The predictive value of partial MGMT promoter methylation for IDH-wild-type glioblastoma patients.

IF 2.4 Q2 CLINICAL NEUROLOGY

Neuro-oncology practice Pub Date : 2023-04-01 DOI:10.1093/nop/npac070

Matthew Torre, Patrick Y Wen, J Bryan Iorgulescu

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引用次数: 1

Abstract

Background: Glioblastoma patients with hypermethylation of the O⁶-methylguanine-methyltransferase (MGMT) gene promoter have significantly improved survival when treated with temozolomide compared to patients with unmethylation of the MGMT promoter. However, the prognostic and predictive significance of partial MGMT promoter methylation is unclear.

Methods: The National Cancer Database was queried for patients newly diagnosed in 2018 with histopathologically confirmed isocitrate dehydrogenase (IDH)-wildtype glioblastoma. The overall survival (OS) associated with MGMT promoter methylation status was assessed using multivariable Cox regression with Bonferroni correction for multiple testing (P < .008 was significant).

Results: Three thousand eight hundred twenty-five newly diagnosed IDH-wildtype glioblastoma patients were identified. The MGMT promoter was unmethylated in 58.7% (n = 2245), partially methylated in 4.8% (n = 183), hypermethylated in 3.5% (n = 133), and methylated not otherwise specified (NOS; likely consisting predominantly of hypermethylated cases) in 33.0% (n = 1264) of cases. Among patients that received first-line single-agent chemotherapy (ie likely temozolomide), compared to partial methylation (referent), MGMT promoter unmethylation was associated with worse OS (hazard ratio [HR] 1.94; 95% confidence interval [95 CI]: 1.54-2.44; P < .001) in multivariable Cox regression adjusted for major prognostic confounders. In contrast, a significant OS difference was not observed between partially methylated promoters and either hypermethylated (HR 1.02; 95 CI: 0.72-1.46; P = .90) or methylated NOS (HR 0.99; 95 CI: 0.78-1.26; P = .93) promoters. Among IDH-wildtype glioblastoma patients who did not receive first-line chemotherapy, MGMT promoter methylation status was not associated with significant differences in OS (P = 0.39-0.83).

Conclusions: Compared to MGMT promoter unmethylation, partial methylation was predictive of improved OS among IDH-wildtype glioblastoma patients treated with first-line single-agent chemotherapy-supporting the use of temozolomide therapy in these patients.

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MGMT启动子部分甲基化对idh野生型胶质母细胞瘤患者的预测价值。

背景:与MGMT启动子未甲基化的患者相比，使用替莫唑胺治疗o6 -甲基鸟嘌呤-甲基转移酶(MGMT)基因启动子高甲基化的胶质母细胞瘤患者的生存率显著提高。然而，部分MGMT启动子甲基化的预后和预测意义尚不清楚。方法:查询国家癌症数据库2018年新诊断的组织病理学证实的异柠檬酸脱氢酶(IDH)野生型胶质母细胞瘤患者。使用多变量Cox回归评估与MGMT启动子甲基化状态相关的总生存期(OS)，并对多重测试进行Bonferroni校正(P < 0.008具有显著性)。结果:新诊断的idh野生型胶质母细胞瘤患者共3825例。MGMT启动子未甲基化的发生率为58.7% (n = 2245)，部分甲基化的发生率为4.8% (n = 183)，高甲基化的发生率为3.5% (n = 133)，其他未甲基化的发生率为NOS;可能主要由高甲基化病例组成，占33.0% (n = 1264)的病例。在接受一线单药化疗(如替莫唑胺)的患者中，与部分甲基化(参比)相比，MGMT启动子未甲基化与更差的OS相关(风险比[HR] 1.94;95%置信区间[95 CI]: 1.54-2.44;P < 0.001)，校正了主要预后混杂因素的多变量Cox回归。相比之下，部分甲基化启动子和任何一种高甲基化启动子之间没有观察到显著的OS差异(HR 1.02;95 ci: 0.72-1.46;P = 0.90)或甲基化NOS (HR 0.99;95 ci: 0.78-1.26;P = .93)启动子。在未接受一线化疗的idh野生型胶质母细胞瘤患者中，MGMT启动子甲基化状态与OS的显着差异无关(P = 0.39-0.83)。结论:与MGMT启动子未甲基化相比，在接受一线单药化疗的idh野生型胶质母细胞瘤患者中，部分甲基化可预测OS的改善，支持在这些患者中使用替莫唑胺治疗。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Neuro-oncology practice CLINICAL NEUROLOGY-

CiteScore

5.30

自引率

11.10%

发文量

期刊介绍： Neuro-Oncology Practice focuses on the clinical aspects of the subspecialty for practicing clinicians and healthcare specialists from a variety of disciplines including physicians, nurses, physical/occupational therapists, neuropsychologists, and palliative care specialists, who have focused their careers on clinical patient care and who want to apply the latest treatment advances to their practice. These include: Applying new trial results to improve standards of patient care Translating scientific advances such as tumor molecular profiling and advanced imaging into clinical treatment decision making and personalized brain tumor therapies Raising awareness of basic, translational and clinical research in areas of symptom management, survivorship, neurocognitive function, end of life issues and caregiving