Trial reportOncotarget2015
Biomarker-driven stratification of disease-risk in non-metastatic medulloblastoma: Results from the multi-center HIT-SIOP-PNET4 clinical trial.
Trial report in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
32 citing papers in PubMed.
- Prognostic relevance of clinical and molecular risk factors in children with high-risk medulloblastoma treated in the phase II trial PNET HR+5.Neuro-oncology · 2021Trial
- Relapse patterns and outcome after relapse in standard risk medulloblastoma: a report from the HIT-SIOP-PNET4 study.Journal of neuro-oncology · 2016Trial
- In silico drug sensitivity predicts subgroup-specific therapeutics in medulloblastoma patients.Scientific reports · 2025Article
- The role of DNA methylation in directing treatment in medulloblastoma.Epigenomics · 2025Review
- Old Tools in a New Era: The Continued Relevance of Chemotherapy in Pediatric Neuro-Oncology.Current oncology (Toronto, Ont.) · 2025Review
- Molecular and clinical heterogeneity within MYC-family amplified medulloblastoma is associated with survival outcomes: A multicenter cohort study.Neuro-oncology · 2025Article
- Arrested development: the dysfunctional life history of medulloblastoma.Genes & development · 2025Review
- Real-life experience with a "modified-MEMMAT" regimen for relapsed medulloblastoma.Therapeutic advances in medical oncology · 2025Article
- Review
- Molecular characterisation defines clinically-actionable heterogeneity within Group 4 medulloblastoma and improves disease risk-stratification.Acta neuropathologica · 2023Article
- How Genetics and Genomics Advances Are Rewriting Pediatric Cancer Research and Clinical Care.Medicina (Kaunas, Lithuania) · 2022Review
- Clinical implications of the 2021 edition of the WHO classification of central nervous system tumours.Nature reviews. Neurology · 2022Review
- Clinical Trials in High-Risk Medulloblastoma: Evolution of the SIOP-Europe HR-MB Trial.Cancers · 2022Review
- Review
- Review
- Pattern of Relapse and Treatment Response in WNT-Activated Medulloblastoma.Cell reports. Medicine · 2020Article
- Medulloblastoma genomics in the modern molecular era.Brain pathology (Zurich, Switzerland) · 2020Review
- Molecular stratifications, biomarker candidates and new therapeutic options in current medulloblastoma treatment approaches.Cancer metastasis reviews · 2020Review
- Canadian Pediatric Neuro-Oncology Standards of Practice.Frontiers in oncology · 2020Article
- Updates on Management of Adult Medulloblastoma.Current treatment options in oncology · 2019Review
Corrections and comments
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Authors and funding
14 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeTo improve stratification of risk-adapted treatment for non-metastatic (M0), standard-risk medulloblastoma patients by prospective evaluation of biomarkers of reported biological or prognostic significance, alongside clinico-pathological variables, within the multi-center HIT-SIOP-PNET4 trial.
methodsFormalin-fixed paraffin-embedded tumor tissues were collected from 338 M0 patients (>4.0 years at diagnosis) for pathology review and assessment of the WNT subgroup (MBWNT) and genomic copy-number defects (chromosome 17, MYC/MYCN, 9q22 (PTCH1) and DNA ploidy). Clinical characteristics were reviewed centrally.
resultsThe favorable prognosis of MBWNT was confirmed, however better outcomes were observed for non-MBWNT tumors in this clinical risk-defined cohort compared to previous disease-wide clinical trials. Chromosome 17p/q defects were heterogeneous when assessed at the cellular copy-number level, and predicted poor prognosis when they occurred against a diploid (ch17(im)/diploid(cen)), but not polyploid, genetic background. These factors, together with post-surgical tumor residuum (R+) and radiotherapy delay, were supported as independent prognostic markers in multivariate testing. Notably, MYC and MYCN amplification were not associated with adverse outcome. In cross-validated survival models derived for the clinical standard-risk (M0/R0) disease group, (ch17(im)/diploid(cen); 14% of patients) predicted high disease-risk, while the outcomes of patients without (ch17(im)/diploid(cen)) did not differ significantly from MBWNT, allowing re-classification of 86% as favorable-risk.
conclusionsBiomarkers, established previously in disease-wide studies, behave differently in clinically-defined standard-risk disease. Distinct biomarkers are required to assess disease-risk in this group, and define improved risk-stratification models. Routine testing for specific patterns of chromosome 17 imbalance at the cellular level, and MBWNT, provides a strong basis for incorporation into future trials.
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