MGMT Promoter Methylation Predicts Overall Survival after Chemotherapy for 1p/19q-Codeleted Gliomas.

Autor:	Kinslow CJ; Department of Radiation Oncology, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, New York, New York.; Herbert Irving Comprehensive Cancer Center, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, New York, New York., Rae AI; Department of Neurological Surgery, Oregon Health & Sciences University, Portland, Oregon., Taparra K; Department of Radiation Oncology, Stanford University, Stanford, California., Kumar P; Department of Radiation Oncology, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, New York, New York., Siegelin MD; Herbert Irving Comprehensive Cancer Center, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, New York, New York.; Departments of Pathology and Cell Biology, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, New York, New York., Grinband J; Program in Imaging and Cognitive Sciences, Columbia University, New York, New York.; David Mahoney Center for Brain and Behavior Research, Columbia University, New York, New York., Gill BJA; Herbert Irving Comprehensive Cancer Center, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, New York, New York.; Department of Neurological Surgery, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, New York, New York., McKhann GM; Herbert Irving Comprehensive Cancer Center, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, New York, New York.; Department of Neurological Surgery, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, New York, New York., Sisti MB; Herbert Irving Comprehensive Cancer Center, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, New York, New York.; Department of Neurological Surgery, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, New York, New York., Bruce JN; Herbert Irving Comprehensive Cancer Center, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, New York, New York.; Department of Neurological Surgery, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, New York, New York., Canoll PD; Herbert Irving Comprehensive Cancer Center, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, New York, New York.; Department of Radiation Oncology, Stanford University, Stanford, California., Iwamoto FM; Herbert Irving Comprehensive Cancer Center, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, New York, New York.; Department of Neurology, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, New York, New York., Horowitz DP; Department of Radiation Oncology, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, New York, New York.; Herbert Irving Comprehensive Cancer Center, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, New York, New York., Kachnic LA; Department of Radiation Oncology, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, New York, New York.; Herbert Irving Comprehensive Cancer Center, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, New York, New York., Neugut AI; Herbert Irving Comprehensive Cancer Center, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, New York, New York.; Department of Medicine, Vagelos College of Physicians and Surgeons, and Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, New York., Yu JB; Department of Radiation Oncology, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, New York, New York.; Herbert Irving Comprehensive Cancer Center, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, New York, New York., Cheng SK; Department of Radiation Oncology, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, New York, New York.; Herbert Irving Comprehensive Cancer Center, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, New York, New York., Wang TJC; Department of Radiation Oncology, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, New York, New York.; Herbert Irving Comprehensive Cancer Center, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, New York, New York.
Jazyk:	angličtina
Zdroj:	Clinical cancer research : an official journal of the American Association for Cancer Research [Clin Cancer Res] 2023 Nov 01; Vol. 29 (21), pp. 4399-4407.
DOI:	10.1158/1078-0432.CCR-23-1295
Abstrakt:	Purpose: While MGMT promoter methylation (mMGMT) is predictive of response to alkylating chemotherapy and guides treatment decisions in glioblastoma, its role in grade 2 and 3 glioma remains unclear. Recent data suggest that mMGMT is prognostic of progression-free survival in 1p/19q-codeleted oligodendrogliomas, but an effect on overall survival (OS) has not been demonstrated. Experimental Design: We identified patients with newly diagnosed 1p/19q-codeleted gliomas and known MGMT promoter status in the National Cancer Database from 2010 to 2019. Multivariable Cox proportional hazards regression modeling was used to assess the effect of mMGMT on OS after adjusting for age, sex, race, comorbidity, grade, extent of resection, chemotherapy, and radiotherapy. Results: We identified 1,297 eligible patients, 938 (72.3%) of whom received chemotherapy in their initial course of treatment. The MGMT promoter was methylated in 1,009 (77.8%) patients. Unmethylated MGMT (uMGMT) was associated with worse survival compared with mMGMT [70% {95% confidence interval (CI), 64%-77%} vs. 81% (95% CI, 78%-85%); P < 0.001; adjusted HR (aHR), 2.35 (95% CI, 1.77-3.14)]. uMGMT was associated with worse survival in patients who received chemotherapy [63% (95% CI, 55-73%) vs. 80% (95% CI, 76%-84%); P < 0.001; aHR, 2.61 (95% CI, 1.89-3.60)] but not in patients who did not receive chemotherapy [P = 0.38; HR, 1.31 (95% CI, 0.71-2.42)]. Similar results were observed regardless of World Health Organization grade and after single- or multiagent chemotherapy. Conclusions: Our study demonstrates an association between mMGMT and OS in 1p/19q-codeleted gliomas. MGMT promoter status should be considered as a stratification factor in future clinical trials of 1p/19q-codeleted gliomas that use OS as an endpoint. (©2023 American Association for Cancer Research.)
Databáze:	MEDLINE
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