Prognostic significance of genome-wide DNA methylation profiles within the randomized, phase 3, EORTC CATNON trial on non-1p/19q deleted anaplastic glioma. Issue 9 (29th April 2021)

• Record Type: Journal Article
• Authors: Tesileanu, C Mircea S; van den Bent, Martin J; Sanson, Marc; Wick, Wolfgang; Brandes, Alba A; Clement, Paul M; Erridge, Sara C; Vogelbaum, Michael A; Nowak, Anna K; Baurain, Jean F; Mason, Warren P; Wheeler, Helen; Chinot, Olivier L; Gill, Sanjeev; Griffin, Matthew; Rogers, Leland; Taal, Walter; Rudà, Roberta; Weller, Michael; McBain, Catherine; van Linde, Myra E; Sabedot, Thais S; Hoogstrate, Youri; von Deimling, Andreas; de Heer, Iris; van IJcken, Wilfred F J; Brouwer, Rutger W W; Aldape, Kenneth; Jenkins, Robert B; Dubbink, Hendrikus J; Kros, Johan M; Wesseling, Pieter; Cheung, Kin Jip; Golfinopoulos, Vassilis; Baumert, Brigitta G; Gorlia, Thierry; Noushmehr, Houtan; French, Pim J;
• Is Part Of: Neuro-oncology. Volume 23:Issue 9(2021)
• Page Start: 1547
• Page End: 1559
• Publication Date: 2021-04-29
• Subjects: 1p/19q non-codeleted -- anaplastic glioma -- DNA methylation profiling -- IDH mutant -- patient prognostication; Brain Neoplasms -- Periodicals; Brain -- Tumors -- Periodicals; Brain -- Cancer -- Periodicals; Nervous system -- Cancer -- Periodicals; 616.99481
• DOI: 10.1093/neuonc/noab088
• Languages: English
• ISSNs: 1522-8517

Abstract

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 tumor classifiers were used for risk stratification. Next-generation sequencing (NGS) was performed using 1 of the 2 glioma-tailored NGS panels. The primary endpoint was overall survival measured from the date of randomization. Results: Full analysis (genome-wide DNA methylation and NGS) was successfully performed on 654 tumors. Of these, 432 tumors were IDH1/2mt anaplastic astrocytomas. Both epigenetic classifiers identified poor prognosis patients that partially overlapped. A predictive prognostic Cox proportional hazard 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.