Keywords
How to Cite
Abstract
Objective. To evaluate the effectiveness of the combined method of treatment of patients with rectal cancer using several variants of polyradiomodification (CT+PRM).
Material and methods. To increase the effectiveness of the «short» course of neoadjuvant radiation therapy (RT) 5×5 Gy until total focal dose Gy, the concept of polyradiomodification proposed by S. P. Yarmonenko (1982) was used [1]. Three radiomodifiers were used: local intracavitary microwave hyperthermia (MWH), Metronidazole (MZ) as part of a polymer composition for intrarectal administration, and the chemotherapy drug Capecitabine (Cap).
Four variants of the PRM have been created, divided into two-component and three-component. Two-component variants were used when the MWH was not possible in the case of stenosis or localization of cancer in the upper ampullary rectum. Initially, Capecitabine was used at a daily dose of 1.5 g/m2 on 1–5 days in combination with a double administration of Metronidazole («Cap5+MZ») and surgery 3 weeks after RT, and later the dose of Capecitabine was increased to 2.0 g/m2 on 1–14 days («Cap14+MZ») with surgery 4–6 weeks after RT. With three-component versions of PRM, 3 additional sessions of MWH were used: «Cap5+MZ+MWH» and «Cap14+MZ+MWH». A total of 241 patients were included in the study.
Results. The total toxicity in CT+PRM was 33.4%, and the overall rate of postoperative complications was 14.9%. The 5-year relapse-free survival (RFS) rate of 80.5% was achieved due to pronounced local control: cancer recurrence was detected only in 1 (0.4%) of 241 patients. This made it possible to perform sphincter-sparing operations (SSO) without compromising oncological results in 211 (86.7%) patients out of 241. The most pronounced therapeutic pathomorphosis in the tumor was achieved with «Cap14+MZ» and «Cap14+MZ+MWH»: pathomorphosis of the III degree was achieved in 9 (30.0%) of 30 patients with «Cap14+MZ», and in 13 (25.0%) of 52 patients with «Cap14+MZ+MWH», a complete pathomorphological response was detected in 7 (23.4%) of 30 patients with «Cap14+MZ», and in 9 (17.3%) of 52 patients with «Cap14+MZ+MWH». When reaching the III–IV degree of pathomorphosis, distant metastases were detected in 6.3% of patients, at the II degree and below — in 19.7% (p=0.01).
Conclusion. When using CT+PRM, 5-year RFS rate was increased to 80.5%, and the frequency of SSO was increased to 86.7%, with a low level of postoperative complications (14.9%) and acceptable toxicity (33.4%).
References
Ярмоненко С.П. Полирадиомодификация как новый подход к повышению эффективности лучевой терапии опухолей: Радиомодификаторы в лучевой терапии опухолей. Обнинск, 1982:126–127 [Yarmonenko S.P. Polyradiomodification as a new approach to improving the effectiveness of radiation therapy of tumors: Radiomodifiers in radiation therapy of tumors. Obninsk, 1982:126–127 (In Russ.)].
NCCN Clinical Practice Guidelines in Oncology // Rectal Cancer. 2015;2.
Glynne-Jones R, Wyrwicz L, Tiret E, Brown G, C. Ro¨ del, Cervantes A, Arnold D, on behalf of the ESMO Guidelines Committee. Rectal cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up // Annals of Oncology. 2017;28 (Suppl. 4):iv22–iv40. https: // doi: 10.1093/annonc/mdx224
NICE clinical quideline 131 2011. quidance.nice.org.uk/cg131
Chau I, Brown G, Cunningham D et al. Neoadjuvant capecitabine and oxaliplatin followed by synchronous che-moradiation and total mesorectal excision in magnetic resonance imaging-defined poor-risk rectal cancer // J Clin Oncol. 2006;24:668–74.
Fernandez-Martos C, Pericay C, Aparicio J et al. Phase II, randomized study of concomitant chemoradiotherapy followed by surgery and adjuvant capecitabine plus oxaliplatin (CAPOX) compared with induction CAPOX followed by concomitant chemoradiotherapy and surgery in magnetic resonance imaging-defined, locally advanced rectal cancer: Grupo cancer de recto 3 study // J Clin Oncol. 2010;28:859–65.
Maréchal R, Vos B, Polus M et al. Short course chemotherapy followed by concomitant chemoradiotherapy and surgery in locally advanced rectal cancer: a randomized multicentric phase II study // Ann Oncol. 2012;23:1525–30.
Okuyama T, Sameshima S, Takeshita E et al. Therapeutic effects of oxaliplatin-based neoadjuvant chemotherapy and chemoradiotherapy in patients with locally advanced rectal cancer: a single-center, retrospective cohort study // World J Surg Oncol. 2018;16(1):105.
Perez K, Pricolo V, Vrees M et al. A phase II study of complete neoadjuvant therapy in rectal cancer (CONTRE): The Brown University Oncology Group // J Clin Oncol. 2013;31:335.
Aghili M, Sotoudeh S, Ghalehtaki R et al. Preoperative short course radiotherapy with concurrent and consolidation chemotherapies followed by delayed surgery in locally advanced rectal cancer: preliminary results // Radiat Oncol. J. 2018;36(1):17–24.
Gao Y, Zhang X, An X et al. Oxaliplatin and capecitabine concomitant with neoadjuvant radiotherapy and extended to the resting period in high risk locally advanced rectal cancer // Strahlenther Onkol. 2014;190:158–64.
Gao YH, Lin JZ, An X et al. Neoadjuvant Sandwich Treatment with Oxaliplatin and Capecitabine Administered Prior to, Concurrently With, and Following Radiation Therapy in Locally Advanced Rectal Cancer: A Prospective Phase 2 Trial. // Int J Radiat Oncol Biol Phys. 2014;90(5):1153–60. https: // doi: 10.1016/j.ijrobp.2014.07.021
Garcia-Aguilar J, Marcet J, Coutsoftides T et al. Impact of neoadjuvant chemotherapy following chemora-diation on tumor response, adverse events, and surgical complications in patients with advanced rectal cancer treated with TME // J Clin Oncol. 2011;29(15_suppl):3514–3514. https: // doi: 10.1200/jco.2011.29.15_suppl.3514
Garcia-Aguilar J, Smith DD, Avila K et al. Optimal timing of surgery after chemoradiation for advanced rectal cancer: preliminary results of a multicenter, nonrandomized phase II prospective trial // Ann Surg. 2011;254:97–102.
Gatta G, Faivre J, Capocaccia R et al. Survival of colorectal cancer patients in Europe during the period 1978–89 // Eur J Cancer. 1998;34:2176–83.
Tang J, Wu X, Bai Y et al. Long-Term Outcome of Oxaliplatin and Capecitabine (XELOX) Concomitant with Neoadjuvant Radiotherapy and Extended to the Resting Period in High Risk Locally Advanced Rectal Cancer / // J Cancer. 2018;Apr 6;9(8):1365–70.
Xiao J, Chen Z, Li W et al. Sandwich-like neoadjuvant therapy with bevacizumab for locally advanced rectal cancer: a phase II trial // Cancer Chemother Pharmacol 2015;Jul 8;76(1):21–7.
Zampino MG, Magni E, Leonardi MC et al. Capecitabine initially concomitant to radiotherapy then perioperatively administered in locally advanced rectal cancer // Int J Radiat Oncol Biol Phys. 2009;75:421–7.
Малеева К.П., Каримов Н.А., Мулатов А.А., Порфильев В.В, Порфирьева С.В. Радиочувствительность опухолей и способы радиомодификации // Международный студенческий научный вестник. 2018;2:22 [Maleeva K.P., Karimov N.A., Mulatov A.A., Porfilev V.V., Porfirieva S.V. Radiosensitivity of tumors and methods of radiomodification // International Student Scientific Bulletin. 2018;2:22 (In Russ.)].
Бойко А.В., Дарьялова С.Л., Демидова Л.В. и др. Радиомодификация при лучевой терапии больных со злокачественными опухолями (методические рекомендации). М., 1996 [Boyko A.V., Daryalova S.L., Demidova L.V et al. Radiomodification in radiation therapy of patients with malignant tumors (methodological recommendations). M., 1996 (In Russ.)].
Barsukov I., Tkachev SI, Nikolaev AV et al. Preoperative thermoradiotherapy in the combined treatment of rectal tumors is the inferior ampullar segmento// Problems in Oncology. 1999;45(6):665–669.
Барсуков Ю.А., Ткачев С.И., Мамедли З.З. и др. Комбинированное лечение больных с запущенными стадиями рака дистальных отделов прямой кишки в условиях неоадъювантной термолучевой терапии // Тазовая хирургия и онкология. 2020;10(3–4):43–53 [Barsukov Yu.A., Tkachev S.I., Mammadli Z.Z., Perevoshchikov A.G., Vlasov O.A., Kulushev V.M., Aliev V.A., Goncharov S.V. Combined treatment of patients with advanced stages of cancer of the distal rectum in the conditions of neoadjuvant thermal radiation therapy // Pelvic surgery and oncology. 2020;10(3–4):43–53 (In Russ.)].
Терапевтическая радиология. Руководство для врачей / Под ред. А.Ф.Цыба, Ю.С.Мардынского. М: ООО «МК», 2010 [Therapeutic radiology. Manual for doctors / Ed. by A.F.Tsyb, Yu.S.Mardynsky. M: LLC «MK», 2010 (In Russ.)].
Барсуков Ю.А. «Рак прямой кишки и анального канала: перспективы комбинированного лечения». М.: 2019;6:274–341 [Barsukov Yu.A. «Cancer of the rectum and anal canal: prospects of combined treatment». Moscow: 2019;6:274–341 (In Russ.)].
Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 Published: May 28, 2009 (v4.03: June 14, 2010) U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES. National Institutes of Health. National Cancer Institute.
Лавникова Г.А. Некоторые закономерности лучевого патоморфоза опухолей человека и их практическое использование // Вестн. АМН СССР. 1976. № 6:13–19 [Lavnikova G.A. Some regularities of radiation pathomorphosis of human tumors and their practical use // Bullet Acad Med Scienc USSR. 1976;6:13–19 (In Russ.)].
Dworak O, Keilholz L, Hoffmann A. Pathological features of rectal cancer after preoperative radiochemotherapy // Int J Colorectal Dis. 1997;12(1):19–23.
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
© АННМО «Вопросы онкологии», Copyright (c) 2021