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01-06-2016 | Consensus Paper

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

Authors: 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

Published in: Acta Neuropathologica | Issue 6/2016

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 Published and unpublished data over the past 5 years were reviewed, and a consensus was reached regarding the level of evidence for currently available biomarkers.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.

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Title: Risk stratification of childhood medulloblastoma in the molecular era: the current consensus
Authors: 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
Publication date: 01-06-2016
Publisher: Springer Berlin Heidelberg
Published in: Acta Neuropathologica / Issue 6/2016
Print ISSN: 0001-6322
Electronic ISSN: 1432-0533
DOI: https://doi.org/10.1007/s00401-016-1569-6

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

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