Pham John, Cote David J, Kang Keiko, Briggs Robert G, Gomez David, Prasad Apurva, Daggupati Sindhu, Sisti Jonathan, Chow Frances, Attenello Frank, Chen Clark C, Zada Gabriel
Department of Neurosurgery, The Warren Alpert Medical School of Brown University, Providence, RI, 02903, USA.
Department of Neurosurgery, University of Southern California Keck School of Medicine, Los Angeles, CA, 90033, USA.
J Neurooncol. 2025 May;172(3):655-665. doi: 10.1007/s11060-025-04952-y. Epub 2025 Feb 5.
Methylation of the O-methylguanine-DNA methyltransferase (MGMT) promoter is an important prognostic marker in glioblastoma (GBM); however, its implementation in clinical practice remains understudied. Here, we assessed the prevalence of MGMT methylation status among GBM patients in the United States. Additionally, we evaluated treatment practices and survival outcomes of GBM patients according to MGMT promoter methylation status.
The National Cancer Database was queried to identify all adult U.S. patients (≥ 18 years) diagnosed with IDH-wildtype GBM between 2018 and 2020. Treatment regimen was grouped into no chemotherapy and no radiotherapy, chemotherapy alone (without radiotherapy), radiotherapy alone (without chemotherapy), and chemoradiotherapy (chemotherapy and radiotherapy). Survival data were analyzed using Kaplan-Meier survival curves, log-rank tests, and multivariable Cox proportional hazard modeling.
A total of 20,734 patients were included, of whom 6,404 (30.9%) had MGMT-methylated GBM, 9,065 (43.7%) had MGMT-unmethylated tumors, and 5,265 (25.4%) had unknown methylation status. The median and three-year overall survival were 12.4 months and 15.5%, respectively, for the entire cohort (16.4 months and 23.9% for MGMT-methylated patients and 11.8 months and 9.8% for MGMT-unmethylated patients, p < 0.001). Chemoradiotherapy was less commonly used for elderly (≥ 70 years, 58.5%) than non-elderly (< 70 years, 79.2%) patients. Among elderly patients, radiotherapy alone was more commonly administered than chemotherapy alone for patients with MGMT-unmethylated tumors (11.2% vs. 2.1%) and MGMT-methylated tumors (6.6% vs. 3.9%). However, chemotherapy alone was associated with a lower mortality risk (HR 0.71, 95% CI 0.51-0.99, p = 0.04) than radiotherapy alone for elderly patients with MGMT-methylated tumors, while chemotherapy alone was associated with a higher mortality risk (HR 1.63, 95% CI 1.09-2.44, p = 0.02) than radiotherapy alone for elderly patients with MGMT-unmethylated tumors. Patients who were elderly, uninsured, insured through Medicaid, lived in zip codes with lower median education levels, or received care at non-academic programs were less likely to undergo MGMT testing.
A high proportion of GBM patients in the United States undergo MGMT promoter testing, though significant sociodemographic disparities exist. While there was a decrease in chemoradiotherapy use with increasing age, radiotherapy alone was more commonly administered to elderly patients than chemotherapy alone irrespective of MGMT promoter methylation status.
O-甲基鸟嘌呤-DNA甲基转移酶（MGMT）启动子甲基化是胶质母细胞瘤（GBM）的一个重要预后标志物；然而，其在临床实践中的应用仍研究不足。在此，我们评估了美国GBM患者中MGMT甲基化状态的流行情况。此外，我们根据MGMT启动子甲基化状态评估了GBM患者的治疗方法和生存结果。
查询国家癌症数据库，以识别2018年至2020年间诊断为异柠檬酸脱氢酶（IDH）野生型GBM的所有美国成年患者（≥18岁）。治疗方案分为无化疗和无放疗、单纯化疗（无放疗）、单纯放疗（无化疗）以及放化疗（化疗和放疗）。使用Kaplan-Meier生存曲线、对数秩检验和多变量Cox比例风险模型分析生存数据。
共纳入20734例患者，其中6404例（30.9%）为MGMT甲基化的GBM，9065例（43.7%）为MGMT未甲基化肿瘤，5265例（25.4%）甲基化状态未知。整个队列的中位总生存期和三年总生存率分别为12.4个月和15.5%（MGMT甲基化患者为16.4个月和23.9%，MGMT未甲基化患者为11.8个月和9.8%，p<0.001）。与非老年患者（<70岁，79.2%）相比，老年患者（≥70岁，58.5%）较少接受放化疗。在老年患者中，对于MGMT未甲基化肿瘤患者（11.2%对2.1%）和MGMT甲基化肿瘤患者（6.6%对3.9%），单纯放疗比单纯化疗更常用。然而，对于MGMT甲基化肿瘤的老年患者，单纯化疗与较低的死亡风险相关（风险比[HR]0.71，95%置信区间[CI]0.51-0.99，p=0.04），而对于MGMT未甲基化肿瘤的老年患者，单纯化疗与较高的死亡风险相关（HR 1.63，95%CI 1.09-2.44，p=0.02）。年龄较大、未参保、通过医疗补助计划参保、居住在教育水平中位数较低的邮政编码地区或在非学术项目接受治疗的患者进行MGMT检测的可能性较小。
美国有很大比例的GBM患者接受了MGMT启动子检测，尽管存在显著的社会人口统计学差异。虽然随着年龄增长放化疗的使用减少，但无论MGMT启动子甲基化状态如何，老年患者中单纯放疗比单纯化疗更常用。
