老年胶质母细胞瘤患者MGMT甲基化状态对放化疗及预后影响

Effect of MGMT gene methylation status on chemoradiotherapy and prognosis in elderly patients with glioblastoma

目的探讨O-6-甲基鸟嘌呤-DNA甲基转移酶(MGMT)基因启动子甲基化状态对老年胶质母细胞瘤(GBM)治疗及预后的影响。方法回顾性分析天津市环湖医院2012—2018年收治的65例新诊断的老年GBM患者的临床资料。所有患者均在术后接受了调强放疗,49例患者接受了替莫唑胺单药化疗。依据MGMT启动子甲基化状态分为MGMT(+)组和MGMT(-)组,比较两组生存情况。采用Kaplan-Meier法生存分析并应用log-rank法行单因素预后分析,Cox模型多因素预后分析。结果全组中位总生存期为18.0个月。MGMT(+)组、MGMT(-)组中位总生存期分别为27个、15.3个月。单因素分析显示肿瘤数目、MGMT基因启动子甲基化、同步放化疗与预后相关(P=0.029、P=0.001、P<0.001)。多因素分析显示肿瘤数目、同步放化疗是影响老年GBM患者预后因素(P=0.037、P=0.004)。MGMT(+)组中同步放化疗与单纯放疗患者中位总生存期分别为27.0个月和12.0个月(P=0.040);MGMT(-)组中同步放化疗与单纯放疗患者中位总生存期分别为17.0个月和10.0个月(P=0.122)。结论 MGMT启动子甲基化状态与老年GBM患者的预后密切相关,在常规分割放疗的基础上联合替莫唑胺同步及序贯化疗可能带来进一步生存获益。

Objective To investigate the effect of O-6-methylguananine-DNA methyltransferase(MGMT)gene promoter methylation status on the treatment and prognosis of elderly patients newly-diagnosed with glioblastoma(GBM).Methods Clinical data of 65 newly-diagnosed GBM patients admitted to Tianjin Huanhu Hospital from January 2012 to December 2018 were retrospectively analyzed.All patients received intensity-modulated radiotherapy after surgery and 49 patients received temozolomide(TMZ)monotherapy.All patients were divided into the MGMT(+)group and MGMT(-)group according to the methylation status of MGMT promoter.Kaplan-Meier method and log-rank test were used for univariate survival analysis,and Cox regression model was used for multivariate prognostic analysis.Results The median overall survival(OS)for all patients was 18.0 months.The median OS was 27.0 months and 15.3 months in the MGMT(+)group and MGMT(-)group,respectively.Univariate analysis revealed that tumor number,MGMT promoter methylation,postoperative concurrent chemoradiotherapy were significantly related to clinical prognosis(P=0.029,P=0.001 and P<0.001).In multivariate analysis,tumor number and postoperative concurrent chemoradiotherapy were identified as significant prognostic factors for OS(P=0.037,P=0.004).In the MGMT(+)group,the median OS was 27.0 months for patients receiving concurrent chemoradiotherapy and 12.0 months for radiotherapy alone(P=0.040).In the MGMT(-)group,the median OS was 17.0 months for concurrent chemoradiotherapy patients and 10.0 months for radiotherapy alone(P=0.122).Conclusions MGMT promoter methylation status is significantly associated with longer OS in elderly GBM patients.Conventional fractional radiotherapy combined with concurrent and sequential TMZ chemotherapy probably yields better survival benefits.