Successful downstaging of high rectal and recto-sigmoid cancer by neo-adjuvant chemo-radiotherapy
Brian O'Neill, Gina Brown, Andrew Wotherspoon, Sarah Burton, Andy Norman, Diana Tait, Brian O'Neill, Gina Brown, Andrew Wotherspoon, Sarah Burton, Andy Norman, Diana Tait
Abstract
Purpose: The benefit of neoadjuvant therapy for tumours above the peritoneal reflection is not clear. The purpose of this study is to demonstrate the feasibility and downstaging of treating locally advanced tumours from high rectum to distal sigmoid with preoperative chemoradiotherapy (CRT).
Methods and materials: Seventeen patients with high rectal, rectosigmoid or distal sigmoid tumours above the peritoneal reflection received neoadjuvant CRT, selected on MRI findings indicating T4 disease or threatened circumferential resection margin. All patients were administered neoadjuvant chemotherapy, with Oxaliplatin or Mitomycin C and a Fluoropyrimidine. The pelvis received long-course CT-planned conformal RT, 45 Gy in 25 fractions, with a boost of 5.4-9 Gy in 3-5 fractions. Thirteen patients were treated with concomitant oral or intravenous Fluoropyrimidine chemotherapy.
Results: Median follow-up was 37 months. Overall survival was 82.35% (95% Confidence Interval (CI) 54.7-93.9) and disease free survival 81.25% (95% CI 52.5-93.5). Only 1 patient suffered loco-regional relapse. Chemotherapy regimens were well tolerated, though some patients required dose reductions. Nine patients (52.9%) lowered pathologic disease AJCC stage, i.e. 'downstaged'. Six patients (35.3%) achieved complete pathological response. Clear margins were attained in all but 1 patient. Three patients were converted from cT4 to ypT3. No patient required a gap during CRT. One patient suffered a grade III acute toxicity, but no grade IV (RTOG). There were 3 grade III and 3 grade IV late toxicities (LENT-SOMA).
Conclusions: Locally advanced high rectal and recto-sigmoid tumours may be treated with pre-operative CRT with acceptable toxicity, impressive down-staging, and clear surgical margins.
Keywords: chemoradiotherapy; chemotherapy; downstaging; radiotherapy; total mesorectal excision.
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References
- ICRU report 50: Prescribing, recording and reporting photon beam therapy. ICRU; Bethesda, MD: 1993.
- Improved survival with preoperative radiotherapy in resectable rectal cancer. Swedish Rectal Cancer Trial. N Engl J Med. 1997;336:980–7.
- Adjuvant radiotherapy for rectal cancer: a systematic overview of 8,507 patients from 22 randomised trials. Lancet. 2001;358:1291–304.
- AJCC Cancer Staging Handbook. Sixth edition. American Joint Committe on Cancer; 2002.
- Balch GC, Mithani SK, Shyr Y, et al. Prognostic significance of response to neoadjuvant chemoradiation therapy for rectal cancer. ASCO Annual Meeting, abstr. 2003;1047
- Burton S, Brown G, Daniels I, et al. MRI identified prognostic features of tumors in distal sigmoid, rectosigmoid and upper rectum: Treatment with radiotherapy and chemotherapy. Int J Radiat Oncol Biol Phys. 2006;65:445–51.
- Camma C, Giunta M, Fiorica F, et al. Preoperative radiotherapy for resectable rectal cancer: A meta-analysis. Jama. 2000;284:1008–15.
- 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;88:1017–24.
- Chau I, Brown G, Cunningham D, et al. Neoadjuvant capecitabine and oxaliplatin followed by synchronous chemoradiation and total mesorectal excision in magnetic resonance imaging-defined poor-risk rectal cancer. J Clin Oncol. 2006;24:668–74.
- Gerard JP, 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. Journal of Clinical Oncology. 2005;23:247s. suppl; abstr 3504.
- Heald RJ, Ryall RD. Recurrence and survival after total mesorectal excision for rectal cancer. Lancet. 1986;1:1479–82.
- Kapiteijn E, Marijnen CA, Nagtegaal ID, et al. Preoperative radiotherapy combined with total mesorectal excision for resectable rectal cancer. N Engl J Med. 2001;345:638–46.
- 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.
- Martenson JAJR, Willett CG, Sargent DJ, et al. 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;22:3277–83.
- Mawdsley S, Glynne-Jones R, Grainger J, et al. Can. histopathologic assessment of circumferential margin after preoperative pelvic chemoradiotherapy for T3–4 rectal cancer predict for 3-year disease-free survival. Int J Radiat Oncol Biol Phys. 2005;63:745–52.
- The Mercury Study Group. Diagnostic accuracy of preoperative magnetic resonance imaging in predicting curative resection of rectal cancer: prospective observational study. BMJ. 2006;333:779.
- Pilipshen SJ, Heilweil M, Quan SH, et al. Patterns of pelvic recurrence following definitive resections of rectal cancer. Cancer. 1984;53:1354–62.
- Quirke P. Minimum dataset for Colorectal Cancer Histopathology Reports. Royal College of Pathologists; 1998.
- Rao S, Cunningham D, Price T, et al. Phase II study of capecitabine and mitomycin C as first-line treatment in patients with advanced colorectal cancer. Br J Cancer. 2004;91:839–43.
- Rodel C, Martus P, Papadoupolos T, et al. Prognostic significance of tumor regression after preoperative chemoradiotherapy for rectal cancer. J Clin Oncol. 2005;23:8688–96.
- Sauer R, Becker H, Hohenberger W, et al. Preoperative versus postoperative chemoradiotherapy for rectal cancer. N Engl J Med. 2004;351:1731–40.
- Shivnani T, Small W, Stryker SJ, et al. Preoperative chemoradiation in Rectal Cancer: Correlation Of tumor response with survival. J Clin Oncol proc, abstr. 2004;247
- Treurniet-Donker AD, Van Putten WL, Wereldsma JC, et al. Postoperative radiation therapy for rectal cancer. An interim analysis of a prospective, randomized multicenter trial in The Netherlands. Cancer. 1991;67:2042–8.
- Willett C, Tepper JE, Cohen A, et al. Local failure following curative resection of colonic adenocarcinoma. Int J Radiat Oncol Biol Phys. 1984;10:645–51.
- Willett CG, Fung CY, Kaufman DS, et al. Postoperative radiation therapy for high-risk colon carcinoma. J Clin Oncol. 1993;11:1112–7.
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