高剂量放疗联合非甲基化 O(6)-甲基鸟嘌呤-DNA 甲基转移酶治疗新诊断的低级别胶质瘤。

High-dose radiotherapy in newly diagnosed low-grade gliomas with nonmethylated O(6)-methylguanine-DNA methyltransferase.

机构信息

Department of Radiation Oncology, Beijing Tiantan Hospital, Capital Medical University, No. 119 South Fourth Ring West Road, Fengtai District, Beijing, 100070, People's Republic of China.

Department of Molecular Neuropathology, Beijing Neurosurgical Institute, Capital Medical University, Beijing, 100070, People's Republic of China.

出版信息

Radiat Oncol. 2021 Aug 19;16(1):157. doi: 10.1186/s13014-021-01878-3.

DOI:10.1186/s13014-021-01878-3

PMID:34412650

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8375106/

Abstract

BACKGROUND

Patients with low-grade gliomas (LGGs) harboring O-methylguanine-DNA methyltransferase promoter nonmethylation (MGMT-non-pM) have a particularly short survival and are great resistance to chemotherapy. The objective of this study was to assess the efficacy of high-dose radiotherapy (RT) for LGGs with MGMT-non-pM.

METHODS

268 patients with newly diagnosed adult supratentorial LGGs from the multicenter Chinese Glioma Cooperative Group (CGCG) received postoperative RT during 2005-2018. MGMT promoter methylation analysis was conducted by pyrosequencing in all patients. Univariate and multivariate analysis were performed using the Cox regression to determine the prognostic factors for overall survival (OS) and progression-free survival (PFS). RT dose-response on MGMT status defined subtypes was analyzed.

RESULTS

On univariate analysis, the following were statistically significant favorable factors for both PFS and OS: oligodendrogliomas(p = 0.002 and p = 0.005), high-dose RT (> 54 Gy) (p = 0.021 and p = 0.029) and 1p/19q codeletion (p < 0.001 and p = 0.001). On multivariate analysis, RT dose (> 54 Gy vs. ≤ 54 Gy) and IDH mutation were independently prognostic markers for OS (HR, 0.47; 95%CI, 0.22-0.98; p = 0.045; and HR, 0.44; 95%CI, 0.21-0.96; p = 0.038, respectively) and PFS (HR, 0.48; 95%CI, 0.26-0.90; p = 0.022; and HR, 0.51; 95%CI, 0.26-0.98; p = 0.044, respectively). High-dose RT was associated with longer OS (HR, 0.56; 95%CI, 0.32-0.96; p = 0.036) and PFS (HR, 0.58; 95%CI, 0.35-0.96; p = 0.033) than low-dose RT in MGMT-non-pM subtype. In contrast, no significant difference in either OS (p = 0.240) or PFS (p = 0.395) was observed with high-dose RT in the MGMT-pM subtype.

CONCLUSIONS

High-dose RT (> 54 Gy) is an independently protective factor for LGGs and is associated with improved survival in patients with MGMT-non-pM.

摘要

背景

低级别胶质瘤（LGG）患者的 O6-甲基鸟嘌呤-DNA 甲基转移酶启动子非甲基化（MGMT-非 pM）生存期特别短，对化疗有很强的抵抗力。本研究旨在评估高剂量放疗（RT）对 MGMT-非 pM 的 LGG 的疗效。

方法

2005 年至 2018 年间，来自中国胶质瘤协作组（CGCG）的 268 名新诊断的成人幕上 LGG 患者接受了术后 RT。对所有患者进行焦磷酸测序分析 MGMT 启动子甲基化情况。采用 Cox 回归进行单因素和多因素分析，确定总生存期（OS）和无进展生存期（PFS）的预后因素。分析 RT 剂量对 MGMT 状态定义亚型的反应。

结果

单因素分析显示，以下因素对 PFS 和 OS 均有统计学意义：少突胶质细胞瘤（p=0.002 和 p=0.005）、高剂量 RT（>54 Gy）（p=0.021 和 p=0.029）和 1p/19q 共缺失（p<0.001 和 p=0.001）。多因素分析显示，RT 剂量（>54 Gy 与≤54 Gy）和 IDH 突变是 OS（HR，0.47；95%CI，0.22-0.98；p=0.045；和 HR，0.44；95%CI，0.21-0.96；p=0.038）和 PFS（HR，0.48；95%CI，0.26-0.90；p=0.022；和 HR，0.51；95%CI，0.26-0.98；p=0.044）的独立预后标志物。高剂量 RT 与低剂量 RT 相比，在 MGMT-非 pM 亚组中，OS（HR，0.56；95%CI，0.32-0.96；p=0.036）和 PFS（HR，0.58；95%CI，0.35-0.96；p=0.033）更长。相反，在 MGMT-pM 亚组中，高剂量 RT 对 OS（p=0.240）或 PFS（p=0.395）均无显著影响。