Therapeutic irradiation in the management of gynecological cancer and predictability of radiation-induced complications

Abstract

Background. Today, applying radiotherapy (RT) in management of both primary and secondary vaginal cancer (SVC) take pride of place in the spectrum of specialized treatments for cancer patients. Secondary vaginal tumors are more common (6% to 33%) in cervical cancer (CC) patients, while in uterine cancer (UC) occur in 8–10% of cases treated either surgically, or by means of radiotherapy, otherwise via a combination approach. Therefore, RT is administered in about 80% of primary vaginal cancer and particularly SVC patients. When using even the most advanced radiotherapy equipment implying the cutting-edge technologies, there is a risk of radiation-induced complications in healthy organs and tissues that fall under the irradiation area. Keeping in mind the key radiobiological paradigms makes it possible not only to predict the probability of tumor resorption upon radiation exposure, but also to assess the biological effectiveness of absorbed dose, as well as the risk of late radiation complications. Purpose – to enhance the effectiveness and assess the toxicity of SVC RT via ascertaining BT (brachytherapy) most suitable techniques depending on the type of ionizing radiation and exploring predictability of radiation-induced complications in terms of biomolecular cell properties. Materials and methods. Clinical study was performed at the National Cancer Institute Clinic (Radiation Oncology Department), using a high-energy BT unit with a HDR 192Ir source. The SVC patients (n = 106) were treated according to the developed BT methods. They had been pretreated for the CC (n = 65) with squamous cell carcinoma histologically diagnosed in the most cases or UC (n = 41) with histologically prevalent adenocarcinoma of a variable grade. Patients had a locally advanced pelvic tumor process with tumor staging II–III, T2-3N0-1M0. Along with clinical study the radiobiological research was conducted to count the apoptotic cells in both intact and irradiated peripheral blood lymphocytes (PBL), as well as the level of SH-groups of plasma proteins and peptides in gynecological cancer patients and healthy donors to predict the risk of radiation-induced complications. Results and discussion. Given the delayed effect of RT, the treatment effective- ness was analyzed immediately after RT session and also 3 months upon completion of the conservative therapy. Thus, positive tumor response upon three months of observation over time was registered in 67.9 ± 5.2% of patients in study group I, in 72.5 ± 6.9% in study group II, and in 51.3 ± 6.8% in comparison group. Hence the values in study groups were higher than in comparison group by 16.6% and 21.2% respectively. All patients tolerated BT satisfactorily. Neither general nor local rectum or bladder severe (above grade II) toxicities were noted both during treatment and over the next 3 months upon its completion in all the patients regardless of study group. Results obtained in radiobiological studies correlated with clinical and literature data. Conclusions. Decrease in manifestations of RT toxicity, namely of the ear- ly radiation reactions from interfacing critical organs was established in groups I and II vs comparison group I, especially in group I where a high- energy 192Ir source was used in the SBD irradiation mode of 3 Gy twice a week. The obtained results of the experimental study suggest that the content of SH-groups in blood plasma and the level of PBL apoptosis can be considered as additional predictive measures of radiosensitivity of non-malignant cells from the irradiated tumor environment.

Keywords

• secondary vaginal cancer
• high-dose rate (hdr) brachytherapy, 192ir and 60со high dose-rate sources
• radiosensitivity biomarkers
• peripheral blood lymphocytes
• apoptotic cells