{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:27:05Z","timestamp":1787012825664,"version":"build-2736575974"},"reference-count":47,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:00:00Z","timestamp":1787011200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:00:00Z","timestamp":1787011200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82373237"],"award-info":[{"award-number":["82373237"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82103207"],"award-info":[{"award-number":["82103207"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003399","name":"Science and Technology Commission of Shanghai Municipality","doi-asserted-by":"publisher","award":["24010702200"],"award-info":[{"award-number":["24010702200"]}],"id":[{"id":"10.13039\/501100003399","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sig Transduct Target Ther"],"DOI":"10.1038\/s41392-026-02868-1","type":"journal-article","created":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:02:45Z","timestamp":1787011365000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A multicohort, biomarker-driven phase 2 trial of personalized total neoadjuvant therapy with targeted agents for high-risk rectal cancer (The TRAINER study)"],"prefix":"10.1038","volume":"11","author":[{"given":"Tao","family":"Ma","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingyi","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sen","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abe","family":"Fingerhut","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haiqin","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ximo","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Zhong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengqin","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naijipu","family":"Abuduaini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaohan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanyu","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lixuan","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zicheng","family":"Qu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyu","family":"Ding","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiding","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shubei","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yimin","family":"Han","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Ou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weixiang","family":"Qi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianwen","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lui","family":"Ng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8332-4710","authenticated-orcid":false,"given":"Youqiong","family":"Ye","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7023-2400","authenticated-orcid":false,"given":"Junke","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minhua","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8849-6597","authenticated-orcid":false,"given":"Chi Chung","family":"Foo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gang","family":"Cai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenghao","family":"Cai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0006-4517","authenticated-orcid":false,"given":"Bo","family":"Feng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,8,18]]},"reference":[{"key":"2868_CR1","doi-asserted-by":"publisher","first-page":"1114","DOI":"10.1056\/NEJMoa060829","volume":"355","author":"B Jean-Fran\u00e7ois","year":"2006","unstructured":"Jean-Fran\u00e7ois, B. et al. Chemotherapy with preoperative radiotherapy in rectal cancer. N. Engl. J. Med. 355, 1114\u20131123 (2006).","journal-title":"N. Engl. J. Med."},{"key":"2868_CR2","doi-asserted-by":"publisher","first-page":"696","DOI":"10.1093\/annonc\/mdu560","volume":"26","author":"AJ Breugom","year":"2015","unstructured":"Breugom, A. J. et al. Adjuvant chemotherapy for rectal cancer patients treated with preoperative (chemo)radiotherapy and total mesorectal excision: a Dutch Colorectal Cancer Group (DCCG) randomized phase III trial. Ann. Oncol. 26, 696\u2013701 (2015).","journal-title":"Ann. Oncol."},{"key":"2868_CR3","doi-asserted-by":"publisher","first-page":"1356","DOI":"10.1093\/annonc\/mdu147","volume":"25","author":"R Glynne-Jones","year":"2014","unstructured":"Glynne-Jones, R. et al. 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\u20131362 (2014).","journal-title":"Ann. Oncol."},{"key":"2868_CR4","doi-asserted-by":"publisher","first-page":"3111","DOI":"10.1200\/JCO.19.00016","volume":"37","author":"YS Hong","year":"2019","unstructured":"Hong, Y. S. et al. Oxaliplatin-based adjuvant chemotherapy for rectal cancer after preoperative chemoradiotherapy (ADORE): long-term results of a randomized controlled trial. JCO 37, 3111\u20133123 (2019).","journal-title":"JCO"},{"key":"2868_CR5","doi-asserted-by":"publisher","first-page":"1681","DOI":"10.1200\/JCO.21.01667","volume":"40","author":"J Jin","year":"2022","unstructured":"Jin, J. et al. Multicenter, randomized, phase III trial of short-term radiotherapy plus chemotherapy versus long-term chemoradiotherapy in locally advanced rectal cancer (STELLAR). JCO 40, 1681\u20131692 (2022).","journal-title":"JCO"},{"key":"2868_CR6","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. 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. 22, 702\u2013715 (2021).","journal-title":"Lancet Oncol."},{"key":"2868_CR7","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1016\/S1470-2045(20)30555-6","volume":"22","author":"RR Bahadoer","year":"2021","unstructured":"Bahadoer, R. R. 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. 22, 29\u201342 (2021).","journal-title":"Lancet Oncol."},{"key":"2868_CR8","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. et al. Organ preservation in patients with rectal adenocarcinoma treated with total neoadjuvant therapy. JCO 40, 2546\u20132556 (2022).","journal-title":"JCO"},{"key":"2868_CR9","doi-asserted-by":"publisher","first-page":"3753","DOI":"10.1200\/JCO.2011.34.9068","volume":"29","author":"UB Patel","year":"2011","unstructured":"Patel, U. B. et al. Magnetic resonance imaging\u2013detected tumor response for locally advanced rectal cancer predicts survival outcomes: MERCURY experience. JCO 29, 3753\u20133760 (2011).","journal-title":"JCO"},{"key":"2868_CR10","doi-asserted-by":"publisher","first-page":"575","DOI":"10.1016\/S1470-2045(11)70097-3","volume":"12","author":"W Van Gijn","year":"2011","unstructured":"Van Gijn, W. et al. Preoperative radiotherapy combined with total mesorectal excision for resectable rectal cancer: 12-year follow-up of the multicentre, randomised controlled TME trial. Lancet Oncol. 12, 575\u2013582 (2011).","journal-title":"Lancet Oncol."},{"key":"2868_CR11","doi-asserted-by":"publisher","first-page":"1731","DOI":"10.1056\/NEJMoa040694","volume":"351","author":"R Sauer","year":"2004","unstructured":"Sauer, R., R\u00f6del, C., Martus, P., Hess, C. F. & Schmidberger, H. Preoperative versus postoperative chemoradiotherapy for rectal cancer. N. Engl. J. Med. 351, 1731\u20131740 (2004).","journal-title":"N. Engl. J. Med."},{"key":"2868_CR12","doi-asserted-by":"publisher","first-page":"1926","DOI":"10.1200\/JCO.2011.40.1836","volume":"30","author":"R Sauer","year":"2012","unstructured":"Sauer, R. et al. Preoperative versus postoperative chemoradiotherapy for locally advanced rectal cancer: results of the German CAO\/ARO\/AIO-94 randomized phase III trial after a median follow-Up of 11 years. JCO 30, 1926\u20131933 (2012).","journal-title":"JCO"},{"key":"2868_CR13","doi-asserted-by":"publisher","unstructured":"Liu, J. et al. Optimizing total neoadjuvant therapy in locally advanced rectal cancer: risk stratification should not be overlooked. Future Oncol. 1\u201310, https:\/\/doi.org\/10.1080\/14796694.2025.2507560 (2025).","DOI":"10.1080\/14796694.2025.2507560"},{"key":"2868_CR14","doi-asserted-by":"publisher","first-page":"2335","DOI":"10.1056\/NEJMoa032691","volume":"350","author":"H Hurwitz","year":"2004","unstructured":"Hurwitz, H. et al. Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N. Engl. J. Med 350, 2335\u20132342 (2004).","journal-title":"N. Engl. J. Med"},{"key":"2868_CR15","doi-asserted-by":"publisher","first-page":"1539","DOI":"10.1200\/JCO.2006.09.6305","volume":"25","author":"BJ Giantonio","year":"2007","unstructured":"Giantonio, B. J. et al. Bevacizumab in combination with oxaliplatin, fluorouracil, and leucovorin (FOLFOX4) for previously treated metastatic colorectal cancer: results from the Eastern Cooperative Oncology Group study E3200. JCO 25, 1539\u20131544 (2007).","journal-title":"JCO"},{"key":"2868_CR16","doi-asserted-by":"publisher","first-page":"788","DOI":"10.1016\/j.clon.2021.06.006","volume":"33","author":"F De Felice","year":"2021","unstructured":"De Felice, F. et al. Intensified total neoadjuvant therapy in patients with locally advanced rectal cancer: a phase II Trial. Clin. Oncol. 33, 788\u2013794 (2021).","journal-title":"Clin. Oncol."},{"key":"2868_CR17","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s40880-018-0294-z","volume":"38","author":"X Yu","year":"2018","unstructured":"Yu, X. et al. Neoadjuvant oxaliplatin and capecitabine combined with bevacizumab plus radiotherapy for locally advanced rectal cancer: results of a single-institute phase II study. Cancer Commun. 38, 1\u20139 (2018).","journal-title":"Cancer Commun."},{"key":"2868_CR18","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1016\/j.ejca.2019.01.006","volume":"110","author":"G Masi","year":"2019","unstructured":"Masi, G. et al. Total neoadjuvant approach with FOLFOXIRI plus bevacizumab followed by chemoradiotherapy plus bevacizumab in locally advanced rectal cancer: the TRUST trial. Eur. J. Cancer110, 32\u201341 (2019).","journal-title":"Eur. J. Cancer"},{"key":"2868_CR19","doi-asserted-by":"publisher","first-page":"LBA3504","DOI":"10.1200\/JCO.2023.41.17_suppl.LBA3504","volume":"41","author":"T Conroy","year":"2023","unstructured":"Conroy, T. et al. Total neoadjuvant therapy with mFOLFIRINOX versus preoperative chemoradiation in patients with locally advanced rectal cancer: 7-year results of PRODIGE 23 phase III trial, a UNICANCER GI trial. JCO 41, LBA3504\u2013LBA3504 (2023).","journal-title":"JCO"},{"key":"2868_CR20","doi-asserted-by":"publisher","first-page":"iv22","DOI":"10.1093\/annonc\/mdx224","volume":"28","author":"R Glynne-Jones","year":"2017","unstructured":"Glynne-Jones, R. et al. Rectal cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann. Oncol. 28, iv22\u2013iv40 (2017).","journal-title":"Ann. Oncol."},{"key":"2868_CR21","doi-asserted-by":"publisher","first-page":"e766","DOI":"10.1097\/SLA.0000000000005799","volume":"278","author":"EA Dijkstra","year":"2023","unstructured":"Dijkstra, E. A. et al. Locoregional failure during and after short-course radiotherapy followed by chemotherapy and surgery compared with long-course chemoradiotherapy and surgery: a 5-year follow-up of the RAPIDO trial. Ann. Surg.278, e766\u2013e772 (2023).","journal-title":"Ann. Surg."},{"key":"2868_CR22","doi-asserted-by":"publisher","first-page":"LBA3511","DOI":"10.1200\/JCO.2024.42.17_suppl.LBA3511","volume":"42","author":"X Wang","year":"2024","unstructured":"Wang, X. et al. Total neoadjuvant treatment with long-course radiotherapy versus concurrent chemoradiotherapy in local advanced rectal cancer with high risk factors (TNTCRT): a multicenter, randomized, open-label, phase 3 trial. JCO 42, LBA3511\u2013LBA3511 (2024).","journal-title":"JCO"},{"key":"2868_CR23","doi-asserted-by":"publisher","first-page":"1620","DOI":"10.1200\/JCO.2011.39.6036","volume":"30","author":"A Dewdney","year":"2012","unstructured":"Dewdney, A. et al. 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). JCO 30, 1620\u20131627 (2012).","journal-title":"JCO"},{"key":"2868_CR24","doi-asserted-by":"publisher","first-page":"614","DOI":"10.1634\/theoncologist.2010-0285","volume":"16","author":"M Nogu\u00e9","year":"2011","unstructured":"Nogu\u00e9, M. et al. Addition of bevacizumab to XELOX induction therapy plus concomitant capecitabine-based chemoradiotherapy in magnetic resonance imaging\u2013defined poor-prognosis locally advanced rectal cancer: the AVACROSS study. Oncologist 16, 614\u2013620 (2011).","journal-title":"Oncologist"},{"key":"2868_CR25","first-page":"200","volume":"18","author":"C Borg","year":"2019","unstructured":"Borg, C. et al. Efficacy and safety of two neoadjuvant strategies with bevacizumab in MRI-defined locally advanced T3 resectable rectal cancer: final results of a randomized, noncomparative phase 2 INOVA study. Clin. Colorectal Cancer 18, 200\u2013208.e1 (2019).","journal-title":"Clin. Colorectal Cancer"},{"key":"2868_CR26","doi-asserted-by":"publisher","first-page":"2205","DOI":"10.1093\/annonc\/mdu377","volume":"25","author":"C Borg","year":"2014","unstructured":"Borg, C. et al. Pathological response and safety of two neoadjuvant strategies with bevacizumab in MRI-defined locally advanced T3 resectable rectal cancer: a randomized, noncomparative phase II study. Ann. Oncol. 25, 2205\u20132210 (2014).","journal-title":"Ann. Oncol."},{"key":"2868_CR27","doi-asserted-by":"publisher","first-page":"3308","DOI":"10.1200\/JCO.23.02261","volume":"42","author":"F Xia","year":"2024","unstructured":"Xia, F. et al. Randomized phase II trial of immunotherapy-based total neoadjuvant therapy for proficient mismatch repair or microsatellite stable locally advanced rectal cancer (TORCH). JCO 42, 3308\u20133318 (2024).","journal-title":"JCO"},{"key":"2868_CR28","doi-asserted-by":"publisher","first-page":"3520","DOI":"10.1200\/JCO.2023.41.16_suppl.3520","volume":"41","author":"FS Verheij","year":"2023","unstructured":"Verheij, F. S. et al. Sustained organ preservation in patients with rectal cancer treated with total neoadjuvant therapy: Long-term results of the OPRA trial. JCO41, 3520\u20133520 (2023).","journal-title":"JCO"},{"key":"2868_CR29","doi-asserted-by":"publisher","first-page":"1298","DOI":"10.1093\/annonc\/mdz186","volume":"30","author":"B Cise\u0142","year":"2019","unstructured":"Cise\u0142, B. et al. Long-course preoperative chemoradiation versus 5 \u00d7 5 Gy and consolidation chemotherapy for clinical T4 and fixed clinical T3 rectal cancer: long-term results of the randomized Polish II study. Ann. Oncol. 30, 1298\u20131303 (2019).","journal-title":"Ann. Oncol."},{"key":"2868_CR30","doi-asserted-by":"publisher","first-page":"1188","DOI":"10.1093\/annonc\/mdv112","volume":"26","author":"C Cremolini","year":"2015","unstructured":"Cremolini, C. et al. Early tumor shrinkage and depth of response predict long-term outcome in metastatic colorectal cancer patients treated with first-line chemotherapy plus bevacizumab: results from phase III TRIBE trial by the Gruppo Oncologico del Nord Ovest. Ann. Oncol. 26, 1188\u20131194 (2015).","journal-title":"Ann. Oncol."},{"key":"2868_CR31","doi-asserted-by":"publisher","first-page":"882","DOI":"10.1016\/j.annonc.2024.06.015","volume":"35","author":"ZY Lin","year":"2024","unstructured":"Lin, Z. Y. et al. Neoadjuvant short-course radiotherapy followed by camrelizumab and chemotherapy in locally advanced rectal cancer (UNION): early outcomes of a multicenter randomized phase III trial. Ann. Oncol. 35, 882\u2013891 (2024).","journal-title":"Ann. Oncol."},{"key":"2868_CR32","doi-asserted-by":"publisher","first-page":"242","DOI":"10.3390\/cancers13020242","volume":"13","author":"A Hoeben","year":"2021","unstructured":"Hoeben, A., Joosten, E. A. J. & van den Beuken-van Everdingen, M. H. J. Personalized medicine: recent progress in cancer therapy. Cancers 13, 242 (2021).","journal-title":"Cancers"},{"key":"2868_CR33","doi-asserted-by":"publisher","first-page":"2297","DOI":"10.1056\/NEJMoa2404512","volume":"392","author":"A Cercek","year":"2025","unstructured":"Cercek, A. et al. Nonoperative management of mismatch repair-deficient tumors. N. Engl. J. Med. 392, 2297\u20132308 (2025).","journal-title":"N. Engl. J. Med."},{"key":"2868_CR34","doi-asserted-by":"publisher","first-page":"1570","DOI":"10.1016\/j.ccell.2024.07.004","volume":"42","author":"W-W Xiao","year":"2024","unstructured":"Xiao, W.-W. et al. Effect of neoadjuvant chemoradiotherapy with or without PD-1 antibody sintilimab in pMMR locally advanced rectal cancer: A randomized clinical trial. Cancer Cell 42, 1570\u20131581.e4 (2024).","journal-title":"Cancer Cell"},{"key":"2868_CR35","doi-asserted-by":"publisher","first-page":"3209","DOI":"10.3390\/cancers15123209","volume":"15","author":"MA Gambacorta","year":"2023","unstructured":"Gambacorta, M. A. et al. pCR and 2-year disease-free survival: a combination of the two endpoints as a new classification for locally advanced rectal cancer patients\u2014an updated pooled analysis of eleven international randomized trials. Cancers 15, 3209 (2023).","journal-title":"Cancers"},{"key":"2868_CR36","doi-asserted-by":"publisher","first-page":"990","DOI":"10.1016\/j.ejca.2010.12.015","volume":"47","author":"D Sargent","year":"2011","unstructured":"Sargent, D. et al. Two or three year disease-free survival (DFS) as a primary end-point in stage III adjuvant colon cancer trials with fluoropyrimidines with or without oxaliplatin or irinotecan: data from 12,676 patients from MOSAIC, X-ACT, PETACC-3, C-06, C-07 and C89803. Eur. J. Cancer 47, 990\u2013996 (2011).","journal-title":"Eur. J. Cancer"},{"key":"2868_CR37","doi-asserted-by":"publisher","first-page":"1304","DOI":"10.1093\/annonc\/mdz193","volume":"30","author":"J Souglakos","year":"2019","unstructured":"Souglakos, J. et al. Three- versus six-month adjuvant FOLFOX or CAPOX for high-risk stage II and stage III colon cancer patients: the efficacy results of Hellenic Oncology Research Group (HORG) participation to the International Duration Evaluation of Adjuvant Chemotherapy (IDEA) project. Ann. Oncol. 30, 1304\u20131310 (2019).","journal-title":"Ann. Oncol."},{"key":"2868_CR38","doi-asserted-by":"publisher","first-page":"805","DOI":"10.1038\/s41571-021-00538-5","volume":"18","author":"E Fokas","year":"2021","unstructured":"Fokas, E. et al. International consensus recommendations on key outcome measures for organ preservation after (chemo)radiotherapy in patients with rectal cancer. Nat. Rev. Clin. Oncol. 18, 805\u2013816 (2021).","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"2868_CR39","doi-asserted-by":"publisher","first-page":"4633","DOI":"10.1200\/JCO.2011.37.7176","volume":"29","author":"M Maas","year":"2011","unstructured":"Maas, M. et al. Wait-and-see policy for clinical complete responders after chemoradiation for rectal cancer. J. Clin. Oncol. 29, 4633\u20134640 (2011).","journal-title":"J. Clin. Oncol."},{"key":"2868_CR40","doi-asserted-by":"publisher","first-page":"228","DOI":"10.1016\/j.ejca.2008.10.026","volume":"45","author":"EA Eisenhauer","year":"2009","unstructured":"Eisenhauer, E. A. et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur. J. Cancer 45, 228\u2013247 (2009).","journal-title":"Eur. J. Cancer"},{"key":"2868_CR41","doi-asserted-by":"publisher","first-page":"1426","DOI":"10.1016\/S1470-2045(16)30269-8","volume":"17","author":"DS Stintzing","year":"2016","unstructured":"Stintzing, D. S. et al. FOLFIRI plus cetuximab versus FOLFIRI plus bevacizumab for metastatic colorectal cancer (FIRE-3): a post-hoc analysis of tumour dynamics in the final RAS wild-type subgroup of this randomised double-blind phase 3 trial. Lancet Oncol. 17, 1426\u20131434 (2016).","journal-title":"Lancet Oncol."},{"key":"2868_CR42","doi-asserted-by":"publisher","first-page":"3764","DOI":"10.1200\/JCO.2012.42.8532","volume":"31","author":"H Piessevaux","year":"2013","unstructured":"Piessevaux, H. et al. Use of early tumor shrinkage to predict long-term outcome in metastatic colorectal cancer treated with cetuximab. J. Clin. Oncol 31, 3764\u20133775 (2013).","journal-title":"J. Clin. Oncol"},{"key":"2868_CR43","doi-asserted-by":"publisher","first-page":"956","DOI":"10.3109\/0284186X.2012.752580","volume":"52","author":"DP Modest","year":"2013","unstructured":"Modest, D. P. et al. Early tumor shrinkage in patients with metastatic colorectal cancer receiving first-line treatment with cetuximab combined with either CAPIRI or CAPOX: an analysis of the German AIO KRK 0104 trial. Acta Oncol. 52, 956\u2013962 (2013).","journal-title":"Acta Oncol."},{"key":"2868_CR44","doi-asserted-by":"publisher","first-page":"427","DOI":"10.1200\/jco.2013.31.4_suppl.427","volume":"31","author":"UR Mansmann","year":"2013","unstructured":"Mansmann, U. R. et al. Deepness of response: a quantitative analysis of its impact on post-progression survival time after first-line treatment in patients with mCRC. JCO 31, 427\u2013427 (2013).","journal-title":"JCO"},{"key":"2868_CR45","doi-asserted-by":"publisher","first-page":"205","DOI":"10.1097\/01.sla.0000133083.54934.ae","volume":"240","author":"D Dindo","year":"2004","unstructured":"Dindo, D., Demartines, N. & Clavien, P.-A. Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann. Surg. 240, 205\u2013213 (2004).","journal-title":"Ann. Surg."},{"key":"2868_CR46","doi-asserted-by":"publisher","first-page":"2680","DOI":"10.1002\/1097-0142(19940601)73:11<2680::AID-CNCR2820731105>3.0.CO;2-C","volume":"73","author":"A-M Mandard","year":"1994","unstructured":"Mandard, A.-M. et al. Pathologic assessment of tumor regression after preoperative chemoradiotherapy of esophageal carcinoma. Clinicopathologic correlations. Cancer 73, 2680\u20132686 (1994).","journal-title":"Cancer"},{"key":"2868_CR47","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1016\/j.radonc.2021.01.002","volume":"157","author":"I Imam","year":"2021","unstructured":"Imam, I., Hammarstr\u00f6m, K., Sj\u00f6blom, T. & Glimelius, B. Neoadjuvant rectal (NAR) score: Value evaluating the efficacy of neoadjuvant therapy and prognostic significance after surgery?. Radiother. Oncol. 157, 70\u201377 (2021).","journal-title":"Radiother. Oncol."}],"container-title":["Signal Transduction and Targeted Therapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41392-026-02868-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41392-026-02868-1","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41392-026-02868-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:02:47Z","timestamp":1787011367000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41392-026-02868-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,18]]},"references-count":47,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["2868"],"URL":"https:\/\/doi.org\/10.1038\/s41392-026-02868-1","relation":{},"ISSN":["2059-3635"],"issn-type":[{"value":"2059-3635","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,18]]},"assertion":[{"value":"12 November 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 May 2026","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"8 June 2026","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 August 2026","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Ethics"}}],"article-number":"333"}}