{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T22:03:14Z","timestamp":1788386594485,"version":"build-2803163510"},"reference-count":20,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T00:00:00Z","timestamp":1774569600000},"content-version":"vor","delay-in-days":22,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Public Health System"},{"name":"FIBICO-Consejer\u00eda Salud Junta de Andaluc\u00eda 2018"},{"name":"Spanish Association of Surgeons (AEC) 2010"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,3,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Despite adjuvant systemic chemotherapy after surgical resection in patients with pT4 stage colon cancer, a high percentage of them will develop peritoneal metastases. Intraoperative hyperthermic intraperitoneal chemotherapy (HIPEC) is a treatment option with the goal of preventing metachronous peritoneal metastases. The aim of this study was to report the longer-term outcomes of peritoneal control with the use of intraoperative HIPEC based on mitomycin C after the last enrolled patient of the HIPECT4 trial reached 36 months follow-up.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Between November 2015 and March 2021, patients with resectable primary clinical T4 N0-2M0 were included and randomized (1:1) to either adjuvant HIPEC with mitomycin C (30\u2005mg\/m2, 60\u2005minutes) or standard treatment. The primary endpoint was locoregional control at 36 months. Kaplan\u2013Meier survival analysis with a log-rank test was used to compare the two study groups.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>A total of 184 patients were included and followed up at 36 months. The locoregional control rate was improved with HIPEC compared with adjuvant chemotherapy alone (hazard ratio 0.19, 95% confidence interval 0.04 to 0.86; P = 0.031). Three years overall survival and disease-free survival did not differ between patients assigned to the HIPEC and control groups. Subgroup analysis showed better locoregional control with the use of HIPEC for patients with definitive pT4 colon cancer (hazard ratio 0.08, 0.01 to 0.65; P = 0.017) and per protocol (receiving adjuvant chemotherapy) patients (hazard ratio 0.18, 0.04 to 0.83; P = 0.028). The pattern of recurrence was modified significantly using HIPEC with less peritoneal relapse.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The long-term outcome analysis of the HIPECT4 trial demonstrated that using mitomycin C-based HIPEC reduced peritoneal recurrence in patients with locally advanced colon cancer without increasing toxicity. However, there was no difference in overall survival and disease-free survival.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Registration number<\/jats:title>\n                    <jats:p>NCT02614534 (https:\/\/clinicaltrials.gov\/).<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/bjsopen\/zrag002","type":"journal-article","created":{"date-parts":[[2026,1,3]],"date-time":"2026-01-03T12:22:38Z","timestamp":1767442958000},"source":"Crossref","is-referenced-by-count":2,"title":["Efficacy and safety of intraoperative hyperthermic intraperitoneal chemotherapy for locally advanced colorectal cancer (HIPECT4): final analysis of randomized clinical trial"],"prefix":"10.1093","volume":"10","author":[{"given":"Alvaro","family":"Arjona-S\u00e1nchez","sequence":"first","affiliation":[{"name":"Unit of Oncologic and Pancreatic Surgery, University Hospital Reina Sof\u00eda , C\u00f3rdoba ,","place":["Spain"]},{"name":"Maim\u00f3nides Biomedical Research Institute of C\u00f3rdoba (IMIBIC)\/Reina Sofia University Hospital\/University of C\u00f3rdoba , Cordoba ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto","family":"Guti\u00e9rrez-Calvo","sequence":"additional","affiliation":[{"name":"Unit of Peritoneal Oncologic Surgery, Surgery Department, Hospital Pr\u00edncipe de Asturias, Alcal\u00e1 de Henares , Madrid ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan J","family":"Segura-Sampedro","sequence":"additional","affiliation":[{"name":"General & Digestive Surgery Service, Hospital Universitario Son Espases , Palma de Mallorca ,","place":["Spain"]},{"name":"School of Medicine, Universidad CEU San Pablo , 28003 Madrid ,","place":["Spain"]},{"name":"General & Digestive Surgery Service, Hospital Universitario La Paz , Madrid ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafael","family":"Morales","sequence":"additional","affiliation":[{"name":"Unit of Oncologic and Pancreatic Surgery, Hospital Son Spaces , Palma de Mallorca ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Estibalitz","family":"P\u00e9rez-Viejo","sequence":"additional","affiliation":[{"name":"Unit of Oncologic Surgery, Hospital University Fuenlabrada , Madrid ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vanessa","family":"Concepci\u00f3n-Mart\u00edn","sequence":"additional","affiliation":[{"name":"Unit of Peritoneal Oncologic Surgery and Colorectal Surgery, Hospital University Nuestra Se\u00f1ora de la Candelaria , Tenerife ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susana","family":"S\u00e1nchez-Garc\u00eda","sequence":"additional","affiliation":[{"name":"Unit of Surgery, Hospital University Ciudad Real , Ciudad Real ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alfonso","family":"Garc\u00eda-Fadrique","sequence":"additional","affiliation":[{"name":"Department of Surgery, Instituto Valenciano de Oncolog\u00eda , Valencia ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabel","family":"Prieto-Nieto","sequence":"additional","affiliation":[{"name":"Unit of Oncologic Surgery, University Hospital La Paz , Madrid ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lana","family":"Bijelic","sequence":"additional","affiliation":[{"name":"Unit of Surgery, Consorci Sanitari Integral, Hospital de Sant Joan Desp\u00ed Moises Broggi , Barcelona ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Torres-Melero","sequence":"additional","affiliation":[{"name":"Unit of Surgery, Hospital de Torrec\u00e1rdenas , Almer\u00eda ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Ramirez-Faraco","sequence":"additional","affiliation":[{"name":"Unit of Oncologic Surgery, University General Hospital Reina Sofia , Murcia ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arancha","family":"Prada-Villaverde","sequence":"additional","affiliation":[{"name":"Unit of Surgery, Hospital University Infanta Cristina , Badajoz ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joaquin","family":"Carrasco-Campos","sequence":"additional","affiliation":[{"name":"Unit of Surgery, Hospital Regional University of Malaga , Malaga ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuel","family":"Artiles-Armas","sequence":"additional","affiliation":[{"name":"Department of General and Digestive Surgery, University Hospital Gran Canaria Dr. Negr\u00edn, Las Palmas de Gran Canaria , Canary Islands ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pedro","family":"Villarejo-Campos","sequence":"additional","affiliation":[{"name":"Unit of Oncologic Surgery, Hospital Fundaci\u00f3n Jimenez Diaz , Madrid ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gloria","family":"Ortega-P\u00e9rez","sequence":"additional","affiliation":[{"name":"Unit of Surgery, MD Anderson Cancer Center , Madrid ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enrique","family":"Boldo-Roda","sequence":"additional","affiliation":[{"name":"Unit of Surgery, Hospital Provincial Castell\u00f3n , Castell\u00f3n ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan M","family":"S\u00e1nchez-Hidalgo","sequence":"additional","affiliation":[{"name":"Unit of Oncologic and Pancreatic Surgery, University Hospital Reina Sof\u00eda , C\u00f3rdoba ,","place":["Spain"]},{"name":"Maim\u00f3nides Biomedical Research Institute of C\u00f3rdoba (IMIBIC)\/Reina Sofia University Hospital\/University of C\u00f3rdoba , Cordoba ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela","family":"Casado-Adam","sequence":"additional","affiliation":[{"name":"Unit of Oncologic and Pancreatic Surgery, University Hospital Reina Sof\u00eda , C\u00f3rdoba ,","place":["Spain"]},{"name":"Maim\u00f3nides Biomedical Research Institute of C\u00f3rdoba (IMIBIC)\/Reina Sofia University Hospital\/University of C\u00f3rdoba , Cordoba ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lidia","family":"Rodr\u00edguez-Ortiz","sequence":"additional","affiliation":[{"name":"Unit of Oncologic and Pancreatic Surgery, University Hospital Reina Sof\u00eda , C\u00f3rdoba ,","place":["Spain"]},{"name":"Maim\u00f3nides Biomedical Research Institute of C\u00f3rdoba (IMIBIC)\/Reina Sofia University Hospital\/University of C\u00f3rdoba , Cordoba ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Blanca","family":"Rufian-And\u00fajar","sequence":"additional","affiliation":[{"name":"Unit of Oncologic and Pancreatic Surgery, University Hospital Reina Sof\u00eda , C\u00f3rdoba ,","place":["Spain"]},{"name":"Maim\u00f3nides Biomedical Research Institute of C\u00f3rdoba (IMIBIC)\/Reina Sofia University Hospital\/University of C\u00f3rdoba , Cordoba ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enrique","family":"Aranda","sequence":"additional","affiliation":[{"name":"Maim\u00f3nides Biomedical Research Institute of C\u00f3rdoba (IMIBIC)\/Reina Sofia University Hospital\/University of C\u00f3rdoba , Cordoba ,","place":["Spain"]},{"name":"Unit of Medical Oncology, University Hospital Reina Sofia , C\u00f3rdoba ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria T","family":"Cano-Osuna","sequence":"additional","affiliation":[{"name":"Maim\u00f3nides Biomedical Research Institute of C\u00f3rdoba (IMIBIC)\/Reina Sofia University Hospital\/University of C\u00f3rdoba , Cordoba ,","place":["Spain"]},{"name":"Unit of Medical Oncology, University Hospital Reina Sofia , C\u00f3rdoba ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cesar","family":"D\u00edaz-L\u00f3pez","sequence":"additional","affiliation":[{"name":"Unit of Oncologic and Pancreatic Surgery, University Hospital Reina Sof\u00eda , C\u00f3rdoba ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Romero-Ruiz","sequence":"additional","affiliation":[{"name":"Maim\u00f3nides Biomedical Research Institute of C\u00f3rdoba (IMIBIC)\/Reina Sofia University Hospital\/University of C\u00f3rdoba , Cordoba ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Carmen","family":"Vazquez-Borrego","sequence":"additional","affiliation":[{"name":"Maim\u00f3nides Biomedical Research Institute of C\u00f3rdoba (IMIBIC)\/Reina Sofia University Hospital\/University of C\u00f3rdoba , Cordoba ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastian","family":"Rufi\u00e1n-Pe\u00f1a","sequence":"additional","affiliation":[{"name":"Unit of Oncologic and Pancreatic Surgery, University Hospital Reina Sof\u00eda , C\u00f3rdoba ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,3,27]]},"reference":[{"key":"2026043016084907400_zrag002-B1"},{"key":"2026043016084907400_zrag002-B2","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1002\/bjs.8679","article-title":"Incidence, prevalence and risk factors for peritoneal carcinomatosis from colorectal cancer","volume":"99","author":"Segelman","year":"2012","journal-title":"Br J Surg"},{"key":"2026043016084907400_zrag002-B3","doi-asserted-by":"crossref","first-page":"1709","DOI":"10.1016\/S1470-2045(16)30500-9","article-title":"Prognosis of patients with peritoneal metastatic colorectal cancer given systemic therapy: an analysis of individual patient data from prospective randomised trials from the analysis and research in cancers of the digestive system (ARCAD) database","volume":"17","author":"Franko","year":"2016","journal-title":"Lancet Oncol"},{"key":"2026043016084907400_zrag002-B4","doi-asserted-by":"crossref","first-page":"2405","DOI":"10.1016\/j.ejso.2021.05.009","article-title":"Risk of metachronous peritoneal metastases in patients with pT4a versus pT4b colon cancer: an international multicentre cohort study","volume":"47","author":"Bastiaenen","year":"2021","journal-title":"Eur J Surg Oncol"},{"key":"2026043016084907400_zrag002-B5","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1016\/S2468-1253(19)30239-0","article-title":"Adjuvant hyperthermic intraperitoneal chemotherapy in patients with locally advanced colon cancer (COLOPEC): a multicentre, open-label, randomised trial","volume":"4","author":"Klaver","year":"2019","journal-title":"Lancet Gastroenterol Hepatol"},{"key":"2026043016084907400_zrag002-B6","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1200\/JCO.22.02644","article-title":"Adjuvant hyperthermic intraperitoneal chemotherapy in patients with locally advanced colon cancer (COLOPEC): 5-year results of a randomized multicenter trial","volume":"42","author":"Zwanenburg","year":"2024","journal-title":"J Clin Oncol"},{"key":"2026043016084907400_zrag002-B7","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1001\/jamasurg.2023.0662","article-title":"Efficacy and safety of intraoperative hyperthermic intraperitoneal chemotherapy for locally advanced colon cancer: a phase 3 randomized clinical trial","volume":"158","author":"Arjona-S\u00e1nchez","year":"2023","journal-title":"JAMA Surg"},{"key":"2026043016084907400_zrag002-B8","doi-asserted-by":"crossref","first-page":"znaf076","DOI":"10.1093\/bjs\/znaf076","article-title":"Adjuvant hyperthermic intraperitoneal chemotherapy in patients with colon cancer at high risk of peritoneal metastases: individual patient data meta-analysis","volume":"112","author":"Hamm","year":"2025","journal-title":"Br J Surg"},{"key":"2026043016084907400_zrag002-B9","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1186\/s12885-018-4096-0","article-title":"HIPECT4: multicentre, randomized clinical trial to evaluate safety and efficacy of hyperthermic intraperitoneal chemotherapy (HIPEC) with mitomycin C used during surgery for treatment of locally advanced colorectal carcinoma","volume":"18","author":"Arjona-S\u00e1nchez","year":"2018","journal-title":"BMC Cancer"},{"key":"2026043016084907400_zrag002-B10","doi-asserted-by":"crossref","first-page":"2655","DOI":"10.1002\/sim.8565","article-title":"On permutation tests for comparing restricted mean survival time with small sample from randomized trials","volume":"39","author":"Horiguchi","year":"2020","journal-title":"Stat Med"},{"key":"2026043016084907400_zrag002-B11","doi-asserted-by":"crossref","first-page":"2409","DOI":"10.1002\/sim.4274","article-title":"\u201cThe use of restricted mean survival time to estimate the treatment effect in randomized clinical trials when the proportional hazards assumption is in doubt","volume":"30","author":"Royston","year":"2011","journal-title":"Stat Med"},{"key":"2026043016084907400_zrag002-B12","doi-asserted-by":"crossref","first-page":"1147","DOI":"10.1016\/S1470-2045(20)30322-3","article-title":"Second-look surgery plus hyperthermic intraperitoneal chemotherapy versus surveillance in patients at high risk of developing colorectal peritoneal metastases (PROPHYLOCHIP-PRODIGE 15): a randomised, phase 3 study","volume":"21","author":"Go\u00e9r\u00e9","year":"2020","journal-title":"Lancet Oncol"},{"key":"2026043016084907400_zrag002-B13","doi-asserted-by":"crossref","first-page":"1291","DOI":"10.1016\/j.annonc.2020.06.022","article-title":"Localised colon cancer: ESMO clinical practice guidelines for diagnosis, treatment and follow-up","volume":"31","author":"Argil\u00e9s","year":"2020","journal-title":"Ann Oncol"},{"key":"2026043016084907400_zrag002-B14","doi-asserted-by":"crossref","first-page":"108642","DOI":"10.1016\/j.ejso.2024.108642","article-title":"Efficacy of systemic chemotherapy on high-risk stage II and III mucnious colon cancer. CHEMUCCA study part I","volume":"50","author":"Trinidad-Guti\u00e9rrez","year":"2024","journal-title":"Eur J Surg Oncol"},{"key":"2026043016084907400_zrag002-B15","doi-asserted-by":"crossref","first-page":"1541","DOI":"10.1200\/JCO.22.00046","article-title":"Preoperative chemotherapy for operable colon cancer: mature results of an international randomized controlled trial","volume":"41","author":"Morton","year":"2023","journal-title":"J Clin Oncol"},{"key":"2026043016084907400_zrag002-B16","doi-asserted-by":"crossref","first-page":"2978","DOI":"10.1200\/JCO.23.01889","article-title":"Neoadjuvant chemotherapy with oxaliplatin and fluoropyrimidine versus upfront surgery for locally advanced colon cancer: the randomized, phase III OPTICAL trial","volume":"42","author":"Hu","year":"2024","journal-title":"J Clin Oncol"},{"key":"2026043016084907400_zrag002-B17","doi-asserted-by":"crossref","first-page":"520","DOI":"10.1016\/j.annonc.2024.12.013","article-title":"Neo-adjuvant FOLFOX with and without panitumumab for patients with KRAS-wt locally advanced colon cancer: results following an extended biomarker panel on the FOxTROT trial embedded phase II population","volume":"36","author":"Seligmann","year":"2025","journal-title":"Ann Oncol"},{"key":"2026043016084907400_zrag002-B18","year":"2026"},{"key":"2026043016084907400_zrag002-B19","doi-asserted-by":"publisher","DOI":"10.1093\/bjr\/tqaf217","article-title":"CT staging performance in an international trial of neoadjuvant chemotherapy for locally advanced colon cancer","author":"Platt","year":"2025","journal-title":"Br J Radiol"},{"key":"2026043016084907400_zrag002-B20","doi-asserted-by":"crossref","first-page":"2363","DOI":"10.1056\/NEJMoa2201445","article-title":"PD-1 Blockade in mismatch repair-deficient, locally advanced rectal cancer","volume":"386","author":"Cercek","year":"2022","journal-title":"N Engl J Med"}],"container-title":["BJS Open"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/bjsopen\/article-pdf\/10\/2\/zrag002\/67600195\/zrag002.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bjsopen\/article-pdf\/10\/2\/zrag002\/67600195\/zrag002.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T20:08:56Z","timestamp":1777579736000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/bjsopen\/article\/doi\/10.1093\/bjsopen\/zrag002\/8550803"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,5]]},"references-count":20,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2026,3,5]]}},"URL":"https:\/\/doi.org\/10.1093\/bjsopen\/zrag002","relation":{},"ISSN":["2474-9842"],"issn-type":[{"value":"2474-9842","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026,4]]},"published":{"date-parts":[[2026,3,5]]},"article-number":"zrag002"}}