Neoadjuvant Therapy of Rectal Cancer_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

XIAO Yi

Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China;

Corresponding author：

Keywords：

Rectal cancer; Preoperative chemoradiotherapy; Neoadjuvant therapy

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Objective To discuss the important role of preoperative chemoradiotherapy in the treatment of mid-low rectal cancer.
Methods From the surgical point of view, the evidences from clinic trials in literatures of recent years and also from the results of our single institution were analyzed.
Results Preoperative radiotherapy with total dosage of 50 Gy had showed more and more advantages in the past two decades. Preoperative radiotherapy with concomitant chemotherapy had definite effects in downing stage and improving local control, while its role in sphincter preserving kept in controversy. However, this combined preoperative therapies had not improved long-term survival in rectal cancer. By now, there were no proper indicators to predict the effects of therapies.
Conclusion Preoperative chemoradiotherapy is still the only way to improve the rate of R0 resection and decrease the rate of local currence after surgery for patients with mid-low advanced rectal cancer.

Citation： XIAO Yi. Neoadjuvant Therapy of Rectal Cancer. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2010, 17(9): 906-909. doi: Copy

1.	Higgins GA, Humphrey EW, Dwight RW, et al. Preoperative radiation and surgery for cancer of the rectum. Veterans Administration Surgical Oncology Group Trial Ⅱ [J]. Cancer, 1986; 58(2): 352359.
2.	Gérard A, Buyse M, Nordlinger B, et al. Preoperative radiotherapy as adjuvant treatment in rectal cancer. Final results of a randomized study of the European Organization for Research and Treatment of Cancer (EORTC) [J]. Ann Surg, 1988; 208(5): 606614.
3.	Hyams DM, Mamounas EP, Petrelli N, et al. A clinical trial to evaluate the worth of preoperative multimodality therapy in patients with operable carcinoma of the rectum: a progress report of National Surgical Breast and Bowel Project Protocol R03 [J]. Dis Colon Rectum, 1997; 40(2): 131139.
4.	Medical Research Council Rectal Cancer Working Party. Randomised trial of surgery alone versus radiotherapy followed by surgery for potentially operable locally advanced rectal cance [J]. Lancet, 1996; 348(9042): 16051610.
5.	Stockholm Colorectal Cancer Study Group. Randomized study on preoperative radiotherapy in rectal carcinoma [J]. Ann Surg Oncol, 1996; 3(5): 423430.
6.	Swedish Rectal Cancer Trial. Improved survival with preoperative radiotherapy in resectable rectal cancer [J]. N Engl J Med, 1997; 336(14): 980987.
7.	Kapiteijn E, Marijnen CA, Nagtegaal ID, et al; Dutch Colorectal Cancer Group. Preoperative radiotherapy combined with total mesorectal excision for resectable rectal cancer [J]. N Engl J Med, 2001; 345(9): 638646.
8.	Mohiuddin M, Marks G. High dose preoperative irradiation for cancer of the rectum, 19761988 [J]. Int J Radiat Oncol Biol Phys, 1991; 20(1): 3743.
9.	Janjan NA, Crane CN, Feig BW, et al. Prospective trial of preoperative concomitant boost radiotherapy with continuous infusion 5fluorouracil for locally advanced rectal cancer [J]. Int J Radiat Oncol Biol Phys, 2000; 47(3): 713718.
10.	Sauer R, Becker H, Hohenberger W, et al. Preoperative versus postoperative chemoradiotherapy for rectal cancer [J]. N Engl J Med, 2004; 351(17): 17311740.
11.	Bosset JF, Collette L, Calais G, et al. Chemotherapy with preoperative radiotherapy in rectal cancer [J]. N Engl J Med, 2006; 355(11): 11141123.
12.	Gérard JP, Conroy T, Bonnetain F, et al. Preoperative radiotherapy with or without concurrent fluorouracil and leucovorin in T34 rectal cancers: results of FFCD 9203 [J]. J Clin Oncol, 2006; 24(28): 46204625.
13.	吴文铭, 邱辉忠, 吴斌, 等. 临床病理指标预测直肠癌新辅助治疗疗效的初步探讨 [J].中华外科杂志, 2010; 48(3): 333337.
14.	Capirci C, Valentini V, Cionini L, et al. Prognostic value of pathologic complete response after neoadjuvant therapy in locally advanced rectal cancer: Longterm analysis of 566 ypCR patients [J]. Int J Radiat Oncol Biol Phys, 2008; 72(1): 99107.
15.	Mohiuddin M, Winter K, Mitchell E, et al. Randomized phase Ⅱ study of neoadjuvant combinedmodality chemoradiation for distal rectal cancer: Radiation Therapy Oncology Group Trial 0012 [J]. J Clin Oncol, 2006; 24(4): 650655.
16.	Ryan DP, Niedzwiecki D, Hollis D, et al. Phase Ⅰ/Ⅱ study of preoperative oxaliplatin, fluorouracil, and externalbeam radiation therapy in patients with locally advanced rectal cancer: Cancer and Leukemia Group B 89901 [J]. J Clin Oncol, 2006; 24(16): 25572562.
17.	SebagMontefiore D, Stephens RJ, Steele R, et al. Preoperative radiotherapy versus selective postoperative chemoradiotherapy in patients with rectal cancer (MRC CR07 and NCICCTG C016): a multicentre, randomised trial [J]. Lancet, 2009; 373(9666): 811820.
18.	Chau I, Brown G, Cunningham D, et al. Neoadjuvant capecitabine and oxaliplatin followed by synchronous chemoradiation and total mesorectal excision in magnetic resonance imagingdefined poorrisk rectal cancer [J]. J Clin Oncol 2006; 24(4): 668674.
19.	Carlomagno C, Farella A, Bucci L, et al. Neoadjuvant treatment of rectal cancer with capecitabine and oxaliplatin in combination with radiotherapy: a phase Ⅱ study [J]. Ann Oncol, 2009; 20(5): 906912.
20.	Aschele C, Pinto C, Cordio S, et al. Preoperative fluorouracil (FU)based chemoradiation with and without weekly oxaliplatin in locally advanced rectal cancer: Pathologic response analysis of the Studio Terapia Adiuvante Retto (STAR)01 randomized phase Ⅲ trial [J]. J Clin Oncol, 2009; 27: 18s (suppl; abstr CRA4008).
21.	Gerard J, Azria D, GourgouBourgade S, et al. Randomized multicenter phase Ⅲ trial comparing two neoadjuvant chemoradiotherapy (CTRT) regimens (RT45Cap versus RT50Capox) in patients (pts) with locally advanced rectal cancer (LARC): Results of the ACCORD 12/0405 PRODIGE 2 [J]. J Clin Oncol, 2009; 27: 18s (suppl; abstr LBA4007).
22.	Crane CH, Eng C, Feig BW, et al. Phase Ⅱ trial of neoadjuvant bevacizumab, capecitabine, and radiotherapy for locally advanced rectal cancer [J]. Int J Radiat Oncol Biol Phys, 2010; 76(3): 824830.
23.	Allegra CJ, Yothers G, O’Connell MJ, et al. Initial safety report of NSABP C08: a randomized phase Ⅲ study of modified FOLFOX6 with or without bevacizumab for the adjuvant treatment of patients with stage Ⅱ or Ⅲ colon cancer [J]. J Clin Oncol, 2009; 27(2): 33853390.
24.	肖毅, 邱辉忠. 基于NCCN指南的直肠癌外科治疗 [J]. 癌症进展杂志, 2009; 7(3): 229234.
25.	Moreno García V, Cejas P, Blanco Codesido M, et al. Prognostic value of carcinoembryonic antigen level in rectal cancer treated with neoadjuvant chemoradiotherapy [J]. Int J Colorectal Dis, 2009; 24(7): 741748.
26.	GrilloRuggieri F, Mantello G, Berardi R, et al. Mucinous rectal adenocarcinoma can be associated to tumor downstaging after preoperative chemoradiotherapy [J]. Dis Colon Rectum, 2007; 50(10): 15941603.
27.	Kuremsky JG, Tepper JE, McLeod HL. Biomarkers for response to neoadjuvant chemoradiation for rectal cancer [J]. Int J Radiat Oncol Biol Phys, 2009; 74(3): 673688.
28.	HabrGama A, Perez RO, Nadalin W, et al. Operative versus nonoperative treatment for stage 0 distal rectal cancer following chemoradiation therapy: longterm results [J]. Ann Surg, 2004; 240(4): 711718.
29.	Hiotis SP, Weber SM, Cohen AM, et al. Assessing the predictive value of clinical complete response to neoadjuvant therapy for rectal cancer: an analysis of 488 patients [J]. J Am Coll Surg, 2002; 194(2): 131135.
30.	肖毅, 吴斌, 林国乐, 等. 直肠癌术前放化疗后完全缓解病例的处理 [J]. 中国实用外科杂志, 2008; 28(5): 362364.

1. Higgins GA, Humphrey EW, Dwight RW, et al. Preoperative radiation and surgery for cancer of the rectum. Veterans Administration Surgical Oncology Group Trial Ⅱ [J]. Cancer, 1986; 58(2): 352359.
2. Gérard A, Buyse M, Nordlinger B, et al. Preoperative radiotherapy as adjuvant treatment in rectal cancer. Final results of a randomized study of the European Organization for Research and Treatment of Cancer (EORTC) [J]. Ann Surg, 1988; 208(5): 606614.
3. Hyams DM, Mamounas EP, Petrelli N, et al. A clinical trial to evaluate the worth of preoperative multimodality therapy in patients with operable carcinoma of the rectum: a progress report of National Surgical Breast and Bowel Project Protocol R03 [J]. Dis Colon Rectum, 1997; 40(2): 131139.
4. Medical Research Council Rectal Cancer Working Party. Randomised trial of surgery alone versus radiotherapy followed by surgery for potentially operable locally advanced rectal cance [J]. Lancet, 1996; 348(9042): 16051610.
5. Stockholm Colorectal Cancer Study Group. Randomized study on preoperative radiotherapy in rectal carcinoma [J]. Ann Surg Oncol, 1996; 3(5): 423430.
6. Swedish Rectal Cancer Trial. Improved survival with preoperative radiotherapy in resectable rectal cancer [J]. N Engl J Med, 1997; 336(14): 980987.
7. Kapiteijn E, Marijnen CA, Nagtegaal ID, et al; Dutch Colorectal Cancer Group. Preoperative radiotherapy combined with total mesorectal excision for resectable rectal cancer [J]. N Engl J Med, 2001; 345(9): 638646.
8. Mohiuddin M, Marks G. High dose preoperative irradiation for cancer of the rectum, 19761988 [J]. Int J Radiat Oncol Biol Phys, 1991; 20(1): 3743.
9. Janjan NA, Crane CN, Feig BW, et al. Prospective trial of preoperative concomitant boost radiotherapy with continuous infusion 5fluorouracil for locally advanced rectal cancer [J]. Int J Radiat Oncol Biol Phys, 2000; 47(3): 713718.
10. Sauer R, Becker H, Hohenberger W, et al. Preoperative versus postoperative chemoradiotherapy for rectal cancer [J]. N Engl J Med, 2004; 351(17): 17311740.
11. Bosset JF, Collette L, Calais G, et al. Chemotherapy with preoperative radiotherapy in rectal cancer [J]. N Engl J Med, 2006; 355(11): 11141123.
12. Gérard JP, Conroy T, Bonnetain F, et al. Preoperative radiotherapy with or without concurrent fluorouracil and leucovorin in T34 rectal cancers: results of FFCD 9203 [J]. J Clin Oncol, 2006; 24(28): 46204625.
13. 吴文铭, 邱辉忠, 吴斌, 等. 临床病理指标预测直肠癌新辅助治疗疗效的初步探讨 [J].中华外科杂志, 2010; 48(3): 333337.
14. Capirci C, Valentini V, Cionini L, et al. Prognostic value of pathologic complete response after neoadjuvant therapy in locally advanced rectal cancer: Longterm analysis of 566 ypCR patients [J]. Int J Radiat Oncol Biol Phys, 2008; 72(1): 99107.
15. Mohiuddin M, Winter K, Mitchell E, et al. Randomized phase Ⅱ study of neoadjuvant combinedmodality chemoradiation for distal rectal cancer: Radiation Therapy Oncology Group Trial 0012 [J]. J Clin Oncol, 2006; 24(4): 650655.
16. Ryan DP, Niedzwiecki D, Hollis D, et al. Phase Ⅰ/Ⅱ study of preoperative oxaliplatin, fluorouracil, and externalbeam radiation therapy in patients with locally advanced rectal cancer: Cancer and Leukemia Group B 89901 [J]. J Clin Oncol, 2006; 24(16): 25572562.
17. SebagMontefiore D, Stephens RJ, Steele R, et al. Preoperative radiotherapy versus selective postoperative chemoradiotherapy in patients with rectal cancer (MRC CR07 and NCICCTG C016): a multicentre, randomised trial [J]. Lancet, 2009; 373(9666): 811820.
18. Chau I, Brown G, Cunningham D, et al. Neoadjuvant capecitabine and oxaliplatin followed by synchronous chemoradiation and total mesorectal excision in magnetic resonance imagingdefined poorrisk rectal cancer [J]. J Clin Oncol 2006; 24(4): 668674.
19. Carlomagno C, Farella A, Bucci L, et al. Neoadjuvant treatment of rectal cancer with capecitabine and oxaliplatin in combination with radiotherapy: a phase Ⅱ study [J]. Ann Oncol, 2009; 20(5): 906912.
20. Aschele C, Pinto C, Cordio S, et al. Preoperative fluorouracil (FU)based chemoradiation with and without weekly oxaliplatin in locally advanced rectal cancer: Pathologic response analysis of the Studio Terapia Adiuvante Retto (STAR)01 randomized phase Ⅲ trial [J]. J Clin Oncol, 2009; 27: 18s (suppl; abstr CRA4008).
21. Gerard J, Azria D, GourgouBourgade S, et al. Randomized multicenter phase Ⅲ trial comparing two neoadjuvant chemoradiotherapy (CTRT) regimens (RT45Cap versus RT50Capox) in patients (pts) with locally advanced rectal cancer (LARC): Results of the ACCORD 12/0405 PRODIGE 2 [J]. J Clin Oncol, 2009; 27: 18s (suppl; abstr LBA4007).
22. Crane CH, Eng C, Feig BW, et al. Phase Ⅱ trial of neoadjuvant bevacizumab, capecitabine, and radiotherapy for locally advanced rectal cancer [J]. Int J Radiat Oncol Biol Phys, 2010; 76(3): 824830.
23. Allegra CJ, Yothers G, O’Connell MJ, et al. Initial safety report of NSABP C08: a randomized phase Ⅲ study of modified FOLFOX6 with or without bevacizumab for the adjuvant treatment of patients with stage Ⅱ or Ⅲ colon cancer [J]. J Clin Oncol, 2009; 27(2): 33853390.
24. 肖毅, 邱辉忠. 基于NCCN指南的直肠癌外科治疗 [J]. 癌症进展杂志, 2009; 7(3): 229234.
25. Moreno García V, Cejas P, Blanco Codesido M, et al. Prognostic value of carcinoembryonic antigen level in rectal cancer treated with neoadjuvant chemoradiotherapy [J]. Int J Colorectal Dis, 2009; 24(7): 741748.
26. GrilloRuggieri F, Mantello G, Berardi R, et al. Mucinous rectal adenocarcinoma can be associated to tumor downstaging after preoperative chemoradiotherapy [J]. Dis Colon Rectum, 2007; 50(10): 15941603.
27. Kuremsky JG, Tepper JE, McLeod HL. Biomarkers for response to neoadjuvant chemoradiation for rectal cancer [J]. Int J Radiat Oncol Biol Phys, 2009; 74(3): 673688.
28. HabrGama A, Perez RO, Nadalin W, et al. Operative versus nonoperative treatment for stage 0 distal rectal cancer following chemoradiation therapy: longterm results [J]. Ann Surg, 2004; 240(4): 711718.
29. Hiotis SP, Weber SM, Cohen AM, et al. Assessing the predictive value of clinical complete response to neoadjuvant therapy for rectal cancer: an analysis of 488 patients [J]. J Am Coll Surg, 2002; 194(2): 131135.
30. 肖毅, 吴斌, 林国乐, 等. 直肠癌术前放化疗后完全缓解病例的处理 [J]. 中国实用外科杂志, 2008; 28(5): 362364.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Neoadjuvant Therapy of Rectal Cancer

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