Advances in organ preserving strategies in rectal cancer patients

Siegel, 2016, Cancer statistics, 2016, CA A Cancer J Clin, 66, 7, 10.3322/caac.21332 Peeters, 2007, The TME trial after a median follow-up of 6 years, Ann Surg, 246, 693, 10.1097/01.sla.0000257358.56863.ce Guren, 2005, Quality of life and functional outcome following anterior or abdominoperineal resection for rectal cancer, Eur J Surg Oncol, 31, 735, 10.1016/j.ejso.2005.05.004 Fazio, 2007, A randomized multicenter trial to compare long-term functional outcome, quality of life, and complications of surgical procedures for low rectal cancers, Ann Surg, 246, 481, 10.1097/SLA.0b013e3181485617 Anderin, 2010, A population-based study on outcome in relation to the type of resection in low rectal cancer, Dis Colon Rectum, 53, 753, 10.1007/DCR.0b013e3181cf7e27 Bregendahl, 2013, Bowel dysfunction after low anterior resection with and without neoadjuvant therapy for rectal cancer: a population-based cross-sectional study, Colorectal Dis, 15, 1130 You, 2007, Is the increasing rate of local excision for stage I rectal cancer in the United States justified?, Ann Surg, 245, 726, 10.1097/01.sla.0000252590.95116.4f Bosch, 2013, Predicting lymph node metastasis in pT1 colorectal cancer: a systematic review of risk factors providing rationale for therapy decisions, Endoscopy, 45, 827, 10.1055/s-0033-1344238 Sebag-Montefiore, 2009, Preoperative radiotherapy versus selective postoperative chemoradiotherapy in patients with rectal cancer (MRC CR07 and NCIC-CTG C016): a multicentre, randomised trial, Lancet, 373, 811, 10.1016/S0140-6736(09)60484-0 Kapiteijn, 2001, Preoperative radiotherapy combined with total mesorectal excision for resectable rectal cancer, N Engl J Med, 345, 638, 10.1056/NEJMoa010580 Peeters, 2007, 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, 246, 693, 10.1097/01.sla.0000257358.56863.ce Martin, 2012, Systematic review and meta-analysis of outcomes following pathological complete response to neoadjuvant chemoradiotherapy for rectal cancer, Br J Surg, 99, 918, 10.1002/bjs.8702 Bökkerink, 2011, The CARTS study: chemoradiation therapy for rectal cancer in the distal rectum followed by organ-sparing transanal endoscopic microsurgery, BMC Surg, 11, 34, 10.1186/1471-2482-11-34 Habr-Gama, 2004, Operative versus nonoperative treatment for stage 0 distal rectal cancer following chemoradiation therapy: long-term results, Ann Surg, 240, 711, 10.1097/01.sla.0000141194.27992.32 Beets, 2015, A new paradigm for rectal cancer: organ preservation: introducing the International Watch & Wait Database (IWWD), Eur J Surg Oncol J Eur Soc Surg Oncol Br Assoc Surg Oncol, 41, 1562 Li, 2015, Evaluating local lymph node metastasis with magnetic resonance imaging, endoluminal ultrasound and computed tomography in rectal cancer: a meta-analysis, Colorectal Dis, 17, O129, 10.1111/codi.12909 Beets-Tan, 2013, Magnetic resonance imaging for the clinical management of rectal cancer patients: recommendations from the 2012 European Society of Gastrointestinal and Abdominal Radiology (ESGAR) consensus meeting, Eur Radiol, 23, 2522, 10.1007/s00330-013-2864-4 Al-Sukhni, 2012, Diagnostic accuracy of MRI for assessment of T category, lymph node metastases, and circumferential resection margin involvement in patients with rectal cancer: a systematic review and meta-analysis, Ann Surg Oncol, 19, 2212, 10.1245/s10434-011-2210-5 Taylor, 2008, A systematic approach to the interpretation of preoperative staging MRI for rectal cancer, AJR Am J Roentgenol, 191, 1827, 10.2214/AJR.08.1004 Brown, 2004, High-resolution MRI of the anatomy important in total mesorectal excision of the rectum, AJR Am J Roentgenol, 182, 431, 10.2214/ajr.182.2.1820431 Chand, 2014, Mucinous carcinoma of the rectum: a distinct clinicopathological entity, Tech Coloproctol, 18, 335, 10.1007/s10151-013-1099-3 Oberholzer, 2012, Rectal cancer: mucinous carcinoma on magnetic resonance imaging indicates poor response to neoadjuvant chemoradiation, Int J Radiat Oncol Biol Phys, 82, 842, 10.1016/j.ijrobp.2010.08.057 Heriot, 2004, Does positron emission tomography change management in primary rectal cancer? A prospective assessment, Dis Colon Rectum, 47, 451, 10.1007/s10350-003-0089-3 Brush, 2011, The value of FDG positron emission tomography/computerised tomography (PET/CT) in pre-operative staging of colorectal cancer: a systematic review and economic evaluation, Health Technol Assess, 15, 1, 10.3310/hta15350 Fernandez-Esparrach, 2011, EUS and magnetic resonance imaging in the staging of rectal cancer: a prospective and comparative study, Gastrointest Endosc, 74, 347, 10.1016/j.gie.2011.03.1257 Puli, 2009, How good is endoscopic ultrasound in differentiating various T stages of rectal cancer? Meta-analysis and systematic review, Ann Surg Oncol, 16, 254, 10.1245/s10434-008-0231-5 Morino, 2015, Early rectal cancer: the European Association for Endoscopic Surgery (EAES) clinical consensus conference, Surg Endosc, 29, 755, 10.1007/s00464-015-4067-3 Perez, 2013, Transanal endoscopic microsurgery for residual rectal cancer (ypT0-2) following neoadjuvant chemoradiation therapy: another word of caution, Dis Colon Rectum, 56, 6, 10.1097/DCR.0b013e318273f56f Lee, 2015, Prognostic factors for low rectal cancer patients undergoing intersphincteric resection after neoadjuvant chemoradiation, J Surg Oncol, 111, 1054, 10.1002/jso.23932 Fujita, 2014, Incidence and prognosis of lower rectal cancer with limited extramesorectal lymph node metastasis, Int J Celiac Dis, 29, 1077, 10.1007/s00384-014-1940-9 Engelen, 2008, Location of involved mesorectal and extramesorectal lymph nodes in patients with primary rectal cancer: preoperative assessment with MR imaging, Eur J Surg Oncol J Eur Soc Surg Oncol Br Assoc Surg Oncol, 34, 776 Wang, 2005, Patterns of neoplastic foci and lymph node micrometastasis within the mesorectum, Langenbeck's Arch Surg, 390, 312, 10.1007/s00423-005-0562-7 Moreno, 2015, Magnetic resonance imaging of rectal cancer: staging and restaging evaluation, Abdom Imag, 40, 2613, 10.1007/s00261-015-0394-z Han, 2016, Endoscopic criteria for evaluating tumor stage after preoperative chemoradiation therapy in locally advanced rectal cancer, Canc Res Treat Off J Kor Canc Assoc, 48, 567 Ogura, 2015, Endoscopic evaluation of clinical response after preoperative chemoradiotherapy for lower rectal cancer: the significance of endoscopic complete response, Int J Celiac Dis, 30, 367, 10.1007/s00384-014-2105-6 Smith, 2012, The surgical significance of residual mucosal abnormalities in rectal cancer following neoadjuvant chemoradiotherapy, Br J Surg, 99, 993, 10.1002/bjs.8700 van der Paardt, 2013, Patients who undergo preoperative chemoradiotherapy for locally advanced rectal cancer restaged by using diagnostic MR imaging: a systematic review and meta-analysis, Radiology, 269, 101, 10.1148/radiol.13122833 Kim, 2009, Locally advanced rectal cancer: added value of diffusion-weighted MR imaging in the evaluation of tumor response to neoadjuvant chemo- and radiation therapy, Radiology, 253, 116, 10.1148/radiol.2532090027 Lambregts, 2011, Diffusion-weighted MRI for selection of complete responders after chemoradiation for locally advanced rectal cancer: a multicenter study, Ann Surg Oncol, 18, 2224, 10.1245/s10434-011-1607-5 van Heeswijk, 2017, DWI for assessment of rectal cancer nodes after chemoradiotherapy: is the absence of nodes at DWI proof of a negative nodal status?, AJR Am J Roentgenol, 208, W79, 10.2214/AJR.16.17117 Patel, 2011, Magnetic resonance imaging-detected tumor response for locally advanced rectal cancer predicts survival outcomes: MERCURY experience, J Clin Oncol Off J Am Soc Clin Oncol, 29, 3753, 10.1200/JCO.2011.34.9068 Shihab, 2011, MRI predictive factors for long-term outcomes of low rectal tumours, Ann Surg Oncol, 18, 3278, 10.1245/s10434-011-1776-2 Capirci, 2009, The role of dual-time combined 18-fluorodeoxyglucose positron emission tomography and computed tomography in the staging and restaging workup of locally advanced rectal cancer, treated with preoperative chemoradiation therapy and radical surgery, Int J Radiat Oncol Biol Phys, 74, 1461, 10.1016/j.ijrobp.2008.10.064 Joye, 2014, The role of diffusion-weighted MRI and (18)F-FDG PET/CT in the prediction of pathologic complete response after radiochemotherapy for rectal cancer: a systematic review, Radiother Oncol J Eur Soc Ther Radiol Oncol, 113, 158, 10.1016/j.radonc.2014.11.026 Lahaye, 2009, Locally advanced rectal cancer: MR imaging for restaging after neoadjuvant radiation therapy with concomitant chemotherapy. Part II. What are the criteria to predict involved lymph nodes?, Radiology, 252, 81, 10.1148/radiol.2521081364 Harisinghani, 2003, Noninvasive detection of clinically occult lymph-node metastases in prostate cancer, N Engl J Med, 348, 2491, 10.1056/NEJMoa022749 Rockall, 2005, Diagnostic performance of nanoparticle-enhanced magnetic resonance imaging in the diagnosis of lymph node metastases in patients with endometrial and cervical cancer, J Clin Oncol Off J Am Soci of Clin Oncol, 23, 2813, 10.1200/JCO.2005.07.166 Soreide, 2009, Endoscopy, morphology, morphometry and molecular markers: predicting cancer risk in colorectal adenoma, Expert Rev Mol Diagn, 9, 125, 10.1586/14737159.9.2.125 Rasheed, 2008, Can depth of tumour invasion predict lymph node positivity in patients undergoing resection for early rectal cancer? A comparative study between T1 and T2 cancers, Colorectal Dis, 10, 231, 10.1111/j.1463-1318.2007.01411.x Bach, 2009, A predictive model for local recurrence after transanal endoscopic microsurgery for rectal cancer, Br J Surg, 96, 280, 10.1002/bjs.6456 Kikuchi, 1995, Management of early invasive colorectal cancer. Risk of recurrence and clinical guidelines, Dis Colon Rectum, 38, 1286, 10.1007/BF02049154 Bosch, 2013, Predicting lymph node metastasis in pT1 colorectal cancer: a systematic review of risk factors providing rationale for therapy decisions, Endoscopy, 45, 827, 10.1055/s-0033-1344238 Bentrem, 2005, T1 adenocarcinoma of the rectum: transanal excision or radical surgery?, Ann Surg, 242, 472, 10.1097/01.sla.0000183355.94322.db Lee, 2003, Transanal endoscopic microsurgery and radical surgery for T1 and T2 rectal cancer, Surg Endosc, 17, 1283, 10.1007/s00464-002-8814-x Endreseth, 2005, Transanal excision vs. Major surgery for T1 rectal cancer, Dis Colon Rectum, 48, 1380, 10.1007/s10350-005-0044-6 Ptok, 2007, Oncological outcome of local vs radical resection of low-risk pT1 rectal cancer, Arch Surg, 142, 649, 10.1001/archsurg.142.7.649 De Graaf, 2009, Transanal endoscopic microsurgery versus total mesorectal excision of T1 rectal adenocarcinomas with curative intention, Eur J Surg Oncol, 35, 1280, 10.1016/j.ejso.2009.05.001 Palma, 2009, Local excision of early rectal cancer: is transanal endoscopic microsurgery an alternative to radical surgery?, Revista espanola de enfermedades digestivas organo oficial de la Sociedad Espanola de Patologia Digestiva, 101, 172 Nash, 2009, Long-term survival after transanal excision of T1 rectal cancer, Dis Colon Rectum, 52, 577, 10.1007/DCR.0b013e3181a0adbd Stitzenberg, 2013, Practice patterns and long-term survival for early-stage rectal cancer, J Clin Oncol, 31, 4276, 10.1200/JCO.2013.49.1860 Gopaul, 2004, Outcome of local excision of rectal carcinoma, Dis Colon Rectum, 47, 1780, 10.1007/s10350-004-0678-9 Landmann, 2007, Limitations of early rectal cancer nodal staging may explain failure after local excision, Dis Colon Rectum, 50, 1520, 10.1007/s10350-007-9019-0 Rahbari, 2013, Neoadjuvant radiotherapy for rectal cancer: meta-analysis of randomized controlled trials, Ann Surg Oncol, 20, 4169, 10.1245/s10434-013-3198-9 Erlandsson, 2017, Optimal fractionation of preoperative radiotherapy and timing to surgery for rectal cancer (Stockholm III): a multicentre, randomised, non-blinded, phase 3, non-inferiority trial, Lancet Oncol, 18, 336, 10.1016/S1470-2045(17)30086-4 Pettersson, 2015, Tumour regression in the randomized Stockholm III Trial of radiotherapy regimens for rectal cancer, Br J Surg, 102, 972, 10.1002/bjs.9811 Smart, 2016, Multicentre study of short-course radiotherapy and transanal endoscopic microsurgery for early rectal cancer, Br J Surg, 10.1002/bjs.10171 Lezoche, 2005, Long-term results in patients with T2-3 N0 distal rectal cancer undergoing radiotherapy before transanal endoscopic microsurgery, Br J Surg, 92, 1546, 10.1002/bjs.5178 Lezoche, 2008, A prospective randomized study with a 5-year minimum follow-up evaluation of transanal endoscopic microsurgery versus laparoscopic total mesorectal excision after neoadjuvant therapy, Surg Endosc, 22, 352, 10.1007/s00464-007-9596-y Pucciarelli, 2013, Local excision after preoperative chemoradiotherapy for rectal cancer: results of a multicenter phase II clinical trial, Dis Colon Rectum, 56, 1349, 10.1097/DCR.0b013e3182a2303e Verseveld, 2015, Chemoradiation therapy for rectal cancer in the distal rectum followed by organ-sparing transanal endoscopic microsurgery (CARTS study), Br J Surg, 102, 853, 10.1002/bjs.9809 Garcia-Aguilar, 2015, Organ preservation for clinical T2N0 distal rectal cancer using neoadjuvant chemoradiotherapy and local excision (ACOSOG Z6041): results of an open-label, single-arm, multi-institutional, phase 2 trial, Lancet Oncol, 16, 1537, 10.1016/S1470-2045(15)00215-6 Appelt, 2015, High-dose chemoradiotherapy and watchful waiting for distal rectal cancer: a prospective observational study, Lancet Oncol, 16, 919, 10.1016/S1470-2045(15)00120-5 Rullier, 2017, Organ preservation for rectal cancer (GRECCAR 2): a prospective, randomised, open-label, multicentre, phase 3 trial, Lancet, 10.1016/S0140-6736(17)31056-5 Perez, 2014, Transanal local excision for distal rectal cancer and incomplete response to neoadjuvant chemoradiation – does baseline staging matter?, Dis Colon Rectum, 57, 1253, 10.1097/DCR.0000000000000215 Glimelius, 2013, Rectal cancer: ESMO clinical practice guidelines for diagnosis, treatment and follow-up, Ann Oncol Off J Eur Soc Med Oncol/ESMO, 24 Maas, 2010, Long-term outcome in patients with a pathological complete response after chemoradiation for rectal cancer: a pooled analysis of individual patient data, Lancet Oncol, 11, 835, 10.1016/S1470-2045(10)70172-8 Habr-Gama, 2014, Local recurrence after complete clinical response and watch and wait in rectal cancer after neoadjuvant chemoradiation: impact of salvage therapy on local disease control, Int J Radiat Oncol Biol Phys, 88, 822, 10.1016/j.ijrobp.2013.12.012 Dossa, 2017, A watch-and-wait approach for locally advanced rectal cancer after a clinical complete response following neoadjuvant chemoradiation: a systematic review and meta-analysis, Lancet Gastroenterolhepatol, 10.1016/S2468-1253(17)30074-2 Schell, 2002, Transanal excision of locally advanced rectal cancers downstaged using neoadjuvant chemoradiotherapy, J Am Coll Surg, 194, 584, 10.1016/S1072-7515(02)01128-6 Maas, 2011, Wait-and-see policy for clinical complete responders after chemoradiation for rectal cancer, J Clin Oncol Off J Am Soc Clin Oncol, 29, 4633, 10.1200/JCO.2011.37.7176 Creavin, 2017, Organ preservation with local excision or active surveillance following chemoradiotherapy for rectal cancer, Br J Canc, 116, 169, 10.1038/bjc.2016.417 Petrelli, 2016, Increasing the interval between neoadjuvant chemoradiotherapy and surgery in rectal cancer: a meta-analysis of published studies, Ann Surg, 263, 458, 10.1097/SLA.0000000000000368 Cotte, 2016, Pathologic response, when increased by longer interval, is a marker but not the cause of good prognosis in rectal cancer: 17-year follow-up of the lyon R90-01 randomized trial, Int J Radiat Oncol Biol Phys, 94, 544, 10.1016/j.ijrobp.2015.10.061 Rombouts, 2016, Treatment interval between neoadjuvant chemoradiotherapy and surgery in rectal cancer patients: a population-based study, Ann Surg Oncol, 23, 3593, 10.1245/s10434-016-5294-0 Lefevre, 2016, Effect of interval (7 or 11 weeks) between neoadjuvant radiochemotherapy and surgery on complete pathologic response in rectal cancer: a multicenter, randomized, controlled trial (GRECCAR-6), J Clin Oncol Off J Am Soc Clin Oncol, 10.1200/JCO.2016.67.6049 Nakamura, 2014, Neoadjuvant chemoradiation therapy using concurrent S-1 and irinotecan in rectal cancer: impact on long-term clinical outcomes and prognostic factors, Int J Radiat Oncol Biol Phys, 89, 547, 10.1016/j.ijrobp.2014.03.007 Jung, 2015, A randomized phase 2 study of neoadjuvant chemoradiaton therapy with 5-fluorouracil/leucovorin or Irinotecan/S-1 in patients with locally advanced rectal cancer, Int J Radiat Oncol Biol Phys, 93, 1015, 10.1016/j.ijrobp.2015.08.037 An, 2013, Short term results of neoadjuvant chemoradiotherapy with fluoropyrimidine alone or in combination with oxaliplatin in locally advanced rectal cancer: a meta analysis, Eur J Canc, 49, 843, 10.1016/j.ejca.2012.09.026 Shih, 2006, Bevacizumab: an angiogenesis inhibitor for the treatment of solid malignancies, Clin Ther, 28, 1779, 10.1016/j.clinthera.2006.11.015 Ribero, 2007, Bevacizumab improves pathologic response and protects against hepatic injury in patients treated with oxaliplatin-based chemotherapy for colorectal liver metastases, Cancer, 110, 2761, 10.1002/cncr.23099 Willett, 2009, Efficacy, safety, and biomarkers of neoadjuvant bevacizumab, radiation therapy, and fluorouracil in rectal cancer: a multidisciplinary phase II study, J Clin Oncol Off J Am Soc Clin Oncol, 27, 3020, 10.1200/JCO.2008.21.1771 Willett, 2010, A safety and survival analysis of neoadjuvant bevacizumab with standard chemoradiation in a phase I/II study compared with standard chemoradiation in locally advanced rectal cancer, Oncol, 15, 845, 10.1634/theoncologist.2010-0030 Crane, 2010, Phase II trial of neoadjuvant bevacizumab, capecitabine, and radiotherapy for locally advanced rectal cancer, Int J Radiat Oncol Biol Phys, 76, 824, 10.1016/j.ijrobp.2009.02.037 Dipetrillo, 2012, Neoadjuvant bevacizumab, oxaliplatin, 5-fluorouracil, and radiation for rectal cancer, Int J Radiat Oncol Biol Phys, 82, 124, 10.1016/j.ijrobp.2010.08.005 Nogue, 2011, Addition of bevacizumab to XELOX induction therapy plus concomitant capecitabine-based chemoradiotherapy in magnetic resonance imaging-defined poor-prognosis locally advanced rectal cancer: the AVACROSS study, Oncol, 16, 614, 10.1634/theoncologist.2010-0285 Morris, 2016, Increased tumor response to neoadjuvant therapy among rectal cancer patients taking angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, Cancer, 10.1002/cncr.30079 Shen, 2011, The carboxypeptidase ACE shapes the MHC class I peptide repertoire, Nat Immunol, 12, 1078, 10.1038/ni.2107 Danilov, 2003, Angiotensin-converting enzyme (CD143) is abundantly expressed by dendritic cells and discriminates human monocyte-derived dendritic cells from acute myeloid leukemia-derived dendritic cells, Exp Hematol, 31, 1301, 10.1016/j.exphem.2003.08.018 Yazawa, 2011, Angiotensin-converting enzyme inhibition promotes coronary angiogenesis in the failing heart of Dahl salt-sensitive hypertensive rats, J Card Fail, 17, 1041, 10.1016/j.cardfail.2011.09.002 Burbach, 2014, Impact of radiotherapy boost on pathological complete response in patients with locally advanced rectal cancer: a systematic review and meta-analysis, Radiother Oncol J Eur Soc Ther Radiol Oncol, 113, 1, 10.1016/j.radonc.2014.08.035 Yamoah, 2015, Radiation therapy intensification for solid tumors: a systematic review of randomized trials, Int J Radiat Oncol Biol Phys, 93, 737, 10.1016/j.ijrobp.2015.07.2284 Appelt, 2013, Radiation dose-response model for locally advanced rectal cancer after preoperative chemoradiation therapy, Int J Radiat Oncol Biol Phys, 85, 74, 10.1016/j.ijrobp.2012.05.017 Rijkmans, 2017, Endorectal brachytherapy boost after external beam radiation therapy in elderly or medically inoperable patients with rectal cancer: primary outcomes of the phase 1 HERBERT study, Int J Radiat Oncol Biol Phys, 98, 908, 10.1016/j.ijrobp.2017.01.033 Dhadda, 2017, Organ preservation using contact radiotherapy for early rectal cancer: outcomes of patients treated at a single centre in the UK, Clin Oncol, 29, 198, 10.1016/j.clon.2016.09.014 Gerard, 2002, Long-term control of T2-T3 rectal adenocarcinoma with radiotherapy alone, Int J Radiat Oncol Biol Phys, 54, 142, 10.1016/S0360-3016(02)02879-1 Myerson, 2007, Conservative alternatives to extirpative surgery for rectal cancer, Clin Oncol, 19, 682, 10.1016/j.clon.2007.07.003 Ortholan, 2012, Correlation in rectal cancer between clinical tumor response after neoadjuvant radiotherapy and sphincter or organ preservation: 10-year results of the Lyon R 96-02 randomized trial, Int J Radiat Oncol Biol Phys, 83, e165, 10.1016/j.ijrobp.2011.12.002 Frin, 2017, Organ or sphincter preservation for rectal cancer. The role of contact X-ray brachytherapy in a monocentric series of 112 patients, Eur J Canc, 72, 124, 10.1016/j.ejca.2016.11.007 Smith, 2016, Contact radiotherapy boost in association with “watch and wait” for rectal cancer: initial experience and outcomes from a shared programme between a district general hospital network and a regional oncology centre, Colorectal Dis, 18, 861, 10.1111/codi.13296 Gerard, 2003, Radiotherapy alone in the curative treatment of rectal carcinoma, Lancet Oncol, 4, 158, 10.1016/S1470-2045(03)01020-9 Gerard, 2004, Improved sphincter preservation in low rectal cancer with high-dose preoperative radiotherapy: the lyon R96-02 randomized trial, J Clin Oncol Off J Am Soc Clin Oncol, 22, 2404, 10.1200/JCO.2004.08.170 Jakobsen, 2012, Dose-effect relationship in chemoradiotherapy for locally advanced rectal cancer: a randomized trial comparing two radiation doses, Int J Radiat Oncol Biol Phys, 84, 949, 10.1016/j.ijrobp.2012.02.006 Doornebosch, 2012, Transanal endoscopic microsurgery for T1 rectal cancer: size matters!, Surg Endosc, 26, 551, 10.1007/s00464-011-1918-4 Borstlap, 2016, A multi-centred randomised trial of radical surgery versus adjuvant chemoradiotherapy after local excision for early rectal cancer, BMC Cancer, 16, 513, 10.1186/s12885-016-2557-x Pucciarelli, 2016, Rectal sparing approach after preoperative radio and/or chemotherapy in patients with rectal cancer (ReSARCh), Tech Coloproctol Organ Preservation in Locally Advanced Rectal Cancer (PRONAR). https://clinicaltrials.gov/ct2/show/NCT03064646?term=pronar&cond=Rectal+Cancer&rank=1. [Accessed 25 July 2017]. Tailored Operative or Non-operative Management for Low-risk Rectal Cancer After Intensive Neoadjuvant Treatment. [Accessed 25 July 2017]. Optimisation of Response for Organ Preservation in Rectal Cancer: Neoadjuvant Chemotherapy and Radiochemotherapy vs. Radiochemotherapy (GRECCAR 12). http://www.centreoscarlambret.fr/recherche-cancerologique/essais-cliniques/protocole-greccar-12119. [Accessed 9 June 2017]. Five Fractions of Radiotherapy Followed by FOLFOX Chemotherapy as Organ-Sparing Treatment for Low Risk Rectal Cancer. [Accessed 25 July 2017]. Safety of a Boost (CXB or EBRT) in Combination With Neoadjuvant Chemoradiotherapy for Early Rectal Adenocarcinoma (OPERA). https://clinicaltrials.gov/ct2/show/NCT02505750121. [Accessed 9 June 2017]. Dose-escalation Trial of Preoperative Radiotherapy and Concurrent Chemotherapy in Locally Advanced Rectal Cancer. https://clinicaltrials.gov/ct2/show/NCT02964468122. [Accessed 9 June 2017]. Radiation Dose Escalation in Locally Advanced Rectal Cancer (RaDE). https://clinicaltrials.gov/ct2/show/NCT02603302123. [Accessed 9 June 2017]. No Surgery Trial/Two Dose-escalation Strategies. [Accessed 25 July 2017].