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Introduction. The use of neoadjuvant thermochemoradiotherapy in combined treatment of intermediate-risk rectal cancer is justified by high recurrence rates and low disease-free survival indicators when using neoadjuvant radiation therapy alone. This approach reduces cancer recurrence from 8.4 to 0.7 % and increases 5-year disease-free survival from 60.3 to 81.3 %. However, it leads to increased frequency and severity of treatment-related toxicity. Previous studies have only examined general characteristics of toxic manifestations without detailed analysis of their patterns.
Aim. To study the nature and frequency of treatment-related toxicity in patients with intermediate-risk rectal cancer receiving short-course neoadjuvant thermochemoradiotherapy as part of combined-modality treatment.
Materials and Methods. Toxic manifestations were analyzed in 337 patients with intermediate-risk rectal cancer. Among them, 190 patients received neoadjuvant radiation therapy using a "short" course of 5 Gy fractions to a total dose of 25 Gy, while 147 patients underwent combined treatment with radiation therapy modulation through three distinct radioprotective approaches: three sessions of local microwave hyperthermia using "Yakh-3" or "Yakh-4" devices, two intrarectal administrations of a metronidazole-containing biopolymer composition (10 g/m²) prior to the 3rd and 5th radiation sessions, and a two-week oral course of capecitabine at a daily dose of 2.0 g/m². Surgical interventions were performed 4-6 weeks after completing radiation therapy.
Results. Toxic manifestations were observed in 25 (13.2 %) of 190 patients receiving radiation therapy alone, compared to 46 (31.3 %) of 147 patients undergoing thermochemoradiotherapy (p = 0.00001). The combined-modality treatment group predominantly exhibited gastrointestinal toxicity (36.7 %, 54/147 cases), while hematological toxicity was more common in the radiation-only group (10.5 %, 20/190 cases).
Conclusion. Although neoadjuvant thermochemoradiotherapy increased toxic manifestations in intermediate-risk patients, all subjects successfully completed the full course of planned therapy while achieving superior long-term outcomes compared to neoadjuvant radiation therapy alone.
References
Барсуков Ю.А., Ткачев С.И., Власов О.А. Персонализированный подход к выбору оптимального варианта комбинированного лечения больных раком прямой кишки с различным риском прогрессирования заболевания. В кн. Барсукова Ю.А. Рак прямой кишки и анального канала: перспективы комбинированного лечения. М.: ООО МК. 2019: 851. [Barsukov Yu.A., Tkachev S.I., Vlasov O.A. Personalized approach to choosing the optimal option for combined treatment of patients with rectal cancer with different risks of disease progression. In Barsukov Yu.A. Rectal and anal canal cancer: prospects for combined treatment. M.: MK LLC. 2019: 851 (In Rus)].
Бойко А.В., Дарьялова С.Л., Демидова Л.В., et al. Радиомодификация при лучевой терапии больных со злокачественными опухолями. Методические рекомендации. М. 1996: 11. [Boyko A.V., Daryalova S.L., Demidova L.V., et al. Radiomodification in radiation therapy of patients with malignant tumors. Clinical guidelines. Moscow. 1996: 11 (In Rus)].
Цыб А.Ф., Гулидов И.А. Современное состояние лучевой терапии злокачественных новообразований. В кн. Терапевтическая радиология. Руководство для врачей. M.: ООО МК. 2010: 550. [Tsyb A.F., Gulidov I.A. Current state of radiation therapy of malignant neoplasms. In the book Therapeutic radiology. Medical guidelines. M.: MK LLC. 2010: 550 (In Rus)].
Курпешев О.К., Медынский Ю.С. Радиомодификаторы в лучевой терапии опухолей. В кн. Терапевтическая радиология. Руководство для врачей, M.: ООО МК. 2010: 550. [Kurpeshev O.K., Medynsky Yu.S. Radiomodifiers in radiation therapy of tumors. In the book Therapeutic radiology. Medical guidelines. M.: MK LLC. 2010: 550 (In Rus)].
Барсуков Ю.А., Ткачев С.И., Мамедли З.З, et al. Радиомодификаторы в комбинированном лечении больных раком прямой кишки. Вопросы онкологии. 2021; 67(4): 525-530.-DOI: 10.37469/0507-3758-2021-67-4-525-530. [Barsukov Yu.A., Tkachev S.I., Mamedli Z.Z., et al. Radiomodifiers in the combined treatment of patients with rectal cancer. Voprosy Onkologii = Problems in Oncology. 2021; 67(4): 525-530.-DOI: 10.37469/0507-3758-2021-67-4-525-530 (In Rus)].
Ярмоненко С.П., Вайнсон А.А. Радиобиология человека и животных. М: Высшая школа. 2004: 549. [Yarmonenko S.P., Vainson A.A. Radiobiology of man and animals. Moscow: Vysshaya Shkola; 2004: 549 (In Rus)].
Ярмоненко С.П. Полирадиомодификация как новый подход к повышению эффективности лучевой терапии опухолей: радиомодификаторы в лучевой терапии опухолей. Обнинск: С.П. Ярмоненко. 1982: 126-127. [Yarmonenko S.P. Polyradiomodification as a new approach to increasing the effectiveness of tumor radiation therapy: radiomodifiers in tumor radiation therapy. Obninsk: S.P. Yarmonenko. 1982: 126-127 (In Rus)].
Патент № 2477641. Барсуков Ю.А., Ткачев С.И., Кузьмичев Д.В., et al. Способ лечения рака прямой кишки («короткий» курс облучения с локальной СВЧ-гипертермией, Капецитабином и Метронидазолом внутриректально). Российская Федерация. 20.03.2013.-URL: https://elibrary.ru/download/elibrary_37508048_10187814.pdf [Patent No. 2477641. Barsukov Yu.A., Tkachev S.I., Kuzmichev D.V., et al. A method of treating rectal cancer (‘short’ course of radiation with local microwave hyperthermia, Capecitabine and Metronidazole intrarectally). Russian Federation. 20.03.2013.-URL: https://elibrary.ru/download/elibrary_37508048_10187814.pdf (In Rus)].
Патент № 2234318. Барсуков Ю.А., Олтаржевская Н.Д., Ткачев С.И., et al. Способ лечения рака прямой кишки. Российская Федерация. 20.08.2004.-URL: https://elibrary.ru/download/elibrary_37941828_62170998.pdf. [Patent No. 2234318. Barsukov Yu.A., Oltarzhevskaya N.D., Tkachev S.I., et al. Method of treatment rectal cancer. Russian Federation. 20.08.2004.-URL: https://elibrary.ru/download/elibrary_37941828_62170998.pdf (In Rus)].
Барсуков Ю.А., Ткачев С.И., Мамедли З.З., et al. Результаты применения комбинированного метода лечения больных раком прямой кишки со средним риском прогрессирование опухолевого процесса. Хирургия. Журнал имени Н.И. Пирогова. 2022; 12: 36-43.-DOI: 10.17116/hirurgia202212236. [Barsukov Yu.A., Tkachev S.I., Mamedli Z.Z., et al. Results of using a combined method of treating patients with rectal cancer with an average risk of tumor progression. Surgery. Pirogov Journal. 2022; 12: 36-43.-DOI: 10.17116/hirurgia202212236 (In Rus)].
Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0. Bethesda, MD: National Cancer Institute; 2009 May 28 [updated 2010 Jun 14].-URL: https://evs.nci.nih.gov/ftp1/CTCAE/CTCAE_4.03/CTCAE_4.03_2010-06-14_QuickReference_8.5x11.pdf.
Bujko K., Nowacki M.P., Bebenek M., et al. Long-term result of a randomized trial comparing preoperative shot-course radiotherapy with preoperative conventionally fractionation chemoradiation for rectal cancer. Br J Surg. 2006; 93(10): 1215-23.-DOI: 10.1002/bjs.5506.
Ngan S., Fisher R., Mockay J., et al. Aсute advents in a randomized trial of short-course versus long-course preoperative radiotherapy for T3 adenocarcinoma of the rectum. A Trans-Tasman Radiology Group trial (TROG 01 04). Eur J Cancer. 2007; 5(suppl. 4): 237.-DOI: 10.1016/S1359-6349(07)70936-9.
Birgisson H., Pahlmon L., Gunnarsson U., et al. Adverse effects of preoperative radiation therapy for rectal cancer long-term follow-up of the Swedish Rectal Cancer Trial. J Clin Oncol. 2005; 23(34): 8697-705.-DOI: 10.1200/JCO.2005.02.9017.
Birgisson H., Pahlvan L., Gunnarsson U., Glimelius B. Late gastrointestinal disorders after rectal cancer surgery with and without preoperative radiation therapy. Br J Surg. 2008; 95(2): 206-13.-DOI: 10.1002/bjs.5918.
Holm T., Singomklao T., Rutgvist L.E., Cedtrmork B. Adjuvant preoperative radiotherapy in patients with rectal carcinoma. Advers effects during long-term follow-up of two randomized trial. Cancer. 1996; 78(5): 968-76.-DOI: 10.1002/(SICI)1097-0142(19960901)78:5<968::AID-CNCR5>3.0.CO;2-8.
Palta M., Willett C.G., Czito B.G. Сравнение длинного и короткого курсов лучевой терапии при раке прямой кишки. В кн. Д.Г. Скоулфилд, К. Энг. Колоректальный рак — диагностика и тактика лечения. М. 2019: 191-207. [Palta M., Chistopher G., Willett О, Briag G. Short-course versus long-course chemoradiation in rectal cancer--time to change strategies? In Scholefield D., Eng C. Colorectal cancer: Diagnosis and clinical management. Moscow. 2019: 191-207 (In Rus)].
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