  • Till Milde
  • Olaf Witt
  • Katja von Hoff
  • Torsten Pietsch
  • Paul A. Northcott
  • Amar Gajjar
  • Giles W. Robinson
  • Laetitia Padovani
  • Nicolas André
  • Maura Massimino
  • Barry Pizer
  • Roger Packer
  • Stefan Rutkowski
  • Stefan M. Pfister
  • Michael D. Taylor
  • Scott L. Pomeroy
Consensus Paper

Abstract

Historical risk stratification criteria for medulloblastoma rely primarily on clinicopathological variables pertaining to age, presence of metastases, extent of resection, histological subtypes and in some instances individual genetic aberrations such as MYC and MYCN amplification. In 2010, an international panel of experts established consensus defining four main subgroups of medulloblastoma (WNT, SHH, Group 3 and Group 4) delineated by transcriptional profiling. This has led to the current generation of biomarker-driven clinical trials assigning WNT tumors to a favorable prognosis group in addition to clinicopathological criteria including MYC and MYCN gene amplifications. However, outcome prediction of non-WNT subgroups is a challenge due to inconsistent survival reports. In 2015, a consensus conference was convened in Heidelberg with the objective to further refine the risk stratification in the context of subgroups and agree on a definition of risk groups of non-infant, childhood medulloblastoma (ages 3–17). Published and unpublished data over the past 5 years were reviewed, and a consensus was reached regarding the level of evidence for currently available biomarkers. The following risk groups were defined based on current survival rates: low risk (>90 % survival), average (standard) risk (75–90 % survival), high risk (50–75 % survival) and very high risk (<50 % survival) disease. The WNT subgroup and non-metastatic Group 4 tumors with whole chromosome 11 loss or whole chromosome 17 gain were recognized as low-risk tumors that may qualify for reduced therapy. High-risk strata were defined as patients with metastatic SHH or Group 4 tumors, or MYCN-amplified SHH medulloblastomas. Very high-risk patients are Group 3 with metastases or SHH with TP53 mutation. In addition, a number of consensus points were reached that should be standardized across future clinical trials. Although we anticipate new data will emerge from currently ongoing and recently completed clinical trials, this consensus can serve as an outline for prioritization of certain molecular subsets of tumors to define and validate risk groups as a basis for future clinical trials.

Keywords

Medulloblastoma Subgroups WNT SHH Group 3 Group 4 p53 Genomics Outcomes 

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Copyright information

© Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  • Vijay Ramaswamy
    • 1
  • Marc Remke
    • 2
    • 3
  • Eric Bouffet
    • 1
  • Simon Bailey
    • 4
  • Steven C. Clifford
    • 4
  • Francois Doz
    • 5
  • Marcel Kool
    • 6
  • Christelle Dufour
    • 7
  • Gilles Vassal
    • 7
  • Till Milde
    • 8
    • 9
  • Olaf Witt
    • 8
    • 9
  • Katja von Hoff
    • 10
  • Torsten Pietsch
    • 11
  • Paul A. Northcott
    • 12
  • Amar Gajjar
    • 12
  • Giles W. Robinson
    • 12
  • Laetitia Padovani
    • 13
  • Nicolas André
    • 14
  • Maura Massimino
    • 15
  • Barry Pizer
    • 16
  • Roger Packer
    • 17
  • Stefan Rutkowski
    • 10
  • Stefan M. Pfister
    • 6
    • 8
  • Michael D. Taylor
    • 18
  • Scott L. Pomeroy
    • 19
  1. 1.Division of Haematology/OncologyHospital for Sick ChildrenTorontoCanada
  2. 2.Department of Pediatric Oncology, Hematology, and Clinical ImmunologyUniversity Hospital DüsseldorfDüsseldorfGermany
  3. 3.Department of Pediatric Neuro-OncogenomicsGerman Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ)DüsseldorfGermany
  4. 4.Northern Institute for Cancer ResearchNewcastle UniversityNewcastle-upon-TyneUK
  5. 5.Department of Paediatric, Adolescents and Young Adults OncologyCurie Institute, and University Paris DescartesParisFrance
  6. 6.Division of Pediatric Neurooncology (B062)DKFZ, and German Cancer Consortium (DKTK)HeidelbergGermany
  7. 7.Department of Pediatric and Adolescent OncologyInstitut Gustave-RoussyVillejuifFrance
  8. 8.Department of Pediatric Oncology, Hematology and Clinical ImmunologyUniversity Hospital HeidelbergHeidelbergGermany
  9. 9.Clinical Cooperation Unit Pediatric Oncology (G340)DKFZHeidelbergGermany
  10. 10.Department of Pediatric Hematology and OncologyUniversity Medical Center Hamburg-EppendorfHamburgGermany
  11. 11.NeuropathologyUniversity of BonnBonnGermany
  12. 12.St. Jude’s Research HospitalMemphisUSA
  13. 13.Aix-Marseille Université, Inserm, CRO2 UMR_S 911Marseille Cedex 05France
  14. 14.Department of Pediatric Hematology and OncologyAP-HMMarseilleFrance
  15. 15.Fondazione IRCCS “Istituto Nazionale dei Tumori”MilanItaly
  16. 16.Department of OncologyAlder Hey Children’s NHS Foundation TrustLiverpoolUK
  17. 17.Department of NeurologyChildren’s National Medical CenterWashington, DCUSA
  18. 18.Division of NeurosurgeryHospital for Sick ChildrenTorontoCanada
  19. 19.Department of NeurologyBoston Children’s Hospital and Harvard Medical SchoolBostonUSA

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