Surgery and OncologySurgery and OncologyХирургия и онкология2949-5857Publishing House ABV Press14110.17650/2220-3478-2015-5-3-33-37ORIGINAL REPORTSОРИГИНАЛЬНЫЕ ИССЛЕДОВАНИЯTumor regression after neoadjuvant chemotherapy in locally advanced colon cancerЛечебный патоморфоз опухоли после проведения предоперационной химиотерапии при распространенном раке ободочной кишкиRasulovA. O.РасуловА. О.
Russian Federation
KulushevV. M.КулушевВ. М.
Russian Federation
kulushev@rambler.ruAnanievV. S.АнаньевВ. С.
Russian Federation
FedyaninM. Yu.ФедянинМ. Ю.
Russian Federation
KozlovN. A.КозловН. А.
Russian Federation
N. N. Blokhin Russian Cancer Research Center at the Ministry of Health of RussiaФГБУ «РОНЦ им. Н. Н. Блохина» Минздрава России23 Kashirskoe Shosse, Moscow, 115478, RussiaРоссия, 115478, Москва, Каширское шоссе, 23081020155333370810201508102015Copyright ©; 2015, Rasulov A.O., Kulushev V.M., Ananiev V.S., Fedyanin M.Y., Kozlov N.A.Copyright ©; 2015, Расулов А.О., Кулушев В.М., Ананьев В.С., Федянин М.Ю., Козлов Н.А.2015Rasulov A.O., Kulushev V.M., Ananiev V.S., Fedyanin M.Y., Kozlov N.A.Расулов А.О., Кулушев В.М., Ананьев В.С., Федянин М.Ю., Козлов Н.А.https://creativecommons.org/licenses/by/4.0https://onco-surgery.info/jour/article/view/141

Background. Our aim was to investigate efficacy of neoadjuvant chemotherapy in colon cancer based on tumor regression.

Materials and methods. This retrospective study included colon cancer patients, who underwent treatment at the department of oncoproctology of Russian N. N. Blokhin Cancer Research Center during 2007–2014 and who received a minimum of 2 cycles of neoadjuvant chemotherapy. Primary endpoint was tumor regression. Tumor regression was analyzed separately considering treatment scheme, number of treatment cycles and presence of lymph node metastases.

Results. 18 patients were included (9 male and 9 female). 9 patients had locally advanced T4N0–2M0 colon cancer and 9 patients had metastatic T3–4N0–2M1 colon cancer. 17 (94.4 %) patients had macroscopic signs of residual tumor. Grade 1 and 2 tumor regression(Dworak) was observed in 6 (33.3 %) and 10 (55.5 %) patients respectively. 2 (11.1 %) patients had no signs of tumor regression. Grade 2 tumor regression was most frequently (in 6/10 patients) observed after XELOX or FOLFOX chemotherapy.

Conclusions. Neoadjuvant chemotherapy leads to tumor regression inn most colorectal cancer patients. In our group chemotherapy regimens including oxliplatin were more effective.

neoadjuvant chemotherapyadjuvant chemotherapylarge bowel cancercolon cancerlocally advanced cancertherapeutic pathomorphism of tumorXELOX regimenFOLFOX regimendistant metastasesнеоадъювантная химиотерапияадъювантная химиотерапиярак толстой кишкирак ободочной кишкиместно-распространенная опухольлечебный патоморфоз опухолисхема XELOXсхема FOLFOXотдаленные метастазы1. Landmann R. G., Weiser M. R. Surgical management of locally advanced and locally recurrent colon cancer. Clin Colon Rectal Surg 2005;18(3):182–9.Landmann R. G., Weiser M. R. Surgical management of locally advanced and locally recurrent colon cancer. Clin Colon Rectal Surg 2005;18(3):182–9.2. Costa S. R., Henriques A. C., Horta S. H. et al. En-bloc pancreatoduodenectomy and right hemicolectomy for treating locally advanced right colon cancer (T4): a series of five patients. Arq Gastroenterol 2009;46(2):151–3.Costa S. R., Henriques A. C., Horta S. H. et al. En-bloc pancreatoduodenectomy and right hemicolectomy for treating locally advanced right colon cancer (T4): a series of five patients. Arq Gastroenterol 2009;46(2):151–3.3. Henriques A. C., Waisberg J., Possendoro Kde A. En-bloc pancreaticoduodenectomy and right hemicolectomy for locally advanced right colon cancer treatment. Rev Col Bras Cir 2010;37(3):247–9.Henriques A. C., Waisberg J., Possendoro Kde A. En-bloc pancreaticoduodenectomy and right hemicolectomy for locally advanced right colon cancer treatment. Rev Col Bras Cir 2010;37(3):247–9.4. Fahmy R. G., Dass C. R., Sun L. Q. et al. Transcription factor Egr-1 supports FGF-dependent angiogenesis during neovascularization and tumor growth. Nat Med 2003;9(8):1026–32.Fahmy R. G., Dass C. R., Sun L. Q. et al. Transcription factor Egr-1 supports FGF-dependent angiogenesis during neovascularization and tumor growth. Nat Med 2003;9(8):1026–32.5. Miki C., Tanaka K., Inoue Y. et al. Perioperative host-tumor inflammatory interactions: a potential trigger for disease recurrence following a curative resection for colorectal cancer. Surg Today 2008;38(7):579–84.Miki C., Tanaka K., Inoue Y. et al. Perioperative host-tumor inflammatory interactions: a potential trigger for disease recurrence following a curative resection for colorectal cancer. Surg Today 2008;38(7):579–84.6. Pantel K., Cote R. J., Fodstad O. Detection and clinical importance of micrometastatic disease. J Natl Cancer Inst 1999;91(13):1113–24.Pantel K., Cote R. J., Fodstad O. Detection and clinical importance of micrometastatic disease. J Natl Cancer Inst 1999;91(13):1113–24.7. Tanaka K., Shimada H., Miura M. et al. Metastatic tumor doubling time: most important prehepatectomy predictor of survival and nonrecurrence of hepatic colorectal cancer metastasis. World J Surg 2004;28(3):263–70.Tanaka K., Shimada H., Miura M. et al. Metastatic tumor doubling time: most important prehepatectomy predictor of survival and nonrecurrence of hepatic colorectal cancer metastasis. World J Surg 2004;28(3):263–70.8. Finlay I. G., Meek D., Brunton F., McArdle C. S. Growth rate of hepatic metastases in colorectal carcinoma. Br J Surg 1988;75(7):641–4.Finlay I. G., Meek D., Brunton F., McArdle C. S. Growth rate of hepatic metastases in colorectal carcinoma. Br J Surg 1988;75(7):641–4.9. van Cutsem E., Costa F. Progress in the adjuvant treatment of colon cancer. Has it influenced clinical practice? JAMA2005;294(21):2758–60.van Cutsem E., Costa F. Progress in the adjuvant treatment of colon cancer. Has it influenced clinical practice? JAMA2005;294(21):2758–60.10. O,Connell M. J. Oxaliplatin or irinotecan as adjuvant therapy for colon cancer: the results are in. J Clin Oncol 2009;27(19):3082–4.O,Connell M. J. Oxaliplatin or irinotecan as adjuvant therapy for colon cancer: the results are in. J Clin Oncol 2009;27(19):3082–4.11. Andre T., Boni C., Navarro M. et al. Improved overall survival with oxaliplatin, fluorouracil and leucovorin as adjuvant treatment in stage II or III colon cancer in the MOSAIC trial. J Clin Oncol 2009;27(19):3109–16.Andre T., Boni C., Navarro M. et al. Improved overall survival with oxaliplatin, fluorouracil and leucovorin as adjuvant treatment in stage II or III colon cancer in the MOSAIC trial. J Clin Oncol 2009;27(19):3109–16.12. WHO Classification of tumors of the digestive system. By eds.: F. T. Bosman, F. Carneiro, R. H. Hruban et al. Lyon: IARC, 2010. 417 p.WHO Classification of tumors of the digestive system. By eds.: F. T. Bosman, F. Carneiro, R. H. Hruban et al. Lyon: IARC, 2010. 417 p.13. Dworak O., Keilholz L., Hoffmann A. Pathological features of rectal cancer after preoperative radiochemotherapy. Int J Colorectal Dis 1997;12(1):19–23.Dworak O., Keilholz L., Hoffmann A. Pathological features of rectal cancer after preoperative radiochemotherapy. Int J Colorectal Dis 1997;12(1):19–23.14. van Gijn W., Marijnen C. A., Nagtegaal I. D. et al. Preoperative radiotherapy combined with total mesorectal excision for resectable rectal cancer: 12-year follow-up of the multicentre, randomised controlled TME trial. Lancet Oncol 2011;12(6):575–82.van Gijn W., Marijnen C. A., Nagtegaal I. D. et al. Preoperative radiotherapy combined with total mesorectal excision for resectable rectal cancer: 12-year follow-up of the multicentre, randomised controlled TME trial. Lancet Oncol 2011;12(6):575–82.15. Fokas E., Liersch T., Fietkau R. et al. Tumor regression grading after preoperative chemoradiotherapy for locally advanced rectal carcinoma revisited: updated results of the CAO/ARO/AIO-94 trial. J Clin Oncol 20014;32(5). Published online ahead of print at www.jco.org.Fokas E., Liersch T., Fietkau R. et al. Tumor regression grading after preoperative chemoradiotherapy for locally advanced rectal carcinoma revisited: updated results of the CAO/ARO/AIO-94 trial. J Clin Oncol 20014;32(5). Published online ahead of print at www.jco.org.16. Hong Y. S., Nam B. H., Kim K. P. et al. Adjuvant chemotherapy with oxaliplatin/ 5-fluorouracil/leucovorin (FOLFOX) versus 5-fluorouracil/leucovorin (FL) for rectal cancer patients whose postoperative yp stage 2 or 3 after preoperative chemoradiotherapy: Updated results of 3-year disease-free survival from a randomized phase II study (The ADORE). J Clin Oncol 2014;32:5s (suppl; abstr 3502).Hong Y. S., Nam B. H., Kim K. P. et al. Adjuvant chemotherapy with oxaliplatin/ 5-fluorouracil/leucovorin (FOLFOX) versus 5-fluorouracil/leucovorin (FL) for rectal cancer patients whose postoperative yp stage 2 or 3 after preoperative chemoradiotherapy: Updated results of 3-year disease-free survival from a randomized phase II study (The ADORE). J Clin Oncol 2014;32:5s (suppl; abstr 3502).17. Saltz L., Niedzwiecki D., Hollis D. et al. Irinotecan fluorouracil plus leucovorin is not superior to fluorouracil plus leucovorin alone as adjuvant treatment for stage III colon cancer: results of CALGB 89803. J Clin Oncol 2007;25(23):3456–61.Saltz L., Niedzwiecki D., Hollis D. et al. Irinotecan fluorouracil plus leucovorin is not superior to fluorouracil plus leucovorin alone as adjuvant treatment for stage III colon cancer: results of CALGB 89803. J Clin Oncol 2007;25(23):3456–61.18. Ycou M., Raoul J. L., Douillard J. Y. et al. A phase III randomised trial of LV5FU2 + irinotecan versus LV5FU2 alone in adjuvant high-risk colon cancer (FNCLCC Accord02/ FFCD9802). Ann Oncol 2009;20(4):674–80.Ycou M., Raoul J. L., Douillard J. Y. et al. A phase III randomised trial of LV5FU2 + irinotecan versus LV5FU2 alone in adjuvant high-risk colon cancer (FNCLCC Accord02/ FFCD9802). Ann Oncol 2009;20(4):674–80.19. van Cutsem E., Labianca R., Bodoky G. et al. Randomized phase III trial comparing biweekly infusional fluorouracil/ leucovorin alone or with irinotecan in the adjuvant treatment of stage III colon cancer: PETACC – 3. J Clin Oncol 2009;27(19): 3117–25.van Cutsem E., Labianca R., Bodoky G. et al. Randomized phase III trial comparing biweekly infusional fluorouracil/ leucovorin alone or with irinotecan in the adjuvant treatment of stage III colon cancer: PETACC – 3. J Clin Oncol 2009;27(19): 3117–25.20. de Gramont A., van Catsem E., Tabernero J. et al. AVANT: Results from a randomized three-arm multinational phase III study to investigate bevacizumab with either XELOX or FOLFOX4 versus FOLFOX4 alone as adjuvant treatment for colon cancer. J Clin Oncol 2011;29 (suppl 4; abstr 358).de Gramont A., van Catsem E., Tabernero J. et al. AVANT: Results from a randomized three-arm multinational phase III study to investigate bevacizumab with either XELOX or FOLFOX4 versus FOLFOX4 alone as adjuvant treatment for colon cancer. J Clin Oncol 2011;29 (suppl 4; abstr 358).21. Primrose J., Falk S., Finch-Jones M. et al. Systemic chemotherapy with or without cetuximab in patients with resectable colorectal liver metastasis: the New EPOC randomised controlled trial. Lancet Oncol 2014;15(6):601–11.Primrose J., Falk S., Finch-Jones M. et al. Systemic chemotherapy with or without cetuximab in patients with resectable colorectal liver metastasis: the New EPOC randomised controlled trial. Lancet Oncol 2014;15(6):601–11.22. Nordlinger B., Sorbye H., Glimelius B. et al. Perioperative FOLFOX4 chemotherapy and surgery versus surgery alone for resectable liver metastases from colorectal cancer (EORTC 40983): long-term results of a randomised, controlled, phase 3 trial. Lancet Oncol 013;14(12): 1208–15.Nordlinger B., Sorbye H., Glimelius B. et al. Perioperative FOLFOX4 chemotherapy and surgery versus surgery alone for resectable liver metastases from colorectal cancer (EORTC 40983): long-term results of a randomised, controlled, phase 3 trial. Lancet Oncol 013;14(12): 1208–15.23. Ychou M., Hohenberger W., Thezenas S. et al. A randomized phase III study comparing adjuvant 5-fluorouracil/folinic acidwith FOLFIRI in patients following complete resection of liver metastases from colorectal cancer. Ann Oncol 2009;20(12):1964–70.Ychou M., Hohenberger W., Thezenas S. et al. A randomized phase III study comparing adjuvant 5-fluorouracil/folinic acidwith FOLFIRI in patients following complete resection of liver metastases from colorectal cancer. Ann Oncol 2009;20(12):1964–70.24. de Gramont A., Figer A., Seymour M. et al. Leucovorin and fluorouracil with or without oxaliplatin as first-line treatment in advanced colorectal cancer. J Clin Oncol 2000;18(16):2938–47.de Gramont A., Figer A., Seymour M. et al. Leucovorin and fluorouracil with or without oxaliplatin as first-line treatment in advanced colorectal cancer. J Clin Oncol 2000;18(16):2938–47.25. Giacchetti S., Perpoint B., Zidani R. et al. Phase III multicenter randomized trial of oxaliplatin added to chronomodulated fluorouracil-leucovorin as first-line treatment of metastatic colorectal cancer. J Clin Oncol 2000;18(1):136–47.Giacchetti S., Perpoint B., Zidani R. et al. Phase III multicenter randomized trial of oxaliplatin added to chronomodulated fluorouracil-leucovorin as first-line treatment of metastatic colorectal cancer. J Clin Oncol 2000;18(1):136–47.26. Foxtrot Collaborative Group. Feasibility of preoperative chemotherapy for locally advanced, operable colon cancer: the pilot phase of a randomised controlled trial. Lancet Oncol 2012;13(11):1152–60.Foxtrot Collaborative Group. Feasibility of preoperative chemotherapy for locally advanced, operable colon cancer: the pilot phase of a randomised controlled trial. Lancet Oncol 2012;13(11):1152–60.27. Chan G., Hassanain M., Chaudhury P. et al. Pathological response grade of colorectal liver metastases treated with neoadjuvant chemotherapy. HPB (Oxford) 2010;12(4): 277–84.Chan G., Hassanain M., Chaudhury P. et al. Pathological response grade of colorectal liver metastases treated with neoadjuvant chemotherapy. HPB (Oxford) 2010;12(4): 277–84.