The role of concomitant and adjuvant use of temozolomide in the primary radiation treatment of glioblastoma

Objective. To study the effect of temozolomide on subsequent overall survival, depending on the variant of its use at various stages of primary treatment of glioblastoma. Material and methods. According to the 2021 WHO classification criteria, 178 patients with grade 4 glioma were diagnosed with glioblastoma (GBM) without a mutation in the IDH1 gene based on molecular biological data. Of the 178 patients, 134 (75.3%) had radiotherapy with temozolomide (TMZ) at a dose of 75 mg/m2 (TMZ/RT), 44 had radiation therapy without TMZ (RT; 24.7%). Subsequently, standard adjuvant drug therapy of the 1st line with TMZ at a dose of 200 mg/m2 was included in the treatment program in 158 patients (88.8%). Results. There was no significant increase in survival when using TMZ on the background of radiation therapy. The median overall survival in the TMZ/RT and RT groups was 20.08 (95% Cl: 16.2—23.8) and 17.97 months (95% Cl: 13.6—22.4), respectively (p=0.148). However, 21.5% and 4.5% of patients in the study groups survived the 60-month period. Only in the absence of rapid early progression (NonREP), the TMZ/RT program has significant advantages compared with radiation therapy alone and subsequent adjuvant TMZ, the median overall survival was 26.58 months versus 20.99 months (p=0.012). With REP, the differences in survival in the TMZ/RT and RT groups lose their significance, the medians are 14.75 and 17.22 months, respectively (p=0.949). For overall survival, the isoeffective dose level (<59.5≥Gy), calculated using the linear-quadratic model with a/β=7.5 (OR=0.220; p<0.001) and second-line therapy with bevacizumab (OR=0.464; p<0.001) have a greater specific weight. The resection volume ≥70% with microsurgical intervention (OR=0.437; p=0.001), the use of TMZ in the adjuvant regimen (OR=0.532; p=0.046) are statistically significant in terms of overall survival, in contrast to TMZ against the background of RT (OR=0.737; p=0.119). Conclusion. According to our study, the role of temozolomide in combination with radiation therapy is somewhat exaggerated; the adjuvant regimen of taking an alkylating agent is more significant in the primary treatment program for GBM. A protocol with concomitant and sequential use of temozolomide on the background of radiation therapy should remain the standard in the treatment of glioblastomas.