Stereotactic radiosurgery of radioresistant glioblastomas. The ways of overcoming radioresistance of hypoxic tumors

Abstract

Background. Taking into account high degree of resistance of glioblastoma to radiation therapy, and also low overall survival rates of patients, it is necessary to develop improved methods of treating this pathology, in particular, complex combined treatment with radiation therapy and radiosensitizers. Purpose – to assess the effectiveness of radiosensitization of hypoxic tumors in radiosurgical treatment of glioblastomas; to increase non-recurrent and overall survival rate of patients. Materials and methods. Stereotactic radiosurgery (SRS) of glioblastoma was performed in 106 patients (average age – 53 years), 66 males (62,26%) and 40 females (37,73%). The average dose was 18 Gy in a single-fraction SRS, and 32 Gy (7 Gy per fraction) in multi-fraction SRS. The average volume tumor was 29 cm3 . The treatment group consisted of 66 patients who underwent SRS with radiosensitization. 40 patients made up the control group and underwent SRS without radiosensitization. Results. Median overall survival (MOS) was 20 months in the group with radiosensitization, whereas in the control group it was 12 months. 10-month recurrence-free period after radiosurgery was observed in 95,4% of the patients of the group with radiosensitization and in 70,6% of the patients of the control group. MOS after SRS was similar between the patients with wild-type IDH tumors and patients with tumors with IDH mutation (10,0 months and 11,0 months respectively), and also between the patients with MGMT-methylated tumors and patients with MGMT-nonmethylated tumors (11,2 and 10,2 months respectively). Among all the treated patients, in 20 of them (16,6%) side radiation effects after SRS were observed, and in 9 patients (7,5%) radiation necrosis developed in 3 to 16 months after SRS. The signs of moderate toxicity in the form of vomiting were observed in 6,6% of the patients of the subgroup with metronidazole. There were no signs of toxicity in the subgroup with nimorazole. Conclusions. Radiosensitization improves rates of overall survival by 53,3% and recurrence-free survival by 24,8 % in performing SRS of hypoxic radioresistant glioblastomas. Nimorazole and metronidazole are powerful radiosensitizers which increase radiosensitivity of tumor cells through enhancing oxygen saturation of hypoxic cells. In order to determine indications for performing SRS with radiosensitization and periods for performing an SRS session we must take into consideration the result of an oxygen test (level of oxygen saturation of the tumor), the peak of signal intensity in the zone of active tumor growth and the peak of saturation of the whole tumor volume.