{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T20:19:42Z","timestamp":1793305182479,"version":"4.5.0"},"reference-count":39,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,7,26]],"date-time":"2024-07-26T00:00:00Z","timestamp":1721952000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,7,26]],"date-time":"2024-07-26T00:00:00Z","timestamp":1721952000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Cancer"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Recent data have demonstrated that in locally advanced rectal cancer (LARC), a total neoadjuvant therapy (TNT) approach improves compliance with chemotherapy and increases rates of tumor response compared to neoadjuvant chemoradiation (CRT) alone. They further indicate that the optimal sequencing of TNT involves consolidation (rather than induction) chemotherapy to optimize complete response rates. Data, largely from retrospective studies, have also shown that patients with clinical complete response (cCR) after TNT may be managed safely with the watch and wait approach (WW) instead of preemptive total mesorectal resection (TME). However, the optimal consolidation chemotherapy regimen to achieve cCR has not been established, and a randomized clinical trial has not robustly evaluated cCR as a primary endpoint. Collaborating with a multidisciplinary oncology team and patient groups, we designed this NCI-sponsored study of chemotherapy intensification to address these issues and to drive up cCR rates, to provide opportunity for organ preservation, improve quality of life for patients and improve survival outcomes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      In this NCI-sponsored multi-group randomized, seamless phase II\/III trial (1:1), up to 760 patients with LARC, T4N0, any T with node positive disease (any T, N\u2009+) or T3N0 requiring abdominoperineal resection or coloanal anastomosis and distal margin within 12\u00a0cm of anal verge will be enrolled. Stratification factors include tumor stage (T4 vs T1-3), nodal stage (N\u2009+\u2009vs N0) and distance from anal verge (0\u20134; 4\u20138; 8\u201312\u00a0cm). Patients will be randomized to receive neoadjuvant long-course chemoradiation (LCRT) followed by consolidation doublet (mFOLFOX6 or CAPOX) or triplet chemotherapy (mFOLFIRINOX) for 3\u20134\u00a0months. LCRT in both arms involves 4500\u00a0cGy in 25 fractions over 5\u00a0weeks\u2009+\u2009900\u00a0cGy boost in 5 fractions with a fluoropyrimidine (capecitabine preferred). Patients will undergo assessment 8\u201312 (\u00b1\u20094) weeks post-TNT completion. The primary endpoint for the phase II portion will compare cCR between treatment arms. A total number of 312 evaluable patients (156 per arm) will provide statistical power of 90.5% to detect a 17% increase in cCR rate, at a one-sided alpha\u2009=\u20090.048. The primary endpoint for the phase III portion will compare disease-free survival (DFS) between treatment arms. A total of 285 DFS events will provide 85% power to detect an effect size of hazard ratio 0.70 at a one-sided alpha of 0.025, requiring enrollment of 760 patients (380 per arm). Secondary objectives include time-to event outcomes (overall survival, organ preservation time and time to distant metastasis) and adverse event rates. Biospecimens including archival tumor tissue, plasma and buffy coat, and serial rectal MRIs will be collected for exploratory correlative research. This study, activated in late 2022, is open across the NCTN and had accrued 330 patients as of May 2024. Study support: U10CA180821, U10CA180882, U24 CA196171;\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/acknowledgments.alliancefound.org\">https:\/\/acknowledgments.alliancefound.org<\/jats:ext-link>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>Building on data from modern day rectal cancer trials and patient input from national advocacy groups, we have designed The Janus Rectal Cancer Trial studying chemotherapy intensification via a consolidation chemotherapy approach with the intent to enhance cCR and DFS rates, increase organ preservation rates, and improve quality of life for patients with rectal cancer.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration<\/jats:title>\n                    <jats:p>Clinicaltrials.gov ID: NCT05610163; Support includes U10CA180868 (NRG) and U10CA180888 (SWOG).<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12885-024-12529-7","type":"journal-article","created":{"date-parts":[[2024,7,26]],"date-time":"2024-07-26T18:03:38Z","timestamp":1722017018000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":45,"title":["Alliance A022104\/NRG-GI010: The Janus Rectal Cancer Trial: a randomized phase II\/III trial testing the efficacy of triplet versus doublet chemotherapy regarding clinical complete response and disease-free survival in patients with locally advanced rectal cancer"],"prefix":"10.1186","volume":"24","author":[{"given":"Janet A.","family":"Alvarez","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Shi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arvind","family":"Dasari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julio","family":"Garcia-Aguilar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanna","family":"Sanoff","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas J.","family":"George","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theodore","family":"Hong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Greg","family":"Yothers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip","family":"Philip","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Garth","family":"Nelson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tareq","family":"Al Baghdadi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olatunji B.","family":"Alese","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wini","family":"Zambare","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dana","family":"Omer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Floris S.","family":"Verheij","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aron","family":"Bercz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min Jung","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Buckley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hannah","family":"Williams","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manju","family":"George","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reese","family":"Garcia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Phuong","family":"Gallagher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eileen M.","family":"O\u2019Reilly","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey A.","family":"Meyerhardt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jamie","family":"Crawley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ardaman","family":"Shergill","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natally","family":"Horvat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul B.","family":"Romesser","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William","family":"Hall","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. Joshua","family":"Smith","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,7,26]]},"reference":[{"issue":"1","key":"12529_CR1","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1016\/S1470-2045(20)30555-6","volume":"22","author":"RR Bahadoer","year":"2021","unstructured":"Bahadoer RR, Dijkstra EA, van Etten B, et al. Short-course radiotherapy followed by chemotherapy before total mesorectal excision (TME) versus preoperative chemoradiotherapy, TME, and optional adjuvant chemotherapy in locally advanced rectal cancer (RAPIDO): a randomised, open-label, phase 3 trial. Lancet Oncol. 2021;22(1):29\u201342. https:\/\/doi.org\/10.1016\/S1470-2045(20)30555-6.","journal-title":"Lancet Oncol"},{"issue":"6","key":"12529_CR2","doi-asserted-by":"publisher","first-page":"e180071","DOI":"10.1001\/jamaoncol.2018.0071","volume":"4","author":"A Cercek","year":"2018","unstructured":"Cercek A, Roxburgh CSD, Strombom P, et al. Adoption of total neoadjuvant therapy for locally advanced rectal cancer. JAMA Oncol. 2018;4(6):e180071. https:\/\/doi.org\/10.1001\/jamaoncol.2018.0071.","journal-title":"JAMA Oncol"},{"key":"12529_CR3","doi-asserted-by":"publisher","unstructured":"Chau I, Brown G, Cunningham D, et al. Neoadjuvant capecitabine and oxaliplatin followed by synchronous chemoradiation and total mesorectal excision in magnetic resonance imaging\u2013defined poor-risk rectal cancer. J Clin Oncol. Published online September 21, 2016. https:\/\/doi.org\/10.1200\/JCO.2005.04.4875","DOI":"10.1200\/JCO.2005.04.4875"},{"issue":"15_suppl","key":"12529_CR4","doi-asserted-by":"publisher","first-page":"4007","DOI":"10.1200\/JCO.2020.38.15_suppl.4007","volume":"38","author":"T Conroy","year":"2020","unstructured":"Conroy T, Lamfichekh N, Etienne PL, et al. Total neoadjuvant therapy with mFOLFIRINOX versus preoperative chemoradiation in patients with locally advanced rectal cancer: Final results of PRODIGE 23 phase III trial, a UNICANCER GI trial. J Clin Oncol. 2020;38(15_suppl):4007\u20134007. https:\/\/doi.org\/10.1200\/JCO.2020.38.15_suppl.4007.","journal-title":"J Clin Oncol"},{"issue":"8","key":"12529_CR5","doi-asserted-by":"publisher","first-page":"1722","DOI":"10.1093\/annonc\/mdv223","volume":"26","author":"C Fernandez-Martos","year":"2015","unstructured":"Fernandez-Martos C, Garcia-Albeniz X, Pericay C, et al. 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\u2020. Ann Oncol. 2015;26(8):1722\u20138. https:\/\/doi.org\/10.1093\/annonc\/mdv223.","journal-title":"Ann Oncol"},{"issue":"1","key":"12529_CR6","doi-asserted-by":"publisher","first-page":"e215445","DOI":"10.1001\/jamaoncol.2021.5445","volume":"8","author":"E Fokas","year":"2022","unstructured":"Fokas E, Schlenska-Lange A, Polat B, et al. Chemoradiotherapy plus induction or consolidation chemotherapy as total neoadjuvant therapy for patients with locally advanced rectal cancer: long-term results of the CAO\/ARO\/AIO-12 randomized clinical trial. JAMA Oncol. 2022;8(1):e215445. https:\/\/doi.org\/10.1001\/jamaoncol.2021.5445.","journal-title":"JAMA Oncol"},{"issue":"8","key":"12529_CR7","doi-asserted-by":"publisher","first-page":"957","DOI":"10.1016\/S1470-2045(15)00004-2","volume":"16","author":"J Garcia-Aguilar","year":"2015","unstructured":"Garcia-Aguilar J, Chow OS, Smith DD, et al. Effect of adding mFOLFOX6 after neoadjuvant chemoradiation in locally advanced rectal cancer: a multicentre, phase 2 trial. Lancet Oncol. 2015;16(8):957\u201366. https:\/\/doi.org\/10.1016\/S1470-2045(15)00004-2.","journal-title":"Lancet Oncol"},{"issue":"1","key":"12529_CR8","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.clcc.2017.06.008","volume":"17","author":"AJ Franke","year":"2018","unstructured":"Franke AJ, Parekh H, Starr JS, Tan SA, Iqbal A, George TJ. Total neoadjuvant therapy: a shifting paradigm in locally advanced rectal cancer management. Clin Colorectal Cancer. 2018;17(1):1\u201312. https:\/\/doi.org\/10.1016\/j.clcc.2017.06.008.","journal-title":"Clin Colorectal Cancer"},{"issue":"23","key":"12529_CR9","doi-asserted-by":"publisher","first-page":"2546","DOI":"10.1200\/JCO.22.00032","volume":"40","author":"J Garcia-Aguilar","year":"2022","unstructured":"Garcia-Aguilar J, Patil S, Gollub MJ, et al. Organ preservation in patients with rectal adenocarcinoma treated with total neoadjuvant therapy. J Clin Oncol. 2022;40(23):2546\u201356. https:\/\/doi.org\/10.1200\/JCO.22.00032.","journal-title":"J Clin Oncol"},{"issue":"5","key":"12529_CR10","doi-asserted-by":"publisher","first-page":"702","DOI":"10.1016\/S1470-2045(21)00079-6","volume":"22","author":"T Conroy","year":"2021","unstructured":"Conroy T, Bosset JF, Etienne PL, et al. Neoadjuvant chemotherapy with FOLFIRINOX and preoperative chemoradiotherapy for patients with locally advanced rectal cancer (UNICANCER-PRODIGE 23): a multicentre, randomised, open-label, phase 3 trial. Lancet Oncol. 2021;22(5):702\u201315. https:\/\/doi.org\/10.1016\/S1470-2045(21)00079-6.","journal-title":"Lancet Oncol"},{"issue":"3","key":"12529_CR11","doi-asserted-by":"publisher","first-page":"267","DOI":"10.1007\/s11912-012-0234-z","volume":"14","author":"A Dewdney","year":"2012","unstructured":"Dewdney A, Cunningham D. Toward the non-surgical management of locally advanced rectal cancer. Curr Oncol Rep. 2012;14(3):267\u201376. https:\/\/doi.org\/10.1007\/s11912-012-0234-z.","journal-title":"Curr Oncol Rep"},{"issue":"7","key":"12529_CR12","doi-asserted-by":"publisher","first-page":"675","DOI":"10.1016\/j.canrad.2013.06.043","volume":"17","author":"R Glynne-Jones","year":"2013","unstructured":"Glynne-Jones R, Harrison M, Hughes R. Challenges in the neoadjuvant treatment of rectal cancer: balancing the risk of recurrence and quality of life. Cancer Radiother J Soc Francaise Radiother Oncol. 2013;17(7):675\u201385. https:\/\/doi.org\/10.1016\/j.canrad.2013.06.043.","journal-title":"Cancer Radiother J Soc Francaise Radiother Oncol"},{"issue":"9","key":"12529_CR13","doi-asserted-by":"publisher","first-page":"835","DOI":"10.1016\/S1470-2045(10)70172-8","volume":"11","author":"M Maas","year":"2010","unstructured":"Maas M, Nelemans PJ, 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(9):835\u201344. https:\/\/doi.org\/10.1016\/S1470-2045(10)70172-8.","journal-title":"Lancet Oncol"},{"issue":"4","key":"12529_CR14","doi-asserted-by":"publisher","first-page":"711","DOI":"10.1097\/01.sla.0000141194.27992.32","volume":"240","author":"A Habr-Gama","year":"2004","unstructured":"Habr-Gama A, Perez RO, Nadalin W, et al. Operative versus nonoperative treatment for stage 0 distal rectal cancer following chemoradiation therapy: long-term results. Ann Surg. 2004;240(4):711\u20137. https:\/\/doi.org\/10.1097\/01.sla.0000141194.27992.32. discussion 717-718.","journal-title":"Ann Surg"},{"issue":"1","key":"12529_CR15","doi-asserted-by":"publisher","first-page":"767","DOI":"10.1186\/s12885-015-1632-z","volume":"15","author":"JJ Smith","year":"2015","unstructured":"Smith JJ, Chow OS, Gollub MJ, et al. Organ Preservation in Rectal Adenocarcinoma: a phase II randomized controlled 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 nonoperative management. BMC Cancer. 2015;15(1):767. https:\/\/doi.org\/10.1186\/s12885-015-1632-z.","journal-title":"BMC Cancer"},{"key":"12529_CR16","doi-asserted-by":"publisher","unstructured":"Verheij FS, Omer DM, Williams H, et al. Long-term results of organ preservation in patients with rectal adenocarcinoma treated with total neoadjuvant therapy: the randomized phase II OPRA trial. J Clin Oncol. Published online October 26, 2023. https:\/\/doi.org\/10.1200\/JCO.23.01208","DOI":"10.1200\/JCO.23.01208"},{"issue":"3","key":"12529_CR17","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1016\/j.clcc.2016.02.012","volume":"15","author":"LM Wiltink","year":"2016","unstructured":"Wiltink LM, Nout RA, van der Voort van Zyp JRN, et al. Long-term health-related quality of life in patients with rectal cancer after preoperative short-course and long-course (Chemo) radiotherapy. Clin Colorectal Cancer. 2016;15(3):93\u20139. https:\/\/doi.org\/10.1016\/j.clcc.2016.02.012.","journal-title":"Clin Colorectal Cancer"},{"issue":"10","key":"12529_CR18","doi-asserted-by":"publisher","first-page":"1032","DOI":"10.1097\/DCR.0000000000000862","volume":"60","author":"BJP Hupkens","year":"2017","unstructured":"Hupkens BJP, Martens MH, Stoot JH, et al. Quality of life in rectal cancer patients after chemoradiation: watch-and-wait policy versus standard resection - a matched-controlled study. Dis Colon Rectum. 2017;60(10):1032\u201340. https:\/\/doi.org\/10.1097\/DCR.0000000000000862.","journal-title":"Dis Colon Rectum"},{"issue":"7","key":"12529_CR19","doi-asserted-by":"publisher","first-page":"897","DOI":"10.1097\/DCR.0000000000001646","volume":"63","author":"FF Quezada-Diaz","year":"2020","unstructured":"Quezada-Diaz FF, Smith JJ, Jimenez-Rodriguez RM, et al. Patient-reported bowel function in patients with rectal cancer managed by a watch-and-wait strategy after neoadjuvant therapy: a case-control study. Dis Colon Rectum. 2020;63(7):897\u2013902. https:\/\/doi.org\/10.1097\/DCR.0000000000001646.","journal-title":"Dis Colon Rectum"},{"issue":"4","key":"12529_CR20","doi-asserted-by":"publisher","first-page":"e185896","DOI":"10.1001\/jamaoncol.2018.5896","volume":"5","author":"JJ Smith","year":"2019","unstructured":"Smith JJ, Strombom P, Chow OS, et al. Assessment of a watch-and-wait strategy for rectal cancer in patients with a complete response after neoadjuvant therapy. JAMA Oncol. 2019;5(4):e185896. https:\/\/doi.org\/10.1001\/jamaoncol.2018.5896.","journal-title":"JAMA Oncol"},{"key":"12529_CR21","doi-asserted-by":"publisher","unstructured":"Cremolini C, Antoniotti C, Stein A, et al. Individual patient data meta-analysis of FOLFOXIRI plus bevacizumab versus doublets plus bevacizumab as initial therapy of unresectable metastatic colorectal cancer. J Clin Oncol Off J Am Soc Clin Oncol. Published online August 20, 2020:JCO2001225. https:\/\/doi.org\/10.1200\/JCO.20.01225","DOI":"10.1200\/JCO.20.01225"},{"issue":"13","key":"12529_CR22","doi-asserted-by":"publisher","first-page":"1670","DOI":"10.1200\/JCO.2006.09.0928","volume":"25","author":"A Falcone","year":"2007","unstructured":"Falcone A, Ricci S, Brunetti I, et al. Phase III trial of infusional fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFOXIRI) compared with infusional fluorouracil, leucovorin, and irinotecan (FOLFIRI) as first-line treatment for metastatic colorectal cancer: the Gruppo Oncologico Nord Ovest. J Clin Oncol Off J Am Soc Clin Oncol. 2007;25(13):1670\u20136. https:\/\/doi.org\/10.1200\/JCO.2006.09.0928.","journal-title":"J Clin Oncol Off J Am Soc Clin Oncol"},{"issue":"17","key":"12529_CR23","doi-asserted-by":"publisher","first-page":"1609","DOI":"10.1056\/NEJMoa1403108","volume":"371","author":"F Loupakis","year":"2014","unstructured":"Loupakis F, Cremolini C, Masi G, et al. Initial therapy with FOLFOXIRI and bevacizumab for metastatic colorectal cancer. N Engl J Med. 2014;371(17):1609\u201318. https:\/\/doi.org\/10.1056\/NEJMoa1403108.","journal-title":"N Engl J Med"},{"issue":"13","key":"12529_CR24","doi-asserted-by":"publisher","first-page":"1306","DOI":"10.1016\/S1470-2045(15)00122-9","volume":"16","author":"C Cremolini","year":"2015","unstructured":"Cremolini C, Loupakis F, Antoniotti C, et al. FOLFOXIRI plus bevacizumab versus FOLFIRI plus bevacizumab as first-line treatment of patients with metastatic colorectal cancer: updated overall survival and molecular subgroup analyses of the open-label, phase 3 TRIBE study. Lancet Oncol. 2015;16(13):1306\u201315. https:\/\/doi.org\/10.1016\/S1470-2045(15)00122-9.","journal-title":"Lancet Oncol"},{"issue":"4","key":"12529_CR25","doi-asserted-by":"publisher","first-page":"702","DOI":"10.1093\/annonc\/mdu580","volume":"26","author":"T Gruenberger","year":"2015","unstructured":"Gruenberger T, Bridgewater J, Chau I, et al. Bevacizumab plus mFOLFOX-6 or FOLFOXIRI in patients with initially unresectable liver metastases from colorectal cancer: the OLIVIA multinational randomised phase II trial. Ann Oncol Off J Eur Soc Med Oncol. 2015;26(4):702\u20138. https:\/\/doi.org\/10.1093\/annonc\/mdu580.","journal-title":"Ann Oncol Off J Eur Soc Med Oncol"},{"key":"12529_CR26","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdy149.022","volume":"29","author":"H Schmoll","year":"2018","unstructured":"Schmoll H, Garlipp B, Junghan\u00df C, et al. FOLFOX\/bevacizumab +\/- irinotecan in advanced colorectal cancer (CHARTA): Long term outcome. Ann Oncol. 2018;29: v108. https:\/\/doi.org\/10.1093\/annonc\/mdy149.022.","journal-title":"Ann Oncol"},{"issue":"7","key":"12529_CR27","doi-asserted-by":"publisher","first-page":"921","DOI":"10.1634\/theoncologist.2018-0344","volume":"24","author":"HI Hurwitz","year":"2019","unstructured":"Hurwitz HI, Tan BR, Reeves JA, et al. Phase II randomized trial of sequential or concurrent FOLFOXIRI-Bevacizumab versus FOLFOX-Bevacizumab for Metastatic Colorectal Cancer (STEAM). Oncologist. 2019;24(7):921\u201332. https:\/\/doi.org\/10.1634\/theoncologist.2018-0344.","journal-title":"Oncologist"},{"issue":"15_suppl","key":"12529_CR28","doi-asserted-by":"publisher","first-page":"3507","DOI":"10.1200\/JCO.2019.37.15_suppl.3507","volume":"37","author":"J Sastre","year":"2019","unstructured":"Sastre J, Vieitez JM, Gomez-Espa\u00f1a MA, et al. Randomized phase III study comparing FOLFOX + bevacizumab versus folfoxiri + bevacizumab (BEV) as 1st line treatment in patients with metastatic colorectal cancer (mCRC) with \u22653 baseline circulating tumor cells (bCTCs). J Clin Oncol. 2019;37(15_suppl):3507\u20133507. https:\/\/doi.org\/10.1200\/JCO.2019.37.15_suppl.3507.","journal-title":"J Clin Oncol"},{"issue":"8","key":"12529_CR29","doi-asserted-by":"publisher","first-page":"1386","DOI":"10.1093\/annonc\/mdw235","volume":"27","author":"E Van Cutsem","year":"2016","unstructured":"Van Cutsem E, Cervantes A, Adam R, et al. ESMO consensus guidelines for the management of patients with metastatic colorectal cancer. Ann Oncol Off J Eur Soc Med Oncol. 2016;27(8):1386\u2013422. https:\/\/doi.org\/10.1093\/annonc\/mdw235.","journal-title":"Ann Oncol Off J Eur Soc Med Oncol"},{"issue":"3","key":"12529_CR30","doi-asserted-by":"publisher","first-page":"329","DOI":"10.6004\/jnccn.2021.0012","volume":"19","author":"AB Benson","year":"2021","unstructured":"Benson AB, Venook AP, Al-Hawary MM, et al. Colon cancer, version 2.2021, NCCN clinical practice guidelines in oncology. J Natl Compr Cancer Netw JNCCN. 2021;19(3):329\u201359. https:\/\/doi.org\/10.6004\/jnccn.2021.0012.","journal-title":"J Natl Compr Cancer Netw JNCCN."},{"issue":"1","key":"12529_CR31","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1093\/annonc\/mdx738","volume":"29","author":"T Yoshino","year":"2018","unstructured":"Yoshino T, Arnold D, Taniguchi H, et al. Pan-asian adapted ESMO consensus guidelines for the management of patients with metastatic colorectal cancer: a JSMO-ESMO initiative endorsed by CSCO, KACO, MOS, SSO and TOS. Ann Oncol Off J Eur Soc Med Oncol. 2018;29(1):44\u201370. https:\/\/doi.org\/10.1093\/annonc\/mdx738.","journal-title":"Ann Oncol Off J Eur Soc Med Oncol"},{"key":"12529_CR32","doi-asserted-by":"publisher","unstructured":"Fokas E, Allg\u00e4uer M, Polat B, et al. Randomized phase II trial of chemoradiotherapy plus induction or consolidation chemotherapy as total neoadjuvant therapy for locally advanced rectal cancer: CAO\/ARO\/AIO-12. J Clin Oncol. Published online May 31, 2019. https:\/\/doi.org\/10.1200\/JCO.19.00308","DOI":"10.1200\/JCO.19.00308"},{"issue":"7","key":"12529_CR33","doi-asserted-by":"publisher","first-page":"874","DOI":"10.1007\/s12094-018-1997-y","volume":"21","author":"AK Boysen","year":"2019","unstructured":"Boysen AK, Schou JV, Spindler KLG. Cell-free DNA and preoperative chemoradiotherapy for rectal cancer: a systematic review. Clin Transl Oncol Off Publ Fed Span Oncol Soc Natl Cancer Inst Mex. 2019;21(7):874\u201380. https:\/\/doi.org\/10.1007\/s12094-018-1997-y.","journal-title":"Clin Transl Oncol Off Publ Fed Span Oncol Soc Natl Cancer Inst Mex"},{"key":"12529_CR34","doi-asserted-by":"publisher","first-page":"101893","DOI":"10.1016\/j.ctrv.2019.101893","volume":"79","author":"D Massihnia","year":"2019","unstructured":"Massihnia D, Pizzutilo EG, Amatu A, et al. Liquid biopsy for rectal cancer: A systematic review. Cancer Treat Rev. 2019;79:101893. https:\/\/doi.org\/10.1016\/j.ctrv.2019.101893.","journal-title":"Cancer Treat Rev"},{"issue":"1","key":"12529_CR35","doi-asserted-by":"publisher","first-page":"218","DOI":"10.1016\/j.ejso.2021.08.034","volume":"48","author":"M Morais","year":"2022","unstructured":"Morais M, Pinto DM, Machado JC, Carneiro S. ctDNA on liquid biopsy for predicting response and prognosis in locally advanced rectal cancer: A systematic review. Eur J Surg Oncol J Eur Soc Surg Oncol Br Assoc Surg Oncol. 2022;48(1):218\u201327. https:\/\/doi.org\/10.1016\/j.ejso.2021.08.034.","journal-title":"Eur J Surg Oncol J Eur Soc Surg Oncol Br Assoc Surg Oncol"},{"issue":"8","key":"12529_CR36","doi-asserted-by":"publisher","first-page":"e1003741","DOI":"10.1371\/journal.pmed.1003741","volume":"18","author":"Y Wang","year":"2021","unstructured":"Wang Y, Yang L, Bao H, et al. Utility of ctDNA in predicting response to neoadjuvant chemoradiotherapy and prognosis assessment in locally advanced rectal cancer: a prospective cohort study. PLoS Med. 2021;18(8):e1003741. https:\/\/doi.org\/10.1371\/journal.pmed.1003741.","journal-title":"PLoS Med"},{"issue":"8","key":"12529_CR37","doi-asserted-by":"publisher","first-page":"1124","DOI":"10.1001\/jamaoncol.2019.0528","volume":"5","author":"T Reinert","year":"2019","unstructured":"Reinert T, Henriksen TV, Christensen E, et al. Analysis of plasma cell-free DNA by ultradeep sequencing in patients with stages I to III colorectal cancer. JAMA Oncol. 2019;5(8):1124\u201331. https:\/\/doi.org\/10.1001\/jamaoncol.2019.0528.","journal-title":"JAMA Oncol"},{"issue":"24","key":"12529_CR38","doi-asserted-by":"publisher","first-page":"2261","DOI":"10.1056\/NEJMoa2200075","volume":"386","author":"J Tie","year":"2022","unstructured":"Tie J, Cohen JD, Lahouel K, et al. Circulating tumor DNA analysis guiding adjuvant therapy in stage II colon cancer. N Engl J Med. 2022;386(24):2261\u201372. https:\/\/doi.org\/10.1056\/NEJMoa2200075.","journal-title":"N Engl J Med"},{"issue":"4","key":"12529_CR39","doi-asserted-by":"publisher","first-page":"663","DOI":"10.1136\/gutjnl-2017-315852","volume":"68","author":"J Tie","year":"2019","unstructured":"Tie J, Cohen JD, Wang Y, et al. Serial circulating tumour DNA analysis during multimodality treatment of locally advanced rectal cancer: a prospective biomarker study. Gut. 2019;68(4):663\u201371. https:\/\/doi.org\/10.1136\/gutjnl-2017-315852.","journal-title":"Gut"}],"container-title":["BMC Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12885-024-12529-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12885-024-12529-7\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12885-024-12529-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,7,26]],"date-time":"2024-07-26T18:04:04Z","timestamp":1722017044000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmccancer.biomedcentral.com\/articles\/10.1186\/s12885-024-12529-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,7,26]]},"references-count":39,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["12529"],"URL":"https:\/\/doi.org\/10.1186\/s12885-024-12529-7","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2024.04.25.24306396","asserted-by":"object"}]},"ISSN":["1471-2407"],"issn-type":[{"value":"1471-2407","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,7,26]]},"assertion":[{"value":"22 May 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 June 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 July 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"As of March 1, 2019, all U.S.-based sites must be members of the NCI Central Institutional Review Board (NCI CIRB) in order to participate in CTEP and Division of Cancer Prevention studies open to the NCTN and NCI Community Oncology Research Program (NCORP) Research Bases. In addition, U.S.-based sites must accept the NCI CIRB review to activate new studies at the site after March 1, 2019. Local IRB review will continue to be accepted for studies that are not reviewed by the CIRB, or if the study was previously open at the site under the local IRB. International sites should continue to submit Research Ethics Board (REB) approval to the CTSU Regulatory Office following country-specific regulations. Refer to the protocol in supplementary material for additional information. The patient must be aware of the neoplastic nature of his\/her disease and willingly consent after being informed of the procedure to be followed, the experimental nature of the therapy, alternatives, potential benefits, side-effects, risks, and discomforts. Current human protection committee approval of this protocol and a consent form is required prior to patient consent and registration. Patients with an impaired decision-making capacity may be enrolled in this study, where institutional policy and IRB of record allow.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Appropriate consent was obtained for images used in this manuscript.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"JA declare that they have no competing interests.QS reports consulting\/advisory role from Yiviva Inc, Boehringer Ingelheim Pharmaceuticals, Inc, Regeneron Pharmaceuticals, Inc., Hoosier\u00a0Cancer Research Network, Kronos Bio, and Mirati Therapeutics Inc; Honorarium\/speaker role from Chugai Pharmaceutical Co., Ltd (to myself), research funds from Celgene\/BMS, Roche\/Genentech, Janssen, Novartis (to institution).AD reports grants or contracts from HUTCHMED International Corporation, Eisai and Crinetics; consulting fees from HUTCHMED, Crinetics, and AAA; and Advisory Board participation for Oncobay.JGA claims ownership\/equity interests for Intuitive Surgical Inc.JGA serves as a consulting\/advisory role for Medtronic, Intuitive Surgical, and Johnson & Johnson.HS research funding: AstraZeneca, Roche, Amgen, Bristol-Myers Squibb, Pfizer, BioMed Valley Discoveries, Rgenix, Exelixis.TJG reports consulting\/advisory role from Pfizer\/Array, Tempus Labs, and Billion To One and is supported by an NIH\/NCI Cancer Center Support Grant (P30 CA247796) and an NIH\/NCI NCI-sponsored Clinical Trial Research Specialist (R50 CA281930).PP declare that they have no competing interests.GN declare that they have no competing interests.TA reports advisory role from AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Genentech.OA reports a consulting or advisory role from Taiho Oncology, Pfizer, QED Therapeutics, Seagen, Bristol Myers Squibb, AADi, Seagen and research funding from Bristol-Myers Squibb, Ipsen, Taiho Pharmaceutical, Calithera Biosciences, Corcept Therapeutics, PCI Biotech, SynCoreBio, Hutchison MediPharma, GlaxoSmithKline, Transcenta.WH declare that they have no competing interests.DO declare that they have no competing interests.FV declare that they have no competing interests.AB declare that they have no competing interests.MK declare that they have no competing interests.JB declare that they have no competing interests.HW declare that they have no competing interests.MG declare that they have no competing interests.RG declare that they have no competing interests.PG declare that they have no competing interests.EO reports research funding to institution: Genentech\/Roche, BioNTech, AstraZeneca, Arcus, Elicio, Parker Institute, NIH\/NCI, Digestive Care, Break Through Cancer and consulting\/DSMB in Arcus, Alligator, Agenus, BioNTech, Ipsen, Merck, Moma Therapeutics, Novartis, Syros, Leap Therapeutics, Astellas, BMS, Fibrogen, Revolution Medicine, Merus Agios (spouse), Genentech-Roche (spouse), Eisai (spouse) Servier (Spouse).JM declare that they have no competing interests.NH declare that they have no competing interests.PBR is an EMD Serono consultant and reports support for travel from\u00a0Elekta\u00a0and\u00a0Philips Healthcare\u00a0and prior research funding from\u00a0EMD Serono.JJS received travel support for fellow education from Intuitive Surgical (2015).JJS served as a clinical advisor for Guardant Health (2019).JJS served as a clinical advisor for Foundation Medicine (2022).JJS served as a consultant and speaker for Johnson and Johnson (2022).JJS serves as a clinical advisor and consultant for GSK (2023\u201324).","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"901"}}