Radiation Therapy for Colorectal Cancer

Hee Chul Park; Doo Ho Choi

doi:10.5124/jkma.2010.53.7.592

J Korean Med Assoc > Volume 53(7); 2010 > Article

Park and Choi: Radiation Therapy for Colorectal Cancer

Focused Issue of This Month

Colorectal Cancer

Journal of the Korean Medical Association

Journal of the Korean Medical Association 2010; 53(7): 592-602.

Published online: July 06, 2010

DOI: http://dx.doi.org/10.5124/jkma.2010.53.7.592

Radiation Therapy for Colorectal Cancer

Hee Chul Park, MD, Doo Ho Choi, MD

Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

Corresponding author: Doo Ho Choi. dohochoi@skku.edu

Received May 27, 2010 Accepted June 10, 2010

This is an Open-Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Treatment for high-risk colorectal cancer has evolved from surgical resection alone to the selective use of multimodalities such as chemotherapy and radiation therapy (RT). Postoperative RT can eradicate microscopic disease after surgical resection and preoperative RT leads to decreased tumor burden before the commencement of operation. The role of RT in the management of colon cancer is not confirmatory as of now. While there is some suspicion, no critical evidence can be found. However, some retrospective data support the role of RT to improve the prognosis in patients with colon cancer. Postoperative RT combined with chemotherapy can reduce the locoregional recurrences and exert a critical influence on patients' quality of life. Preoperative RT alone or the combination with chemotherapy down-stages the tumor to decrease the operative morbidity, and promotes the sphincter preservation. Preoperative RT improves local control. In addition, down-staging after neoadjuvant treatment merits attention as prognosticator. Patients who have had better tumor response also had superior survival profile. Treatment approach to locally advanced rectal cancer is changing from postoperative adjuvant one to aggressive application of preoperative modality. Future research efforts will focus the optimal treatment strategies to fortify the complete or near complete response rates. The recent advances in RT technology are also being examined to see whether the tumor response can be enhanced while decreasing toxicity so that more intensive chemotherapy regimens can be combined with RT. This review will trace the evolution of multimodality approach to locally advanced colorectal cancer.

Colon cancer; Rectal cancer; Radiation therapy

References

1. Kim JH. Role of radiotherapy in high-risk colon cancer. J Korean Med Assoc 2002;45:842-850.

2. Willett CG, Fung CY, Kaufman DS, Efird J, Shellito PC. Postoperative radiation therapy for high-risk colon carcinoma. J Clin Oncol 1993;11:1112-1117.

3. Martenson JA Jr, Willett CG, Sargent DJ, Mailliard JA, Donohue JH, Gunderson LL, Thomas CR Jr, Fisher B, Benson AB 3rd, Myerson R, Goldberg RM. Phase III study of adjuvant chemotherapy and radiation therapy compared with chemotherapy alone in the surgical adjuvant treatment of colon cancer: results of intergroup protocol 0130. J Clin Oncol 2004;22:3277-3283.

4. Amos EH, Mendenhall WM, McCarty PJ, Gage JO, Emlet JL, Lowrey GC, Peterson CA, Amos WR. Postoperative radiotherapy for locally advanced colon cancer. Ann Surg Oncol 1996;3:431-436.

5. Fabian C, Giri S, Estes N, Tangen CM, Poplin E, Vogel S, Goodwin W, Rivkin S, Fleming TR, Macdonald JS. Adjuvant continuous infusion 5-FU, whole-abdominal radiation, and tumor bed boost in high-risk stage III colon carcinoma: a Southwest Oncology Group Pilot study. Int J Radiat Oncol Biol Phys 1995;32:457-464.

6. The Gastrointestinal Tumor Study Group. Adjuvant therapy with hepatic irradiation plus fluorouracil in colon carcinoma. Int J Radiat Oncol Biol Phys 1991;21:1151-1156.

7. Mendenhall WM, Million RR, Pfaff WW. Patterns of recurrence in adenocarcinoma of the rectum and rectosigmoid treated with surgery alone: implications in treatment planning with adjuvant radiation therapy. Int J Radiat Oncol Biol Phys 1983;9:977-985.

8. Rich T, Gunderson LL, Lew R, Galdibini JJ, Cohen AM, Donaldson G. Patterns of recurrence of rectal cancer after potentially curative surgery. Cancer 1983;52:1317-1329.

9. Douglass HO Jr, Moertel CG, Mayer RJ, Thomas PR, Lindblad AS, Mittleman A, Stablein DM, Bruckner HW. Survival after postoperative combination treatment of rectal cancer. N Engl J Med 1986;315:1294-1295.

10. Krook JE, Moertel CG, Gunderson LL, Wieand HS, Collins RT, Beart RW, Kubista TP, Poon MA, Meyers WC, Mailliard JA, et al. Effective surgical adjuvant therapy for high-risk rectal carcinoma. N Engl J Med 1991;324:709-715.

11. NIH consensus conference. Adjuvant therapy for patients with colon and rectal cancer. JAMA 1990;264:1444-1450.

12. O'Connell MJ, Martenson JA, Wieand HS, Krook JE, Macdonald JS, Haller DG, Mayer RJ, Gunderson LL, Rich TA. 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.

13. Tepper JE, O'Connell M, Niedzwiecki D, Hollis DR, Benson AB 3rd, Cummings B, Gunderson LL, Macdonald JS, Martenson JA, Mayer RJ. Adjuvant therapy in rectal cancer: analysis of stage, sex, and local control-final report of intergroup 0114. J Clin Oncol 2002;20:1744-1750.

14. Lee JH, Lee JH, Ahn JH, Bahng H, Kim TW, Kang YK, Lee KH, Kim JC, Yu CS, Kim JH, Ahn SD, Kim WK, Kim SH, Lee JS. Randomized trial of postoperative adjuvant therapy in stage II and III rectal cancer to define the optimal sequence of chemo-therapy and radiotherapy: a preliminary report. J Clin Oncol 2002;20:1751-1758.

15. Kim YS, Kim JH, Choi EK, Ahn SD, Lee S, Kim KJ, Lee JH, Kim JC, You CS, Kim HC. Optimal scheme of postoperative chemoradiotherapy in rectal cancer: Phase III prospective randomized trial. J Korean Soc Ther Radiol Oncol 2002;20:53-61.

16. Fisher B, Wolmark N, Rockette H, Redmond C, Deutsch M, Wickerham DL, Fisher ER, Caplan R, Jones J, Lerner 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.

17. Wolmark N, Wieand HS, Hyams DM, Colangelo L, Dimitrov NV, Romond EH, Wexler M, Prager D, Cruz AB Jr, Gordon PH, Petrelli NJ, Deutsch M, Mamounas E, Wickerham DL, Fisher ER, Rockette H, Fisher B. 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.

18. Gunderson LL, Sargent DJ, Tepper JE, O'Connell MJ, Allmer C, Smalley SR, Martenson JA, Haller DG, Mayer RJ, Rich TA, Ajani JA, Macdonald JS, Goldberg RM. 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.

19. Gunderson LL, Sargent DJ, Tepper JE, Wolmark N, O'Connell MJ, Begovic M, Allmer C, Colangelo L, Smalley SR, Haller DG, Martenson JA, Mayer RJ, Rich TA, Ajani JA, MacDonald JS, Willett CG, Goldberg RM. 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.

20. Withers HR, Haustermans K. Where next with preoperative radiation therapy for rectal cancer? Int J Radiat Oncol Biol Phys 2004;58:597-602.

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

22. Kapiteijn E, Marijnen CA, Nagtegaal ID, Putter H, Steup WH, Wiggers T, Rutten HJ, Pahlman L, Glimelius B, van Krieken JH, Leer JW, van de Velde CJ. Dutch Colorectal Cancer Group. Preoperative radiotherapy combined with total mesorectal excision for resectable rectal cancer. N Engl J Med 2001;345:638-646.

23. Peeters KC, van de Velde CJ, Leer JW, Martijn H, Junggeburt JM, Kranenbarg EK, Steup WH, Wiggers T, Rutten HJ, Marijnen CA. 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.

24. Peeters KC, Marijnen CA, Nagtegaal ID, Kranenbarg EK, Putter H, Wiggers T, Rutten H, Pahlman L, Glimelius B, Leer JW, van de Velde CJ. Dutch Colorectal Cancer Group. The TME trial after a median follow-up of 6 years: increased local control but no survival benefit in irradiated patients with resectable rectal carcinoma. Ann Surg 2007;246:693-701.

25. Crane CH, Skibber JM, Feig BW, Vauthey JN, Thames HD, Curley SA, Rodriguez-Bigas MA, Wolff RA, Ellis LM, Delclos ME, Lin EH, Janjan NA. Response to preoperative chemoradiation increases the use of sphincter-preserving surgery in patients with locally advanced low rectal carcinoma. Cancer 2003;97:517-524.

26. 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.

27. 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.

28. Sauer R, Becker H, Hohenberger W, Rödel C, Wittekind C, Fietkau R, Martus P, Tschmelitsch J, Hager E, Hess CF, Karstens JH, Liersch T, Schmidberger H, Raab R. German Rectal Cancer Study Group. Preoperative versus postoperative chemoradiotherapy for rectal cancer. N Engl J Med 2004;351:1731-1740.

29. Guillem JG, Díaz-González JA, Minsky BD, Valentini V, Jeong SY, Rodriguez-Bigas MA, Coco C, Leon R, Hernandez-Lizoain JL, Aristu JJ, Riedel ER, Nitti D, Wong WD, Pucciarelli S. cT3N0 rectal cancer: potential overtreatment with preoperative chemoradiotherapy is warranted. J Clin Oncol 2008;26:368-373.

30. Bujko K, Nowacki MP, Nasierowska-Guttmejer A, Michalski W, Bebenek M, Kryj M. Long-term results of a randomized trial comparing preoperative short-course radiotherapy with preoperative conventionally fractionated chemoradiation for rectal cancer. Br J Surg 2006;93:1215-1223.

31. Siegel R, Burock S, Wernecke KD, Kretzschmar A, Dietel M, Loy V, Koswig S, Budach V, Schlag PM. Preoperative short-course radiotherapy versus combined radiochemotherapy in locally advanced rectal cancer: a multi-centre prospectively randomised study of the Berlin Cancer Society. BMC Cancer 2009;9:50.

32. Collette L, Bosset JF, den Dulk M, Nguyen F, Mineur L, Maingon P, Radosevic-Jelic L, Piérart M, Calais G. European Organisation for Research and Treatment of Cancer Radiation Oncology Group. Patients with curative resection of cT3-4 rectal cancer after preoperative radiotherapy or radiochemotherapy: does anybody benefit from adjuvant fluorouracil-based chemotherapy? A trial of the European Organisation for Research and Treatment of Cancer Radiation Oncology Group J Clin Oncol 2007;25:4379-4386.

33. Rödel C, Martus P, Papadoupolos T, Füzesi L, Klimpfinger M, Fietkau R, Liersch T, Hohenberger W, Raab R, Sauer R, Wittekind C. Prognostic significance of tumor regression after preoperative chemoradiotherapy for rectal cancer. J Clin Oncol 2005;23:8688-8696.

34. Stipa F, Chessin DB, Shia J, Paty PB, Weiser M, Temple LK, Minsky BD, Wong WD, Guillem JG. A pathologic complete response of rectal cancer to preoperative combined-modality therapy results in improved oncological outcome compared with those who achieve no downstaging on the basis of preoperative endorectal ultrasonography. Ann Surg Oncol 2006;13:1047-1053.

35. Kim TH, Chang HJ, Kim DY, Jung KH, Hong YS, Kim SY, Park JW, Oh JH, Lim SB, Choi HS, Jeong SY. Pathologic Nodal Classification Is the Most Discriminating Prognostic Factor for Disease-Free Survival in Rectal Cancer Patients Treated with Preoperative Chemoradiotherapy and Curative Resection. Int J Radiat Oncol Biol Phys 2009.

36. Kim TH, Jeong SY, Choi DH, Kim DY, Jung KH, Moon SH, Chang HJ, Lim SB, Choi HS, Park JG. Lateral lymph node metastasis is a major cause of locoregional recurrence in rectal cancer treated with preoperative chemoradiotherapy and curative resection. Ann Surg Oncol 2008;15:729-737.

37. Baglan KL, Frazier RC, Yan D, Huang RR, Martinez AA, Robertson JM. The dose-volume relationship of acute small bowel toxicity from concurrent 5-FU-based chemotherapy and radiation therapy for rectal cancer. Int J Radiat Oncol Biol Phys 2002;52:176-183.

38. Gallagher MJ, Brereton HD, Rostock RA, Zero JM, Zekoski DA, Poyss LF, Richter MP, Kligerman MM. A prospective study of treatment techniques to minimize the volume of pelvic small bowel with reduction of acute and late effects associated with pelvic irradiation. Int J Radiat Oncol Biol Phys 1986;12:1565-1573.

39. Guerrero Urbano MT, Henrys AJ, Adams EJ, Norman AR, Bedford JL, Harrington KJ, Nutting CM, Dearnaley DP, Tait DM. Intensity-modulated radiotherapy in patients with locally advanced rectal cancer reduces volume of bowel treated to high dose levels. Int J Radiat Oncol Biol Phys 2006;65:907-916.

40. Freedman GM, Meropol NJ, Sigurdson ER, Hoffman J, Callahan E, Price R, Cheng J, Cohen S, Lewis N, Watkins-Bruner D, Rogatko A, Konski A. Phase I trial of preoperative hypofractionated intensity-modulated radiotherapy with incorporated boost and oral capecitabine in locally advanced rectal cancer. Int J Radiat Oncol Biol Phys 2007;67:1389-1393.

41. De Ridder M, Tournel K, Van Nieuwenhove Y, Engels B, Hoorens A, Everaert H, Op de Beeck B, Vinh-Hung V, De Gréve J, Delvaux G, Verellen D, Storme GA. Phase II study of preoperative helical tomotherapy for rectal cancer. Int J Radiat Oncol Biol Phys 2008;70:728-734.

42. Willett CG, Duda DG, di Tomaso E, Boucher Y, Ancukiewicz M, Sahani DV, Lahdenranta J, Chung DC, Fischman AJ, Lauwers GY, Shellito P, Czito BG, Wong TZ, Paulson E, Poleski M, Vujaskovic Z, Bentley R, Chen HX, Clark JW, Jain RK. Efficacy, safety, and biomarkers of neoadjuvant bevacizumab, radiation therapy, and fluorouracil in rectal cancer: a multidisciplinary phase II study. J Clin Oncol 2009;27:3020-3026.

Figure 1

Radiotherapy (RT) planning comparison between intensity modulated radiation therapy (IMRT) and conventional RT. (A) Isodose distribution. IMRT covers the target more conformal than conventional RT. (B) Dose volume histogram. With the same coverage of RT target, small bowel is less irradiated with IMRT.