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Management of Locally Advanced Rectal Cancer

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Colorectal Cancer

Part of the book series: Current Clinical Oncology ((CCO))

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Abstract

The management of locally advanced rectal cancer remains a challenge because of relatively high local recurrence rates, even with optimal surgery. This chapter reviews the evidence from clinical trials for the use of various perioperative strategies based on radiotherapy, chemotherapy, or both in these patients, as well as discusses how these results may inform clinical practice. In particular, two treatment strategies that have been shown to be beneficial and that are standard treatment options for patients with locally advanced disease are short-course preoperative radiotherapy and long-course preoperative chemoradiotherapy. In clinical trials in which these treatments were used in addition to surgery, improvements in local recurrence rates have been observed, although overall survival has less frequently been prolonged. These patients should also receive postoperative adjuvant chemotherapy.

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References

  1. Havenga K, Enker WE, Norstein J, et al. Improved survival and local control after total mesorectal excision or D3 lymphadenectomy in the treatment of primary rectal cancer: an international analysis of 1411 patients. Eur J Surg Oncol 1999;25:368–374.

    Article  PubMed  CAS  Google Scholar 

  2. Nesbakken A, Nygaard K, Westerheim O, Mala T, Lunde OC. Local recurrence after mesorectal excision for rectal cancer. Eur J Surg Oncol 2002;28:126–134.

    Article  PubMed  CAS  Google Scholar 

  3. Heald RJ, Moran BJ, Ryall RD, Sexton R, MacFarlane JK. Rectal cancer: the Basingstoke experience of total mesorectal excision, 1978–1997. Arch Surg 1998;133:894–899.

    Article  PubMed  CAS  Google Scholar 

  4. Kapiteijn E, Marijnen CA, Nagtegaal ID, et al. Preoperative radiotherapy combined with total mesorectal excision for resectable rectal cancer. N Engl J Med 2001;345:638–646.

    Article  PubMed  CAS  Google Scholar 

  5. Houbiers JG, Brand A, van de Watering LM, et al. Randomised controlled trial comparing transfusion of leucocyte-depleted or buffy-coat-depleted blood in surgery for colorectal cancer. Lancet 1994;344:573–578.

    Article  PubMed  CAS  Google Scholar 

  6. Kapiteijn E, Putter H, van de Velde CJ. Impact of the introduction and training of total mesorectal excision on recurrence and survival in rectal cancer in The Netherlands. Br J Surg 2002;89:1142–1149.

    Article  PubMed  CAS  Google Scholar 

  7. Marr R, Birbeck K, Garvican J, et al. The modern abdominoperineal excision: the next challenge after total mesorectal excision. Ann Surg 2005;242:74–82.

    Article  PubMed  Google Scholar 

  8. Minsky BD. Adjuvant therapy for rectal cancer-the transatlantic view. Colorectal Dis 2003;5:416–422.

    Article  PubMed  CAS  Google Scholar 

  9. Gastrointestinal Tumor StudyGroup. Prolongation of the disease-free interval in surgically treated rectal carcinoma. N Engl J Med 1985;312:1465–1472.

    Article  Google Scholar 

  10. Fisher B, Wolmark N, Rockette H, et al. Postoperative adjuvant chemotherapy or radiation therapy for rectal cancer: results from NSABP protocol R-01. J Natl Cancer Inst 1988;80:21–29.

    Article  PubMed  CAS  Google Scholar 

  11. Krook JE, Moertel CG, Gunderson LL, et al. Effective surgical adjuvant therapy for highrisk rectal carcinoma. N Engl J Med 1991;324:709–715.

    Article  PubMed  CAS  Google Scholar 

  12. Tepper JE, O′Connell MJ, Petroni GR, et al. Adjuvant postoperative fluorouracil-modulated chemotherapy combined with pelvic radiation therapy for rectal cancer: initial results of Intergroup 0114. J Clin Oncol 1997;15:2030–2039.

    PubMed  CAS  Google Scholar 

  13. Bosset JF, Magnin V, Maingon P, et al. Preoperative radiochemotherapy in rectal cancer: long-term results of a phase II trial. Int J Radiat Oncol Biol Phys 2000;46:323–327.

    Article  PubMed  CAS  Google Scholar 

  14. 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. Int J Radiat Oncol Biol Phys 2000;47:713–718.

    Article  PubMed  CAS  Google Scholar 

  15. Sauer R, Becker H, Hohenberger W, et al. Preoperative versus postoperative chemoradiotherapy for rectal cancer. N Engl J Med 2004;351:1731–1740.

    Article  PubMed  CAS  Google Scholar 

  16. Guillem JG, Chessin DB, Cohen AM, et al. Long-term oncologic outcome following preoperative combined modality therapy and total mesorectal excision of locally advanced rectal cancer. Ann Surg 2005;241:829–836; discussion 836–838.

    Article  PubMed  Google Scholar 

  17. Gunderson LL, Sargent DJ, Tepper JE, et al. Impact of T and N substage on survival and disease relapse in adjuvant rectal cancer: a pooled analysis. Int J Radiat Oncol Biol Phys 2002;54:386–396.

    Article  PubMed  Google Scholar 

  18. Gunderson LL, Sargent DJ, Tepper JE, et al. Impact of T and N stage and treatment on survival and relapse in adjuvant rectal cancer: a pooled analysis. J Clin Oncol 2004;22:1785–1796.

    Article  PubMed  Google Scholar 

  19. Tobin RL, Mohiuddin M, Marks G. Preoperative irradiation for cancer of the rectum with extrarectal fixation. Int J Radiat Oncol Biol Phys 1991;(21):1127–1132.

    Google Scholar 

  20. Chan AK, Wong AO, Langevin J, et al. Preoperative chemotherapy and pelvic radiation for tethered or fixed rectal cancer: a phase II dose escalation study. Int J Radiat Oncol Biol Phys 2000;48:843–856.

    Article  PubMed  CAS  Google Scholar 

  21. Cedermark B, Johansson H, Rutqvist LE, Wilking N. The Stockholm I trial of preoperative short term radiotherapy in operable rectal carcinoma. A prospective randomized trial. Stockholm Colorectal Cancer Study Group. Cancer 1995;75:2269–2275.

    Article  PubMed  CAS  Google Scholar 

  22. Swedish Rectal Cancer Trial. Improved survival with preoperative radiotherapy in resectable rectal cancer. N Engl J Med 1997;336:980–987.

    Article  Google Scholar 

  23. Martling A, Holm T, Johansson H, Rutqvist LE, Cedermark B. The Stockholm II trial on preoperative radiotherapy in rectal carcinoma: long-term follow-up of a population-based study. Cancer 2001;92:896–902.

    Article  PubMed  CAS  Google Scholar 

  24. Minsky BD, Cohen AM, Enker WE, Kelsen DP, Kemeny N, Frankel J. Efficacy of postoperative 5-FU, high-dose leucovorin, and sequential radiation therapy for clinically resectable rectal cancer. Cancer Invest 1995;13:1–7.

    PubMed  CAS  Google Scholar 

  25. Crane CH, Skibber JM, Feig BW, et al. Response to preoperative chemoradiation increases the use of sphincter-preserving surgery in patients with locally advanced low rectal carcinoma. Cancer 2003;97:517–524.

    Article  PubMed  Google Scholar 

  26. Tominaga T, Sakabe T, Koyama Y, et al. Prognostic factors for patients with colon or rectal carcinoma treated with resection only. Five-year follow-up report. Cancer 1996;78:403–408.

    Article  PubMed  CAS  Google Scholar 

  27. Nagtegaal ID, Marijnen CA, Kranenbarg EK, van de Velde CJ, van Krieken JH. Circumferential margin involvement is still an important predictor of local recurrence in rectal carcinoma: not one millimeter but two millimeters is the limit. Am J Surg Pathol 2002;26:350–357.

    Article  PubMed  Google Scholar 

  28. Wibe A, Rendedal PR, Svensson E, et al. Prognostic significance of the circumferential resection margin following total mesorectal excision for rectal cancer. Br J Surg 2002;89:327–334.

    Article  PubMed  CAS  Google Scholar 

  29. Birbeck KF, Macklin CP, Tiffin NJ, et al. Rates of circumferential resection margin involvement vary between surgeons and predict outcomes in rectal cancer surgery. Ann Surg 2002;235:449–457.

    Article  PubMed  Google Scholar 

  30. Adam IJ, Mohamdee MO, Martin IG, et al. Role of circumferential margin involvement in the local recurrence of rectal cancer. Lancet 1994;344:707–711.

    Article  PubMed  CAS  Google Scholar 

  31. Quirke P, Durdey P, Dixon MF, Williams NS. Local recurrence of rectal adenocarcinoma due to inadequate surgical resection. Histopathological study of lateral tumour spread and surgical excision. Lancet 1986;2:996–999.

    Article  PubMed  CAS  Google Scholar 

  32. Mawdsley S, Glynne-Jones R. The importance of pathological downstaging and the circumferential margin in rectal carcinomas treated with neoadjuvant chemoradiation. Proc Am Soc Clin Oncol 2005;23:281S–3642.

    Google Scholar 

  33. Beets-Tan RG, Beets GL. Rectal cancer: review with emphasis on MR imaging. Radiology 2004;232:335–346.

    Article  PubMed  Google Scholar 

  34. Brown G, Radcliffe AG, Newcombe RG, Dallimore NS, Bourne MW, Williams GT. Preoperative assessment of prognostic factors in rectal cancer using high-resolution magnetic resonance imaging. Br J Surg 2003;90:355–364.

    Article  PubMed  CAS  Google Scholar 

  35. Brown G, Richards CJ, Bourne MW, et al. Morphologic predictors of lymph node status in rectal cancer with use of high-spatial-resolution MR imaging with histopathologic comparison. Radiology 2003;227:371–377.

    Article  PubMed  Google Scholar 

  36. Brown G, Davies S, Williams GT, et al. Effectiveness of preoperative staging in rectal cancer: digital rectal examination, endoluminal ultrasound or magnetic resonance imaging? Br J Cancer 2004;91:23–29.

    Article  PubMed  CAS  Google Scholar 

  37. Beets-Tan RG, Beets GL, Vliegen RF, et al. Accuracy of magnetic resonance imaging in prediction of tumour-free resection margin in rectal cancer surgery. Lancet 2001;357:497–504.

    Article  PubMed  CAS  Google Scholar 

  38. Bartram C, Brown G. Endorectal ultrasound and magnetic resonance imaging in rectal cancer staging. Gastroenterol Clin North Am 2002;31:827–839.

    Article  PubMed  Google Scholar 

  39. Schaffzin DM, Wong WD. Endorectal ultrasound in the preoperative evaluation of rectal cancer. Clin Colorectal Cancer 2004;4:124–132.

    Article  PubMed  Google Scholar 

  40. National Cancer Institute. Adjuvant therapy of rectal cancer. Bethesda, MD, 1991.

    Google Scholar 

  41. Douglass HO Jr, Moertel CG, Mayer RJ, et al. Survival after postoperative combination treatment of rectal cancer. N Engl J Med 1986;315:1294–1295.

    Article  PubMed  Google Scholar 

  42. O’Connell MJ, Martenson JA, Wieand HS, et al. Improving adjuvant therapy for rectal cancer by combining protracted-infusion fluorouracil with radiation therapy after curative surgery. N Engl J Med 1994;331:502–507.

    Article  PubMed  CAS  Google Scholar 

  43. Lee JH, Ahn JH, Bahng H, et al. Randomized trial of postoperative adjuvant therapy in stage II and III rectal cancer to define the optimal sequence of chemotherapy and radiotherapy: a preliminary report. J Clin Oncol 2002;20:1751-1758.

    Google Scholar 

  44. Marijnen CA, Nagtegaal ID, Kapiteijn E, et al. Radiotherapy does not compensate for positive resection margins in rectal cancer patients: report of a multicenter randomized trial. Int J Radiat Oncol Biol Phys 2003;55:1311–1320.

    Article  PubMed  CAS  Google Scholar 

  45. Wolmark N, Wieand HS, Hyams DM, et al. Randomized trial of postoperative adjuvant chemotherapy with or without radiotherapy for carcinoma of the rectum: National Surgical Adjuvant Breast and Bowel Project Protocol R-02. J Natl Cancer Inst 2000;92:388–396.

    Article  PubMed  CAS  Google Scholar 

  46. Gray RG Barnwell J Hills R McConkey C Williams N Kerr D. QUASAR: a randomized study of adjuvant chemotherapy (CT) vs observation including 3238 colorectal cancer patients. Proc Am Soc Clin Oncol 2004;22:245S-3501

    Google Scholar 

  47. Colorectal Cancer Collaborative Group. Adjuvant radiotherapy for rectal cancer: a systematic overview of 8,507 patients from 22 randomised trials. Lancet 2001;358:1291–1304.

    Article  Google Scholar 

  48. Coia LR, Gunderson LL, Haller, et al. Outcomes of patients receiving radiation for carcinoma of the rectum. Results of the 1988–1989 patterns of care study. Cancer 1999;86:1952–

    Article  PubMed  CAS  Google Scholar 

  49. Rominger CJ, Gunderson LL, Gelber RD, Conner N. Radiation therapy alone or in combination with chemotherapy in the treatment of residual or inoperable carcinoma of the rectum and rectosigmoid or pelvic recurrence following colorectal surgery. Radiation Therapy Oncology Group study (76-16). Am J Clin Oncol 1985;8:118–127.

    Article  PubMed  CAS  Google Scholar 

  50. Botwood N, James R, Vernon C, Price P. Raltitrexed (‘Tomudex’) and radiotherapy can be combined as postoperative treatment for rectal cancer. Ann Oncol 2000;11:1023–1028.

    Article  PubMed  CAS  Google Scholar 

  51. James R, Price P, Valentini V. Raltitrexed (Tomudex) concomitant with radiotherapy as adjuvant treatment for patients with rectal cancer: preliminary results of phase I studies. Eur J Cancer 1999;35 Suppl 1:19S–22S.

    Article  Google Scholar 

  52. Roh MS, Colangelo L, Wieand S, et al. Response to preoperative multimodality therapy predicts survival in patients with carcinoma of the rectum. Proc Am Soc Clin Oncol 2004;22:246S–350S.

    Google Scholar 

  53. Minsky BD, Cohen AM, Kemeny N, et al. Combined modality therapy of rectal cancer: decreased acute toxicity with the preoperative approach. J Clin Oncol 1992;10:1218–1224.

    PubMed  CAS  Google Scholar 

  54. Wagman R, Minsky BD, Cohen AM, Guillem JG, Paty PP. Sphincter preservation in rectal cancer with preoperative radiation therapy and coloanal anastomosis: long term follow-up. Int J Radiat Oncol Biol Phys 1998;42:51–57.

    Article  PubMed  CAS  Google Scholar 

  55. Rouanet P, Fabre JM, Dubois JB, et al. Conservative surgery for low rectal carcinoma after high-dose radiation. Functional and oncologic results. Ann Surg 1995;221:67–73.

    Article  PubMed  CAS  Google Scholar 

  56. 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. Dis Colon Rectum 1997;40:131–139.

    Article  PubMed  CAS  Google Scholar 

  57. Minsky BD. Sphincter preservation in rectal cancer. Preoperative radiation therapy followed by low anterior resection with coloanal anastomosis. Semin Radiat Oncol 1998;8:30–35.

    Article  PubMed  CAS  Google Scholar 

  58. Berger C, de Muret A, Garaud P, et al. Preoperative radiotherapy (RT) for rectal cancer: predictive factors of tumor downstaging and residual tumor cell density (RTCD): prognostic implications. Int J Radiat Oncol Biol Phys 1997;37:619–627.

    Article  PubMed  CAS  Google Scholar 

  59. Kaminsky-Forrett MC, Conroy T, Luporsi E, et al. Prognostic implications of downstaging following preoperative radiation therapy for operable T3-T4 rectal cancer. Int J Radiat Oncol Biol Phys 1998;42:935–941.

    Article  PubMed  CAS  Google Scholar 

  60. Janjan NA, Abbruzzese J, Pazdur R, et al. Prognostic implications of response to preoperative infusional chemoradiation in locally advanced rectal cancer. Radiother Oncol 1999;51:153–60.

    Article  PubMed  CAS  Google Scholar 

  61. Janjan NA, Crane C, Feig BW, et al. Improved overall survival among responders to preoperative chemoradiation for locally advanced rectal cancer. Am J Clin Oncol 2001;24:107–112.

    Article  PubMed  CAS  Google Scholar 

  62. Mawdsley S, Glynne-Jones R. The importance of pathological downstaging and the circumferential margin in rectal carcinomas treated with neoadjuvant chemoradiation. J Clin Oncol 2005;23:p3642.

    Google Scholar 

  63. Ahmad N, Nagle DA, Topham A. Pathologic complete response predicts long-term survival following preoperative radiation therapy for rectal cancer. Int J Radiat Oncol Biol Phys 1997;39:284(Abstract 2087).

    Article  Google Scholar 

  64. Hughes R, Glynne-Jones R, Grainger J, et al. Can pathological complete response in the primary tumour following pre-operative pelvic chemoradiotherapy for T3-T4 rectal cancer predict for sterilisation of pelvic lymph nodes, a low risk of local recurrence and the appropriateness of local excision? Int J Colorectal Dis 2006;21:11–17.

    Article  PubMed  CAS  Google Scholar 

  65. Vecchio FM, Valentini V, Minsky BD, et al. The relationship of pathologic tumor regression grade (TRG) and outcomes after preoperative therapy in rectal cancer. Int J Radiat Oncol Biol Phys 2005;62:752–760.

    Article  PubMed  Google Scholar 

  66. Bertolini F, Losi L, Iachetta F, et al. Prognostic value of “Dworak” tumor regression grade (TRG) after pre-operative chemo-ratiotherapy in rectal cancer (RC). Proc Am Soc Clin Oncol 2005;23:280S (Abstract 3636).

    Google Scholar 

  67. Dworak O, Keilholz L, Hoffmann A. Pathological features of rectal cancer after preoperative radiochemotherapy. Int J Colorectal Dis 1997;12:19–23.

    Article  PubMed  CAS  Google Scholar 

  68. Marijnen CA, Nagtegaal ID, Klein Kranenbarg E, et al. No downstaging after short-term preoperative radiotherapy in rectal cancer patients. J Clin Oncol 2001;19:1976–1984.

    PubMed  CAS  Google Scholar 

  69. Holm T, Johansson H, Rutqvist LE, Cedermark B. Tumour location and the effects of preoperative radiotherapy in the treatment of rectal cancer. Br J Surg 2001;88:839–843.

    Article  PubMed  CAS  Google Scholar 

  70. Marijnen CA, Peeters K, Putter H, et al. Long term results, toxicity and quality of life in the TME trial. Program and Proceedings of the 2005 Gastrointestinal Cancers Symposium, Hollywood, Florida 2005:Abstract 166.

    Google Scholar 

  71. Marijnen CA, Kapiteijn E, van de Velde CJ, 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;20:817–825.

    Article  PubMed  CAS  Google Scholar 

  72. Peeters KC, van de Velde CJ, Leer JW, et al. Late side effects of short-course preoperative radiotherapy combined with total mesorectal excision for rectal cancer: increased bowel dysfunction in irradiated patients-a Dutch colorectal cancer group study. J Clin Oncol 2005;23:6199–6206.

    Article  PubMed  CAS  Google Scholar 

  73. Minsky BD, Cohen AM, Enker WE, Paty P. Sphincter preservation with preoperative radiation therapy and coloanal anastomosis. Int J Radiat Oncol Biol Phys 1995;31:553–559.

    Article  PubMed  CAS  Google Scholar 

  74. Willett CG, Shellito PC, Rodkey GV, Wood WC. Preoperative irradiation for tethered rectal carcinoma. Radiother Oncol 1991;21:141–142.

    Article  PubMed  CAS  Google Scholar 

  75. Dosoretz DE, Gunderson LL, Hedberg S, et al. Preoperative irradiation for unresectable rectal and rectosigmoid carcinomas. Cancer 1983;52:814–818.

    Article  PubMed  CAS  Google Scholar 

  76. Minsky BD, Cohen AM, Enker WE, Sigurdson E, Harrison LB. Radiation therapy for unresectable rectal cancer. Int J Radiat Oncol Biol Phys 1991;21:1283–1289.

    PubMed  CAS  Google Scholar 

  77. Mendenhall WM, Million RR, Bland KI, Pfaff WW, Copeland EM III. Initially unresectable rectal adenocarcinoma treated with preoperative irradiation and surgery. Ann Surg 1987;205:41–44. Management of Locally Advanced Rectal Cancer 185 186 Chua and Cunningham

    Article  PubMed  CAS  Google Scholar 

  78. Camma C, Giunta M, Fiorica F, Pagliaro L, Craxi A, Cottone M. Preoperative radiotherapy for resectable rectal cancer: a meta-analysis. JAMA 2000;284:1008–1015.

    Article  PubMed  CAS  Google Scholar 

  79. Pahlman L, Glimelius B. Pre-or postoperative radiotherapy in rectal and rectosigmoid carcinoma. Report from a randomized multicenter trial. Ann Surg 1990;211:187–195.

    Article  PubMed  CAS  Google Scholar 

  80. Frykholm GJ, Glimelius B, Pahlman L. Preoperative or postoperative irradiation in adenocarcinoma of the rectum: final treatment results of a randomized trial and an evaluation of late secondary effects. Dis Colon Rectum 1993;36:564–572.

    Article  PubMed  CAS  Google Scholar 

  81. Stein DE, Mahmoud NN, Anne PR, et al. Longer time interval between completion of neoadjuvant chemoradiation and surgical resection does not improve downstaging of rectal carcinoma. Dis Colon Rectum 2003;46:448–453.

    Article  PubMed  Google Scholar 

  82. Roh MS, Petrelli N, Wiend S, et al. Phase III randomized trial of preoperative versus postoperative multimodality therapy in patients with carcinoma of the rectum (NSABP R-03). Proc Am Soc Clin Oncol 2001;20:123A (Abstract 490).

    Google Scholar 

  83. Minsky B, Cohen A, Enker W, et al. Preoperative 5-fluorouracil, low-dose leucovorin, and concurrent radiation therapy for rectal cancer. Cancer 1994;73:273–280.

    Article  PubMed  CAS  Google Scholar 

  84. Minsky BD, Kemeny N, Cohen AM, et al. Preoperative high-dose leucovorin/5-fluorouracil and radiation therapy for unresectable rectal cancer. Cancer 1991;67:2859–2866.

    Article  PubMed  CAS  Google Scholar 

  85. Bosset JF, Calais G, Daban A, et al. Preoperative chemoradiotherapy versus preoperative radiotherapy in rectal cancer patients: assessment of acute toxicity and treatment compliance. Report of the 22921 randomised trial conducted by the EORTC Radiotherapy Group. Eur J Cancer 2004;40:219–224.

    Article  PubMed  CAS  Google Scholar 

  86. Bosset JF, Calais G, Mineur L, et al. Preoperative radiation (Preop RT) in rectal cancer: effect and timing of additional chemotherapy (CT) 5-year results of the EORTC 22921 trial. Proc Am Soc Clin Oncol 2005;23:247S(Abstract 3505).

    Google Scholar 

  87. Bosset JF, Calais G, Mineur L, et al. Enhanced tumorocidal effect of chemotherapy with preoperative radiotherapy for rectal cancer:preliminary results-EORTC 22921. J Clin Oncol 2005;23:5620–5627.

    Article  PubMed  CAS  Google Scholar 

  88. Gerard J, Bonnetain F, Conroy T, et al. Preoperative (preop) radiotherapy (RT) 5 FU/folinic acid (FA) in T3-4 rectal cancers: results of the FFCD 9203 randomized trial. Proc Am Soc Clin Oncol 2005;23:247S (Abstract 3504).

    Google Scholar 

  89. Rich TA, Skibber JM, Ajani JA, et al. Preoperative infusional chemoradiation therapy for stage T3 rectal cancer. Int J Radiat Oncol Biol Phys 1995;32:1025–1029.

    Article  PubMed  CAS  Google Scholar 

  90. Minsky BD, Cohen AM, Kemeny N, et al. Pre-operative combined 5-FU, low dose leucovorin, and sequential radiation therapy for unresectable rectal cancer. Int J Radiat Oncol Biol Phys 1993;25:821–827.

    PubMed  CAS  Google Scholar 

  91. Minsky BD, Cohen AM, Enker WE, et al. Preoperative 5-FU, low-dose leucovorin, and radiation therapy for locally advanced and unresectable rectal cancer. Int J Radiat Oncol Biol Phys 1997;37:289–295.

    Article  PubMed  CAS  Google Scholar 

  92. Minsky BD, Cohen AM, Kemeny N,et al. The efficacy of preoperative 5-fluorouracil, highdose leucovorin, and sequential radiation therapy for unresectable rectal cancer. Cancer 1993;71:3486–3492.

    Article  PubMed  CAS  Google Scholar 

  93. Marsh RD, Chu NM, Vauthey JN, et al. Preoperative treatment of patients with locally advanced unresectable rectal adenocarcinoma utilizing continuous chronobiologically shaped 5-fluorouracil infusion and radiation therapy. Cancer 1996;78:217–225.

    Article  PubMed  CAS  Google Scholar 

  94. Frykholm GJ, Pahlman L, Glimelius B. Combined chemo-and radiotherapy vs. radiotherapy alone in the treatment of primary, nonresectable adenocarcinoma of the rectum. Int J Radiat Oncol Biol Phys 2001;50:427–434.

    Article  PubMed  CAS  Google Scholar 

  95. Overgaard M, Bertelsen K, Dalmark M, et al. A randomized feasibility study evaluating the effect of radiotherapy alone or combined with 5-fluorouracil in the treatment of locally recurrent or inoperable colorectal carcinoma. Acta Oncol 1993;32:547–553.

    PubMed  CAS  Google Scholar 

  96. Bussieres E, Gilly FN, Rouanet P, et al. Recurrences of rectal cancers: results of a multimodal approach with intraoperative radiation therapy. French Group of IORT. Intraoperative Radiation Therapy. Int J Radiat Oncol Biol Phys 1996;34:49–56.

    Article  PubMed  CAS  Google Scholar 

  97. Minsky BD, Cohen AM, Kemeny N, et al. Enhancement of radiation-induced downstaging of rectal cancer by fluorouracil and high-dose leucovorin chemotherapy. J Clin Oncol 1992;10:79–84.

    PubMed  CAS  Google Scholar 

  98. Kim HK, Jessup JM, Beard CJ, et al. Locally advanced rectal carcinoma: pelvic control and morbidity following preoperative radiation therapy, resection, and intraoperative radiation therapy. Int J Radiat Oncol Biol Phys 1997;38:777-783.

    Google Scholar 

  99. Harrison LB, Minsky BD, Enker WE, et al. High dose rate intraoperative radiation therapy (HDR-IORT) as part of the management strategy for locally advanced primary and recurrent rectal cancer. Int J Radiat Oncol Biol Phys 1998;42:325–330.

    Article  PubMed  CAS  Google Scholar 

  100. Wallace HJ III, Willett CG, Shellito PC, Coen JJ, Hoover HC Jr. Intraoperative radiation therapy for locally advanced recurrent rectal or rectosigmoid cancer. J Surg Oncol 1995;60:122–127.

    Article  PubMed  Google Scholar 

  101. Gunderson LL, Nelson H, Martenson JA, et al. Intraoperative electron and external beam irradiation with or without 5-fluorouracil and maximum surgical resection for previously unirradiated, locally recurrent colorectal cancer. Dis Colon Rectum 1996;39:1379–1395.

    Article  PubMed  CAS  Google Scholar 

  102. Mannaerts GH, Martijn H, Crommelin MA, et al. Intraoperative electron beam radiation therapy for locally recurrent rectal carcinoma. Int J Radiat Oncol Biol Phys 1999;45:297–308.

    Article  PubMed  CAS  Google Scholar 

  103. Dunst J, Reese T, Sutter T, et al. Phase I trial evaluating the concurrent combination of radiotherapy and capecitabine in rectal cancer. J Clin Oncol 2002;20:3983–3991.

    Article  PubMed  CAS  Google Scholar 

  104. Dunst J, Reese T, Debus J, et al. Phase-II-study of preoperative chemoradiation with capecitabine in rectal cancer. Proc Am Soc Clin Oncol 2004;22:259S (Abstract 3559).

    Google Scholar 

  105. Pfeiffer P. High-dose radiotherapy and concurrent UFT plus l-leucovorin in locally advanced rectal cancer: a phase I trial. Acta Oncol 2005;44:224–229.

    Article  PubMed  CAS  Google Scholar 

  106. James RD, Botwood N, Vernon CC, Price P. Raltitrexed plus radiotherapy for the treatment of unresectable/recurrent rectal cancer: a phase I study. Ann Oncol 2003;14:570–573.

    Article  PubMed  CAS  Google Scholar 

  107. Casado E, De Castro J, Castelo B, et al. Phase II study of neoadjuvant treatment of rectal cancer with oxaliplatin, raltitrexed and radiotherapy. Proc Am Soc Clin Oncol 2004;22:305S (Abstract 3746).

    Google Scholar 

  108. Glynne-Jones R, Falk S, Maughan T, Sebag-Montefiore D, Meadows H, Das-Gupta A. Results of preoperative radiation and oxaliplatin in combination with 5-fluorouracil (5-FU) and leucovorin (LV) in locally advanced rectal cancer: a pilot study. Proc Am Soc Clin Oncol 2000;19:310A (Abstract 1225).

    Google Scholar 

  109. Glynne-Jones R, Sebag-Montefiore D, Samuel L, Falk S, Maughan T, McDonald A. Socrates phase II study results: capecitabine (CAP) combined with oxaliplatin (OX) and preoperative radiation (RT) in patients (pts) with locally advanced rectal cancer (LARC). Proc Am Soc Clin Oncol 2005;23:252S (Abstract 3527).

    Google Scholar 

  110. Freyer G, Bossard N, Romestaing P, et al. Addition of oxaliplatin to continuous fluorouracil, l-folinic acid, and concomitant radiotherapy in rectal cancer: the Lyon R 97-03 phase I trial. J Clin Oncol 2001;19:2433–2438.

    PubMed  CAS  Google Scholar 

  111. Aschele C, Friso ML, Pucciarelli S, et al. A phase I–II study of weekly oxaliplatin, 5-fluorouracil continuous infusion and preoperative radiotherapy in locally advanced rectal cancer. Ann Oncol 2005;16:1140–1146.

    Article  PubMed  CAS  Google Scholar 

  112. Carraro S, Roca EL, Cartelli C, et al. Radiochemotherapy with short daily infusion of lowdose oxaliplatin, leucovorin, and 5-FU in T3-T4 unresectable rectal cancer: a phase II IATTGI study. Int J Radiat Oncol Biol Phys 2002;54:397–402.

    Article  PubMed  CAS  Google Scholar 

  113. Machiels JP, Duck L, Honhon B, et al. Phase II study of preoperative oxaliplatin, capecitabine, and external beam radiotherapy in patients with locally advanced rectal adenocarcinoma: the RadiOxCape Study. Program and Proceedings of the 2005 Gastrointestinal Cancers Symposium, Hollywood, Florida 2005:Abstract 245.

    Google Scholar 

  114. Tomirotti M, Asnaghi D, Rovej R, et al. Preoperative chemo/radiotherapy with oxaliplatin and 5FU-AF in rectal cancer. Proc Am Soc Clin Oncol 2004;22:305S (Abstract 3744).

    Google Scholar 

  115. Wolmark N, Wieand S, Kuebler JP, Colangelo L, Smith R. A phase III trial comparing FULV to FULV plus oxaliplatin in stage II or III carcinoma of the colon: results of NSABP protocol C-07. Proc Am Soc Clin Oncol 2005;23:246S (Abstract LBA 3500).

    Google Scholar 

  116. Andre T, Boni C, Mounedji-Boudiaf L, et al. Oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment for colon cancer. N Engl J Med 2004;350:2343–2351.

    Article  PubMed  CAS  Google Scholar 

  117. Alonso V, Salud A, Escudero P, et al. Phase II trial of preoperative chemoradiotherapy with irinotecan and infusional 5-fluorouracil in locally advanced operable rectal carcinoma. Proc Am Soc Clin Oncol 2005;23:256S (Abstract 3542).

    Google Scholar 

  118. Anne PR, Mitchell E, Ahmad N, et al. Radiosensitization in locally advanced adenocarcinoma of the rectum using combined modality therapy (CMT) with CPT-11, 5-fluorouracil concomitant irradiation. Proc Am Soc Clin Oncol 2000;19:250A (Abstract 970).

    Google Scholar 

  119. Dotor E, Navarro M, Vega ME, et al. Irinotecan (CPT-11) and 5-fluorouracil (5-FU) concomitantly with preoperative radiotherapy (RT) in patients (pts) with locally advanced resectable rectal cancer. Updated results of a phase II study. Proc Am Soc Clin Oncol 2004;22:358S (Abstract 4179).

    Google Scholar 

  120. Navarro M, Dotor E, Rivera F, et al. A phase II study of irinotecan (CPT-11) and 5-fluorouracil (5-FU) concomitantly with preoperative radiotherapy (RT) in patients (pts) with locally advanced resectable rectal cancer. Proc Am Soc Clin Oncol 2003;22:308(Abstract 1235).

    Google Scholar 

  121. Mitchell E, Ahmad N, Fry R, et al. Combined modality therapy of locally advanced or recurrent adenocarcinoma of the rectum: preliminary report of a phase I trial of chemotherapy (CT) with CPT-11, 5-FU and concomitant irradiation (RT). Proc Am Soc Clin Oncol 1999;18:247A (Abstract 948).

    Google Scholar 

  122. Levine EL, Gollins S, Susnerwala S, et al. Phase II study of radiotherapy plus concurrent irinotecan (CPT-11) and infusional 5-fluorouracil (5FU) in the treatment of T3-T4 locally advanced inoperable rectal cancer. Proc Am Soc Clin Oncol 2004;22:273S (Abstract 3612).

    Google Scholar 

  123. Willeke F, Tiefenbacher U, Hochhaus A, et al. Phase II trial of capecitabine and irinotecan in combination with concurrent radiotherapy for neoadjuvant treatment of locally advanced rectal cancer. Proc Am Soc Clin Oncol 2005;23:268S(Abstract 3589).

    Google Scholar 

  124. Onaitis MW, Noone RB, Hartwig M, et al. Neoadjuvant chemoradiation for rectal cancer: analysis of clinical outcomes from a 13-year institutional experience. Ann Surg 2001;233:778–785.

    Article  PubMed  CAS  Google Scholar 

  125. Lowy AM, Rich TA, Skibber JM, Dubrow RA, Curley SA. Preoperative infusional chemoradiation, selective intraoperative radiation, and resection for locally advanced pelvic recurrence of colorectal adenocarcinoma. Ann Surg 1996;223:177–185.

    Article  PubMed  CAS  Google Scholar 

  126. Cunningham D, Humblet Y, Siena S, et al. Cetuximab monotherapy and cetuximab plus irinotecan in irinotecan-refractory metastatic colorectal cancer. N Engl J Med 2004;351:337–345.

    Article  PubMed  CAS  Google Scholar 

  127. DIaz Rubio E, Tabernero J, van Cutsem E, et al. Cetuximab in combination with oxaliplatin/ 5-fluorouracil (5-FU)/folinic acid (FA) (FOLFOX-4) in the first-line treatment of patients with epidermal growth factor receptor (EGFR)-expressing metastatic colorectal cancer: An international phase II study. Proc Am Soc Clin Oncol 2005;23:254S (Abstract 3535).

    Google Scholar 

  128. Jennis A, Polikoff J, Mitchell E, et al. Erbitux (cetuximab) plus FOLFOX for colorectal cancer (EXPLORE): preliminary efficacy analysis of a randomized phase III trial. Proc Am Soc Clin Oncol 2005;23:264S (Abstract 3574).

    Google Scholar 

  129. Hurwitz H, Fehrenbacher L, Novotny W, et al. Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med 2004;350:2335–2342.

    Article  PubMed  CAS  Google Scholar 

  130. Giantonio BJ, Catalano PJ, Meropol NJ, et al. High-dose bevacizumab improves survival when combined with FOLFOX4 in previously treated advanced colorectal cancer: Results from the Eastern Cooperative Oncology Group (ECOG) study E3200. Proc Am Soc Clin Oncol 2005;23:1S (Abstract 2).

    Google Scholar 

  131. Hochster HS, Welles L, Hart L, et al. Safety and efficacy of bevacizumab (Bev) when added to oxaliplatin/fluoropyrimidine (O/F) regimens as first-line treatment of metastatic colorectal cancer (mCRC): TREE 1 & 2 Studies. Proc Am Soc Clin Oncol 2005;23:249S (Abstract 3515).

    Google Scholar 

  132. Bonner JA, Giralt J, Harari PM, et al. Cetuximab prolongs survival in patients with locoregionally advanced squamous cell carcinoma of head and neck: a phase III study of high dose radiation therapy with or without cetuximab. Proc Am Soc Clin Oncol 2004;22:489A (Abstract 5507).

    Google Scholar 

  133. Zhu AX, Willett CG. Combined modality treatment for rectal cancer. Semin Oncol 2005;32:103–112.

    Article  PubMed  CAS  Google Scholar 

  134. Shibata D, Guillem JG, Lanouette N, et al. Functional and quality-of-life outcomes in patients with rectal cancer after combined modality therapy, intraoperative radiation therapy, and sphincter preservation. Dis Colon Rectum 2000;43:752–758.

    Article  PubMed  CAS  Google Scholar 

  135. Janjan NA, Khoo VS, Abbruzzese J, et al. Tumor downstaging and sphincter preservation with preoperative chemoradiation in locally advanced rectal cancer: the M. D. Anderson Cancer Center experience. Int J Radiat Oncol Biol Phys 1999;44:1027–1038.

    Article  PubMed  CAS  Google Scholar 

  136. Grann A, Feng C, Wong D, et al. Preoperative combined modality therapy for clinically resectable uT3 rectal adenocarcinoma. Int J Radiat Oncol Biol Phys 2001;49:987–995.

    Article  PubMed  CAS  Google Scholar 

  137. Chau I, Allen M, Cunningham D, et al. Neoadjuvant systemic fluorouracil and mitomycin C prior to synchronous chemoradiation is an effective strategy in locally advanced rectal cancer. Br J Cancer 2003;88:1017–1024.

    Article  PubMed  CAS  Google Scholar 

  138. Chau I, Brown G, Tait D, et al. A multidisciplinary approach using twelve weeks of neoadjuvant capecitabine and oxaliplatin followed by synchronous chemoradiation (CRT) and total mesorectal excision (TME) for MRI defined poor risk rectal cancer, Gastrointestinal Cancers Symposium, Hollywood, Florida, 2005.

    Google Scholar 

  139. Calvo FA, Serrano J, Gomez-Espi M, et al. Neoadjuvant (NA) oxaliplatin (FOLFOX4) followed by chemoradiation (CRT) in locally advanced rectal cancer: intermediate results. Proc Am Soc Clin Oncol 2005;23:277S (Abstract 3624).

    Google Scholar 

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Authors and Affiliations

  1. Department of Medicine, The Royal Marsden Hospital, Surrey, England

    Yu Jo Chua MBBS & David Cunningham MD, FRCP

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  1. Yu Jo Chua MBBS
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  2. David Cunningham MD, FRCP
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  1. Gastrointestinal Oncology Service, Memorial Sloan-Kettering Cancer Center, New York, NY

    Leonard B. Saltz MD

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Chua, Y.J., Cunningham, D. (2007). Management of Locally Advanced Rectal Cancer. In: Markman, M., Saltz, L.B. (eds) Colorectal Cancer. Current Clinical Oncology. Humana Press. https://doi.org/10.1007/978-1-59745-215-1_9

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