The choice of radiotherapy dose fractionation regimen for grade 4 gliomas depending on the status of MGMT

Objective. To investigate the effect of two fractionation regimes on subsequent survival in patients with grade 4 gliomas, depending on the status of MGMT. Material and methods. MGMT status was evaluated in 134 patients: IDH1 mutation was found in 18 patients (13.4%; G4 astrocytoma), while the rest were diagnosed as G4 glioblastoma (GBM) without IDH1 mutation (86.6%). A total of 66 patients were treated with the prescribed dose of 2 Gy, and 68 patients were treated with 3 Gy. Results. Fatal outcome was recorded in 105 (78.4%) patients. Median overall survival in patients with MGMT promoter methylation was 32.5 months (95% Cl: 23.9—41.1), in the absence of methylation — 18.8 months (95% Cl: 16.9—20.7; p=0.007). In gliomas of grade 4 malignancy with MGMT (+), the median overall survival was 59.24 months (95% Cl: 34.6—83.9) with 3 Gy fractionation regimen and 23.75 months (95% Cl: 13.2—34.3; p=0.006) with 2 Gy regimen. For GBM, the reliability between fractionation regimens was maintained (p=0.037). In the absence of MGMT(-) promoter methylation, no differences were noted between the two radiotherapy programs; median overall survival was 20.01 (95% Cl: 17.4—22.6) and 17.22 (95% Cl: 13.2—21.2) months, respectively, for the 3/2 Gy regimens (p=0.731). Conclusion. When the MGMT promoter is methylated, fractionation with a prescribed dose of 3 Gy has a significant advantage over the standard radiation therapy program for both grade 4 gliomas and GBM. In patients without MGMT promoter methylation, more stringent approaches with increasing single dose do not improve treatment outcomes.