Article: article from journal or magazin.
Presence of an oligodendroglioma-like component in newly diagnosed glioblastoma identifies a pathogenetically heterogeneous subgroup and lacks prognostic value: central pathology review of the EORTC_26981/NCIC_CE.3 trial.
Radiation Oncology Groups, National Cancer Institute of Canada Clinical Trials Group
European Organisation for Research, Treatment of Cancer Brain Tumour
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't Publication
Glioblastoma (GBM) is a morphologically heterogeneous tumor type with a median survival of only 15 months in clinical trial populations. However, survival varies greatly among patients. As part of a central pathology review, we addressed the question if patients with GBM displaying distinct morphologic features respond differently to combined chemo-radiotherapy with temozolomide. Morphologic features were systematically recorded for 360 cases with particular focus on the presence of an oligodendroglioma-like component and respective correlations with outcome and relevant molecular markers. GBM with an oligodendroglioma-like component (GBM-O) represented 15% of all confirmed GBM (52/339) and was not associated with a more favorable outcome. GBM-O encompassed a pathogenetically heterogeneous group, significantly enriched for IDH1 mutations (19 vs. 3%, p = 0.003) and EGFR amplifications (71 vs. 48%, p = 0.04) compared with other GBM, while co-deletion of 1p/19q was found in only one case and the MGMT methylation frequency was alike (47 vs. 46%). Expression profiles classified most of the GBM-O into two subtypes, 36% (5/14 evaluable) as proneural and 43% as classical GBM. The detection of pseudo-palisading necrosis (PPN) was associated with benefit from chemotherapy (p = 0.0002), while no such effect was present in the absence of PPN (p = 0.86). In the adjusted interaction model including clinical prognostic factors and MGMT status, PPN was borderline nonsignificant (p = 0.063). Taken together, recognition of an oligodendroglioma-like component in an otherwise classic GBM identifies a pathogenetically mixed group without prognostic significance. However, the presence of PPN may indicate biological features of clinical relevance for further improvement of therapy.
Adolescent, Adult, Aged, Brain Neoplasms/genetics, Brain Neoplasms/pathology, Chemoradiotherapy, Clinical Trials, Phase III as Topic, DNA Methylation, Dacarbazine/analogs & derivatives, Dacarbazine/therapeutic use, Female, Glioblastoma/genetics, Glioblastoma/pathology, Humans, Male, Middle Aged, Mutation, Oligodendroglioma/genetics, Oligodendroglioma/pathology, Prognosis, Receptor, Epidermal Growth Factor/genetics, Receptor, Epidermal Growth Factor/metabolism, Survival Analysis, Treatment Outcome, Young Adult
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