Multidisciplinary Management of Locally Advanced Rectal Cancer—An Evolving Landscape?

Clinical Colorectal Cancer - Tập 14 Số 4 - Trang 251-261 - 2015
Margaret Lee1, Peter Gibbs2, Rachel Wong3
1Eastern Health, Department of Medical Oncology, Australia; Monash University, Faculty of Medicine, Nursing and Health Sciences, Australia.
2Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia; Department of Medical Oncology, The Royal Melbourne Hospital & Western Health, Australia.
3Eastern Health, Department of Medical Oncology, Australia; Monash University, Faculty of Medicine, Nursing and Health Sciences, Australia; Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia. Electronic address: [email protected].

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MacFarlane, 1993, Mesorectal excision for rectal cancer, Lancet, 341, 457, 10.1016/0140-6736(93)90207-W

Havenga, 1999, Improved survival and local control after total mesorectal excision or D3 lymphadenectomy in the treatment of primary rectal cancer: an international analysis of 1411 patients, Eur J Surg Oncol, 25, 368, 10.1053/ejso.1999.0659

2007, Extramural depth of tumor invasion at thin-section MR in patients with rectal cancer: results of the MERCURY study, Radiology, 243, 132, 10.1148/radiol.2431051825

Grassetto, 2011, F-18 FDG PET/CT in rectal carcinoma: where are we now?, Clin Nucl Med, 36, 884, 10.1097/RLU.0b013e318219b507

Sauer, 2004, Preoperative versus postoperative chemoradiotherapy for rectal cancer, N Engl J Med, 351, 1731, 10.1056/NEJMoa040694

Kapiteijn, 2001, Preoperative radiotherapy combined with total mesorectal excision for resectable rectal cancer, N Engl J Med, 345, 638, 10.1056/NEJMoa010580

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

1997, Improved survival with preoperative radiotherapy in resectable rectal cancer. Swedish Rectal Cancer Trial, N Engl J Med, 336, 980, 10.1056/NEJM199704033361402

Minsky, 2012, Short-course radiation versus long-course chemoradiation for rectal cancer: making progress, J Clin Oncol, 30, 3777, 10.1200/JCO.2012.45.0551

Glynne-Jones, 2014, How to select for preoperative short-course radiotherapy, while considering long-course chemoradiotherapy or immediate surgery, and who benefits?, Eur Oncol Haematol, 10, 17, 10.17925/EOH.2014.10.1.17

Berardi, 2014, Locally advanced rectal cancer: the importance of a multidisciplinary approach, World J Gastroenterol, 20, 17279, 10.3748/wjg.v20.i46.17279

Bujko, 2006, Long-term results of a randomized trial comparing preoperative short-course radiotherapy with preoperative conventionally fractionated chemoradiation for rectal cancer, Br J Surg, 93, 1215, 10.1002/bjs.5506

Ngan, 2012, 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, 30, 3827, 10.1200/JCO.2012.42.9597

Latkauskas, 2012, Initial results of a randomized controlled trial comparing clinical and pathological downstaging of rectal cancer after preoperative short-course radiotherapy or long-term chemoradiotherapy, both with delayed surgery, Colorectal Dis, 14, 294, 10.1111/j.1463-1318.2011.02815.x

Siegel, 2009, 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, 9, 50, 10.1186/1471-2407-9-50

Yeo, 2014, Management of recurrent rectal cancer: practical insights in planning and surgical intervention, J Surg Oncol, 109, 47, 10.1002/jso.23457

Glynne-Jones, 2006, Alternative clinical end points in rectal cancer—are we getting closer?, Ann Oncol, 17, 1239, 10.1093/annonc/mdl173

Taylor, 2014, Preoperative magnetic resonance imaging assessment of circumferential resection margin predicts disease-free survival and local recurrence: 5-year follow-up results of the MERCURY study, J Clin Oncol, 32, 34, 10.1200/JCO.2012.45.3258

Hawkes, 2011, Neoadjuvant chemotherapy alone for early-stage rectal cancer: an evolving paradigm?, Semin Radiat Oncol, 21, 196, 10.1016/j.semradonc.2011.02.005

Twelves, 2005, Capecitabine as adjuvant treatment for stage III colon cancer, N Engl J Med, 352, 2696, 10.1056/NEJMoa043116

Cassidy, 2008, Randomized phase III study of capecitabine plus oxaliplatin compared with fluorouracil/folinic acid plus oxaliplatin as first-line therapy for metastatic colorectal cancer, J Clin Oncol, 26, 2006, 10.1200/JCO.2007.14.9898

Hofheinz, 2012, Chemoradiotherapy with capecitabine versus fluorouracil for locally advanced rectal cancer: a randomised, multicentre, non-inferiority, phase 3 trial, Lancet Oncol, 13, 579, 10.1016/S1470-2045(12)70116-X

Francois, 1999, Influence of the interval between preoperative radiation therapy and surgery on downstaging and on the rate of sphincter-sparing surgery for rectal cancer: the Lyon R90-01 randomized trial, J Clin Oncol, 17, 2396, 10.1200/JCO.1999.17.8.2396

Wasserberg, 2014, Interval to surgery after neoadjuvant treatment for colorectal cancer, World J Gastroenterol, 20, 4256, 10.3748/wjg.v20.i15.4256

Petrelli, 2013, Increasing the interval between neoadjuvant chemoradiotherapy and surgery in rectal cancer: a meta-analysis of published studies, Ann Surg

Huntington, 2015, Optimal timing of surgical resection after radiation therapy in locally advanced rectal adenocarcinoma: an analysis of the National Cancer Database (NCDB), J Clin Oncol, 33, 510, 10.1200/jco.2015.33.3_suppl.510

Dhadda, 2009, Regression of rectal cancer with radiotherapy with or without concurrent capecitabine—optimising the timing of surgical resection, Clin Oncol (R Coll Radiol), 21, 23, 10.1016/j.clon.2008.10.011

Sloothaak, 2013, Optimal time interval between neoadjuvant chemoradiotherapy and surgery for rectal cancer, Br J Surg, 100, 933, 10.1002/bjs.9112

Perez, 2012, Optimal timing for assessment of tumor response to neoadjuvant chemoradiation in patients with rectal cancer: do all patients benefit from waiting longer than 6 weeks?, Int J Radiat Oncol Biol Phys, 84, 1159, 10.1016/j.ijrobp.2012.01.096

Pettersson, 2010, Interim analysis of the Stockholm III trial of preoperative radiotherapy regimens for rectal cancer, Br J Surg, 97, 580, 10.1002/bjs.6914

Andre, 2009, Improved overall survival with oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment in stage II or III colon cancer in the MOSAIC trial, J Clin Oncol, 27, 3109, 10.1200/JCO.2008.20.6771

de Gramont, 2000, Leucovorin and fluorouracil with or without oxaliplatin as first-line treatment in advanced colorectal cancer, J Clin Oncol, 18, 2938, 10.1200/JCO.2000.18.16.2938

Kuebler, 2007, Oxaliplatin combined with weekly bolus fluorouracil and leucovorin as surgical adjuvant chemotherapy for stage II and III colon cancer: results from NSABP C-07, J Clin Oncol, 25, 2198, 10.1200/JCO.2006.08.2974

O'Connell, 2014, 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, 32, 1927, 10.1200/JCO.2013.53.7753

Allegra, 2014, Final results from NSABP protocol R-04: neoadjuvant chemoradiation (RT) comparing continuous infusion (CIV) 5-FU with capecitabine (Cape) with or without oxaliplatin (Ox) in patients with stage II and III rectal cancer, J Clin Oncol, 32, 3603, 10.1200/jco.2014.32.15_suppl.3603

Rodel, 2012, Preoperative chemoradiotherapy and postoperative chemotherapy with fluorouracil and oxaliplatin versus fluorouracil alone in locally advanced rectal cancer: initial results of the German CAO/ARO/AIO-04 randomised phase 3 trial, Lancet Oncol, 13, 679, 10.1016/S1470-2045(12)70187-0

Gerard, 2010, Comparison of two neoadjuvant chemoradiotherapy regimens for locally advanced rectal cancer: results of the phase III trial ACCORD 12/0405-Prodige 2, J Clin Oncol, 28, 1638, 10.1200/JCO.2009.25.8376

Aschele, 2011, Primary tumor response to preoperative chemoradiation with or without oxaliplatin in locally advanced rectal cancer: pathologic results of the STAR-01 randomized phase III trial, J Clin Oncol, 29, 2773, 10.1200/JCO.2010.34.4911

Roh, 2011, The impact of capecitabine and oxaliplatin in the preoperative multimodality treatment in patients with carcinoma of the rectum: NSABP R-04, J Clin Oncol, 29, 3503, 10.1200/jco.2011.29.15_suppl.3503

Schmoll, 2014, Preoperative chemoradiotherapy and postoperative chemotherapy with capecitabine and oxaliplatin versus capecitabine alone in locally advanced rectal cancer: disease-free survival results at interim analysis, J Clin Oncol, 32, 3501, 10.1200/jco.2014.32.15_suppl.3501

Rodel, 2014, 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, J Clin Oncol, 32, 3500, 10.1200/jco.2014.32.15_suppl.3500

Schmoll, 2013, Preoperative chemoradiotherapy and postoperative chemotherapy with capecitabine and oxaliplatin versus capecitabine alone in locally advanced rectal cancer: first results of the PETACC-6 randomized phase III trial, J Clin Oncol, 31, 3531, 10.1200/jco.2013.31.15_suppl.3531

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 Cancer, 49, 843, 10.1016/j.ejca.2012.09.026

Gerard, 2012, Clinical outcome of the ACCORD 12/0405 PRODIGE 2 randomized trial in rectal cancer, J Clin Oncol, 30, 4558, 10.1200/JCO.2012.42.8771

Engels, 2012, Current status of intensified neo-adjuvant systemic therapy in locally advanced rectal cancer, Front Oncol, 2, 47, 10.3389/fonc.2012.00047

De Felice, 2014, Neoadjuvant chemoradiotherapy for locally advanced rectal cancer: the debate continues, World J Gastrointest Oncol, 6, 438, 10.4251/wjgo.v6.i12.438

Fernandez-Martos, 2010, J Clin Oncol, 28, 859, 10.1200/JCO.2009.25.8541

Chua, 2010, Neoadjuvant capecitabine and oxaliplatin before chemoradiotherapy and total mesorectal excision in MRI-defined poor-risk rectal cancer: a phase 2 trial, Lancet Oncol, 11, 241, 10.1016/S1470-2045(09)70381-X

Schou, 2012, Induction chemotherapy with capecitabine and oxaliplatin followed by chemoradiotherapy before total mesorectal excision in patients with locally advanced rectal cancer, Ann Oncol, 23, 2627, 10.1093/annonc/mds056

Marechal, 2012, Short course chemotherapy followed by concomitant chemoradiotherapy and surgery in locally advanced rectal cancer: a randomized multicentric phase II study, Ann Oncol, 23, 1525, 10.1093/annonc/mdr473

Fernandez-Martos, 2011, J Clin Oncol, 29, 3552, 10.1200/jco.2011.29.15_suppl.3552

Fernandez-Martos, 2014, J Clin Oncol, 32, 383, 10.1200/jco.2014.32.3_suppl.383

Fernandez-Martos, 2015, Chemoradiation, surgery and adjuvant chemotherapy versus induction chemotherapy followed by chemoradiation and surgery: long-term results of the Spanish GCR-3 phase II randomized trial, Ann Oncol, 10.1093/annonc/mdv223

Calvo, 2014, Preoperative chemoradiation with or without induction oxaliplatin plus 5-fluorouracil in locally advanced rectal cancer. Long-term outcome analysis, Strahlenther Onkol, 190, 149, 10.1007/s00066-013-0469-0

Boland, 2014, The emerging role of neoadjuvant chemotherapy for rectal cancer, J Gastrointest Oncol, 5, 362

Glynne-Jones, 2012, Neoadjuvant chemotherapy in MRI-staged high-risk rectal cancer in addition to or as an alternative to preoperative chemoradiation?, Ann Oncol, 23, 2517, 10.1093/annonc/mds010

Glimelius, 2002, Radiotherapy in rectal cancer, Br Med Bull, 64, 141, 10.1093/bmb/64.1.141

Glimelius, 2013, Neo-adjuvant radiotherapy in rectal cancer, World J Gastroenterol, 19, 8489, 10.3748/wjg.v19.i46.8489

Bruheim, 2010, Late side effects and quality of life after radiotherapy for rectal cancer, Int J Radiat Oncol Biol Phys, 76, 1005, 10.1016/j.ijrobp.2009.03.010

Uehara, 2013, Neoadjuvant oxaliplatin and capecitabine and bevacizumab without radiotherapy for poor-risk rectal cancer: N-SOG 03 phase II trial, Jpn J Clin Oncol, 43, 964, 10.1093/jjco/hyt115

Hasegawa, 2014, Neoadjuvant capecitabine and oxaliplatin (XELOX) combined with bevacizumab for high-risk localized rectal cancer, Cancer Chemother Pharmacol, 73, 1079, 10.1007/s00280-014-2417-9

Schrag, 2014, Neoadjuvant chemotherapy without routine use of radiation therapy for patients with locally advanced rectal cancer: a pilot trial, J Clin Oncol, 32, 513, 10.1200/JCO.2013.51.7904

Ishii, 2010, Medium-term results of neoadjuvant systemic chemotherapy using irinotecan, 5-fluorouracil, and leucovorin in patients with locally advanced rectal cancer, Eur J Surg Oncol, 36, 1061, 10.1016/j.ejso.2010.05.017

Fernandez-Martos, 2012, Neoadjuvant capecitabine, oxliplatin, and bevacizumab (CAPOX-B) in intermediate-risk rectal cancer (RC) patients defined by magnetic resonance (MR): GEMCAD 0801 trial, J Clin Oncol, 30, 3586, 10.1200/jco.2012.30.15_suppl.3586

Fernandez-Martos, 2014, Preoperative chemotherapy in patients with intermediate-risk rectal adenocarcinoma selected by high-resolution magnetic resonance imaging: the GEMCAD 0801 phase II multicenter trial, Oncologist, 19, 1042, 10.1634/theoncologist.2014-0233

Hasegawa, 2002, Neoadjuvant chemotherapy of irinotecan, 5-fluorouracil and leucovorin in patients with advanced rectal cancer. Report of two cases, Hepatogastroenterology, 49, 891

Allegra, 2011, Phase III trial assessing bevacizumab in stages II and III carcinoma of the colon: results of NSABP protocol C-08, J Clin Oncol, 29, 11, 10.1200/JCO.2010.30.0855

Rutten, 2008, Controversies of total mesorectal excision for rectal cancer in elderly patients, Lancet Oncol, 9, 494, 10.1016/S1470-2045(08)70129-3

Borowski, 2010, Volume-outcome analysis of colorectal cancer–related outcomes, Br J Surg, 97, 1416, 10.1002/bjs.7111

Paun, 2010, Postoperative complications following surgery for rectal cancer, Ann Surg, 251, 807, 10.1097/SLA.0b013e3181dae4ed

Glynne-Jones, 2012, Critical appraisal of the “wait and see” approach in rectal cancer for clinical complete responders after chemoradiation, Br J Surg, 99, 897, 10.1002/bjs.8732

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

Lim, 2007, Long-term outcomes of patients with localized rectal cancer treated with chemoradiation or radiotherapy alone because of medical inoperability or patient refusal, Dis Colon Rectum, 50, 2032, 10.1007/s10350-007-9062-x

Yang, 2015, Predicting complete response: is there a role for non-operative management of rectal cancer?, J Gastrointest Oncol, 6, 241

Cerezo, 2013, Current treatment of rectal cancer adapted to the individual patient, Rep Pract Oncol Radiother, 18, 353, 10.1016/j.rpor.2013.08.005

Damin, 2014, Evolving treatment strategies for colorectal cancer: a critical review of current therapeutic options, World J Gastroenterol, 20, 877, 10.3748/wjg.v20.i4.877

Marijnen, 2015, Organ preservation in rectal cancer: have all questions been answered?, Lancet Oncol, 16, e13, 10.1016/S1470-2045(14)70398-5

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

Maas, 2011, Wait-and-see policy for clinical complete responders after chemoradiation for rectal cancer, J Clin Oncol, 29, 4633, 10.1200/JCO.2011.37.7176

Fisher, 1988, Postoperative adjuvant chemotherapy or radiation therapy for rectal cancer: results from NSABP protocol R-01, J Natl Cancer Inst, 80, 21, 10.1093/jnci/80.1.21

Krook, 1991, Effective surgical adjuvant therapy for high-risk rectal carcinoma, N Engl J Med, 324, 709, 10.1056/NEJM199103143241101

Tepper, 2002, Adjuvant therapy in rectal cancer: analysis of stage, sex, and local control—final report of Intergroup 0114, J Clin Oncol, 20, 1744, 10.1200/JCO.2002.07.132

Petersen, 2012, Postoperative adjuvant chemotherapy in rectal cancer operated for cure, Cochrane Database Syst Rev, CD004078

Bosset, 2006, Chemotherapy with preoperative radiotherapy in rectal cancer, N Engl J Med, 355, 1114, 10.1056/NEJMoa060829

Collette, 2007, J Clin Oncol, 25, 4379, 10.1200/JCO.2007.11.9685

Bosset, 2014, Fluorouracil-based adjuvant chemotherapy after preoperative chemoradiotherapy in rectal cancer: long-term results of the EORTC 22921 randomised study, Lancet Oncol, 15, 184, 10.1016/S1470-2045(13)70599-0

Breugom, 2015, Adjuvant chemotherapy for rectal cancer patients treated with preoperative (chemo)radiotherapy and total mesorectal excision: a Dutch Colorectal Cancer Group (DCCG) randomized phase III trialdagger, Ann Oncol, 26, 696, 10.1093/annonc/mdu560

Sainato, 2014, No benefit of adjuvant fluorouracil leucovorin chemotherapy after neoadjuvant chemoradiotherapy in locally advanced cancer of the rectum (LARC): long term results of a randomized trial (I-CNR-RT), Radiother Oncol, 113, 223, 10.1016/j.radonc.2014.10.006

Breugom, 2015, Adjuvant chemotherapy after preoperative (chemo)radiotherapy and surgery for patients with rectal cancer: a systematic review and meta-analysis of individual patient data, Lancet Oncol, 16, 200, 10.1016/S1470-2045(14)71199-4

Petrelli, 2015, A systematic review and meta-analysis of adjuvant chemotherapy after neoadjuvant treatment and surgery for rectal cancer, Int J Colorectal Dis, 30, 447, 10.1007/s00384-014-2082-9

Bujko, 2010, Does adjuvant fluoropyrimidine-based chemotherapy provide a benefit for patients with resected rectal cancer who have already received neoadjuvant radiochemotherapy? A systematic review of randomised trials, Ann Oncol, 21, 1743, 10.1093/annonc/mdq054

Haller, 2005, Phase III study of fluorouracil, leucovorin, and levamisole in high-risk stage II and III colon cancer: final report of Intergroup 0089, J Clin Oncol, 23, 8671, 10.1200/JCO.2004.00.5686

Gray, 2007, Adjuvant chemotherapy versus observation in patients with colorectal cancer: a randomised study, Lancet, 370, 2020, 10.1016/S0140-6736(07)61866-2

2000, Comparison of fluorouracil with additional levamisole, higher-dose folinic acid, or both, as adjuvant chemotherapy for colorectal cancer: a randomised trial. QUASAR Collaborative Group, Lancet, 355, 1588, 10.1016/S0140-6736(00)02214-5

Das, 2006, Clinical and pathologic predictors of locoregional recurrence, distant metastasis, and overall survival in patients treated with chemoradiation and mesorectal excision for rectal cancer, Am J Clin Oncol, 29, 219, 10.1097/01.coc.0000214930.78200.4a

Palta, 2014, Colorectal cancer: adjuvant chemotherapy for rectal cancer—an unresolved issue, Nat Rev Clin Oncol, 11, 182, 10.1038/nrclinonc.2014.43

Minsky, 2007, Adjuvant management of rectal cancer: the more we learn, the less we know, J Clin Oncol, 25, 4339, 10.1200/JCO.2007.12.8892

Hong, 2014, Oxaliplatin, fluorouracil, and leucovorin versus fluorouracil and leucovorin as adjuvant chemotherapy for locally advanced rectal cancer after preoperative chemoradiotherapy (ADORE): an open-label, multicentre, phase 2, randomised controlled trial, Lancet Oncol, 15, 1245, 10.1016/S1470-2045(14)70377-8

Glynne-Jones, 2014, Chronicle: results of a randomised phase III trial in locally advanced rectal cancer after neoadjuvant chemoradiation randomising postoperative adjuvant capecitabine plus oxaliplatin (XELOX) versus control, Ann Oncol, 25, 1356, 10.1093/annonc/mdu147

Gao, 2014, Which is the best postoperative chemotherapy regimen in patients with rectal cancer after neoadjuvant therapy?, BMC Cancer, 14, 888, 10.1186/1471-2407-14-888

Nimeiri, 2013, J Clin Oncol, 31, e14711, 10.1200/jco.2013.31.15_suppl.e14711

Hurwitz, 2013, Efficacy and safety of bevacizumab in metastatic colorectal cancer: pooled analysis from seven randomized controlled trials, Oncologist, 18, 1004, 10.1634/theoncologist.2013-0107

Jonker, 2007, Cetuximab for the treatment of colorectal cancer, N Engl J Med, 357, 2040, 10.1056/NEJMoa071834

Nelson, 2013, Status of targeted therapies in the adjuvant treatment of colon cancer, J Gastrointest Oncol, 4, 245

Fornaro, 2014, Bevacizumab in the pre-operative treatment of locally advanced rectal cancer: a systematic review, World J Gastroenterol, 20, 6081, 10.3748/wjg.v20.i20.6081

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, Oncologist, 16, 614, 10.1634/theoncologist.2010-0285

de Gramont, 2012, Bevacizumab plus oxaliplatin-based chemotherapy as adjuvant treatment for colon cancer (AVANT): a phase 3 randomised controlled trial, Lancet Oncol, 13, 1225, 10.1016/S1470-2045(12)70509-0

Allegra, 2013, Bevacizumab in stage II-III colon cancer: 5-year update of the National Surgical Adjuvant Breast and Bowel Project C-08 trial, J Clin Oncol, 31, 359, 10.1200/JCO.2012.44.4711

Bonner, 2006, Radiotherapy plus cetuximab for squamous-cell carcinoma of the head and neck, N Engl J Med, 354, 567, 10.1056/NEJMoa053422

Dewdney, 2012, Multicenter randomized phase II clinical trial comparing neoadjuvant oxaliplatin, capecitabine, and preoperative radiotherapy with or without cetuximab followed by total mesorectal excision in patients with high-risk rectal cancer (EXPERT-C), J Clin Oncol, 30, 1620, 10.1200/JCO.2011.39.6036

Sclafani, 2014, RAS mutations and cetuximab in locally advanced rectal cancer: results of the EXPERT-C trial, Eur J Cancer, 50, 1430, 10.1016/j.ejca.2014.02.002

Helbling, 2013, Neoadjuvant chemoradiotherapy with or without panitumumab in patients with wild-type KRAS, locally advanced rectal cancer (LARC): a randomized, multicenter, phase II trial SAKK 41/07, Ann Oncol, 24, 718, 10.1093/annonc/mds519

Glynne-Jones, 2013, The status of targeted agents in the setting of neoadjuvant radiation therapy in locally advanced rectal cancers, J Gastrointest Oncol, 4, 264