Palii M. Improvement of radiation therapy for patients with prostate cancer based on clinical, laboratory and molecular biological parameters

The aim of our study was to improve the effectiveness of radiotherapy taking into account the clinical, laboratory and molecular biological parameters of the patient. The study included clinical material from patients with different variants of prostate cancer (РС). To perform our work, we used general clinical methods such as physical examination, determination of GS, disease stage, staging group, Gleason pattern, risk group, type and prevalence of tumor metastasis, assessment of patient survival, and radiological methods such as sonography, radiography, computed tomography, and magnetic resonance imaging. Histological, biochemical, immunochemical, and enzyme-linked immunosorbent assays included assessment of the cellular variant of the tumor, blood tests for AR and GH activity, determination of PSA, TS, LT levels, ARR activity, and ISF1 content, and expression of oncogenic and tumor suppressor microRNAs. Statistical methods included variational, non-parametric, correlation, single and multivariate analysis of variance, and computerized analysis. The theoretical and practical results are to increase the effectiveness of treatment of patients with PCa by developing and implementing an integrated approach with radiation therapy. Based on the study of the expression level of tissue-specific oncogenic and tumor suppressor microRNAs and tumor markers, it became possible to predict the aggressiveness of tumor potential and improve the quality of control over treatment measures. The study found that prostate tissue is characterized by a significant decrease in the expression of microRNA-100 and an increase in the expression of microRNA-34a and -21 by 28.7% and 51.1%, respectively. A direct dependence of microRNA-34a expression in prostate tissue on patient age was demonstrated, while the expression levels of microRNA-145 and microRNA-100 were inversely dependent, and microRNA-34a expression was directly correlated with Gleason score. The developed algorithm, which included radiotherapy in the early postoperative period with the sum of Gleason grades ≥7, allowed to increase the 5-year survival rate of patients and to prolong life expectancy by 1.5 times. The detected correlations between the level of expression of tumor-associated microRNAs -21, -34a and -100 and such indicators of PCa malignancy as the degree of tumor spread, receptor status and proliferative activity of tumors in the presence of PCa recurrence indicate the potential use of these microRNAs to assess the aggressiveness of the tumor process and to prescribe personalized treatment tactics. Practical recommendations are to develop an informational algorithm for the effective use of radiotherapy in different variants of the clinical course of PCa. The prognostic criteria characterizing the characteristics of the organism and the tumor process and influencing the course of the disease were determined. The proposed approaches in the treatment of patients with prostate cancer made it possible to reduce the percentage of recurrence and distant metastasis and thereby significantly improve the immediate and long-term results of treatment. For the first time, the level of tumor development markers and the degree of expression of a number of microRNAs were comprehensively determined in different variants of PCa course to predict the aggressiveness of the disease. Their prognostic significance was proved, the factors influencing the development of complications associated with radiation therapy were identified, and the dependence of the frequency and nature of tumor recurrence, patient survival, and the dynamics of tumor markers and microRNAs on the method of radiation therapy was established. The materials of the dissertation have been implemented in the practice of the SNE "National Cancer Institute" of the Ministry of Health of Ukraine, a number of oncological medical institutions of Ukraine, such as the MNCE "Kyiv City Clinical Oncology Center", ME "Rivne Regional Antitumor Center" Rivne regional council, Medical Center "Universal Clinic "Oberig" (LLC "CAPITAL"). The results of the work belong to the medical field of knowledge, namely oncology.