Abstract | OBJECTIVE: METHODS: Patients (n = 183) of the NOA-04 trial with known MGMT and IDH1 status were analyzed for interdependency of the prognostic vs predictive role of MGMT promoter methylation from IDH1 or 1p/19q status and treatment, using progression-free survival (PFS) as an endpoint. An independent validation cohort of the German Glioma Network (n = 75) and the NOA-08 trial (n = 34) served as a confirmation cohort. RESULTS: In tumors with IDH1 mutation, MGMT promoter methylation was associated with prolonged PFS with chemotherapy ± radiotherapy (RT) or RT-only groups, and is thus prognostic. In tumors without IDH1 mutation, MGMT promoter methylation was associated with increased PFS in patients treated with chemotherapy, but not in those who received RT alone as the first-line treatment, and is thus chemotherapy-predictive. In contrast, 1p/19q codeletions showed no such association with the prognostic vs predictive value of MGMT. CONCLUSIONS: MGMT promoter methylation is a predictive biomarker for benefit from alkylating agent chemotherapy in patients with IDH1-wild-type, but not IDH1-mutant, malignant gliomas of World Health Organization grades III/IV. Combined IDH1/MGMT assessment may help to individualize clinical decision-making in neuro-oncology.
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Authors | Wolfgang Wick, Christoph Meisner, Bettina Hentschel, Michael Platten, Alissa Schilling, Benedikt Wiestler, Michael C Sabel, Susanne Koeppen, Ralf Ketter, Markus Weiler, Ghazaleh Tabatabai, Andreas von Deimling, Dorothee Gramatzki, Manfred Westphal, Gabriele Schackert, Markus Loeffler, Matthias Simon, Guido Reifenberger, Michael Weller |
Journal | Neurology
(Neurology)
Vol. 81
Issue 17
Pg. 1515-22
(Oct 22 2013)
ISSN: 1526-632X [Electronic] United States |
PMID | 24068788
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Validation Study)
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Chemical References |
- Genetic Markers
- Tumor Suppressor Proteins
- Isocitrate Dehydrogenase
- IDH1 protein, human
- DNA Modification Methylases
- MGMT protein, human
- DNA Repair Enzymes
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Topics |
- Adult
- Aged
- Aged, 80 and over
- Chromosomes, Human, Pair 1
(genetics)
- Chromosomes, Human, Pair 19
(genetics)
- DNA Methylation
(genetics)
- DNA Modification Methylases
(genetics)
- DNA Repair Enzymes
(genetics)
- Female
- Genetic Markers
- Glioma
(drug therapy, genetics, radiotherapy)
- Humans
- Isocitrate Dehydrogenase
(genetics)
- Male
- Middle Aged
- Predictive Value of Tests
- Prognosis
- Promoter Regions, Genetic
(genetics)
- Randomized Controlled Trials as Topic
- Tumor Suppressor Proteins
(genetics)
- Young Adult
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