{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T03:07:27Z","timestamp":1788232047149,"version":"build-2803163510"},"reference-count":41,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2024,2,20]],"date-time":"2024-02-20T00:00:00Z","timestamp":1708387200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002794","name":"Cancerfonden","doi-asserted-by":"publisher","award":["190382PJ01H"],"award-info":[{"award-number":["190382PJ01H"]}],"id":[{"id":"10.13039\/501100002794","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Intl Journal of Cancer"],"published-print":{"date-parts":[[2024,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Rectal cancer poses challenges in preoperative treatment response, with up to 30% achieving a complete response (CR). Personalized treatment relies on accurate identification of responders at diagnosis. This study aimed to unravel CR determinants, overall survival (OS), and time to recurrence (TTR) using clinical and targeted sequencing data. Analyzing 402 patients undergoing preoperative treatment, tumor stage, size, and treatment emerged as robust response predictors. CR rates were higher in smaller, early\u2010stage, and intensively treated tumors. Targeted sequencing analyzed 216 cases, while 120 patients provided hotspot mutation data. <jats:italic>KRAS<\/jats:italic> mutation dramatically reduced CR odds by over 50% (odds ratio [OR]\u2009=\u20090.3 in the targeted sequencing and OR\u2009=\u20090.4 hotspot cohorts, respectively). In contrast, <jats:italic>SMAD4<\/jats:italic> and <jats:italic>SYNE1<\/jats:italic> mutations were associated with higher CR rates (OR\u2009=\u20096.0 and 6.8, respectively). Favorable OS was linked to younger age, CR, and low baseline carcinoembryonic antigen levels. Notably, CR and an <jats:italic>APC<\/jats:italic> mutation increased TTR, while a <jats:italic>BRAF<\/jats:italic> mutation negatively affected TTR. Beyond tumor burden, <jats:italic>SMAD4<\/jats:italic> and <jats:italic>SYNE1<\/jats:italic> mutations significantly influenced CR. <jats:italic>KRAS<\/jats:italic> mutations independently correlated with radiotherapy resistance, and <jats:italic>BRAF<\/jats:italic> mutations heightened recurrence risk. Intriguingly, non\u2010responding tumors with initially small sizes carried a higher risk of recurrence. The findings, even if limited in addition to the imperfect clinical factors, offer insights into rectal cancer treatment response, guiding personalized therapeutic strategies. By uncovering factors impacting CR, OS, and TTR, this study underscores the importance of tailored approaches for rectal cancer patients. These findings, based on extensive analysis and mutation data, pave the way for personalized interventions, optimizing outcomes in the challenges of rectal cancer preoperative treatment.<\/jats:p>","DOI":"10.1002\/ijc.34880","type":"journal-article","created":{"date-parts":[[2024,2,20]],"date-time":"2024-02-20T12:57:51Z","timestamp":1708433871000},"page":"40-53","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Clinical and genetic factors associated with tumor response to neoadjuvant (chemo)radiotherapy, survival and recurrence risk in rectal cancer"],"prefix":"10.1002","volume":"155","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8271-2241","authenticated-orcid":false,"given":"Klara","family":"Hammarstr\u00f6m","sequence":"first","affiliation":[{"name":"Department of Immunology, Genetics and Pathology Uppsala University  Uppsala Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3391-1607","authenticated-orcid":false,"given":"Lu\u00eds","family":"Nunes","sequence":"additional","affiliation":[{"name":"Department of Immunology, Genetics and Pathology Uppsala University  Uppsala Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2990-2038","authenticated-orcid":false,"given":"Lucy","family":"Mathot","sequence":"additional","affiliation":[{"name":"Department of Immunology, Genetics and Pathology Uppsala University  Uppsala Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4394-2634","authenticated-orcid":false,"given":"Artur","family":"Mezheyeuski","sequence":"additional","affiliation":[{"name":"Department of Immunology, Genetics and Pathology Uppsala University  Uppsala Sweden"},{"name":"Molecular Oncology Group, Vall d'Hebron Institute of Oncology  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-7711-1962","authenticated-orcid":false,"given":"Emma","family":"Lundin","sequence":"additional","affiliation":[{"name":"Department of Immunology, Genetics and Pathology Uppsala University  Uppsala Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5562-449X","authenticated-orcid":false,"given":"Nafsika","family":"Korsavidou Hult","sequence":"additional","affiliation":[{"name":"Department of Surgical Sciences, Radiology Uppsala University  Uppsala Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0232-2391","authenticated-orcid":false,"given":"Israa","family":"Imam","sequence":"additional","affiliation":[{"name":"Department of Immunology, Genetics and Pathology Uppsala University  Uppsala Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0973-6332","authenticated-orcid":false,"given":"Emerik","family":"Osterlund","sequence":"additional","affiliation":[{"name":"Department of Immunology, Genetics and Pathology Uppsala University  Uppsala Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6668-4140","authenticated-orcid":false,"given":"Tobias","family":"Sj\u00f6blom","sequence":"additional","affiliation":[{"name":"Department of Immunology, Genetics and Pathology Uppsala University  Uppsala Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5440-791X","authenticated-orcid":false,"given":"Bengt","family":"Glimelius","sequence":"additional","affiliation":[{"name":"Department of Immunology, Genetics and Pathology Uppsala University  Uppsala Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,2,20]]},"reference":[{"key":"e_1_2_12_2_1","unstructured":"World Cancer Research Fund International.Worldwide Cancer Data.2020. Accessed November 28 2022.https:\/\/www.wcrf.org\/cancer-trends\/worldwide-cancer-data\/"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.radonc.2016.11.010"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdx224"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470\u20102045(20)30555\u20106"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/codi.13081"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470\u20102045(10)70172\u20108"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140\u20106736(09)60484\u20100"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.sla.0000141194.27992.32"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/bjs.8702"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2005.02.9017"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2012.04.004"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470\u20102045(14)70398\u20105"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers13010016"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.radonc.2021.05.014"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1097\/SLA.0b013e31822b8cfa"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1245\/s10434\u2010016\u20105205\u20104"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1245\/s10434\u2010013\u20102910\u20100"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078\u20100432.CCR\u201019\u20100908"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1080\/23723556.2020.1716618"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00428\u2010019\u201002576\u2010y"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijrobp.2012.12.018"},{"key":"e_1_2_12_23_1","first-page":"3231","article-title":"A common variant in MTHFR influences response to chemoradiotherapy and recurrence of rectal cancer","volume":"5","author":"Nikas JB","year":"2015","journal-title":"Am J Cancer Res"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers15051469"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejso.2018.07.063"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470\u20102045(17)30086\u20104"},{"key":"e_1_2_12_27_1","unstructured":"U.S. National Library of Medicine.ClinicalTrials.gov Database: Data.2022. Accessed November 15 2022.https:\/\/clinicaltrials.gov\/ct2\/show\/NCT03729687?term=larct-us&draw=2&rank=1"},{"key":"e_1_2_12_28_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471\u20102407\u201010\u2010660"},{"key":"e_1_2_12_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmoldx.2015.06.009"},{"key":"e_1_2_12_30_1","doi-asserted-by":"publisher","DOI":"10.1101\/2023.03.28.23287846"},{"key":"e_1_2_12_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0140\u20106736(00)04040\u2010x"},{"key":"e_1_2_12_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/jso.26244"},{"key":"e_1_2_12_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591\u2010022\u201001930\u2010z"},{"key":"e_1_2_12_34_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2017.00465"},{"key":"e_1_2_12_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1927"},{"key":"e_1_2_12_36_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008\u20105472.CAN\u201012\u20102706"},{"key":"e_1_2_12_37_1","doi-asserted-by":"publisher","DOI":"10.1097\/SLA.0000000000003051"},{"key":"e_1_2_12_38_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMc2210175"},{"key":"e_1_2_12_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms11743"},{"key":"e_1_2_12_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.2198"},{"key":"e_1_2_12_41_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0045388"},{"key":"e_1_2_12_42_1","doi-asserted-by":"publisher","DOI":"10.7150\/thno.37794"}],"container-title":["International Journal of Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ijc.34880","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,3]],"date-time":"2024-05-03T12:23:53Z","timestamp":1714739033000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ijc.34880"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,2,20]]},"references-count":41,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2024,7]]}},"alternative-id":["10.1002\/ijc.34880"],"URL":"https:\/\/doi.org\/10.1002\/ijc.34880","archive":["Portico"],"relation":{},"ISSN":["0020-7136","1097-0215"],"issn-type":[{"value":"0020-7136","type":"print"},{"value":"1097-0215","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,2,20]]},"assertion":[{"value":"2023-08-21","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-01-16","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-02-20","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}