Risk stratification of childhood medulloblastoma in the molecular era: the current consensus
Open accessAbstract
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 Published and unpublished data over the past 5 years were reviewed, and a consensus was reached regarding the level of evidence for currently available biomarkers.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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MYC amplifications, G3 molecular group, and presence of metastatic disease-but not iso17-are key prognostic indicators of poor outcome in G3 and G4 cases across a population treated with standard regimens.
“This analysis confirms MYC amplifications, G3 molecular group, and the presence of metastatic disease—but not iso17—as key prognostic indicators of poor outcome in G3 and G4 cases across a population of patients with medulloblastoma treated with standard regimens (20, 21).”
From The Medulloblastoma Meta-Analysis Portal Enables Integrative Exploration of Clinical and Genomic Data from Patients (2025) · cites this paper as [20]
The Background and Very High Risk sections link Group 3, especially metastatic Group 3 with MYC amplification, to poor outcomes; the Abstract also classifies metastatic Group 4 as high risk (pages unavailable). But the Indeterminate Groups section says MYC amplification is not established as high risk in non-metastatic patients and that iso17 may be a high-risk marker in Group 3, rather than ruling it out as prognostic. (LLM, conf=0.88)
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“This analysis confirms MYC amplifications, G3 molecular group, and the presence of metastatic disease—but not iso17—as key prognostic indicators of poor outcome in G3 and G4 cases across a population of patients with medulloblastoma treated with standard regimens (20, 21).”
Self-citation
- Authors
- Ramaswamy, V., Remke, M., Bouffet, E., Bailey, S., Clifford, S. C., Doz, F., Kool, M., Dufour, C., Vassal, G., Milde, T., Witt, O., von Hoff, K., Pietsch, T., Northcott, P. A., Gajjar, A., Robinson, G. W., Padovani, L., André, N., Massimino, M., Pizer, B., Packer, R., Rutkowski, S., Pfister, S. M., Taylor, M. D., & Pomeroy, S. L.
- Affiliations
- Hospital for Sick Children (CA)
- German Cancer Research Center (DE)
- Newcastle University (GB)
- Institut Gustave Roussy (FR)
- University of Bonn (DE)
- St. Jude Children's Research Hospital (US)
- Fondazione IRCCS Istituto Nazionale dei Tumori (IT)
- Alder Hey Children's NHS Foundation Trust (GB)
- Children's National (US)
- University Medical Center Hamburg-Eppendorf (DE)
- Boston Children's Hospital (US)
- Corresponding author
- Ramaswamy, Vijay
- Remke, Marc
- ORCID
- Venue
- Acta Neuropathologica
- Published
- 2016-04-04
- Volume
- 131
- Issue
- 6
- Pages
- 821-831
- ISSN
- 0001-6322 (ISSN-L)
- 1432-0533
- PMC
- PMC4867119
- OpenAlex
- W2338116242
- Cited by
- 654
- References
- 62
- Citations by year
- 2026: 45 · 2025: 61 · 2024: 56 · 2023: 78 · 2022: 62 · 2021: 84 · 2020: 83 · 2019: 66 · 2018: 57 · 2017: 46 · 2016: 13 · 2015: 1
- FWCI
- 44.02
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Acta Neuropathologica (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Newcastle University ePrints (Newcastle Univesity)
- Funders
- Canadian Institutes of Health Research
- Alberta Innovates - Health Solutions
- National Institutes of Health (R01CA159859)
- Topics
- Health Sciences › Medicine › Genetics › Glioma Diagnosis and Treatment
- Health Sciences › Medicine › Neurology › Neuroblastoma Research and Treatments
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Acute Lymphoblastic Leukemia research
- Keywords
- risk stratification, WNT subgroup, SHH subgroup, Group 3 medulloblastoma, Group 4 medulloblastoma, MYCN amplification, MYC amplification, TP53 mutation, chromosome 11 loss, chromosome 17 gain, metastasis, prognosis
- MeSH terms
- Adolescent, Cerebellar Neoplasms, Child, Child, Preschool, Humans, Medulloblastoma, Prognosis, Risk Factors, Biomarkers, Tumor, Gene Expression Profiling
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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