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    Prognostic significance of genome-wide DNA methylation profiles within the randomised, phase 3, EORTC CATNON trial on non-1p/19q deleted anaplastic glioma

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    Authors
    Tesileanu, C. M. S.
    van den Bent, M. J.
    Sanson, M.
    Wick, W.
    Brandes, A. A.
    Clement, P. M.
    Erridge, S. C.
    Vogelbaum, M. A.
    Nowak, A. K.
    Baurain, J. F.
    Mason, W. P.
    Wheeler, H.
    Chinot, O. L.
    Gill, S.
    Griffin, M.
    Rogers, L.
    Taal, W.
    Rudà, R.
    Weller, M.
    McBain, Catherine A
    van Linde, M. E.
    Sabedot, T. S.
    Hoogstrate, Y.
    von Deimling, A.
    de Heer, I.
    Brouwer, R. W. W.
    Aldape, K.
    Jenkins, R. B.
    Dubbink, H. J.
    Kros, J. M.
    Wesseling, P.
    Cheung, K. J.
    Golfinopoulos, V.
    Baumert, B. G.
    Gorlia, T.
    Noushmehr, H.
    French, P. J.
    van Ijken, WJF
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    Affiliation
    Neurology Department, Erasmus MC, Rotterdam, the Netherlands
    Issue Date
    2021
    
    Metadata
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    Abstract
    Background: Survival in patients with IDH1/2 mutant (mt) anaplastic astrocytomas is highly variable. We have used the prospective phase 3 CATNON trial to identify molecular factors related to outcome in IDH1/2mt anaplastic astrocytoma patients. Methods: The CATNON trial randomized 751 adult patients with newly diagnosed 1p/19q non-codeleted anaplastic glioma to 59.4 Gy radiotherapy +/- concurrent and/or adjuvant temozolomide. The presence of necrosis and/or microvascular proliferation was scored at central pathology review. Infinium MethylationEPIC BeadChip arrays were used for genome-wide DNA methylation analysis and the determination of copy number variations (CNV). Two DNA methylation-based tumour classifiers were used for risk stratification. Next-generation sequencing (NGS) was performed using one of two glioma-tailored NGS panels. The primary endpoint was overall survival measured from date of randomization. Results: Full analysis (genome-wide DNA methylation and NGS) was successfully performed on 654 tumours. Of these, 432 tumours were IDH1/2mt anaplastic astrocytomas. Both epigenetic classifiers identified poor prognosis patients that partially overlapped. A predictive prognostic Cox proportional hazards model identified that independent prognostic factors for IDH1/2mt anaplastic astrocytoma patients included; age, mini-mental state examination score, treatment with concurrent and/or adjuvant temozolomide, the epigenetic classifiers, PDGFRA amplification, CDKN2A/B homozygous deletion, PI3K mutations and total CNV load. Independent recursive partitioning analysis highlights the importance of these factors for patient prognostication. Conclusion: Both clinical and molecular factors identify IDH1/2mt anaplastic astrocytoma patients with worse outcome. These results will further refine the current WHO criteria for glioma classification
    Citation
    Tesileanu CMS, van den Bent MJ, Sanson M, Wick W, Brandes AA, Clement PM, et al. Prognostic significance of genome-wide DNA methylation profiles within the randomised, phase 3, EORTC CATNON trial on non-1p/19q deleted anaplastic glioma. Neuro-Oncology. 2021 Apr 29
    Journal
    Neuro Oncology
    URI
    http://hdl.handle.net/10541/624023
    DOI
    10.1093/neuonc/noab088
    PubMed ID
    33914057
    Additional Links
    https://dx.doi.org/10.1093/neuonc/noab088
    Type
    Article
    Language
    en
    ae974a485f413a2113503eed53cd6c53
    10.1093/neuonc/noab088
    Scopus Count
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