Therapeutic pathomorphosis of stage IB–IIA cervical cancer cells after various regimens of preoperative HDR brachytherapy

Abstract

Background. Despite of the constant improvement of existing treatment methods, involving the latest technologies into the treatment programs, the results of the treatment remain unsatisfactory. It is impossible to prevent the dissemination of tumor cells during surgery, which cause the tumor recurrence. Even in case of early stage cervical cancer, after only adequate conducted surgery, the relapse-rate is 20–30%, and the five-year survival rate is 40–60%. The aim of the work is to evaluate the effectiveness of different doses of preoperative HDR-brachytherapy in cervical cancer patients stage IB–IIA, based on the data of therapeutic pathomorphosis of the tumor. Materials and methods. There was investigated the structural and functional status of cells of squamous cell cervical cancer stage IB–IIA in two treatment schemes. According to the first scheme, there was conducted two sessions of brachytherapy with a single dose of 5 Gy with an interval of 7 days, up to the common dose of 10 Gy (5+5 Gy). According to another scheme, the single dose at the first session was 7 Gy, at the second session – 5 Gy, total dose was 12 Gy. The comparison group included primary patients with squamous cell cervical cancer and patients, who received fractional EBRT and EBRT + LDR-brachytherapy, total dose of 20 Gy and 40 Gy respectively. The morphofunctional status of cancer cells was investigated using standard electron microscopy methods. In all studied groups, there was detected the frequency of tumors samples, which contain large cells, the frequency of tumors with the presence of mitoses, and frequency of cases with significant therapeutic pathomorphosis. The obtained data was processed by the application of non-parametric statistical methods, using the «Biostat» software, and non-parametric criterion of the most plausible reliability assessment for small selections. Results. It is established that 26.9% of primary patients with cervical cancer had tumors with large cancer cells. After fractional irradiation with total doses of 20 and 40 Gy, an increase in the frequency of cases of tumors with such cells to 37.5 and 50.0%, respectively, was observed although these changes were unreliable in comparison with the control group of primary patients. However, after the first session of HDR-brachytherapy in a single dose of 5 or 7 Gy, in contrast to the indicators in the group of primary patients, there was a sharp and reliable increase in the frequency of tumors cases with large cancer cells up to 83.3% and 90%, respectively. At the same time, pronounced therapeutic pathomorphosis did not exceed 10.0–16.7% of cases. The second session of HDR brachytherapy at a dose of 5 Gy (total doses of 10 and 12 Gy) led both to a decrease in the frequency of tumors with large cancer cells to the level of control values (20 and 27.3%), and to a dose-dependent increase in the indicators of pronounced therapeutic pathomorphosis ( 40 and 70% respectively). Conclusions. There has been established that HDR-brachytherapy with the initial single dose of 5 or 7 Gy initiate a significant reaction, when the primary population of cancer cells is replaced by others, where prevail their large forms, which may be giant polyploid cancer cells. After the second session of brachytherapy of 5 Gy, the proportion of tumors, which are composed of large cells, significantly decreases simultaneously with the increase of significant therapeutic pathomorphosis in the cellpopulation of cervical cancer. The application of HDR-brachytherapy of 7 Gy at the first session will lead to the higher efficacy of the proposed scheme of the preoperative irradiation in cervical cancer patients stages IB–IIA, when the therapeutic pathomorphosis reaches 70%, when at the same time with a total dose of brachytherapy of 10 Gy, therapeutic pathomorphosis is only 40%.