Optimal therapy for resectable rectal cancer

References

• Cancer Research UK. Worldwide Cancer Statistics. Cancer Research UK; 2012.
   Google Scholar
• Macrae FA. Colorectal cancer: epidemiology, risk factors, and protective factors. UpToDate, 2015.
   Google Scholar
• Rouanet P, Saint-Aubert B, Lemanski C, et al. Restorative and nonrestorative surgery for low rectal cancer after high-dose radiation. Dis Colon Rectum. 2002;45:305–315.
   PubMed Web of Science ®Google Scholar
• Wagman R, Minsky B, Cohen A, et al. Spincter preservation with preoperative raidation therapy and coloanal anastamosis: long term follow-up. Int J Radiat Oncol Biol Phys. 1998;42:51–57.
   PubMed Web of Science ®Google Scholar
• Hyams D, Mamounas E, 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 NSABP R-03. Dis Colon Rectum. 1997;40:131–139.
   PubMed Web of Science ®Google Scholar
• Guillem J, Diaz-Gonzalez J, Minsky B, et al. cT3N0 rectal cancer: potential overtreatment with preoperative chemoreadiaotherapy is warranted. J Clin Oncol. 2008;26:368–373.
   PubMed Web of Science ®Google Scholar
• Kapiteijn E, Marijnen C, Nagtegaal I, et al. Preoperative radiotherapy combined with total mesorectal excision for resectable rectal cancer. N Engl J Med. 2001;345:638–646.
   PubMed Web of Science ®Google Scholar
• Peeters K, Marijnen C, Nagtegaal I, et al. 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.
   PubMed Web of Science ®Google Scholar
• Chan E, Wise P. Chakravarthy A. Controversies in radiation for upper rectal cancers. J Natl Compr Canc Netw. 2012;10:1567–1572.
   PubMed Web of Science ®Google Scholar
• Nissan A, Stojadinovic A, Shia J. Predictors of recurrence in patietns with T2 and early T3, N0 adenocarcinoma of the rectum treated by surgery alone. J Clinical Oncol. 2006;24:4078–4084.
   PubMed Web of Science ®Google Scholar
• Czito B, Willett C. Thirty years of rectal cancer research: a brief history. Oncology. 2008;22:1441–1442.
   PubMed Web of Science ®Google Scholar
• Heald R, Ryall R. Recurrent cancer after restorative resection of the rectum. Br Med J. 1983;284:826–827.
   Google Scholar
• Ceelen W. Progress in Rectal Cancer Treatment. ISRN Gastroenterology, 2012:1–15.
   Google Scholar
• Fisher B, Wolmark N, Rockette H, et al. Postoperative adjuvant chemotherapy or radiation therapy for rectal cancer: results from NSABP protocol R-01. JNCI. 1988;80:21–29.
   PubMed Web of Science ®Google Scholar
• Wolmark N, Wieand S, Hyams D, 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. JNCI. 2000;92:388–396.
   PubMed Web of Science ®Google Scholar
• NIH consensus conference. Adjuvant therapy for patients with colon and rectal cancer. Jama. 1990;264:1444–1450.
   PubMed Web of Science ®Google Scholar
• Sauer R, Becker H, Hohenberger W, et al. Preoperative versus postoperative chemoradiotherapy for rectal cancer. N Engl J Med. 2004;351:1731–1740.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• Loos M, Quentmeier P, Schuster T, et al. Effect of preoperative radio(chemo)therapy on long-term functional outcome in rectal cancer patients: a systematic review and meta-analysis. Ann Surg Oncol. 2013;20:1816–1828.
   PubMed Web of Science ®Google Scholar
• Birgisson H, Pahlman L, Gunnarsson U, et al. Adverse effects of peoperative radiation therapy for rectal cancer: long term follow-up of the Swedish Rectal Cancer Trial. J Clin Oncol. 2005;23:8697–8705.
   PubMed Web of Science ®Google Scholar
• Marijnen C, Kapiteijn E, Velde C, 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 randomised trial. J Clin Oncol. 2002;20:817–825.
   PubMed Web of Science ®Google Scholar
• Marijnen C, Velde C, Putter H, et al. Impact of short-term preoprative radiotherapy on health-related quality of life and sexual functioning in primary rectal cancer: report of a multicenter randomized tiral. J Clin Oncol. 2005;23:1847–1858.
   PubMed Web of Science ®Google Scholar
• Peeters K, Velde C, Leer J, et al. Late side effects of short-course preopeartive radiotherapy combined with total mesorectal excision for rectal cancer: increased bowel dysfunction in irradiated patietns - a Dutch colorectal cancer group study. J Clin Oncol. 2005;23:6199–6206.
   PubMed Web of Science ®Google Scholar
• Wiltink L, Chen T, Nout R, et al. Health-related quality of life 14 years after preoperative short-term radiotherapy and total mesorectal excision for rectal cancer: report of a multicenter randomised trial. Eur J Cancer. 2014;50:2390–2398.
   PubMed Web of Science ®Google Scholar
• Folkesson J, Birgisson H, Pahlman L, et al. Swedish Rectal Cancer Trial: long lasting benefits from radiotherapyon survival and local recurrence rate. J Clin Oncol. 2005;23:5644–5650.
   PubMed Web of Science ®Google Scholar
• Kapiteijn E, Marijnen CAM, et al. Preoperative radiotherapy combined with total mesorectal excision for resectable rectal cancer. N Engl J Med. 2001;345:638–646.
   PubMed Web of Science ®Google Scholar
• Gijn W, Marijnen C, Nagtegaal I, et al. Preopertive radiotherapy combined with total mesorectal excision for resectable rectal cancer: 12 year follow-up of the multicentre, randomised controlled TME trial. Lancet Oncol. 2011;12:575–582.
   PubMed Web of Science ®Google Scholar
• Palta M, Willett C, Czito B. Short-course versus long-course chemoradiation in rectal cancer - time to change strategies? Curr Treat Opinions Oncol. 2014;15:421–428.
   PubMed Web of Science ®Google Scholar
• Quirke P, Steele R, Monson J, et al Effect of the plane of surgery achieved on local recurrence in patients with operable rectal cancer: a prospective study using data from MRC CR07 and NCIC-CTG CO16 randomised clinical trial. Lancet. 2009;373:821–828.
   PubMed Web of Science ®Google Scholar
• Sebag-Montefiore D, Stephens R, Steele R. Preoperative radiotherapy versus selective postoperative chemoradiotherapy in patients with rectal cancer (MRC CR07 and NCIC-CTG C016): a multicentre, randomised trial. Lancet. 2009;373:811–820.
   PubMed Web of Science ®Google Scholar
• Bujko K, Nowack M, 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. 2006;93:1215–1223.
   PubMed Web of Science ®Google Scholar
• Ngan S, Burmeister B, Fisher R, et al. Randomized trial of short-course radiotherapy versus long-course chemoradiation comparing rates of local recurrence in patients with t3 rectal cancer: trans-tasman radiation oncology group trial 01.04. J Clin Oncol. 2012;30:3827–3833.
   PubMed Web of Science ®Google Scholar
• Pettersson D, Cedermark B, Holm T, et al. Interim analysis of the Stockholm III trial of preoperative radiotherapy regimens for rectal cancer. Br J Surg. 2010;97:580–587.
   PubMed Web of Science ®Google Scholar
• Siegel R, Burock S, Wernecke K-D. 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;9:1–6.
   PubMed Web of Science ®Google Scholar
• Bosset J, Calais G, Mineur L, et al. Fluorouracil-based adjuvant chemotherapy after preoperative chemoradiotherapy in rectal cancer: long-term results of the EORTC 22921 randomised study. Lancet Oncol. 2014;15:184–190.
   PubMed Web of Science ®Google Scholar
• Bosset J, Collette L, Calais G, et al. Chemotherapy with preoperative radiotherapy in rectal cancer. N Engl J Med. 2006;355:1114–1123.
   PubMed Web of Science ®Google Scholar
• Bujko K, Glimelius B, Valentini V, et al. Postoperative chemotherpay in patients with rectal cancer receiving preoperative radio (chemo)therapy: a meta-analysis of randomized trials comparing surgery ± a fluoropyrimidine and surgery + a fluoropyrimidine +/- oxaliplatin. Ejso. 2015;41:713–723.
   PubMed Web of Science ®Google Scholar
• Rodel C, Martus P, Papadoupolos T, et al. Prognostic significance of tumor regression after preoperative chemoradiotherapy for rectal cancer. J Clin Oncol. 2005;23:8688–8696.
   PubMed Web of Science ®Google Scholar
• Edge S. AJCC Cancer Staging Manual. ed 7th edition. New York: Springer; 2010. p. 143.
   Google Scholar
• Wheeler J, Warren B, Mortensen N, et al. Quantification of histologic regression of rectal cancer after irradiation: a proposal fro a modified stagign system. Dis Colon Rectum. 2002;45:1051–1056.
   PubMed Web of Science ®Google Scholar
• Vecchio F, Valentini V, Minsky B, et al. The relationship of pathological tumor regression grade (TRG) and outcomes after preoperative therapy in rectal cancer. Int J Radiat Oncol Biol Phys. 2005;62:752–760.
   PubMed Web of Science ®Google Scholar
• Fokas E, Liersch T, Fietkau R, et al. Tumor regression grading after preoperative chemoradiotherapy for locally advanced rectal carcinoma revisited: updated results of the CAO/ARO/AIO-94 trial. J Clin Oncol. 2014;32:1–9.
   PubMed Web of Science ®Google Scholar
• Washington M, Berlin J, Branton P, et al. Protocol for the examination of specimens from patients with primary carcinoma of the colon and rectum. Arc Pathol Lab Med. 2009;133:1539–1551.
   PubMed Web of Science ®Google Scholar
• Huebner M, Wolff B, Smyrk T, et al. Partial pathologic response and nodal status as most significant prognostic factors for advanced rectal cancer treated with preoperative chemoradiotherapy. World J Surg. 2012;36:675–683.
   PubMed Web of Science ®Google Scholar
• Bosset J, Collette L, Calais G, et al. Chemotherapy with preoperative radiotherapy in rectal cancer. N Engl J Med. 2006;355:1114–1123.
   PubMed Web of Science ®Google Scholar
• Hiotis S, Weber S, Cohen A, 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. 2002;194:131–135.
   PubMed Web of Science ®Google Scholar
• Nakagawa W, Rossi B, Ferreira F, et al. Chemoradiation instead of surgery to treat mid and low rectal tumors: is it safe?. Ann Surg Oncol. 2002;9:568–573.
   PubMed Web of Science ®Google Scholar
• Stipa F, Zernecke A, Moore H, et al. Residual mesorectal lymph node involvement following neoadjuvant combined-modality therapy: rationale for radical resection?. Ann Surg Oncol. 2004;11:187–191.
   PubMed Web of Science ®Google Scholar
• Zmora O, Dasilva G, Gurland B, et al. Does rectal wall tumor eradication with preoperative chemoradiation permit a change in the operative strategy?. Dis Colon Rectum. 2004;47:1607–1612.
   PubMed Web of Science ®Google Scholar
• Habr-Gama A, Perez R, Nadalin W, et al. Long-term results of preoperative chemoradiation for distal rectal cancer correlation between final stage and survival. J Gastrointest Surg. 2005;9:90–101.
   PubMed Web of Science ®Google Scholar
• Patel U, Taylor F, Blomqvist L, et al. Magnetic resonance imaging-detected tumor response for distal rectal cancer correlation between final stage and survival outcomes: MERCURY experience. J Clin Oncol. 2011;29:3753–3760.
   PubMed Web of Science ®Google Scholar
• Kristiansen C, Loft A. Bertehlsen A: PET/CT and histopathologic response to preoperative cehmoradiation therapy in locally advanced rectal cancer. Dis Colon Rectum. 2008;51:21–25.
   PubMed Web of Science ®Google Scholar
• Gollub M, Gultekin D, Akin O, et al. Dynamic contrast enhanced-MRI for detection of pathological complete response to neoadjuvant chemotherapy for locally advanced rectal cancer. Eur Radiol. 2012;22:1693–1700.
   PubMed Web of Science ®Google Scholar
• Perez R, Habr-Gama A, Gama-Rodrigues J, et al. Accuracy of positron emission tomography/computed tomography and clinical assessment in the detection of complete rectal tumor regression after neoadjuvant chemoradiation: long-term results of a prospective trial (National Clinical Trial 00254683). Cancer. 2012;118:3501–3511.
   PubMed Web of Science ®Google Scholar
• Zhang C, Tong J, Sun X, et al. 18F-FDG-PET evaluation of treatment response to neo-adjuvant therapy in patients with locally advanced rectal cancer: a meta-analysis. Int J Cancer. 2012;131:2604–2611.
   PubMed Web of Science ®Google Scholar
• Guillem J, Ruby J, Leibold T, et al. Neither FDG-PET Nor CT can distinguish between a pathological complete response and an incomplete response after neoadjuvant chemoradiationin locally advanced rectal cancer: a prospective study. Ann Surg. 2013;258:289–295.
   PubMed Web of Science ®Google Scholar
• Paardt M, Zagers M, Beets-Tan R, et al. Patients who undergo preoperative chemoradiaotherpay for locally advanced rectal cancer restaged by using diagnostic MR imaging: a systematic review and meta-analysis. Radiology. 2013;269:101–112.
   PubMed Web of Science ®Google Scholar
• Zhao R, Wang H, Zhou Z, et al. Restaging of locally advanced rectal cancer with magnetic resonance imaging and endoluminal ultrasound after preoperative chemoradiotherapy: a systemic review and meta-analysis. Dis Colon Rectum. 2014;57:388–395.
   PubMed Web of Science ®Google Scholar
• Hanly A, Ryan E, Rogers A, et al. Multicenter Evaluation of Rectal cancer ReImaging pOst Neoadjuvant (MERRION) Therapy. Ann Surg. 2014;259:723–727.
   PubMed Web of Science ®Google Scholar
• Memon S, Lynch A, Akhurst T, et al. Systemic review of FDG-PET prediction of complete pathological response and survival in rectal cancer. Ann Surg Oncol. 2014;21:3598–3607.
   PubMed Web of Science ®Google Scholar
• Willett C, Ryan D: Neoadjuvant chemoradiotherapy and radiotherapy for rectal cancer, 2015.
   Google Scholar
• Barbaro B, Fiorucci C, Tebala C, et al. Locally advanced rectal cancer: MR imaging in prediction of response after preoperative chemotherapy and radiation therapy. Radiology. 2009;250:730–739.
   PubMed Web of Science ®Google Scholar
• Dresen R, Beets G, Rutten H, et al. Locally advanced rectal cancer: MR imaging for restaging after neoadjuvant radiation therapy with concomitnat chemotherapy. Part I: are we able to predict tumor confined to the rectal wall?. Radiology. 2009;252:81–91.
   PubMed Web of Science ®Google Scholar
• Jonas J, Bahr R. Neoadjuvant chemoradiation treatment impairs accuracy of MRI staging in rectal carcinoma. Gut. 2006;55:1214–1215.
   PubMed Web of Science ®Google Scholar
• Lambregts D, Vandecaveye V, Barbaro B, et al. Diffusion-weighted MRI for selction of complete responders after chemoradiation for locally advanced rectal cancer: a multicenter study. Ann Surg Oncol. 2011;18:2224–2231.
   PubMed Web of Science ®Google Scholar
• Kim S, Lee J, Hong S, et al. Locally advanced rectal cancer: added value of diffusion-weighted MR imaging in the evaluation of tumor response to neoadjuvant chemo- and radiation therapy. Radiology. 2009;253:116–125.
   PubMed Web of Science ®Google Scholar
• Lanbregts D, Maas M, Riedl R, et al. Value of ADC measurements for nodal staging after chemoradiation in locally advanced rectal cancer- a per lesion validation study. Eur Radiol. 2011;21:265–273.
   PubMed Web of Science ®Google Scholar
• Martin S, Heneghan H, Winter D. Systematic review and meta-analysis of outcomes following pathological complete response to neoadjuvant chemoradiatotherapy for rectal cancer. Br J Surg. 2012;99:918–928.
   PubMed Web of Science ®Google Scholar
• Maas M, Nelemans P, Valentini V, et al. Long-term outcome in patients with a pathological complete response after chemoradiation for rectal cancer: a pooled analysis of individual patient data. Lancet Oncol. 2010;11:835–844.
   PubMed Web of Science ®Google Scholar
• Aschele C, Cionin L, Lonardi S, et al. Primary tumor response to preoperative chemoradiation with or without oxaliplatin in locally advanced rectal cancer: pathological results of the STAR-01 randomized phase III trial. J Clin Oncol. 2011;29:2773–2780.
   PubMed Web of Science ®Google Scholar
• Gerard J, Azria D, Gourgou-Bourgade S. Comparison of two neaodjuvant chemoradiotherapy regimens for locally advanced rectal cancer: results of the phase III trial ACCORD 12/0405-Prodige 2. J Clin Oncol. 2010;28.
   PubMed Web of Science ®Google Scholar
• Gerard J, Azria D, Gourgou-Bourgade S, et al. Clinical outcome of the ACCORD 12/0405 PRODIGE 2 randomized trial in rectal cancer. J Clin Oncol. 2012;30.4558–4565.
   PubMed Web of Science ®Google Scholar
• Schmoll H-J, Haustermans K, Price T, et al. Preoperative chemoradiotherapy and postoperative chemotherapy with capecitabine and oxaliplatin versus capecitabine alone in locally advanced rectal cancer: first results of the PETACC-6 randomized trial (abstract 3531). J Clin Oncol. 2013;31.
   Web of Science ®Google Scholar
• Schmoll H-J, Haustermans K, Price T, et al. Preoperative chemoradiotherapy and postoperative chemotherapy with capecitabine with oxaliplatin versus capecitabine alone in locally advanced rectal cancer: disease-free survival results at interim analysis (abstract 3501). J Clin Oncol. 2014;32.
   Web of Science ®Google Scholar
• O’Connell M, Colangelo L, Beart R, et al. Capecitabine and oxaliplatin in the preoperative multimodality treatment of rectal cancer: surgical end points from NSABP trial R-04. J Clin Oncol. 2014;32:1–8.
   PubMed Web of Science ®Google Scholar
• Rodel C, Liersch T, Becker H, et al. Preoperative chemoradiotherapy and postoperative chemotherapy with fluorouracil and oxaliplatin versus fluorouracil alone in locally advanced rectal cancer: inital results of the German CAO/ARO/AOI-04 randomised phase 3 trial. Lancet Oncol. 2012;13:679–687.
   PubMed Web of Science ®Google Scholar
• Rodel C, Liersch T, Fietkau R, et al. Preoperative chemoradiotherapy and postoperative chemotherapy with 5-fluorouracil and oxaliplatin versus 5-fluorouracil alone in locally advanced rectal cancer: results of the German CAO/ARO/AIO-04 randomized phase III trial (abstract 3500). J Clin Oncol. 2014;32.
   Web of Science ®Google Scholar
• Rödel C, Graeven U, Fietkau R, et al. Oxaliplatin added to fluorouracil-based preoperative chemoradiotherapy and postoperative chemotherapy of locally advanced rectal cancer (the German CAO/ARO/AIO-04 study): final results of the multicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 2015;16:979–989.
   PubMed Web of Science ®Google Scholar
• Allegra C, Yothers G, O’Connell M, et al. Neoadjuvant therapy for rectal cancer. Mature results from NSABP R-04 (abstract 390). J Clin Oncol. 2014;32.
   PubMed Web of Science ®Google Scholar
• Navarro M, Dotor E, Rivera F, et al. A Phase II study of preoperative radiotherapy and concomitant weekly irinotecan in combination with protracted venous infusion 5-fluorouracil, for resectable locally advanced rectal cancer. Int J Radiat Oncol Biol Phys. 2006;66.201–205.
   PubMed Web of Science ®Google Scholar
• Willeke F, Horisberger K, Kraus-Tiefenbacher U, et al. A phase II study of capecitabine and irinotecan in combination with concurrent pelvic radiotherapy (CapIri-RT) as neoadjuvant treatment of locally advanced rectal cancer. Br J Cancer. 2007;96:912–917.
   PubMed Web of Science ®Google Scholar
• Gollins S, Myint AS, Haylock B, et al. Preoperative chemoradiotherapy using concurrent capectiabine and irinotecan in magnetic resonance imaging-defined locally advanced rectal cancer: impact on long-term clinical outcomes. J Clin Oncol. 2011;29:1042–1049.
   PubMed Web of Science ®Google Scholar
• Mohiuddin M, Paulus R, Mitchell E, et al. Neoadjuvant chemoradiation for distal rectal cancer: 5-year updated results of a randomized phase 2 study of neoadjuvant combined modality chemoradiation for distal rectal cancer. Int J Radiat Oncol Biol Phys. 2013;86:523–528.
   PubMed Web of Science ®Google Scholar
• Willett C, Duda D, Tomaso E, et al. Efficacy, safety, and biomarkers of neoadjuvant bevacizumab, radiation therpay, and fluorouracil in rectal cancer: a multidisciplinary phase II study. J Clin Oncol. 2009;27:3020–3026.
   PubMed Web of Science ®Google Scholar
• Crane C, Eng C, Feig B, et al. Phase II trial of neoadjuvant bevacizumab, capecitabine, and radiotherapy for locally advanced rectal cancer. Int J Radiat Oncol Biol Phys. 2010;76:824–830.
   PubMed Web of Science ®Google Scholar
• Uehara K, Hiramatsu K, Maeda A, et al. Neoadjuvant oxaliplatin and capecitabine and bevacizumab without radiotherapy for poor-risk rectal cancer: N-SOG 03 Phase II trial. Jpn J Clin Oncol. 2013;43:964–971.
   PubMed Web of Science ®Google Scholar
• Velenik V, Ocvirk J, Oblak I, et al. A phase II study of cetuximab, capecitabine and readioathepray in neoadjuvant treatment of patients with locally advanced resectable rectal cancer. EurJ Surg Oncol. 2010;36:244–250.
   PubMed Web of Science ®Google Scholar
• Horisberger K, Treschl A, Mai S, et al. Cetuximab in combination with capecitabine, irinotecan, and radiotherapy for patietns with locally advanced rectal cancer: results of Phase II MARGIT trial. J Radiat Oncol Biol Phys. 2009;74:1487–1493.
   PubMed Web of Science ®Google Scholar
• Dewdney A, Cunningham D, Tabernero J, et al. Multicenter randomized phase II clinical trial comparing neoadjuvant oxaliplatin, capecitabine, and preoperative radioatherpay with or without cetuximab followed by total mesorectal excision in patients with high-risk rectal cancer (EXPERT-C). J Clin Oncol. 2012;30:1620–1627.
   PubMed Web of Science ®Google Scholar
• Kim S, Shim E, Yeo H, et al. KRAS mutation status and clinical outcome of preoperative chemoradiation with cetuximab in locally advanced rectal cancer: a pooled analysis of 2 phase II trials. Int J Radiat Oncol Biol Phys. 2013;85:992–999.
   Google Scholar
• Helbling D, Bodoky G, Gautschi O, et al. Neoadjuvant chemoradiotherapy with or without panitumumab in patients with wild-type KRAS, locally advnaced rectal cancer (LARC): a randomized, multicenter, phase II trial SAKK 41/07. Ann Oncol. 2013;24:718–725.
   PubMed Web of Science ®Google Scholar
• Sclafani F, Gonzalez D, Cunningham D, et al. TP53 mutational status and cetuximab benefit in rectal cancer: 5-year results of the EXPERT-C trial. J Natl Cancer Inst. 2014;106:1–4.
   Google Scholar
• Roh M, Colangelo L, O’Connell M, et al. Preoperative multimodality therapy improves disease-free survival in patients with carcinoma of the rectum: NSABP R-03. J Clin Oncol. 2009;27:5124–5130.
   PubMed Web of Science ®Google Scholar
• Chau Y, Barbachano Y, Cunningham D, et al. Neoadjuvant capecitabine and oxaliplatin before chemoradiotherapy and total mesorectal exision in MRI-defined poor-risk rectal cancer: a phase 2 trial. Lancet Oncol. 2010;11:241–248.
   PubMed Web of Science ®Google Scholar
• Fernandez-Martos C, Pericay C, Aparicio J, et al. Phase II, randomized study of concomitant chemoradioatherapy followed by surgery and adjuvant capecitabine plus oxaliplatin (CAPOX) compared with induction CAPOX followed by concomitant chemoradiaotherapy and surgery in MRI-defined, locally advanced rectal cancer: Gropo cancer de recto 3 study. J Clin Oncol. 2010;28:859–865.
   PubMed Web of Science ®Google Scholar
• Schou J, Larsen F, Rasch L, et al. Induction chemotherapy with capecitabine and oxaliplatin followed by chemoradiotherapy before total mesorectal excision in patients with locally advanced rectal cancer. Ann Oncol. 2012;23:2627–2633.
   PubMed Web of Science ®Google Scholar
• Marechal R, Vos B, Polus M, et al. Short course chemotherapy followed by concomitant chemoradiotherapy and surgery in locally advanced rectal cancer: a randomized multicentric phase Ii study. Ann Oncol. 2012;23:1525–1530.
   PubMed Web of Science ®Google Scholar
• 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;24:668–674.
   PubMed Web of Science ®Google Scholar
• Schrag D, Weiser MR, Goodman KA, et al. Neoadjuvant chemotherapy without routine use of radiation therapy for patients with locally advanced rectal cancer: a pilot trial. J Clin Oncol. 2014;32:513–518.
   PubMed Web of Science ®Google Scholar
• Bruheim K, Guren M, Skovlund E, et al. Late side effects and quality of life after radiotherapy for rectal cancer. Int J Radiat Oncol Biol Phys. 2010;76:1005–1011.
   PubMed Web of Science ®Google Scholar
• Temple LKF, Wong W, Minsky B. The impact of radiation on functional outcomes in patients with rectal cancer and sphincter preservation. Semin Radiat Oncol. 2003;13:469–477.
   PubMed Web of Science ®Google Scholar
• Palta M, Willett C, Critzo B. Neoadjuvant chemotherapy alone in locally advanced rectal cancer: an interesting prospect but not ready for primetime, gastrointestinal caners symposium. Daily News. 2015.
   Google Scholar
• PROSPECT: Chemotherapy alone or chemotherapy plus radiation therapy in treating patients with locally advanced rectal cancer undergoing surgery. Clinicaltrials.gov, Clinicaltrials.gov, 2012.
   Google Scholar
• Appelt A, Pløen J, Vogelius I, et al. Radiation dose-response model for locally advanced rectal cancer after preoperative chemoradiation therapy. Int J Radiat Oncol Biol Phys. 2013;85:74–80.
   PubMed Web of Science ®Google Scholar
• Gerard J, Chapet O, Nemoz C, et al Improved sphincter preservation in low rectal cancer with high-dose preoperative radiotherapy: the lyon R96-02 randomized trial. J Clin Oncol. 2004;22:2404–2409.
   PubMed Web of Science ®Google Scholar
• Phase III Study Comparing, Efficacy and Safety of a Boost (CXB or EBRT) in Combination With Neoadjuvant Chemoradiotherapy for Early Rectal Adenocarcinoma (OPERA), in ClinicalTrials.gov (ed): ClinicalTrials.gov, 2015
   Google Scholar
• Borschitz T, Wachtlin D, Möhler M, et al. Neoadjuvant chemoradiation and local excision for T2-3 rectal cancer. Ann Surg Oncol. 2008;15:712–720.
   Web of Science ®Google Scholar
• Callender G, Das P, Rodriguez-Bigas M, et al. Local excision after preoperative chemoradiation results in an equivalent outcome to total mesorectal excision in selected patients with T3 rectal cancer. Ann Surg Oncol. 2010;17:441–447.
   PubMed Web of Science ®Google Scholar
• Vendrely VR,E, Rouanet P, Tuech J, et al. Local excision versus total mesorectal excision in patients with good response after neoadjuvant radiochemotherapy for T2-T3 low rectal cancer: preliminary results of the GRECCAR 2 randomized phase 3 trial. USA: American Society of Cancer Oncology; 2012.
   Google Scholar
• Garcia-Aguilar J: Toward curing rectal cancer without surgery, MSKCC, 2014
   Google Scholar
• Garcia-Aguilar J, Shi Q, Thomas C. A phase II trial of neoadjuvant chemoradiation and local excision fro T2N0 rectal cancer: preliminary results of the ACOSOG Z6041trial. Ann Surg Oncol. 2012;19:384–391.
   PubMed Web of Science ®Google Scholar
• Maas M, Nelemans P, Valentini V, et al Long-term outcome in patients with a pathological complete response after chemoradiation for rectal cancer: A pooled analysis of individual patient data. Lancet Oncol. 2010;211:835–844.
   Web of Science ®Google Scholar
• Smith J, Chow O, Eaton A, et al. Organ preservation in patients with rectal cancer with clinical complete response after neoadjuvant therapy. J Clin Oncol. 2015;33(suppl 3; abstr 509).
   Google Scholar
• Helwick H. Observation appropriate for some patients with rectal cancer following neoadjuvant therap. ASCO Post. 2015;6.
   Google Scholar
• Trial Evaluating 3-year Disease Free Survival in Patients With Locally Advanced Rectal Cancer Treated With Chemoradiation Plus Induction or Consolidation Chemotherapy and Total Mesorectal Excision or Non-operative Management, Clinicaltrials.gov. Clinicaltrials.gov, 2013
   Google Scholar
• Vatandoust S, Lam Y, Roy A, et al. Retrospective study of patients (pts) who were managed with Watch and Wait strategy (W&W) after neoadjuvant chemoradiation (NCRT) for locally advanced rectal cancer (LARC). J Clin Oncol. 2015;33(suppl; abstr 3603).
   Google Scholar
• Induction Chemotherapy Before or After Preoperative Chemoradiotherapy and Surgery for Locally Advanced Rectal Cancer (CAOAROAIO-12). ClinicalTrials.gov (ed). ClinicalTrials.gov. 2015.
   Google Scholar
• Randomized Controlled Study on Optimize Neoadjuvant Chemoradiotherapy for Locally Advanced Rectal Cancer. ClinicalTrials.gov, 2013.
   Google Scholar
• Xiang B, Snook A, Magee M, et al. Colorectal cancer immunotherapy. Discov Med. 2013;15:301–308.
   PubMed Web of Science ®Google Scholar
• Le D, Uram J, Wang H. PD-1 Blockade in tumors with mismatch-repair deficiency. N Engl J Med. 2015;372:2509–2520.
   PubMed Web of Science ®Google Scholar
• Hofheinz R-D, Wenz F, Post S, et al. Chemoradiotherapy with capecitabine versus fl uorouracil for locally advanced rectal cancer: a randomised, multicentre, non-inferiority, phase 3 trial. Lancet Oncol. 2012;13:579–588.
   PubMed Web of Science ®Google Scholar
• O’Connell M, Colangelo L, Beart R, et al. Capecitabine and oxaliplatin in the preoperative multimodality treatment of rectal cancer: surgical end points from national surgical adjuvant breast and bowel project trial R-04. J Clin Oncol. 2014;31:1927–1934.
   Web of Science ®Google Scholar
• A La CaRT: Australasian Laparoscopic Cancer of the Rectum Trial: a phase III prospective randomised trial comparing laparoscopic-assisted resection versus open resection for rectal cancer[Internet]. 2010. Available at www.australianclinicaltrials.gov.au
   Google Scholar
• Hernando-Requejo O, Lopez M, Cubillo A, et al. Complete pathological responses in locally advanced rectal cancer after preoperative IMRT and integrated-boost chemoradiation. Strahlenther Onkol. 2014;190:515–520.
   PubMed Web of Science ®Google Scholar
• Zhu J, Liu F, Gu W, et al. Concomitant boost IMRT-based neoadjuvant chemoradiotherapy for clinical stage II/III rectal adenocarcinoma: results of a phase II study. Radiat Oncol. 2014;9.
   Web of Science ®Google Scholar
• Parekh A, Truong M, Pashtan I, et al. Acute gastrointestinal toxicity and tumor response with preoperative intensity modulated radiation therapy for recal cancer. Gastrointest Cancer Res. 2013;6:137–143.
   PubMedGoogle Scholar
• Engels B, Platteaux N, Begin R, et al. Preoperative intensity-modulated and image-guided radiaotherapy with simultaneous integratd boost in locally advanced rectal cancer: report on late toxitiy and outcome. Radiother Oncol. 2014;110:155–159.
   PubMed Web of Science ®Google Scholar