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Prognostic significance of genome-wide DNA methylation profiles within the randomized, phase 3, EORTC CATNON trial on non-1p/19q deleted anaplastic glioma
- Source :
- Neuro-Oncology, Neuro-Oncology, Oxford University Press (OUP), 2021, 23 (9), pp.1547-1559. ⟨10.1093/neuonc/noab088⟩, Neuro-Oncology, 23(9), 1547-1559. Oxford University Press, Neuro-oncology, Vol. xx, no.xx, p. xx (2021), Neuro-Oncology, 2021, 23 (9), pp.1547-1559. ⟨10.1093/neuonc/noab088⟩, Repositório Institucional da USP (Biblioteca Digital da Produção Intelectual), Universidade de São Paulo (USP), instacron:USP, Neuro-oncology, 23(9), 1547-1559. Oxford University Press
- Publication Year :
- 2021
- Publisher :
- Oxford University Press, 2021.
-
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.
- 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
Subjects
Details
- Language :
- English
- ISSN :
- 15235866 and 15228517
- Volume :
- 23
- Issue :
- 9
- Database :
- OpenAIRE
- Journal :
- Neuro-Oncology
- Accession number :
- edsair.doi.dedup.....61e028f0c3a1383a4e27bee5fc95e42b