• 中國醫(yī)學(xué)科學(xué)院 北京協(xié)和醫(yī)學(xué)院 北京協(xié)和醫(yī)院 基本外科（北京 100730）;

目的 論述近年來術(shù)前放化療即新輔助治療在中低位直腸癌綜合治療模式中的作用。
方法 結(jié)合近期文獻(xiàn)及筆者單位的經(jīng)驗(yàn)，從外科治療角度，就新輔助治療的重點(diǎn)關(guān)注問題進(jìn)行闡述。
結(jié)果 新輔助治療經(jīng)過20余年的發(fā)展，總劑量50 Gy的長程放療顯示出較多優(yōu)勢。新輔助治療在腫瘤降期、術(shù)后局部控制率方面取得明顯優(yōu)勢； 但對提高保肛手術(shù)幾率目前還有不同看法； 同時大量的研究結(jié)果沒有發(fā)現(xiàn)該治療方式能提高患者的遠(yuǎn)期存活率； 目前還沒有手段預(yù)測其治療敏感性。
結(jié)論 對于進(jìn)展期中低位直腸癌，新輔助治療仍是提高手術(shù)R0切除率、降低術(shù)后局部復(fù)發(fā)的有效治療方式。

引用本文： 肖毅. 直腸癌新輔助治療. 中國普外基礎(chǔ)與臨床雜志, 2010, 17(9): 906-909. doi: 復(fù)制

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. 吳文銘, 邱輝忠, 吳斌, 等. 臨床病理指標(biāo)預(yù)測直腸癌新輔助治療療效的初步探討 [J].中華外科雜志, 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, 邱輝忠. 基于NCCN指南的直腸癌外科治療 [J]. 癌癥進(jìn)展雜志, 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, 吳斌, 林國樂, 等. 直腸癌術(shù)前放化療后完全緩解病例的處理 [J]. 中國實(shí)用外科雜志, 2008; 28(5): 362364.
  1. 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. 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. 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. 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. 5. Stockholm Colorectal Cancer Study Group. Randomized study on preoperative radiotherapy in rectal carcinoma [J]. Ann Surg Oncol, 1996; 3(5): 423430.
  6. 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. 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. 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. 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. 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. 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. 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. 13. 吳文銘, 邱輝忠, 吳斌, 等. 臨床病理指標(biāo)預(yù)測直腸癌新輔助治療療效的初步探討 [J].中華外科雜志, 2010; 48(3): 333337.
  14. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 24. 肖毅, 邱輝忠. 基于NCCN指南的直腸癌外科治療 [J]. 癌癥進(jìn)展雜志, 2009; 7(3): 229234.
  25. 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. 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. 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. 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. 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. 30. 肖毅, 吳斌, 林國樂, 等. 直腸癌術(shù)前放化療后完全緩解病例的處理 [J]. 中國實(shí)用外科雜志, 2008; 28(5): 362364.