Preoperative Chemoradiation Therapy
Postoperative Chemoradiation Therapy
        Chemotherapy
        Addition of Radiation Therapy
The Role of Oxaliplatin for Localized Disease
Treatment Toxicity

Note: Some citations in the text of this section are followed by a level of evidence. The PDQ editorial boards use a formal ranking system to help the reader judge the strength of evidence linked to the reported results of a therapeutic strategy. (Refer to the PDQ summary on Levels of Evidence for more information.)

The primary treatment for patients with rectal cancer is surgical resection of the primary tumor. Local excision of clinical T1 tumors is an acceptable surgical technique for appropriately selected patients. For all but T1 tumors, a mesorectal excision is the treatment of choice. Very selected patients with T2 tumors may be candidates for local excision. Local failure rates in the range of 4% to 8% following rectal resection with appropriate mesorectal excision (total mesorectal excision [TME] for low/middle rectal tumors and mesorectal excision at least 5 cm below the tumor for high rectal tumors) have been reported.[1-5]

The low incidence of local relapse following meticulous mesorectal excision has led some investigators to question the routine use of adjuvant radiation therapy. Because of an increased tendency for first failure in locoregional sites only, the impact of perioperative radiation therapy is greater in rectal cancer than in colon cancer.[6]

Although postoperative therapy for patients with stage II or III rectal cancer remains an acceptable option, neoadjuvant therapy for rectal cancer, using preoperative chemoradiation, is now the preferred option for patients with stage II and III disease.[7][Level of evidence: 1iA] Benefits of neoadjuvant chemoradiation include tumor regression, downstaging and improvement in resectability, and a higher rate of sphincter preservation and local control.[7] Complete pathologic response rates of 10% to 25% may be achieved with preoperative chemoradiation therapy.[8-15] However, preoperative radiation therapy is associated with increased complications compared to surgery alone; some patients with cancers at a lower risk of local recurrence might be adequately treated with surgery and adjuvant chemotherapy.[16-19]

Multiple phase II studies of preoperative chemoradiation suggested that administering radiation therapy prior to surgery improved the toxicity profile of chemoradiation and enhanced the possibility of sphincter-sparing surgery. The German Rectal Cancer Study Group randomly assigned 823 patients with ultrasound (US)-staged T3/T4 or node-positive rectal cancer to either preoperative chemoradiation therapy or postoperative chemoradiation therapy (50.4 Gy in 28 daily fractions to the tumor and pelvic lymph nodes concurrent with infusional 5-FU 1,000 mg/m² daily for 5 days during the first and fifth weeks of radiation therapy).[7] All patients received a TME and an additional four cycles of 5-FU–based chemotherapy postoperatively. The overall 5-year survival rates were 76% and 74% for preoperative and postoperative chemoradiation, respectively (P = .80). The 5-year cumulative incidence of local relapse was 6% for patients assigned to preoperative chemoradiation and 13% in the postoperative treatment group (P = .006). Grade 3 or grade 4 acute toxic effects occurred in 27% of the patients in the preoperative treatment group as compared with 40% of the patients in the postoperative treatment group (P = .001); the corresponding rates of long-term toxic effects were 14% and 24%, respectively (P = .01).[7][Level of evidence: 1iA] There was no difference in the number of patients receiving an abdominoperineal resection in each arm. However, among the 194 patients with tumors that were determined by the surgeon before randomization to require an abdominoperineal excision, a statistically significant increase in sphincter preservation was achieved among patients who received preoperative chemoradiation (P = .004).

Among the patients assigned to the postoperative chemoradiation therapy arm, 18% actually had pathologically determined stage I disease and were overestimated by endorectal US to have T3/T4 or N1 disease. A similar number of patients were possibly overtreated in the preoperative treatment group. Nevertheless, on the basis of this study, preoperative chemoradiation therapy has become the standard treatment for patients with clinically staged T3/T4 or N1 disease. Postoperative chemotherapy with 4 to 6 months of fluoropyrimidine-based therapy has become a standard treatment, as evidenced by the control arm in current cooperative group studies.

Recent progress in adjuvant postoperative treatment regimens relates to the integration of systemic therapy with radiation therapy, as well as redefining the techniques for both modalities. The efficacy of postoperative radiation therapy and fluorouracil (5-FU)-based chemotherapy for stage II and III rectal cancer was established by a series of prospective, randomized clinical trials from the Gastrointestinal Tumor Study Group (GITSG-7175), the Mayo/North Central Cancer Treatment Group (NCCTG-794751), and the National Surgical Adjuvant Breast and Bowel Project (NSABP R-01).[20-22][Level of evidence: 1iiA] These studies demonstrated an increase in both disease-free survival (DFS) interval and OS when radiation therapy was combined with chemotherapy after surgical resection. Following publication of the results of these trials, experts at a National Cancer Institute-sponsored Consensus Development Conference in 1990 concluded that postoperative combined-modality treatment is recommended for patients with stage II and III rectal carcinoma.[23]

Subsequent studies have attempted to increase the survival benefit by improving radiation sensitization and by identifying the optimal chemotherapeutic agents and delivery systems. The agents associated with the first successful combined-modality treatments were 5-FU and semustine. Semustine is not commercially available, and previous studies have associated this drug with the potential for increased risks of renal toxic effects and leukemia.

A follow-up randomized trial from GITSG demonstrated that semustine does not produce an additive survival benefit to radiation therapy and 5-FU.[24][Level of evidence: 1iiA] The Intergroup 86-47-51 trial (NCCTG-864751) showed a 10% improvement in OS with the use of continuous-infusion 5-FU (225 mg/m²/day) throughout the course of radiation therapy when compared with bolus 5-FU (500 mg/m² times three injections in the first and fifth weeks of radiation).[25][Level of evidence: 1iiA]

Subsequently, several studies attempted to determine the optimal way to deliver adjuvant 5-FU. The final results of Intergroup 0114 (INT-0114) demonstrated no survival or local control benefit with the addition of leucovorin, levamisole, or both to 5-FU administered postoperatively for stage II and III rectal cancers at a median follow-up of 7.4 years.[18][Level of evidence: 1iiA] Another study, Intergroup 0144 (SWOG-9304), was a three-arm randomized trial designed to determine whether continuous-infusion 5-FU throughout the entire standard six-cycle course of adjuvant chemotherapy was more effective than continuous 5-FU only during pelvic radiation.[26]

• Arm 1 received bolus 5-FU in two 5-day cycles before (500 mg/m²/day) and after (450 mg/m²/day) radiation therapy, with protracted venous infusion 5-FU (225 mg/m²/day) during radiation therapy.
• Arm 2 received continuous infusion 5-FU before (300 mg/m²/day for 42 days), after (300 mg/m²/ day for 56 days), and during (225 mg/m²/day) radiation therapy.
• Arm 3 received bolus 5-FU plus leucovorin in two 5-day cycles before (5-FU 425 mg/m²/day; leucovorin 20 mg/m²/day) and after (5-FU 380 mg/m²/day; leucovorin 20 mg/m²/day) radiation therapy, and bolus 5-FU plus leucovorin (5-FU 400 mg/m²/day; leucovorin 20 mg/m²/day; days 1 to 4, every 28 days) during radiation therapy. Levamisole (150 mg/day) was administered in 3-day cycles every 14 days before and after radiation therapy.

Median follow-up was 5.7 years. Lethal toxicity was less than 1%, with grade 3 to 4 hematologic toxicity in 55% and 49% of patients in the two bolus arms, respectively (i.e., arms 1 and 3) versus 4% of patients in the continuous-infusion arm. No DFS, OS, or locoregional failure (LRF) difference was detected (across all arms: 3-year DFS, 67% to 69%; 3-year OS, 81% to 83%; LRF, 4.6% to 8%).[26][Level of evidence: 1iiA]

Although the above data demonstrate a benefit with postoperative radiation therapy and 5-FU chemotherapy for patients with stage II and III rectal cancer, a follow-up study to the NSABP R-01 trial, the NSABP R-02 study, addressed whether the addition of radiation therapy to chemotherapy would enhance the survival advantage reported in R-01.[27][Level of evidence: 1iiA] The addition of radiation, while significantly reducing local recurrence at 5 years (8% for chemotherapy and radiation vs. 13% for chemotherapy alone, P = .02), demonstrated no significant benefit in terms of survival. The interpretation of the interaction of radiation therapy with prognostic factors, however, was challenging. Radiation appeared to improve survival among patients younger than 60 years, as well as among patients who received abdominoperineal resection. This trial has initiated discussion in the oncologic community as to the proper role of postoperative radiation therapy. Omission of radiation therapy seems premature, since locoregional recurrence remains a clinically relevant problem.

Using current surgical techniques, including TME, it may be possible to identify subsets of patients whose chance of pelvic failure is low enough to omit postoperative radiation. A trial conducted by the Dutch Colorectal Cancer Group (CKVO-9504) randomly assigned patients with resectable rectal cancers (stages I–IV) to a short course of radiation (5 Gy × 5 days) followed by TME compared to TME alone and demonstrated no difference in OS at 2 years (82% for both arms).[28][Level of evidence: 1iiA] Local recurrence rates were significantly reduced in the radiation therapy plus TME arm (2.4%) as compared to the TME only arm (8.2%, P < .001).

At present, acceptable postoperative therapy for patients with stage II or III rectal cancer not enrolled in clinical trials includes continuous-infusion 5-FU during 45 Gy to 55 Gy pelvic radiation and four cycles of adjuvant maintenance chemotherapy with bolus 5-FU with or without modulation with leucovorin.

An analysis of patients treated with postoperative chemotherapy and radiation therapy suggests that these patients may have more chronic bowel dysfunction compared to those who undergo surgical resection alone.[29] Improved radiation planning and techniques can be used to minimize treatment-related complications. These techniques include the use of multiple pelvic fields, prone positioning, customized bowel immobilization molds (belly boards), bladder distention, visualization of the small bowel through oral contrast, and the incorporation of three-dimensional or comparative treatment planning.[30,31]

Oxaliplatin has significant activity when combined with 5-FU-leucovorin in patients with metastatic colorectal cancer. In the randomized Multicenter International Study of Oxaliplatin/5-Fluorouracil/Leucovorin in the Adjuvant Treatment of Colon Cancer (MOSAIC) study, the toxic effects and efficacy of FOLFOX4 (a 2-hour infusion of 200 mg/m² leucovorin, followed by a bolus of 400 mg/m² 5-FU, and then a 22-hour infusion of 600 mg/m² 5-FU on 2 consecutive days every 14 days for 12 cycles, plus a 2-hour infusion of 85 mg/m² oxaliplatin on day 1, given simultaneously with the leucovorin) were compared with the same 5-FU-leucovorin regimen without oxaliplatin when administered for 6 months.[32] Each arm of the trial included 1,123 patients. Preliminary results of the study, with 37 months of follow-up, demonstrated a significant improvement in DFS at 3 years (77.8% vs. 72.9%; P = .01) in favor of FOLFOX4. There was no difference in OS.[33][Level of evidence: 1iiDii] Patients treated with FOLFOX4 experienced more frequent toxic effects, consisting mainly of neutropenia (41% >grade 3) and reversible peripheral sensory neuropathy (12.4% >grade 3). These results are still preliminary, and additional information with regard to OS is anticipated. Nevertheless, these data suggest that FOLFOX4 may be a therapeutic option for patients with resected stage III colon cancer.[33]

The results of NSABP C-07 confirm and extend the results of the MOSAIC trial.[34] In NSABP C-07, 2,492 patients with stage II or III colon cancer were randomly assigned to receive either FLOX (2-hour intravenous infusion of 85 mg/m² oxaliplatin on days 1, 15, and 29 of each 8-week treatment cycle, followed by a 2-hour intravenous infusion of 500 mg/m² leucovorin plus bolus 500 mg/m² 5-FU 1 hour after the start of the leucovorin infusion on days 1, 8, 15, 22, 29, and 36, followed by a 2-week rest period, for a total of three cycles [24 weeks]) or the same chemotherapy without oxaliplatin (Roswell Park regimen). The 3- and 4-year DFS rates were 71.8% and 67% for the Roswell Park regimen and 76.1% and 73.2% for FLOX, respectively. The hazard ratio was 0.80 (95% confidence interval [CI], 0.69–0.93), a 20% risk reduction in favor of FLOX (P <.004).

Many academic oncologists recommend that FOLFOX be considered the standard for adjuvant chemotherapy in rectal cancer. However, there are no data in rectal cancer to support this consideration. FOLFOX has become the standard arm in the latest Intergroup study evaluating adjuvant chemotherapy in rectal cancer. The Eastern Cooperative Oncology Group trial ECOG-5202 is randomly assigning patients with stage II or III rectal cancer who have received preoperative or postoperative chemoradiation therapy to 6 months of FOLFOX with or without bevacizumab.

The other large and ongoing study in the United States, NSABP-R-04, is evaluating the role of capecitabine and oxaliplatin administered concurrently with radiation therapy. NSABP-R-04 is randomly assigning patients in a 2 × 2 factorial design to one of the following four treatment groups for clinically staged T3 or T4 or node-positive rectal cancer:

1. Intravenous continuous infusion (IVCI) 5-FU with radiation therapy.
2. Capecitabine with radiation therapy.
3. IVCI 5-FU plus weekly oxaliplatin with radiation therapy.
4. Capecitabine plus weekly oxaliplatin with radiation therapy.

The primary objective of this study is locoregional disease control.

The acute side effects of pelvic radiation therapy for rectal cancer are mainly the result of gastrointestinal toxicity, are self-limiting, and usually resolve within 4 to 6 weeks of completing treatment. Of greater concern is the potential for late morbidity following rectal cancer treatment. Patients who undergo aggressive surgical procedures for rectal cancer can have chronic symptoms, particularly if there is impairment of the anal sphincter.[35] Patients treated with adjuvant radiation therapy appear to have increased chronic bowel dysfunction, anorectal sphincter dysfunction (if the sphincter was surgically preserved), and sexual dysfunction than those who undergo surgical resection alone.[17,36-41]

A Cochrane review highlights the risks of increased surgical morbidity as well as late rectal and sexual function in association with adjuvant therapy.[35] Improved radiation planning and techniques may minimize these acute and late treatment-related complications. These techniques include:[42-44]

• The use of high-energy radiation machines.



• The use of multiple pelvic fields.



• Prone patient positioning.



• Customized patient molds (belly boards) to exclude as much small bowel as possible from the fields and immobilize patients during treatment.



• Bladder distention during radiation therapy to exclude as much small bowel as possible from the fields.



• Visualization of the small bowel through oral contrast during treatment planning so that when possible, the small bowel can be excluded from the radiation field.



• The use of three dimensional or other advanced radiation planning techniques.

In Europe, it is common to deliver preoperative radiation therapy alone in one week (5 Gy x 5 daily treatments) followed by surgery one week later, as compared to the long-course chemoradiation approach in the United States. One reason for this difference is the concern in the U.S. for heightened late effects with high radiation doses per fraction. A Polish study randomized 316 patients between preoperative long course chemoradiation (50.4 Gy in 28 daily fractions with 5-FU and folinic acid) and short-course preoperative radiation therapy (25 Gy in 5 fractions).[41] Although the primary endpoint was sphincter preservation, late toxicity was not statistically significantly different between the two treatment approaches (7% long course vs. 10% short course). Of note, data on anal sphincter and sexual function were not reported, and toxicity was physician determined, not patient reported. Ongoing clinical trials comparing preoperative and postoperative adjuvant chemoradiation therapy should further clarify the impact of either approach on bowel function and other important quality-of-life issues (e.g., sphincter preservation) in addition to the more conventional endpoints of DFS and OS.

References

1. MacFarlane JK, Ryall RD, Heald RJ: Mesorectal excision for rectal cancer. Lancet 341 (8843): 457-60, 1993.  [PUBMED Abstract]
   
   
2. Enker WE, Thaler HT, Cranor ML, et al.: Total mesorectal excision in the operative treatment of carcinoma of the rectum. J Am Coll Surg 181 (4): 335-46, 1995.  [PUBMED Abstract]
   
   
3. Zaheer S, Pemberton JH, Farouk R, et al.: Surgical treatment of adenocarcinoma of the rectum. Ann Surg 227 (6): 800-11, 1998.  [PUBMED Abstract]
   
   
4. Heald RJ, Smedh RK, Kald A, et al.: Abdominoperineal excision of the rectum--an endangered operation. Norman Nigro Lectureship. Dis Colon Rectum 40 (7): 747-51, 1997.  [PUBMED Abstract]
   
   
5. Lopez-Kostner F, Lavery IC, Hool GR, et al.: Total mesorectal excision is not necessary for cancers of the upper rectum. Surgery 124 (4): 612-7; discussion 617-8, 1998.  [PUBMED Abstract]
   
   
6. Gunderson LL, Sosin H: Areas of failure found at reoperation (second or symptomatic look) following "curative surgery" for adenocarcinoma of the rectum. Clinicopathologic correlation and implications for adjuvant therapy. Cancer 34 (4): 1278-92, 1974.  [PUBMED Abstract]
   
   
7. Sauer R, Becker H, Hohenberger W, et al.: Preoperative versus postoperative chemoradiotherapy for rectal cancer. N Engl J Med 351 (17): 1731-40, 2004.  [PUBMED Abstract]
   
   
8. 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 44 (5): 1027-38, 1999.  [PUBMED Abstract]
   
   
9. Crane CH, Skibber JM, Birnbaum EH, et al.: The addition of continuous infusion 5-FU to preoperative radiation therapy increases tumor response, leading to increased sphincter preservation in locally advanced rectal cancer. Int J Radiat Oncol Biol Phys 57 (1): 84-9, 2003.  [PUBMED Abstract]
   
   
10. Grann A, Minsky BD, Cohen AM, et al.: Preliminary results of preoperative 5-fluorouracil, low-dose leucovorin, and concurrent radiation therapy for clinically resectable T3 rectal cancer. Dis Colon Rectum 40 (5): 515-22, 1997.  [PUBMED Abstract]
    
    
11. Rich TA, Skibber JM, Ajani JA, et al.: Preoperative infusional chemoradiation therapy for stage T3 rectal cancer. Int J Radiat Oncol Biol Phys 32 (4): 1025-9, 1995.  [PUBMED Abstract]
    
    
12. Chari RS, Tyler DS, Anscher MS, et al.: Preoperative radiation and chemotherapy in the treatment of adenocarcinoma of the rectum. Ann Surg 221 (6): 778-86; discussion 786-7, 1995.  [PUBMED Abstract]
    
    
13. 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 40 (2): 131-9, 1997.  [PUBMED Abstract]
    
    
14. 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 46 (2): 323-7, 2000.  [PUBMED Abstract]
    
    
15. 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 Am Coll Surg 194 (2): 131-5; discussion 135-6, 2002.  [PUBMED Abstract]
    
    
16. Lai LL, Fuller CD, Kachnic LA, et al.: Can pelvic radiotherapy be omitted in select patients with rectal cancer? Semin Oncol 33 (6 Suppl 11): S70-4, 2006.  [PUBMED Abstract]
    
    
17. 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 23 (25): 6199-206, 2005.  [PUBMED Abstract]
    
    
18. Tepper JE, O'Connell M, Niedzwiecki D, et al.: Adjuvant therapy in rectal cancer: analysis of stage, sex, and local control--final report of intergroup 0114. J Clin Oncol 20 (7): 1744-50, 2002.  [PUBMED Abstract]
    
    
19. 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 22 (10): 1785-96, 2004.  [PUBMED Abstract]
    
    
20. Thomas PR, Lindblad AS: Adjuvant postoperative radiotherapy and chemotherapy in rectal carcinoma: a review of the Gastrointestinal Tumor Study Group experience. Radiother Oncol 13 (4): 245-52, 1988.  [PUBMED Abstract]
    
    
21. Krook JE, Moertel CG, Gunderson LL, et al.: Effective surgical adjuvant therapy for high-risk rectal carcinoma. N Engl J Med 324 (11): 709-15, 1991.  [PUBMED Abstract]
    
    
22. 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 80 (1): 21-9, 1988.  [PUBMED Abstract]
    
    
23. NIH consensus conference. Adjuvant therapy for patients with colon and rectal cancer. JAMA 264 (11): 1444-50, 1990.  [PUBMED Abstract]
    
    
24. Radiation therapy and fluorouracil with or without semustine for the treatment of patients with surgical adjuvant adenocarcinoma of the rectum. Gastrointestinal Tumor Study Group. J Clin Oncol 10 (4): 549-57, 1992.  [PUBMED Abstract]
    
    
25. 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 331 (8): 502-7, 1994.  [PUBMED Abstract]
    
    
26. Smalley SR, Benedetti JK, Williamson SK, et al.: Phase III trial of fluorouracil-based chemotherapy regimens plus radiotherapy in postoperative adjuvant rectal cancer: GI INT 0144. J Clin Oncol 24 (22): 3542-7, 2006.  [PUBMED Abstract]
    
    
27. 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 92 (5): 388-96, 2000.  [PUBMED Abstract]
    
    
28. Kapiteijn E, Marijnen CA, Nagtegaal ID, et al.: Preoperative radiotherapy combined with total mesorectal excision for resectable rectal cancer. N Engl J Med 345 (9): 638-46, 2001.  [PUBMED Abstract]
    
    
29. Kollmorgen CF, Meagher AP, Wolff BG, et al.: The long-term effect of adjuvant postoperative chemoradiotherapy for rectal carcinoma on bowel function. Ann Surg 220 (5): 676-82, 1994.  [PUBMED Abstract]
    
    
30. Koelbl O, Richter S, Flentje M: Influence of patient positioning on dose-volume histogram and normal tissue complication probability for small bowel and bladder in patients receiving pelvic irradiation: a prospective study using a 3D planning system and a radiobiological model. Int J Radiat Oncol Biol Phys 45 (5): 1193-8, 1999.  [PUBMED Abstract]
    
    
31. Gunderson LL, Russell AH, Llewellyn HJ, et al.: Treatment planning for colorectal cancer: radiation and surgical techniques and value of small-bowel films. Int J Radiat Oncol Biol Phys 11 (7): 1379-93, 1985.  [PUBMED Abstract]
    
    
32. André T, Boni C, Mounedji-Boudiaf L, et al.: Oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment for colon cancer. N Engl J Med 350 (23): 2343-51, 2004.  [PUBMED Abstract]
    
    
33. De Gramont A, Banzi M, Navarro M, et al.: Oxaliplatin/5-FU/LV in adjuvant colon cancer: results of the international randomized MOSAIC trial. [Abstract] Proceedings of the American Society of Clinical Oncology 22: A-1015, 2003. 
    
    
34. de Gramont A, Boni C, Navarro M, et al.: Oxaliplatin/5FU/LV in the adjuvant treatment of stage II and stage III colon cancer: efficacy results with a median follow-up of 4 years. [Abstract] J Clin Oncol 23 (Suppl 16): A-3501, 246s, 2005. 
    
    
35. Wong RK, Tandan V, De Silva S, et al.: Pre-operative radiotherapy and curative surgery for the management of localized rectal carcinoma. Cochrane Database Syst Rev (2): CD002102, 2007.  [PUBMED Abstract]
    
    
36. Randomised trial of surgery alone versus surgery followed by radiotherapy for mobile cancer of the rectum. Medical Research Council Rectal Cancer Working Party. Lancet 348 (9042): 1610-4, 1996.  [PUBMED Abstract]
    
    
37. Initial report from a Swedish multicentre study examining the role of preoperative irradiation in the treatment of patients with resectable rectal carcinoma. Swedish Rectal Cancer Trial. Br J Surg 80 (10): 1333-6, 1993.  [PUBMED Abstract]
    
    
38. Dahlberg M, Glimelius B, Graf W, et al.: Preoperative irradiation affects functional results after surgery for rectal cancer: results from a randomized study. Dis Colon Rectum 41 (5): 543-9; discussion 549-51, 1998.  [PUBMED Abstract]
    
    
39. Birgisson H, Påhlman L, Gunnarsson U, et al.: Adverse effects of preoperative radiation therapy for rectal cancer: long-term follow-up of the Swedish Rectal Cancer Trial. J Clin Oncol 23 (34): 8697-705, 2005.  [PUBMED Abstract]
    
    
40. Marijnen CA, van de Velde CJ, Putter H, et al.: Impact of short-term preoperative radiotherapy on health-related quality of life and sexual functioning in primary rectal cancer: report of a multicenter randomized trial. J Clin Oncol 23 (9): 1847-58, 2005.  [PUBMED Abstract]
    
    
41. Bujko K, Nowacki MP, Nasierowska-Guttmejer A, et al.: Long-term results of a randomized trial comparing preoperative short-course radiotherapy with preoperative conventionally fractionated chemoradiation for rectal cancer. Br J Surg 93 (10): 1215-23, 2006.  [PUBMED Abstract]
    
    
42. Martling A, Holm T, Johansson H, et al.: The Stockholm II trial on preoperative radiotherapy in rectal carcinoma: long-term follow-up of a population-based study. Cancer 92 (4): 896-902, 2001.  [PUBMED Abstract]
    
    
43. Dahlberg M, Glimelius B, Påhlman L: Improved survival and reduction in local failure rates after preoperative radiotherapy: evidence for the generalizability of the results of Swedish Rectal Cancer Trial. Ann Surg 229 (4): 493-7, 1999.  [PUBMED Abstract]
    
    
44. Guerrero Urbano MT, Henrys AJ, Adams EJ, et al.: 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 65 (3): 907-16, 2006.  [PUBMED Abstract]
    
    

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