ORGAN-SPARING TREATMENT IN PATIENTS WITH SQUAMOUS CELL CARCINOMA OF THE ANAL CANAL

Objective: to improve the results of treatment in patients with squamous cell carcinoma of the anal canal, by creating a new combination treatment option, and to increase the rate of organ-sparing treatment.

Subjects and methods. A new combination treatment option for squamous cell carcinoma of the anal canal was created, which involved a combination of radiotherapy and a multiple radio modification program (ultrahigh-frequency (UHF) hyperthermia and local metronidazole (MZ) injection and systemic polychemotherapy) (RF patent No. 2427399 “A treatment option for squamous cell carcinoma of the anal canal” registered on 27 August 2011). To evaluate the created treatment option, the latter was analyzed in 157 patients with Т1–4N0–3M0 squamous cell carcinoma of the anal canal, who had been treated in 1990 to 2012. In 22 patients, radiotherapy was performed in combination with 3–5 sessions of local UHF hyperthermia (thermoradiotherapy (TRT)); 88 patients received the latter in combination with polychemotherapy (thermoradiochemotherapy (TRCT)); in addition to TRCT, 47 patients used MZ (TRCT + MZ).

Results. In the TRT, TRCT, and TRCT + MZ groups, organ-sparing treatment was performed in 11 (50 %), 71 (80.7 %), and 44 (93.6 %) patients, respectively. In these groups, the median follow-up was 18.6; 51.7, and 15.5 months, respectively. In the 3 groups, the three-year overall survival rates were 71.4; 90.0, and 96.3 % and the three-year relapse free survival rates were 46.7; 60.6, and 75.0 %, respectively.

Conclusion. The created combination thermochemoradiotherapy involving a polymer combination with MZ (TRCT + MZ) makes it possible to achieve organ-sparing treatment in 93.6 % of the patients and to slightly improve 3-year overall and relapse-free survival rates in patients with squamous cell carcinoma of the anal canal who have received organ-sparing treatment although there is only a tendency for statistical survival difference in this patient group.

1. Статистика злокачественных новообразований в России и странах СНГ в 2010 г. Под ред. М. И. Давыдова, Е. М. Аксель. Вестник РОНЦ им. Н. Н. Блохина РАМН 2011;19(Прил. 1).

2. Малихов А. Г. Комбинированное и комплексное лечение больных плоскоклеточным раком анального канала. Дис. … канд. мед. наук. М., 2003.

3. Ryan D. P., Compton C. C., Mayer R. J. Carcinoma of the anal canal. N Engl J Med 2000;342:792–800.

4. Ramamoorthy S., Luo L., Luo E., Carethers J. M. Tobacco smoking and risk of recurrence for squamous cell cancer of the anus. Cancer Detect Prev 2008; 32(2):116–20.

5. Giuliano A., Palefsky J. The efficacy of quadrivalent HPV (types 6 / 11 / 16 / 18) vaccine in reducing the incidence of HPV infection and HPV-related genital disease in young men. EUROGIN, Nov 10, 2008. Nice, France. Abstr. SS19–7a.

6. Pintor M. P., Northover J. M., Nicholls R. J. Squamous cell carcinoma of the anus at one hospital from 1948 to 1984. Br J Surg 1989;76:806–10.

7. Boman B. M., Moertel C. G., O’Connell M. J. et al. Carcinoma of the anal canal. A clinical and pathologic study of 188 cases. Cancer 1984;54:114–25.

8. Cummings B. J. Concomitant radiotherapy and chemotherapy for anal cancer. Semin Oncol 1992;19:102–8.

9. Scholefield J. H., Nugent K. P. Anal cancer. Position statement of the association of coloproctology of Great Britain and Ireland introduction. Colorectal Dis 2011 Feb;13(Suppl 1):1–2.

10. Deans G. T., McAleer J. J., Spence R. A. Malignant anal tumours. Br J Surg 1994;81:500–8.

11. Homsi J., Garrett C. Melanoma of the anal canal: a case series. Dis Colon Rectum 2007;50:1004–10.

12. Fuchshuber P. R., Rodriguez-Bigas M., Weber T., Petrelli N. J. Anal canal and perianal epidermoid cancers. J Am Coll Surg 1997;185:494–505.

13. Иванкова В. С., Демина Э. Д. Проблемы резистентности опухолей в радиационной онкологии. К.: Здоров’я, 2012. 192 с.

14. Gretschel S., Warnick P., Bembenek A. et al. Lymphatic mapping and sentinel lymph node biopsy in epidermoid carcinoma of the anal canal. Eur J Surg Oncol 2008;34(8):890–4.

15. Deniaud-Alexandre E., Touboul E., Tiret E. et al. Results of definitive irradiation in a series of 305 epidermoid carcinomas of the anal canal. Int J Radiat Oncol Biol Phys 2003;56:1259–73.

16. Grabenbauer G. G., Kessler H., Matzel K. E. et al. Tumor site predicts outcome after radiochemotherapy in squamous-cell carcinoma of the anal region: long-term results of 101 patients. Dis Colon Rectum 2005;48:1742–51.

17. Allal A., Kurtz J. M., Pipard G. et al. Chemoradiotherapy versus radiotherapy alone for anal cancer: a retrospective comparison. Int J Radiat Oncol Biol Phys 1993;27:59–66.

18. Papillon J., Montbarbon J. F., Gerard J. P. et al. Interstitial curietherapy in the conservative treatment of anal and rectal cancers. Int J Radiat Oncol Biol Phys 1989;17:1161–69.

19. Sandhu A. P., Symonds R. P., Robertson A. G. et al. Interstitial iridium-192 implantation combined with external radiotherapy in anal cancer: ten years experience. Int J Radiat Oncol Biol Phys 1998;40:575–81.

20. Touboul E., Schlienger M., Buffat L. et al. Epidermoid carcinoma of the anal canal. Cancer 1994;73:1569–79.

21. Nigro N. D., Vaitkevicius V. K., Considine B. Jr. Combined therapy for cancer of the anal canal: a preliminary report. 1974. Dis Colon Rectum 1993 Jul;36(7):709–11.

22. Ajani J. A., Winter K. A., Gunderson L. L. et al. US intergroup anal carcinoma trial: tumor diameter predicts for colostomy. J Clin Oncol 2009;27:1116–21.

23. Bartelink H., Roelofsen F., Eschwege F. et al. Concomitant radiotherapy and chemotherapy is superior to radiotherapy alone in the treatment of locally advanced anal cancer: Results of a phase III randomized trial of the European Organization for Research and Treatment of Cancer Radiotherapy and Gastrointestinal Cooperative Groups. J Clin Oncol 1997;15:2040–9.

24. Flam M., John M., Pajak T. F. et al. Role of mitomycin in combination with fluorouracil and radiotherapy, and of salvage chemoradiation in the definitive nonsurgical treatment of epidermoid carcinoma of the anal canal: results of a phase III randomized intergroup study. J Clin Oncol 1996;14:2527–39.

25. Ajani J. A., Winter K. A., Gunderson L. L. et al. Fluorouracil, mitomycin, and radiotherapy vs fluorouracil, cisplatin, and radiotherapy for carcinoma of the anal canal: a randomized controlled trial. JAMA 2008 Apr 23;299(16):1914–21.

26. Epidermoid anal cancer: Results from the UKCCCR randomised trial of radiotherapy alone versus radiotherapy, 5-fluorouracil, and mitomycin. UKCCCR Anal Cancer Trial Working Party. UK Co-ordinating Committee on Cancer Research. Lancet 1996;348:1049–54.

27. James R., Meadows H. M. The second UK phase III anal cancer trial of chemoradiation and maintenance therapy (ACT II): Preliminary results on toxicity and outcome. Proc Am Soc Clin Oncol 2003;22:1151.

28. Peiffert D., Gerard J. P., Ducreux M. et al. Induction chemotherapy (ict) and dose intensification of the radiation boost in locally advanced anal canal carcinoma (laacc): Definitive analysis of the Intergroup Accord 03 trial (Fйdйration Nationale des centres de lutte contre le cancer) Fondation Franзaise de Cancйrologie Digestive. Radiother Oncol 2008;88(suppl 2):S20, abstr 65.

29. Lim F., Glynne-Jones R., Chemotherapy / chemoradiation in anal cancer: A systematic review. Cancer Treat Rev 2011;37(7):520–32.

30. Israel L., Aguilera J., Soudant J. et al. Bleomycin and cis-platinum with or without mitomycin C in 110 previously untreated patients with head and neck cancer. Am J Clin Oncol 1983 Jun;6(3):305–11.

31. Wagenaar H. C., Colombo N., Vergote I. et al. Bleomycin, methotrexate, and CCNU in locally advanced or recurrent, inoperable, squamous-cell carcinoma of the vulva: an EORTC Gynaecological Cancer Cooperative Group Study. European Organization for Research and Treatment of Cancer. Gynecol Oncol 2001 Jun;81(3):348–54.

32. Smith H. O., Stringer C. A., Kavanagh J. J. et al. Treatment of advanced or recurrent squamous cell carcinoma of the uterine cervix with mitomycin-C, bleomycin, and cisplatin chemotherapy. Gynecol Oncol 1993 Jan;48(1):11–5.

33. Sadek H., Azli N., Wendling J. L Treatment of advanced squamous cell carcinoma of the skin with cisplatin, 5-fluorouracil, and bleomycin. Cancer 1990 Oct 15;66(8):1692–6.

34. Marshall D. T., Thomas C. R. Carcinoma of the anal canal. Oncol Rev 2009;3:27–40.

35. Алгоритмы диагностики и лечения злокачественных новообразований. Под ред. В. И. Чиссова. М.: ФГБУ «МНИОИ им. П. А. Герцена» Минздравсоцразвития России, 2010. С. 162–170.

36. Шелыгин Ю. А., Нечушкин М. И., Рыбаков Е. Г. Опухоли анального канала и перианальной кожи. М.: Практическая медицина, 2011. 128 с.

37. Мельников О. Р. Диагностика, клиника и лечение рака анального канала. Практическая онкология 2002;3(2):136–44.

38. Кныш В. И., Тимофеев Ю. М. Злокачественные опухоли анального канала. М., 1997.

39. Барсуков Ю. А. Комбинированное и комплексное лечение больных раком прямой кишки. М., 2011.