MGMT promoter methylation in 1p19q-intact gliomas.

Autor: Kinslow CJ; Department of Radiation Oncology, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, 622 West 168th Street, BNH B011, New York, NY, 10032, USA.; Herbert Irving Comprehensive Cancer Center, Vagelos College of Physicians and Surgeons, Columbia University, 1130 St Nicholas Ave, New York, NY, 10032, USA., Siegelin MD; Herbert Irving Comprehensive Cancer Center, Vagelos College of Physicians and Surgeons, Columbia University, 1130 St Nicholas Ave, New York, NY, 10032, USA.; Departments of Pathology and Cell Biology, Vagelos College of Physicians and Surgeons, Columbia University, 1130 St. Nicholas Ave Rm. 1001, New York, NY, 10032, USA., Iwamoto FM; Herbert Irving Comprehensive Cancer Center, Vagelos College of Physicians and Surgeons, Columbia University, 1130 St Nicholas Ave, New York, NY, 10032, USA.; Department of Neurology, Vagelos College of Physicians and Surgeons, Columbia University, 710 West 168th Street, New York, NY, 10032, USA., Gallitto M; Department of Radiation Oncology, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, 622 West 168th Street, BNH B011, New York, NY, 10032, USA.; Herbert Irving Comprehensive Cancer Center, Vagelos College of Physicians and Surgeons, Columbia University, 1130 St Nicholas Ave, New York, NY, 10032, USA., Neugut AI; Herbert Irving Comprehensive Cancer Center, Vagelos College of Physicians and Surgeons, Columbia University, 1130 St Nicholas Ave, New York, NY, 10032, USA.; Department of Medicine, Vagelos College of Physicians and Surgeons, and Department of Epidemiology, Mailman School of Public Health, Columbia University, 722 West 168th St, New York, NY, 10032, USA., Yu JB; Department of Radiation Oncology, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, 622 West 168th Street, BNH B011, New York, NY, 10032, USA.; Herbert Irving Comprehensive Cancer Center, Vagelos College of Physicians and Surgeons, Columbia University, 1130 St Nicholas Ave, New York, NY, 10032, USA., Cheng SK; Department of Radiation Oncology, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, 622 West 168th Street, BNH B011, New York, NY, 10032, USA. sc3225@cumc.columbia.edu.; Herbert Irving Comprehensive Cancer Center, Vagelos College of Physicians and Surgeons, Columbia University, 1130 St Nicholas Ave, New York, NY, 10032, USA. sc3225@cumc.columbia.edu.; Department of Radiation Oncology, James J. Peters Veterans Affairs Medical Center, 130 West Kingsbridge Road, Bronx, NY, 10468, USA. sc3225@cumc.columbia.edu., Wang TJC; Department of Radiation Oncology, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, 622 West 168th Street, BNH B011, New York, NY, 10032, USA. tjw2117@cumc.columbia.edu.; Herbert Irving Comprehensive Cancer Center, Vagelos College of Physicians and Surgeons, Columbia University, 1130 St Nicholas Ave, New York, NY, 10032, USA. tjw2117@cumc.columbia.edu.
Jazyk: angličtina
Zdroj: Journal of neuro-oncology [J Neurooncol] 2024 Jan; Vol. 166 (1), pp. 73-78. Date of Electronic Publication: 2023 Dec 20.
DOI: 10.1007/s11060-023-04515-z
Abstrakt: Objective: Standard-of-care for 1p19q-intact anaplastic gliomas is defined by the international randomized phase III CATNON trial, which found an overall survival (OS) benefit for adjuvant temozolomide (TMZ) when added to radiotherapy. Paradoxically, TMZ did not appear to benefit patients with IDH-wildtype gliomas, regardless of MGMT promoter status. The authors concluded that well-powered prospective study on the clinical efficacy of TMZ for patients with IDH-wildtype anaplastic gliomas (meeting criteria for glioblastoma) is warranted. Given that the prognostic and predictive role of MGMT status for grade 2-3 gliomas is unresolved, we determined the effect of MGMT status on OS in patients with 1p19q-intact gliomas in the National Cancer Database (NCDB).
Methods: We queried the NCDB from 2018 to 2019 for patients with diffuse (grade 2) and anaplastic (grade 3) IDH-wildtype or -mutant astrocytomas who received chemotherapy with follow-up through 2022. The Kaplan-Meier method and Cox proportional hazards regressions models were used to determine the association of MGMT with OS.
Results: We identified 1514 patients who were newly diagnosed with IDH-wildtype (n = 802, 33% methylated) or -mutant astrocytomas (n = 712, 48% methylated) and received chemotherapy during initial management. An unmethylated promoter was associated with poorer survival in patients with IDH-wildtype (3-year OS 34% [95%CI 29-39%] vs. 46% [95%CI 39-54%], p < .001, adjusted HR 1.53 [95%CI 1.24-1.89]) but not IDH-mutant astrocytomas (3-year OS 79% [95%CI 74-84%] vs. 80% [95%CI 75-86%], p =0 .81, HR 1.04 [95%CI 0.73-1.50]).
Conclusions: This ancillary analysis supports conclusions from the CATNON trial for adjuvant TMZ as standard-of-care for anaplastic astrocytomas (IDH-mutant and 1p19q-intact), irrespective of MGMT status. Determining the optimal strategy for diffuse gliomas that are IDH-wildtype will be particularly important. MGMT promoter methylation should be considered as a stratification factor in future clinical trials for these patients.
(© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
Databáze: MEDLINE
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