Problems of Radiation Medicine and Radiobiology

V. S. Ivankova¹, E. A. Domina², T. V. Khrulenko¹, L. M. Baranovska¹, O. O. Hrinchenko²

¹National Cancer Institute of the Ministry of Health of Ukraine, 33/43 Lomonosova St., Kyiv, 03022,
  Ukraine
²R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology, National Academy
  of Sciences of Ukraine, 45 Vasylkivska St., Kyiv, 03022, Ukraine

IRIDIUM-192 RADIOTHERAPY BENEFITS IN THE MANAGEMENT OF GYNECOLOGICAL TUMORS

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, T_2-3N_0-1M₀. 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.

Problems of Radiation Medicine and Radiobiology.
2020;25:569-578. doi: 10.33145/2304-8336-2020-25-569-578

full text

1. Eifel PJ, Berek JS, Markman MA. Cancer of the cervix, vagina, and vulva. In: De Vita VT Jr, Lawrence TS, Rosenberg SA. Cancer: Principles and Practice of Oncology. 9th ed. Philadelphia, Pa: Lippincott Williams & Wilkins; 2011. p. 1311-1344.
2. Ariga T, Toita T, Kasuya G, Nagai Y, Inamine M, Kudaka W, et al. External beam boost irradiation for clinically positive pelvic nodes in patients with uterine cervical cancer. J Radiat Res. 2013;54:690-696. doi: 10.1093/jrr/rrs138.
3. Ivankova VS, Domoina EA, Matviyevska LV, Khrulenko TV, Baranovska LM. [Use of iridium-192 in radiotherapy of vaginal cancer with radiobiological support]. Ukr Radiol J. 2019;27(2):97-102. Ukrainian.
4. Domina E, Philchenkov A, Dubrovska A. Individual response to ionizing radiation and personalized radiotherapy. Crit Rev Oncog. 2018;23(1-2):69-92. doi: 10.1615/CritRevOncog.2018026308.
5. Fedorenko ZP, Mykhailivych YuY, Gulak LO, et al., contributors; Kolesnik OO, chief editor. [Cancer in Ukraine 2017–2018. Incidence, mortality, performance indices of the oncology service]. Bul Nat Cancer Reg Ukr. 2019;20:1-104. Ukrainian.
6. Joiner M, Kogel A. Basic clinical radiobiology. 5th edn. Boca Raton, FL: CRC Press/Taylor & Francis Group; 2019. 350 p.
7. Domina EA, Ivankova VS. [Role of radiobiology in improving the methods of radiation therapy of cancer patients]. Ukr Radiol J. Annex. 2018;2:41-42. Ukrainian.
8. Domina EA. [Role of radiobiology research in radiotherapy development for cancer patients]. Radiol Bull. Inform.-analyt Bull. 2015;1–2(54–55):80-82. Russian.
9. Shulenina LV, Mykhailov VF, Rayeva NF. [MicroRNA in the blood of the prostate cancer patients as a possible indicator of early complications of radiotherapy]. Rad Biol Radioecol. 2017;57(6):598-607. Russian.
10. Domina EA. The dependence of dose-effects in human radiation cytogenetics. Probl Radiac Med Radiobiol. 2019;24:235-249.
11. Kim D, Wang-Chesebro A, Weinberg V, Pouliot J, Chen LM, Speight J, et al. High-dose rate brachytherapy using inverse planning simulated annealing for locoregionally advanced cervical cancer: a clinical report with 2-year follow-up. J Radiat Oncol Biol Phys. 2009;75(5):1329–1334. doi: 10.1016/j.ijrobp.2009.01.002.
12. Ivankova VS, Domina EA, Matviyevska LV, Khrulenko TV, Baranovska LM. [Peculiarities of brachytherapy of secondary vaginal cancer taking into account the radiobiological issues]. Ukr Radiol J. 2017;XXV(2):123-127. Ukrainian.
13. Salani R, Backes FJ, Fung MF, Holschneider CH, Parker LP, Bristow RE, Goff BA. Posttreatment surveillance and diagnosis of recurrence in women with gynecologic malignancies: Society of Gynecologic Oncologists recommendations. Am J Obstet Gynecol. 2011;204(6):466-478. URL: https://doi.org/10.1016/j.ajog.2011.03.008.
14. Kaprin AD, Galkin VN, Ivanov SA, Solodkiy VA, Titova VA. [Brachytherapy in treatment of vaginal cancer]. Biomed Photon. 2016;5(1):22-26. Russian.
15. Kravets OA, Morhov KYu, Novikova OV, Khohlova SV. [Clinical guidelines for the diagnosis and treatment of patients with vaginal cancer]. ONTz Bull. 2014;4:1-60. Russian.
16. Narayan K, van Dyk S, Bernshaw D, Khaw P, Mileshkin L, Kondalsamy-Chennakesavan S. Ultrasound guided conformal brachytherapy of cervix cancer: survival, patterns of failure, and late complications. J Gynecol Oncol 2014;25(3):206-213. doi:10.3802/jgo.2014.25.3.206.
17. Valentin J. Prevention of high-dose-rate brachytherapy accidents. ICRP Publication 97. Ann ICRP. 2005;35(2):1-51. doi: 10.1016/j.icrp.2005.05.002.
18. Stepanenko VF, Birukov VA, Kaprin AD, Petukhov A. [“In vivo” dosimetry for the high-power brachytherapy of prostate cancer using 192Ir: comparison of distribution of planned and measured doses for intracavitary placement of autonomous luminescent microdosimeters]. Radiation and Risk. 2018;27(1):77-83. Russian.
19. Kaprin AD, Galkin VN, Zhavoronkov LP, Ivanov SA, Karyakin OB, Mardynskij YuS, et al. [The synthesis of basic and applied research as the basis for ensuring a high level of scientific results and their implementation in medical practice]. Radiation and Risk. 2017;26(2):26-40. Russian.
20. Ivankova VS, Domina EA. [Problems of tumor resistance in radiation oncology (clinical and radiobiological issues)]. Kyiv: “Zdorovya” Publ;2012. 190 p. Russian.
21. Domina EA, Ivankova VS. [Radiosensitivity predictors of non-malignamt cells in cancer patiernts]. Ukr Radiol J. 2018;suppl 2;39-40. Ukrainian.