Department of Neurosurgery, Computational Neuroscience Outcomes Center, Brigham and Women's Hospital, Boston, MA, USA.
Harvard Medical School, Boston, MA, USA.
J Neurooncol. 2022 May;158(1):111-116. doi: 10.1007/s11060-022-04016-5. Epub 2022 Apr 26.
Gliosarcoma is an uncommon glioblastoma subtype, for which MGMT promoter methylation's relationship with response to temozolomide chemotherapy is unclear. We therefore examined this question using a national cohort.
The National Cancer Database was queried for patients histopathologically diagnosed with gliosarcoma between 2010 and 2019. The associations between MGMT promoter methylation, first-line single-agent chemotherapy-presumed to be temozolomide herein-and overall survival (OS) were examined using log-rank tests and Cox regression, with correction for multiple testing (p < 0.01 was significant).
580 newly-diagnosed gliosarcoma patients with MGMT status were available, among whom 33.6% were MGMT promoter methylated. Median OS for gliosarcoma patients that received standard-of-care temozolomide and radiotherapy was 12.1 months (99% confidence interval [CI] 10.8-15.1) for MGMT promoter unmethylated and 21.4 months (99% CI 15.4-26.2) for MGMT promoter methylated gliosarcomas (p = 0.003). In multivariable analysis of gliosarcoma patients-which included the potential confounders of age, sex, maximal tumor size, extent of resection, and radiotherapy-receipt of temozolomide was associated with improved OS in both MGMT promoter methylated (hazard ratio [HR] 0.23 vs. no temozolomide, 99% CI 0.11-0.47, p < 0.001) and unmethylated (HR 0.50 vs. no temozolomide, 99% CI 0.29-0.89, p = 0.002) gliosarcomas. MGMT promoter methylation was associated with improved OS among temozolomide-treated gliosarcoma patients (p < 0.001), but not in patients who did not receive chemotherapy (p = 0.35).
In a national analysis of gliosarcoma patients, temozolomide was associated with prolonged OS irrespective of MGMT status. These results provide support for the current practice of trimodal therapy for gliosarcoma.
神经胶母肉瘤是一种罕见的胶质母细胞瘤亚型，其 MGMT 启动子甲基化与替莫唑胺化疗反应的关系尚不清楚。因此，我们使用一个全国性队列对此进行了研究。
从 2010 年至 2019 年，对国家癌症数据库中经组织病理学诊断为神经胶母肉瘤的患者进行了查询。使用对数秩检验和 Cox 回归，对 MGMT 启动子甲基化与一线单药化疗（在此假定为替莫唑胺）和总生存期（OS）之间的关系进行了检查，并进行了多次检验校正（p<0.01 为显著）。
共有 580 名新诊断的神经胶母肉瘤患者可获得 MGMT 状态，其中 33.6%的患者 MGMT 启动子甲基化。接受标准替莫唑胺和放疗的神经胶母肉瘤患者的中位 OS 为：MGMT 启动子未甲基化的患者为 12.1 个月（99%置信区间 [CI] 10.8-15.1），MGMT 启动子甲基化的患者为 21.4 个月（99%CI 15.4-26.2）（p=0.003）。在包括年龄、性别、最大肿瘤大小、切除范围和放疗等潜在混杂因素的神经胶母肉瘤患者多变量分析中，接受替莫唑胺治疗与 MGMT 启动子甲基化（风险比 [HR] 0.23 比无替莫唑胺，99%CI 0.11-0.47，p<0.001）和未甲基化（HR 0.50 比无替莫唑胺，99%CI 0.29-0.89，p=0.002）神经胶母肉瘤患者的 OS 改善相关。MGMT 启动子甲基化与替莫唑胺治疗的神经胶母肉瘤患者的 OS 改善相关（p<0.001），但与未接受化疗的患者无关（p=0.35）。
在一项针对神经胶母肉瘤患者的全国性分析中，替莫唑胺与延长 OS 相关，与 MGMT 状态无关。这些结果为神经胶母肉瘤的目前三模态治疗提供了支持。
