Background: Patients with low-grade gliomas (LGGs) harboring O6-methylguanine-DNA methyltransferase promoter nonmethyaltion (MGMT-non-pM) have a particularly short survival and are greatly 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: 269 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 multivariable analyses 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 = 0.017 and p = 0.023) and 1p/19q codeletion (p <0.001 and p = 0.001). On multivariable analyses, RT dose (> 54 Gy vs. ≤ 54 Gy) and IDH mutation were independently prognostic markers for OS (HR, 0.44; 95%CI, 0.21-0.92; p = 0.029; and HR, 0.43; 95%CI, 0.20-0.90; p = 0.025, respectively) and PFS (HR, 0.48; 95%CI, 0.27-0.90; p = 0.021; and HR, 0.52; 95%CI, 0.27-0.98; p = 0.044, respectively). High-dose RT was associated with longer OS (HR, 0.55; 95%CI, 0.32-0.93; p = 0.026) and PFS (HR, 0.57; 95%CI, 0.35-0.93; p = 0.026) 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 associated with improved survival in patients with MGMT-non-pM.