Polyradiomodification in combined treatment for rectal cancer and the role of therapeutic pathomorphosis

Objective: to evaluate the long-term outcomes of combined treatment with polyradiomodification in patients with rectal cancer depending on the grade of therapeutic pathomorphosis. Materials and methods. The study included 241 patients that received combined treatment with polyradiomodification for T2–3N0–2M0 resectable rectal adenocarcinoma of varying degree of differentiation. All patients received a course of preoperative radiation therapy (5 × 5 Gy) combined with capecitabine and metronidazole (in a polymer composition at a dose of 10 g/m2 per rectum) on days 3 and 5. Some patients additionally underwent local hyperthermia. Four different polyradiomodification regimens were used. We assessed the frequency of relapses, metastases, and relapse-free survival depending on the grade of therapeutic pathomorphosis and cancer stage. Results. Median follow-up time was 48.5 months. One patient with stage III therapeutic pathomorphosis had relapse. Distant metastases were diagnosed in 35 (19.7 %) out of 178 participants with grade 0–II therapeutic pathomorphosis and 4 (6.3 %) out of 63 participants with grade III therapeutic pathomorphosis; the difference between these groups was statistically significant (p = 0.01). No metastases were observed in patients with grade IV therapeutic pathomorphosis. Among patients with T2–3N1–2M0 rectal cancer, the five-year relapse-free survival was higher in the group with grade III–IV therapeutic pathomorphosis compared to the group with grade 0–II pathomorphosis: 95.7 % versus 56.7 % (p = 0.00422). Conclusion. Our treatment strategy ensures good local disease control. Patients with grade III–IV therapeutic pathomorphosis have significantly lower frequency of relapses and metastases and better relapse-free survival.

1. Janjan N. A., Crane C., Feig B. W. et al. Improved overall survival among responders to preoperative chemoradiation for locally advanced rectal cancer. Am J Clin Oncol 2001;24(2):107–12. PMID: 11319280.

2. Marijnen C. A., Kapiteijn E., van de Velde C. J. et al. Acute side effects and complications after short-term preoperative radiotherapy combined with total mesorectal excision in primary rectal cancer: report of a multicenter randomized trial. J Clin Oncol 2002;20(3):817–25. PMID: 11821466. DOI: 10.1200/JCO.2002.20.3.817.

3. Bosset J.-F., Collete L., Calais G. et al. Chemotherapy with preoperative radiotherapy in rectal cancer. N Engl J Med 2006;335(11):1114–23. PMID: 16971718. DOI: 10.1056/NEJMoa060829.

4. Gerard J.-P., Conroy T., Bonnetain F. et al. Preoperative radiotherapy with or without concurrent fluorouracil and leucovorin in T3–T4 rectal cancers: results of FFCD 9203. J Clin Oncol 2006; 24 (28):4620–5. PMID: 17008704. DOI: 10.1200/JCO.2006.06.7629.

5. O’Neill B. D. P., Brown G., Heald R. J. et al. Non-operative treatment after neoadjuvant chemoradiotherapy for rectal cancer. Lancet Oncol 2007;8(7):625–33. PMID: 17613424. DOI: 10.1016/S1470-2045 (07)70202-4.

6. Sauer R., Becker H., Hohenberger W. et al. Preoperative versus postoperative chemoradiotherapy for rectal cancer. N Engl J Med 2004;351(17):1731–40. PMID: 15496622. DOI: 10.1056/NEJMoa040694.

7. Capirci C., Valentini V., Cionini L. et al. Prognostic value of pathologic complete response after neoadjuvant therapy in locally advanced rectal cancer: longterm analysis of 566 ypCR patients. Int J Radiat Oncol Biol Phys 2008;72(1):99–107. PMID: 18407433. DOI: 10.1016/j.ijrobp.2007.12.019.

8. Maas M., Nelemans P. J., Valentini V. et al. Long-term outcome in patients with a pathological complete response after chemoradiation for rectal cancer: a pooled analysis of individual patient data. Lancet Oncol 2010;11 (9):835–44. PMID: 20692872. DOI: 10.1016/S1470-2045(10)70172-8.

9. Барсуков Ю. А., Ткачев С. И., Николаев А. В. и др. Предоперационная термолучевая терапия в комбинированном лечении рака нижнеампулярного отдела прямой кишки. Вопросы онкологии 1999;45(6):665–9. [Barsukov Yu. A., Tkachev S. I., Nikolaev A. V. et al. Preoperative thermo-radiotherapy in combined treatment for cancer of the ampullary portion of the rectum. Voprosy onkologii = Problems in Oncology 1999;45(6):665–9. (In Russ.)].

10. Лавникова Г. А., Гош Т. Е., Талалаева А. В. Гистологический метод количественной оценки степени лучевого повреждения опухоли. Медицинская радиология и радиационная безопасность 1977;(3):6–9. [Lavnikova G. A., Gosh T. E., Talalaeva A. V. Histological method for quantitative assessment of radiation damage to the tumor. Meditsinskaya radiologiya i radiatsionnaya bezopasnost = Мedical Radiology and Radiation Safety 1977;(3):6–9. (In Russ.)].

11. Dworak O., Keilholz L., Hoffmann A. Pathological features of rectal cancer after preoperative radiochemotherapy. Int J Colorect Dis 1997;12(1):19–23. PMID: 9112145.

12. Pettersson D., Lorinc E., Holm T. et al. Tumour regression in the randomized Stockholm III Trial of radiotherapy regimens for rectal cancer. Br J Surg 2015;102(8):972–8;discussion 8. PMID: 26095256. DOI: 10.1002/bjs.9811.

13. Faria S., Kopek N., Hijal T. et al. Phase II trial of short-course radiotherapy followed by delayed surgery for locoregionally advanced rectal cancer. Colorectal Dis 2014;16(2):O66–70. PMID: 24148225. DOI: 10.1111/codi.12466