Background. Application of the most advanced radiation technologies of brachytherapy featuring the high dose rate sources i.e. 60Co and 192Ir within contemporary management protocols for gynecological cancer provides maximum dose distribution in the clinical target along with minimal radiation exposure on surrounding organs and tissues. It involves irradiation of large spaces with delivery of high therapeutic doses at the tolerance bound of «critical» organs (bladder, rectum) and tissues. Thus minimization of the early and late radiation complications, life span extent and quality of life increase remain just the issues in contemporary radiation oncology requiring therefore the elaboration of radiobiological criteria along with substantiation of physiсо-engineering properties of the radiation sources. Taking into account the basic radiobiological patterns will ensure a definitive further progress in the field of radiation oncology. Objective: to study and compare the biological effects of 192Ir with the effects of the reference gamma radiation 60Co and increase the effectiveness of brachytherapy using a 192Ir source. Materials and methods. Radiobiological dosimetry on the basis of a test system of peripheral blood lymphocytes from the gynecological cancer patients with subsequent cytogenetic analysis of radiation-induced chromosome aberrations was performed to study and compare the biological effects of 192Ir and reference 60Со γ-radiation, and to enhance the efficiency of 192Ir brachytherapy. Results. Radiation markers, i.e. dicentric chromosomes with an accompanying paired fragment prevailed in the spectrum of radiation-induced damage. Variability of individual cytogenetic parameters of peripheral lymphocytes upon the first fraction of irradiation at the same dose of 5 Gy indicated an individual sensitivity of patients to the 192Ir γ-irradiation. Comprehensive conservative treatment with adjuvant radiotherapy was applied to the patients (n = 98) having got secondary vaginal cancer stage II–III, T2-3N0-1M0. The high dose-rate (HDR) brachytherapy using 192Ir radiation sources was applied in the main study group (n = 37), HDR brachytherapy using 60Co radiation sources was applied in the control group (n = 35). Conclusion. The HDR brachytherapy with 192Ir and 60Co sources on the up-to-date technology intensive devices provides a high accuracy of dose distributions when irradiating the malignant neoplasms with minimized radiation exposure to the «critical» tissues. Treatment results are improved therefore. The use of 192Ir radiation sources compared with 60Co ones resulted in an increased throughput of treatment, enhanced tumor regression, and reduced incidence of radiation effects on the critical organs. Currently we perform the radiobiological studies on somatic cells from cancer patients at the genetic, biochemical, biophysical, and cytological levels in order to receive a biological indication of radiation damage under the impact of 192Ir isotope. Continuation of clinical trials with radiobiological support will provide an opportunity to predict the early and late radiation complications and thus to provide a personalized approach in brachytherapy of cancer patients using the 192Ir sources of γ-rays. Key words: HDR brachytherapy, 192Ir and 60Co high dose rate sources.
The aim: to examine the radiosensitivity of chromosomes of T-lymphocytes in the blood of primary patients with endometrial cancer depending on the radiation dose. It was expected that the investigations would reveal a cytogenetic parameter as a predictor of radiosensitivity in non-malignant cells of patients exposed to curative irradiation. Materials and methods. Blood samples from 20 primary patients and 30 conditionally healthy donors were examined. Peripheral blood T-lymphocytes culture test system with metaphase chromosome aberration analysis was used. X-ray test-irradiation was performed at G0-stage of the cell cycle in the dose range of 0.5–3.0 Gy. Results. It was shown that the spontaneous level of chromosome aberrations in lymphocytes of primary patients before anti-tumour therapy is 7,82±0,33 aberrations/100 metaphases. This is more than 2-fold higher than the upper limit of average population index and approximately 6-fold higher than the data of own control. In our study during X-ray irradiation of cells cultures of patients, it was found for the first time that the total frequency of radiation-induced chromosome aberrations obeys the classical linear quadratic dose dependence with a predominance of linear component values; the frequency of radiation markers – also linear quadratic dose dependence, but with a predominance of quadratic component. Conclusions. High specificity of T-lymphocyte chromosomes to exposure to ionizing radiation as well as strict dependence of chromosome aberration yield on exposure dose justify their use as predictors of radiosensitivity of healthy cells from the tumour environment. The revealed dependences of induction of chromosomal damage in T-lymphocytes of patients with endometrial cancer prove the need for a personalized approach to plan the course of radiation therapy
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.
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