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影响胶质母细胞瘤患者免疫治疗生存结局的分子和临床变量:系统评价和荟萃分析。

Impact of molecular and clinical variables on survival outcome with immunotherapy for glioblastoma patients: A systematic review and meta-analysis.

机构信息

School of Medicine, Nankai University, Tianjin, China.

Department of Neurosurgery, First Medical Center of Chinese PLA General Hospital, Beijing, China.

出版信息

CNS Neurosci Ther. 2022 Oct;28(10):1476-1491. doi: 10.1111/cns.13915. Epub 2022 Jul 13.

Abstract

BACKGROUND

Given that only a subset of patients with glioblastoma multiforme (GBM) responds to immuno-oncology, this study aimed to assess the impact of multiple factors on GBM immunotherapy prognosis and investigate the potential predictors.

METHODS

A quantitative meta-analysis was conducted using the random-effects model. Several potential factors were also reviewed qualitatively.

RESULTS

A total of 39 clinical trials were included after screening 1317 papers. Patients with O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation [hazard ratio (HR) for overall survival (OS) = 2.30, p < 0.0001; HR for progression-free survival (PFS) = 2.10, p < 0.0001], gross total resection (HR for OS = 0.70, p = 0.02; HR for PFS = 0.56, p = 0.004), and no baseline steroid use (HR for OS = 0.52, p = 0.0002; HR for PFS = 0.61, p = 0.02) had a relatively significant favorable OS and PFS following immunotherapy. Patients with a Karnofsky Performance Status score < 80 (HR = 1.73, p = 0.0007) and undergoing two prior relapses (HR = 2.08, p = 0.003) were associated with worse OS. Age, gender, tumor programmed death-ligand 1 expression, and history of chemotherapy were not associated with survival outcomes. Notably, immunotherapy significantly improved the OS among patients undergoing two prior recurrences (HR = 0.40, p = 0.008) but not among patients in any other subgroups, as opposed to non-immunotherapy.

CONCLUSION

Several factors were associated with prognostic outcomes of GBM patients receiving immunotherapy; multiple recurrences might be a candidate predictor. More marker-driven prospective studies are warranted.

摘要

背景

鉴于胶质母细胞瘤(GBM)患者中只有一部分对免疫肿瘤学有反应,因此本研究旨在评估多种因素对 GBM 免疫治疗预后的影响,并探讨潜在的预测因素。

方法

使用随机效应模型进行定量荟萃分析。还定性地回顾了一些潜在的因素。

结果

经过筛选 1317 篇论文,共纳入 39 项临床试验。MGMT 启动子甲基化的患者(总生存期的 HR=2.30,p<0.0001;无进展生存期的 HR=2.10,p<0.0001)、大体全切除(总生存期的 HR=0.70,p=0.02;无进展生存期的 HR=0.56,p=0.004)和无基线类固醇使用的患者(总生存期的 HR=0.52,p=0.0002;无进展生存期的 HR=0.61,p=0.02)在接受免疫治疗后,OS 和 PFS 相对较好。卡氏功能状态评分<80(HR=1.73,p=0.0007)和经历两次复发的患者(HR=2.08,p=0.003)的 OS 较差。年龄、性别、肿瘤程序性死亡配体 1 表达和化疗史与生存结局无关。值得注意的是,与非免疫治疗相比,免疫治疗显著改善了经历两次复发的患者的 OS(HR=0.40,p=0.008),但对其他亚组患者无影响。

结论

多种因素与接受免疫治疗的 GBM 患者的预后结果相关;多次复发可能是一个候选预测因素。需要更多的标志物驱动的前瞻性研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3980/9437230/50ea1ce2621a/CNS-28-1476-g005.jpg

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