Influence of clinical and molecular genetic characteristics on the first relapse-free period in patients with glioblastoma in the era of modern chemoradiotherapy
Authors: Sklyar S. S. , Matsko M. V. 
Published: September 2022

Introduction. Due to the active research of the molecular and genetic features of glioblastoma, the performance of the biological processes occurring in tumor cells has become more distinct. In the modern scientific literature, the number of scientific studies is growing, which emphasizes the priority importance of the genetic status of the tumor in the prognosis of the disease.

Purpose statement. To study the influence of clinical and molecular genetic factors on the median of the first relapse-free period.

Materials and methods. The first progression-free survival (PFS) was analyzed in 30 patients aged 28 to 81 years with glioblastoma. The diagnosis was established in accordance with the WHO classification of CNS tumors in 2021. After the first operation, all patients underwent a course of radiation therapy (LT) (60Gr) and chemotherapy with temozolomide (2–18 cycles). In each case, clinical parameters such as the patient’s age, functional status on the Karnovsky scale both before and after surgery, features of the neuroimaging picture (prevalence of the tumor process, localization, tumor volume), treatment (degree of tumor resection, radiation therapy with or without temozolomide and the number of cycles of chemotherapy) and molecular genetic parameters of tumor (determination of the mRNA expression level of genes: MGMT, VEGF, PDGFRA, β-tubulin III, ERCC-1, TOP2A) were studied.

Results. Of all the studied clinical parameters, only the postoperative functional status on the Karnovsky scale (p = 0.001) influenced the median of PFS. The median of the first PFS was not affected by such radiological characteristics as involvement of basal structures of the brain in the tumor process (p = 0.9), the side of the lesion (p = 0.67), the prevalence of the tumor process (p = 0.6) and the volume of the tumor (p = 0.52). The duration of the first PFS with statistical reliability was higher in the group of patients after subtotal resection of the tumor (14.9 months; p ³ 0.05). The median of the first PFS was influenced by the presence of a mutation in the IDH1 gene (22.5 vs 11.5 months) and the expression level of the MGMT gene (p = 0.036). Total tumor resection increases the first BRP only at a high level of MGMT gene expression, although without statistically significant differences (7.6 vs 2.7 months; p = 0.6). The addition of temozolomide to radiation therapy (75 mg/m2, orally, daily) led to an increase in the first relapse-free period by more than 6.9 months, but only in patients with low expression of the MGMT gene in the tumor.

Conclusion. In the conditions of standard patient therapy (surgical removal of the tumor, chemoradiotherapy followed by adjuvant therapy with temozolomide), the first PFS primarily depends on the molecular genetic characteristics of the tumor, namely, the presence of a mutation in the IDH1 gene and the level of MGMT in the tumor. For patients with an expected lack of response to therapy (i.e., a high level of MGMT gene activity), the role of other factors increases, and first of all, the volume of cytoreduction.