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3 results on '"1p/19q non-codeleted"'

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

Author

Wilfred F. J. van IJcken, Marc Sanson, Thais S. Sabedot, C Mircea S Tesileanu, Roberta Rudà, Thierry Gorlia, Olivier Chinot, Iris de Heer, Leland Rogers, Kenneth Aldape, Alba A. Brandes, Walter Taal, Kin Jip Cheung, Anna K. Nowak, Robert B. Jenkins, Michael A. Vogelbaum, Vassilis Golfinopoulos, Pim J. French, Wolfgang Wick, Myra van Linde, Hendrikus J. Dubbink, Johan M. Kros, M. Weller, Matthew E. Griffin, Rutger W W Brouwer, Brigitta G. Baumert, Sanjeev Gill, Houtan Noushmehr, Paul Clement, Catherine McBain, Helen Wheeler, Jean Francois Baurain, Pieter Wesseling, Sara Erridge, Youri Hoogstrate, Warren P. Mason, Andreas von Deimling, Martin J. van den Bent, Institut de neurophysiopathologie (INP), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Service d’Oncologie Médicale [Hôpital de la Timone - APHM], Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Neurology, Cell biology, Pathology, UCL - SSS/IREC/MIRO - Pôle d'imagerie moléculaire, radiothérapie et oncologie, RS: GROW - R3 - Innovative Cancer Diagnostics & Therapy, and Radiotherapie

Subjects
Oncology, Cancer Research, ASTROCYTOMAS, [SDV]Life Sciences [q-bio], ESTUDOS PROSPECTIVOS, 1p/19q non-codeleted, 0302 clinical medicine, CDKN2A, Clinical endpoint, anaplastic glioma, Prospective Studies, Sequence Deletion, 0303 health sciences, Brain Neoplasms, Homozygote, Glioma, Prognosis, Isocitrate Dehydrogenase, 3. Good health, patient prognostication, GRADE, Chromosomes, Human, Pair 1, DNA methylation, SURVIVAL, DNA methylation profiling, IDH1, Life Sciences & Biomedicine, medicine.drug, Adult, medicine.medical_specialty, DNA Copy Number Variations, Clinical Neurology, Clinical Investigations, IDH mutant, CLASSIFICATION, 03 medical and health sciences, SDG 3 - Good Health and Well-being, Internal medicine, medicine, AcademicSubjects/MED00300, Humans, 030304 developmental biology, Temozolomide, Science & Technology, Proportional hazards model, business.industry, CENTRAL-NERVOUS-SYSTEM, DNA Methylation, medicine.disease, Mutation, AcademicSubjects/MED00310, Neurology (clinical), Neurosciences & Neurology, business, 030217 neurology & neurosurgery, Anaplastic astrocytoma
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.

Published
2021

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

Abstract

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. 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. 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. 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.

Published
2021

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

Author

Tesileanu CMS, van den Bent MJ, Sanson M, Wick W, Brandes AA, Clement PM, Erridge SC, Vogelbaum MA, Nowak AK, Baurain JF, Mason WP, Wheeler H, Chinot OL, Gill S, Griffin M, Rogers L, Taal W, Rudà R, Weller M, McBain C, van Linde ME, Sabedot TS, Hoogstrate Y, von Deimling A, de Heer I, van IJcken WFJ, Brouwer RWW, Aldape K, Jenkins RB, Dubbink HJ, Kros JM, Wesseling P, Cheung KJ, Golfinopoulos V, Baumert BG, Gorlia T, Noushmehr H, and French PJ

Subjects
Adult, Chromosomes, Human, Pair 1, DNA Copy Number Variations, DNA Methylation, Homozygote, Humans, Isocitrate Dehydrogenase genetics, Mutation, Prognosis, Prospective Studies, Sequence Deletion, Brain Neoplasms genetics, Brain Neoplasms therapy, Glioma genetics, Glioma therapy
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., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Society for Neuro-Oncology.)

Published
2021
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