Medical Radiology and radiation safety Medical Radiology and radiation safety Медицинская радиология и радиационная безопасность 1024-6177 2618-9615 29422 10.12737/1024-6177-2019-64-4-64-75 Обзор Review Обзор Hyperthermia for deep seated tumours – possibilities of heating with capacitive devices Гипертермия опухолей глубокой локализации: возможности емкостного метода Курпешев О. К. Kurpeshev O. K.

доктор медицинских наук;

doctor of medical sciences;

 ван дер Зее Я. van der Zee J. Кавагнаро М. Cavagnaro M. Сибирский научно-исследовательский институт гипертермии Искитим-5 Россия Siberian Scientific Research Institute of Hyperthermia Iskitim-5 Russian Federation 64 4 64 75 https://zh-szf.ru/en/nauka/article/29422/view

Рассмотрены общие принципы проведения емкостной электромагнитной гипертермии (ЭМГТ), распределение электромагнитной энергии в различных экспериментальных моделях и опухолях больных, особенности конструкции аппликаторов различных гипертермических систем и их возможности в создании гипертермического режима в новообразованиях глубокой локализации. При классической емкостной ЭМГТ основным препятствием в достижении необходимого температурного режима в таких опухолях является перегрев подкожно-жировой клетчатки (ПЖК) под электродами. При некоторых емкостных гипертермических системах нагрев жировой ткани еще больше усиливается из-за несоответствия конструкции аппликаторов техническим требованиям. При емкостной ЭМГТ на частотах 8–13,56 МГц получение минимального гипертермического режима возможно при выходных мощностях 500–800 Вт, максимального –1000–1200 Вт и выше. Анализируются результаты применения различных емкостных гипертермических систем у больных со злокачественными новообразованиями внутренних органов.

The review examines the general principles of capacitive electromagnetic hyperthermia (EMHT), the distribution of electromagnetic energy in various experimental models and in patients’ tumors, the design features of applicators from various capacitive hyperthermic systems and their role in achieving hyperthermic mode in tumors of deep localization. In classical capacitive EMHT, the main obstacle in achieving the required temperature in such tumors is overheating of the subcutaneous fatty tissue under the electrodes. For some capacitive hyperthermic systems, the heating of adipose tissues is enhanced due to the fact that the applicator design does not conform to certain technical requirements. In capacitive EMHT at frequencies of 8–13.56 MHz, obtaining the minimum hyperthermic mode is possible with output powers of 500–800 W, maximum – 1000–1200 W and above. The results of the use of various hyperthermic capacitive systems in patients with malignant tumors of internal organs are analyzed.

 лучевая терапия химиотерапия электромагнитные поля гипертермия емкостной метод radiation therapy thermoradiotherapy electromagnetic fields hyperthermia capacitive devices

IntroductionExperimental and clinical studies have shown that loсo-regional hyperthermia (LRHT) at temperatures of 40–46 °C is a powerful adjuvant of radio- (RT), chemo- (CT) and chemoradiotherapy (CRT). This is explained by the variety of its biological actions: direct cell kill, radio-, chemo- and immunomodulation, as well as suppressing the development of drug resistance of tumor cells [1–17]. In most studies, the dependence of the results of hyperthermia (HT) on the temperature level and the duration of heating, i.e. on the heat dose, has been demonstrated [8, 18–23]. For LRHT, electromagnetic field (EMF) in the microwave and radio frequency range is mainly used. With EMHT, the intensity of heat generation and the temperature distribution depends on the dielectric and thermodynamic properties of the tissues, the blood perfusion, and the method of heating. Therefore, there is a variation in temperature in the heated volume of tissue and it may change during the HT session. Thermometry is mainly carried out by invasive methods, by introduction of thermal sensors into the tumor. In clinical conditions however, this method of thermometry does not allow the evaluation of the quality of treatment very well, since the number of thermometry sensors introduced into the tumor is limited, and temperature indicators are largely dependent on their location.  

Berdov BA, Kurpeshev OK, Mardynsky YuS. Influence of hyperthermia and hyperglycemia on the efficacy of radiotherapy for cancer patients. Rusian Oncol J. 1996;(1):12-6. (Russian). Berdov BA, Kurpeshev OK, Mardynsky YuS. Influence of hyperthermia and hyperglycemia on the efficacy of radiotherapy for cancer patients. Rusian Oncol J. 1996;(1):12-6. (Russian). Pankratov VA, Andreev VG, Rozhnov VA, et al. Simultaneous use of chemo- and radiotherapy with independent conservative and combined treatment of patients with locally advanced cancer of the larynx and the laryngopharynx. Siberian Oncol J. 2007;(1):18-22. (Russian). Pankratov VA, Andreev VG, Rozhnov VA, et al. Simultaneous use of chemo- and radiotherapy with independent conservative and combined treatment of patients with locally advanced cancer of the larynx and the laryngopharynx. Siberian Oncol J. 2007;(1):18-22. (Russian). Van der Zee J, Vujaskovic Z, Kondo M, Sugahara T. Part I. Clinical Hyperthermia. The Kadota Fund International Forum 2004 - Clinical group consensus. Int J Hyperterm. 2008;24(2):111-22. Van der Zee J, Vujaskovic Z, Kondo M, Sugahara T. Part I. Clinical Hyperthermia. The Kadota Fund International Forum 2004 - Clinical group consensus. Int J Hyperterm. 2008;24(2):111-22. Westermann A, Mella O, Van der Zee J, et al. Long-term survival data of triple modality treatment of stage IIB-III-IVA cervical cancer with the combination of radiotherapy, chemotherapy and hyperthermia - an update. Int J Hyperterm. 2012;28(6):549-53. DOI: 10.3109/02656736.2012.673047. Westermann A, Mella O, Van der Zee J, et al. Long-term survival data of triple modality treatment of stage IIB-III-IVA cervical cancer with the combination of radiotherapy, chemotherapy and hyperthermia - an update. Int J Hyperterm. 2012;28(6):549-53. DOI: 10.3109/02656736.2012.673047. Kurpeshev OK, Mardinsky YuS, Maksimov SA. Combined treatment of patients with oral cancer using the “conditionally-dynamic” mode of fractionation of radiation therapy and locoregional hyperthermia. Siberian medical review. 2011;67(1):80-4. (Russian). Kurpeshev OK, Mardinsky YuS, Maksimov SA. Combined treatment of patients with oral cancer using the “conditionally-dynamic” mode of fractionation of radiation therapy and locoregional hyperthermia. Siberian medical review. 2011;67(1):80-4. (Russian). Ohguri T. Current Status of Clinical Evidence for Electromagnetic Hyperthermia on Prospective Trials. Thermal Med. 2015;31(2):5-12. Ohguri T. Current Status of Clinical Evidence for Electromagnetic Hyperthermia on Prospective Trials. Thermal Med. 2015;31(2):5-12. Van der Zee J, Van Rhoon GC. Hyperthermia with radiotherapy and with systemic therapies. In.: Breast Cancer: Innovations in Research and Management (Eds: U. Veronesi A. Goldhirsch P. Veronesi OD. Gentilini MCL). Springer Int. Publ. 2017:855-62. DOI: 10.1007/978-3-319-48848-6_75. Van der Zee J, Van Rhoon GC. Hyperthermia with radiotherapy and with systemic therapies. In.: Breast Cancer: Innovations in Research and Management (Eds: U. Veronesi A. Goldhirsch P. Veronesi OD. Gentilini MCL). Springer Int. Publ. 2017:855-62. DOI: 10.1007/978-3-319-48848-6_75. Kurpeshev OK, van der Zee J. Analysis of results of randomized studies on hyperthermia in Oncology. Medical radiology and radiation safety. 2018; 63(2):52-67. (Russian). DOI: 10.12737/article_5b179d60437d54.24079640. Kurpeshev OK, van der Zee J. Analysis of results of randomized studies on hyperthermia in Oncology. Medical radiology and radiation safety. 2018; 63(2):52-67. (Russian). DOI: 10.12737/article_5b179d60437d54.24079640. Konoplyannikov AG, Dedenkov AN, Kurpeshev OK, et al. Local hyperthermia in radiation therapy of malignant neoplasms. Scientific review. Ed. A.F. Tsyb. Series overview information in medicine and health. Moscow: The Medicine. Oncology. 1983. 72 p. (Russian). Konoplyannikov AG, Dedenkov AN, Kurpeshev OK, et al. Local hyperthermia in radiation therapy of malignant neoplasms. Scientific review. Ed. A.F. Tsyb. Series overview information in medicine and health. Moscow: The Medicine. Oncology. 1983. 72 p. (Russian). Kurpeshev OK. Patterns of radiosensitizing and damaging effects of hyperthermia on normal and tumor tissues (experimental clinical study): - Author’s abstract. diss. PhD Med. Obninsk, 1989. 35 p. (Russian). Kurpeshev OK. Patterns of radiosensitizing and damaging effects of hyperthermia on normal and tumor tissues (experimental clinical study): - Author’s abstract. diss. PhD Med. Obninsk, 1989. 35 p. (Russian). Kurpeshev OK. Possibilities and prospects for the use of hyperthermia in medicine. Clinical Medicine. 1996. (1):14-6. (Russian). Kurpeshev OK. Possibilities and prospects for the use of hyperthermia in medicine. Clinical Medicine. 1996. (1):14-6. (Russian). Pankratov VA, Andreev VG, Kurpeshev OK, et al. Application of thermochemical treatment in patients with locally advanced cancer of the larynx and hypopharynx. Russian Oncol J. 2006;(4):20-3. (Russian). Pankratov VA, Andreev VG, Kurpeshev OK, et al. Application of thermochemical treatment in patients with locally advanced cancer of the larynx and hypopharynx. Russian Oncol J. 2006;(4):20-3. (Russian). Wainson AA, Mescherikova VV, Lavrova Yu E, Mazokhin VN. The efficacy of simultaneous and sequential irradiation and hyperthermic treatment of tumor cells in vitro and transplantable tumors in vivo. Radiat Biol Radioecol. 2012;52(5):510-6. Russian Wainson AA, Mescherikova VV, Lavrova Yu E, Mazokhin VN. The efficacy of simultaneous and sequential irradiation and hyperthermic treatment of tumor cells in vitro and transplantable tumors in vivo. Radiat Biol Radioecol. 2012;52(5):510-6. Russian Wainson AA, Mescherikova VV, Tkachev SI. Radio-thermomodifying effect of cisplatin, Gemzar and Paclitaxel on tumor cells in vitro. Medical Radiology and Radiation Safety. 2016; 61(2):25-9. Russian Wainson AA, Mescherikova VV, Tkachev SI. Radio-thermomodifying effect of cisplatin, Gemzar and Paclitaxel on tumor cells in vitro. Medical Radiology and Radiation Safety. 2016; 61(2):25-9. Russian Kurpeshev OK, Tsyb AF, Mardynsky YuS, Berdov BA. Mechanisms of development and ways of overcoming chemo-resistance of tumors. Part 3. Possible ways to overcome the chemoresistance of tumors. Russian Oncol J. 2003;(2):50-2. (Russian). Kurpeshev OK, Tsyb AF, Mardynsky YuS, Berdov BA. Mechanisms of development and ways of overcoming chemo-resistance of tumors. Part 3. Possible ways to overcome the chemoresistance of tumors. Russian Oncol J. 2003;(2):50-2. (Russian). Toraya-Brown S, Sheen MR, Zhang P, et al. Local hyperthermia treatment of tumors induces CD8+ T cell-mediated resistance against distal and secondary tumors. Nanomedicine. 2014;10(6):1273-85. DOI: 10.1016/j.nano.2014.01.011. Toraya-Brown S, Sheen MR, Zhang P, et al. Local hyperthermia treatment of tumors induces CD8+ T cell-mediated resistance against distal and secondary tumors. Nanomedicine. 2014;10(6):1273-85. DOI: 10.1016/j.nano.2014.01.011. Van der Heijden AG, Dewhirst MW. Effects of hyperthermia in neutralizing mechanisms of drug resistance in non-muscleinvasive bladder cancer. Int J Hyperterm. 2016;32(4):434-45. http://dx.doi.org/10.3109/02656736.2016.1155761 Van der Heijden AG, Dewhirst MW. Effects of hyperthermia in neutralizing mechanisms of drug resistance in non-muscleinvasive bladder cancer. Int J Hyperterm. 2016;32(4):434-45. http://dx.doi.org/10.3109/02656736.2016.1155761 Franckena M, Fatehi D, de Bruijne M, et al. Hyperthermia dose-effect relationship in 420 patients with cervical cancer treated with combined radiotherapy and hyperthermia. Eur J Cancer. 2009; 45:1969-78. DOI: 10.1016/j.ejca.2009.03.009. Franckena M, Fatehi D, de Bruijne M, et al. Hyperthermia dose-effect relationship in 420 patients with cervical cancer treated with combined radiotherapy and hyperthermia. Eur J Cancer. 2009; 45:1969-78. DOI: 10.1016/j.ejca.2009.03.009. Dewhirst MW, Sim DA, Sapareto S, Connor WG. Importance of minimum tumor temperature in determining early and long-term responses of spontaneous canine and feline tumors to heat and radiation. Cancer Res. 1984;44(1):43-50. Dewhirst MW, Sim DA, Sapareto S, Connor WG. Importance of minimum tumor temperature in determining early and long-term responses of spontaneous canine and feline tumors to heat and radiation. Cancer Res. 1984;44(1):43-50. Sherar M, Liu FF, Pintilie M, et al. Relationship between thermal dose and outcome in thermoradiotherapy treatments for superficial recurrences of breast cancer: data from a phase III trial. Int J Radiat Oncol Biol Phys. 1997;39(2):371-80. Sherar M, Liu FF, Pintilie M, et al. Relationship between thermal dose and outcome in thermoradiotherapy treatments for superficial recurrences of breast cancer: data from a phase III trial. Int J Radiat Oncol Biol Phys. 1997;39(2):371-80. Jones EL, Oleson JR, Prosnitz LR, et al. Randomized trial of hyperthermia and radiation for superficial tumors. J Clin Oncol. 2005; 23:3079-85. Jones EL, Oleson JR, Prosnitz LR, et al. Randomized trial of hyperthermia and radiation for superficial tumors. J Clin Oncol. 2005; 23:3079-85. Hand JW, Machin D, Vernon CC, Whaley JB. Analysis of thermal parameters obtained during phase III trials of hyperthermia as an adjunct to radiotherapy in the treatment of breast carcinoma. Int J Hyperterm. 1997;13(4):343-64. Hand JW, Machin D, Vernon CC, Whaley JB. Analysis of thermal parameters obtained during phase III trials of hyperthermia as an adjunct to radiotherapy in the treatment of breast carcinoma. Int J Hyperterm. 1997;13(4):343-64. Xia T, Sun Q, Shi X, et al. Relationship between thermal parameters and tumor response in hyperthermia combined with radiation therapy. Int J Clin Oncol. 2001; 6(3):138-42. Xia T, Sun Q, Shi X, et al. Relationship between thermal parameters and tumor response in hyperthermia combined with radiation therapy. Int J Clin Oncol. 2001; 6(3):138-42. Canters RAM, Wust P, Bakker JF, Van Rhoon G. A literature survey on indicators for characterization and optimization of SAR distributions in deep hyperthermia, a plea for standardization. Int J Hyperterm. 2009;25:593-608. Canters RAM, Wust P, Bakker JF, Van Rhoon G. A literature survey on indicators for characterization and optimization of SAR distributions in deep hyperthermia, a plea for standardization. Int J Hyperterm. 2009;25:593-608. Bruggmoser G, Bauchowitz S, Canters R, et al. Guideline for the clinical application, documentation and analysis of clinical studies for regional deep hyperthermia. Strahlenther Onkol. 2012;188(Suppl. 2):198-211. DOI: 10.1007/s00066-012-0176-2. Bruggmoser G, Bauchowitz S, Canters R, et al. Guideline for the clinical application, documentation and analysis of clinical studies for regional deep hyperthermia. Strahlenther Onkol. 2012;188(Suppl. 2):198-211. DOI: 10.1007/s00066-012-0176-2. Abe M, Hiraoka M, Takahashi M.I, et al. Multi-Institutional Studies on Hyperthermia Using an 8-MHz Radiofrequency Capacitive Heating Device (Thermotron RF-8) in Combination With Radiation for Cancer Therapy. Cancer 1986;58(8):1589-95. Abe M, Hiraoka M, Takahashi M.I, et al. Multi-Institutional Studies on Hyperthermia Using an 8-MHz Radiofrequency Capacitive Heating Device (Thermotron RF-8) in Combination With Radiation for Cancer Therapy. Cancer 1986;58(8):1589-95. Sidi J, Jasmin C, Convert G, et al. Shortwave regional hyperthermia of the pelvis. Biomed Thermol. 1982;107:739-44. Sidi J, Jasmin C, Convert G, et al. Shortwave regional hyperthermia of the pelvis. Biomed Thermol. 1982;107:739-44. Van Rhoon GC, Sowinski MJ, Van Den Berg et al. A ring capacitor applicator in hyperthermia: energy distributions in a fat-muscle layered model for different ring electrode configurations. Int J Radiat Oncol BioL Phys. 1990;18:77-85. Van Rhoon GC, Sowinski MJ, Van Den Berg et al. A ring capacitor applicator in hyperthermia: energy distributions in a fat-muscle layered model for different ring electrode configurations. Int J Radiat Oncol BioL Phys. 1990;18:77-85. Kim KS, Hernandez D, Lee SY. Time-multiplexed two-channel capacitive radiofrequency hyperthermia with nanoparticle mediation. BioMed Eng OnLine. 2015;14:95. DOI: 10.1186/s12938-015-0090-9. Kim KS, Hernandez D, Lee SY. Time-multiplexed two-channel capacitive radiofrequency hyperthermia with nanoparticle mediation. BioMed Eng OnLine. 2015;14:95. DOI: 10.1186/s12938-015-0090-9. Brezovich I. A. Heating of subcutaneous fat in localized current field hyperthermia with external electrodes. Med Phys. 1979;6(4):352. Brezovich I. A. Heating of subcutaneous fat in localized current field hyperthermia with external electrodes. Med Phys. 1979;6(4):352. Brezovich I.A, Lilly M.B, Durant J.R, et al. A practical system for clinical hyperthermia radiofrequency. Int J Radiat Oncol Biol Phys.1981;7(3):423-30. Brezovich I.A, Lilly M.B, Durant J.R, et al. A practical system for clinical hyperthermia radiofrequency. Int J Radiat Oncol Biol Phys.1981;7(3):423-30. Yanagawa S, Sone Y, Doi H, Yamamoto G. A new procedure for the prevention of surface overheating in deep hyperthermia using RF capacitive heating equipment. Jpn J Hyperterm Oncol. 1985;1:187-91. Yanagawa S, Sone Y, Doi H, Yamamoto G. A new procedure for the prevention of surface overheating in deep hyperthermia using RF capacitive heating equipment. Jpn J Hyperterm Oncol. 1985;1:187-91. Van Rhoon GC, Van der Zee J, Broekmeyer-Reurink MP, et al. Radiofrequency capacitive heating of deep-seated tumours using pre-cooling of the subcutaneous tissues: results on thermometry in Dutch patients. Int J Hyperterm. 1992; 8:843-854. Van Rhoon GC, Van der Zee J, Broekmeyer-Reurink MP, et al. Radiofrequency capacitive heating of deep-seated tumours using pre-cooling of the subcutaneous tissues: results on thermometry in Dutch patients. Int J Hyperterm. 1992; 8:843-854. Kato H, Hiraoka M, Nakajima T, Ishida T. Deep heating characteristics of an RF capacitive heating device. Int J Hyperterm. 1985;1:15-28. Kato H, Hiraoka M, Nakajima T, Ishida T. Deep heating characteristics of an RF capacitive heating device. Int J Hyperterm. 1985;1:15-28. Rhee JG, Lee CKK, Osborn J, et al. Precooling prevents overheating of subcutaneous fat in the use of RF capacitive heating. Int J Radiat Oncol Biol Phis. 1991;20(5):1009-15. DOI: http://dx.doi.org/10.1016/0360-3016(91)90198-D. Rhee JG, Lee CKK, Osborn J, et al. Precooling prevents overheating of subcutaneous fat in the use of RF capacitive heating. Int J Radiat Oncol Biol Phis. 1991;20(5):1009-15. DOI: http://dx.doi.org/10.1016/0360-3016(91)90198-D. Kumagae K, Saito K. Air Gap Filler Material for Hot Spot Reduction in the Capacitive Heating Device. Thermal Med. 2016;32(2):5-11. Kumagae K, Saito K. Air Gap Filler Material for Hot Spot Reduction in the Capacitive Heating Device. Thermal Med. 2016;32(2):5-11. Tanaka H, Kato H, Nishida T, et al. Physical basis of RF hyperthermia for cancer therapy (2). Measurement of distribution of absorbed power from radiofrequency exposure in agar phantom. J Radiat Res. 1981;22:101-8. Tanaka H, Kato H, Nishida T, et al. Physical basis of RF hyperthermia for cancer therapy (2). Measurement of distribution of absorbed power from radiofrequency exposure in agar phantom. J Radiat Res. 1981;22:101-8. Lee CKK, Song CW, Rhee JG, Levitt SH. Clinical Experience with Thermotron RF-8 Capacitive Heating for Bulky Tumors: University of Minnesota Experience. Radiol Clin of North America. 1989;27(3):543-58. Lee CKK, Song CW, Rhee JG, Levitt SH. Clinical Experience with Thermotron RF-8 Capacitive Heating for Bulky Tumors: University of Minnesota Experience. Radiol Clin of North America. 1989;27(3):543-58. Chen C-C, Kiang J-F. Efficacy of Magnetic and Capacitive Hyperthermia on Hepatocellular Carcinoma. Progress Electromagn Res. 2018;64:181-92. Chen C-C, Kiang J-F. Efficacy of Magnetic and Capacitive Hyperthermia on Hepatocellular Carcinoma. Progress Electromagn Res. 2018;64:181-92. Frija E, Cavagnaro M. A comparison between radiative and capacitive systems in deep hyperthermia treatments. 31st An Meet of the Eur Soc for Hyperterm Oncol. Greece, Athens, 21-23 June 2017:62-3. OP-07. Frija E, Cavagnaro M. A comparison between radiative and capacitive systems in deep hyperthermia treatments. 31st An Meet of the Eur Soc for Hyperterm Oncol. Greece, Athens, 21-23 June 2017:62-3. OP-07. Beck M, Chrozon B, Lim A, et al. SAR profiles generated with a capacitive hyperthermia system in a porcine phantom. Strahlenther Onkol. 2018;194:493-4. Beck M, Chrozon B, Lim A, et al. SAR profiles generated with a capacitive hyperthermia system in a porcine phantom. Strahlenther Onkol. 2018;194:493-4. Kok HP, Navarro F, Strigari L, et al. Locoregional hyperthermia of deep-seated tumors applied with capacitive and radiative systems: a simulation study. Int J Hyperterm. 2018. https://doi.org/10.1080/02656736.2018.1448119 Kok HP, Navarro F, Strigari L, et al. Locoregional hyperthermia of deep-seated tumors applied with capacitive and radiative systems: a simulation study. Int J Hyperterm. 2018. https://doi.org/10.1080/02656736.2018.1448119 Lopatin VF. Method of local UHF hyperthermia. Med Fizika. 2011;(4):85-95. (Russian). Lopatin VF. Method of local UHF hyperthermia. Med Fizika. 2011;(4):85-95. (Russian). Seong J, Lee HS, Han KH, et al. Combined treatment of radiotherapy and hyperthermia for unresectable hepatocellular carcinoma. Yonsei Medical J. 1994;35(3):252-9. Seong J, Lee HS, Han KH, et al. Combined treatment of radiotherapy and hyperthermia for unresectable hepatocellular carcinoma. Yonsei Medical J. 1994;35(3):252-9. Kim SW, Yea JW, Kim• JH. et al. Selecting patients for hyperthermia combined with preoperative chemoradiotherapy for locally advanced rectal cancer. Int J Clin Oncol. 2018;23(2);287-97. DOI: 10.1007/s10147-017-1213-z. Kim SW, Yea JW, Kim• JH. et al. Selecting patients for hyperthermia combined with preoperative chemoradiotherapy for locally advanced rectal cancer. Int J Clin Oncol. 2018;23(2);287-97. DOI: 10.1007/s10147-017-1213-z. Lee S-Y, Kim J-H, Han Y-H, Cho D-H. The effect of modulated electro-hyperthermia on temperature and blood flow in human cervical carcinoma. Int J Hyperterm. 2018. https://doi.org/10.1080/02656736.2018.1423709 Lee S-Y, Kim J-H, Han Y-H, Cho D-H. The effect of modulated electro-hyperthermia on temperature and blood flow in human cervical carcinoma. Int J Hyperterm. 2018. https://doi.org/10.1080/02656736.2018.1423709 Rusakov SV, Sas A, Sas O, Sas N. A method for the treatment of solid malignant tumors by the method of Oncothermia (medical technology). Moscow. 2011:96 p. (Russian). Rusakov SV, Sas A, Sas O, Sas N. A method for the treatment of solid malignant tumors by the method of Oncothermia (medical technology). Moscow. 2011:96 p. (Russian). Noh JM, Kim HY, Park HC, et al. In vivo verification of regional hyperthermia in the liver. Radiat Oncol J. 2014;32(4):256-61. Noh JM, Kim HY, Park HC, et al. In vivo verification of regional hyperthermia in the liver. Radiat Oncol J. 2014;32(4):256-61. Yu JI, Park HC, Choi DH. Prospective phase II trial of regional hyperthermia and whole liver irradiation for numerous chemorefractory liver metastases from colorectal cancer. Radiat Oncol J. 2016;34(1):34-44. DOI: 10.3857/roj.2016.34.1.34. Yu JI, Park HC, Choi DH. Prospective phase II trial of regional hyperthermia and whole liver irradiation for numerous chemorefractory liver metastases from colorectal cancer. Radiat Oncol J. 2016;34(1):34-44. DOI: 10.3857/roj.2016.34.1.34. Park JS, Park HC, Choi DH, et al. Prognostic and predictive value of liver volume in colorectal cancer patients with unresectable liver metastases. Radiat Oncol J. 2014;32(2):77-83. Park JS, Park HC, Choi DH, et al. Prognostic and predictive value of liver volume in colorectal cancer patients with unresectable liver metastases. Radiat Oncol J. 2014;32(2):77-83. Yeo SG, Kim DY, Kim TH, et al. Whole-liver radiotherapy for end-stage colorectal cancer patients with massive liver metastases and advanced hepatic dysfunction. Radiat Oncol. 2010;5:97. Yeo SG, Kim DY, Kim TH, et al. Whole-liver radiotherapy for end-stage colorectal cancer patients with massive liver metastases and advanced hepatic dysfunction. Radiat Oncol. 2010;5:97. Borgelt BB, Gelber R, Brady LW, Griffin T, Hendrickson FR. The palliation of hepatic metastases: results of the Radiation Therapy Oncology Group pilot study. Int J Radiat Oncol Biol Phys. 1981;7(5):587-91. Borgelt BB, Gelber R, Brady LW, Griffin T, Hendrickson FR. The palliation of hepatic metastases: results of the Radiation Therapy Oncology Group pilot study. Int J Radiat Oncol Biol Phys. 1981;7(5):587-91. Ohguri T, Imada H, Yahara K, et al. Radiotherapy with 8-MHz radiofrequency-capacitive regional hyperthermia for stage III non-small-cell lung cancer: the radiofrequency-output power correlates with the intraesophageal temperature and clinical outcomes. Int J Radiat Oncol Biol Phys. 2009;73(1):128-35. DOI: 10.1016/j.ijrobp.2008.03.059. Ohguri T, Imada H, Yahara K, et al. Radiotherapy with 8-MHz radiofrequency-capacitive regional hyperthermia for stage III non-small-cell lung cancer: the radiofrequency-output power correlates with the intraesophageal temperature and clinical outcomes. Int J Radiat Oncol Biol Phys. 2009;73(1):128-35. DOI: 10.1016/j.ijrobp.2008.03.059. Harima Y, Nagata K, Harima K, et al. A randomized clinical trial of radiation therapy versus thermoradiotherapy in stage IIIB cervical carcinoma. Int J Hyperterm. 2001;17(2):97-105. DOI: 10.1080/02656730010001333. Harima Y, Nagata K, Harima K, et al. A randomized clinical trial of radiation therapy versus thermoradiotherapy in stage IIIB cervical carcinoma. Int J Hyperterm. 2001;17(2):97-105. DOI: 10.1080/02656730010001333. Harima Y, Ohguri T, Imada H, et al. A multicentre randomised clinical trial of chemoradiotherapy plus hyperthermia versus chemoradiotherapy alone in patients with locally advanced cervical cancer. Int J Hyperterm. 2016;32(7):801-8. Harima Y, Ohguri T, Imada H, et al. A multicentre randomised clinical trial of chemoradiotherapy plus hyperthermia versus chemoradiotherapy alone in patients with locally advanced cervical cancer. Int J Hyperterm. 2016;32(7):801-8. Gordeev SS. Master class on the use of local hyperthermia in patients with rectal cancer in Krasnodar. Onkol Coloproctology J. 2013; 3(2):9-10. (Russian). Gordeev SS. Master class on the use of local hyperthermia in patients with rectal cancer in Krasnodar. Onkol Coloproctology J. 2013; 3(2):9-10. (Russian). Startseva JA, Choynzonov ET. Local hyperthermia in the combined treatment of patients with malignant neoplasms. Russian Cancer J. 2015;(4):47-8. (Russian). http://www.studmedlib.ru/ru/doc/1028-99844-SCN0030.html Startseva JA, Choynzonov ET. Local hyperthermia in the combined treatment of patients with malignant neoplasms. Russian Cancer J. 2015;(4):47-8. (Russian). http://www.studmedlib.ru/ru/doc/1028-99844-SCN0030.html Hiraoka M, Jo S, Akuta K. Radiofrequency capacitive hyperthermia for deep-seated tumors. I. Studies on thermometry. Cancer. 1987; (60):121-7. Hiraoka M, Jo S, Akuta K. Radiofrequency capacitive hyperthermia for deep-seated tumors. I. Studies on thermometry. Cancer. 1987; (60):121-7. Hiraoka M, Jo S, Akuta K, et al. Radiofrequency capacitive hyperthermia for deep-seated tumors II. Effects of thermoradiotherapy. Cancer. 1987;60:128-35. Hiraoka M, Jo S, Akuta K, et al. Radiofrequency capacitive hyperthermia for deep-seated tumors II. Effects of thermoradiotherapy. Cancer. 1987;60:128-35. Vasanthan A, Mitsumori M, Park JH, et al. Regional hyperthermia combined with radiotherapy for uterine cervical cancers: a multi-institutional prospective randomized trial of the international atomic energy agency. Int J Radiat Oncol Biol Phys. 2005;61(1):145-53. Vasanthan A, Mitsumori M, Park JH, et al. Regional hyperthermia combined with radiotherapy for uterine cervical cancers: a multi-institutional prospective randomized trial of the international atomic energy agency. Int J Radiat Oncol Biol Phys. 2005;61(1):145-53. Konishi F, Furuta K, Kanazawa K, et al. The effect of hyperthermia in the preoperative combined treatment of radiation, hyperthermia and chemotherapy for rectal carcinoma. Jpn J Gastroenterol Surg. 1994;(27):789-796. Konishi F, Furuta K, Kanazawa K, et al. The effect of hyperthermia in the preoperative combined treatment of radiation, hyperthermia and chemotherapy for rectal carcinoma. Jpn J Gastroenterol Surg. 1994;(27):789-796. Yoshida M, Shioura H, Tomi M, et al. Multimodal combination therapy including hyperthermia for inoperable pancreatic cancer. Proc 7th Int Cong Hypertherm Oncol. Rome. 1996;2:38-9. Yoshida M, Shioura H, Tomi M, et al. Multimodal combination therapy including hyperthermia for inoperable pancreatic cancer. Proc 7th Int Cong Hypertherm Oncol. Rome. 1996;2:38-9. Nagata Y, Hiraoka M, Akuta K, et al. Radiofrequency thermotherapy for malignant liver tumors. Cancer. 1990; 65(8):1730-6. Nagata Y, Hiraoka M, Akuta K, et al. Radiofrequency thermotherapy for malignant liver tumors. Cancer. 1990; 65(8):1730-6. Nagata Y, Hiraoka M, Nishimura Y, et al. Clinical results of radiofrequency hyperthermia for malignant liver tumors. Int J Radiat Oncol Biol Phys. 1997;38(2):359-5. Nagata Y, Hiraoka M, Nishimura Y, et al. Clinical results of radiofrequency hyperthermia for malignant liver tumors. Int J Radiat Oncol Biol Phys. 1997;38(2):359-5. Hamazoe R, Maeta M, Murakami A, et al. Heating efficiency of radiofrequency capacitive hyperthermia for treatment of deep-seated tumors in the peritoneal cavity. J Surg Oncol.1991;48:176-9. Hamazoe R, Maeta M, Murakami A, et al. Heating efficiency of radiofrequency capacitive hyperthermia for treatment of deep-seated tumors in the peritoneal cavity. J Surg Oncol.1991;48:176-9. Nakajima K, Hisazumi H, Yamamoto H, et al. A study of regional temperature rise in bladder cancer patients during RF-hyperthermia. Jpn J Hyperterm Oncol. 1986(2):43-8. Nakajima K, Hisazumi H, Yamamoto H, et al. A study of regional temperature rise in bladder cancer patients during RF-hyperthermia. Jpn J Hyperterm Oncol. 1986(2):43-8. Nakajima K, Hisazumi H. Studies of temperature rise in subcutaneous fat tissue during RF-hyperthermia. Jpn J Hyperterm Oncol. 1987;(3):87-91. Nakajima K, Hisazumi H. Studies of temperature rise in subcutaneous fat tissue during RF-hyperthermia. Jpn J Hyperterm Oncol. 1987;(3):87-91. Kubota Y, Sakai N, Watai K, et al. Hyperthermia by regional capacitive heating. In: Hyperthermic oncology. 1988, Vol. 2. Sugahara T, Saito M. (Eds.). Taylor & Francis, London, 1989, 605-8. Kubota Y, Sakai N, Watai K, et al. Hyperthermia by regional capacitive heating. In: Hyperthermic oncology. 1988, Vol. 2. Sugahara T, Saito M. (Eds.). Taylor & Francis, London, 1989, 605-8. Masunaga S-I, Hiraoka M, Akuta K. Non-randomized trials of thermoradiotherapy versus radiotherapy for preoperative treatment of invasive urinary bladder cancer. J Jpn Soc Ther Radiol Oncol. 1990;2:313-20. Masunaga S-I, Hiraoka M, Akuta K. Non-randomized trials of thermoradiotherapy versus radiotherapy for preoperative treatment of invasive urinary bladder cancer. J Jpn Soc Ther Radiol Oncol. 1990;2:313-20. Lee CK, Song CW, Rhee JG, et al. Clinical experience using 8 MHz radiofrequency capacitive hyperthermia in combination with radiotherapy: results of a phase I/II study. Int J Radiat Oncol Biol Phys. 1995;32(3):733-45. DOI: 10.1016/0360-3016(94)00608-N. Lee CK, Song CW, Rhee JG, et al. Clinical experience using 8 MHz radiofrequency capacitive hyperthermia in combination with radiotherapy: results of a phase I/II study. Int J Radiat Oncol Biol Phys. 1995;32(3):733-45. DOI: 10.1016/0360-3016(94)00608-N.