1. Adjuvant hyperthermic intraperitoneal chemotherapy in patients with locally advanced colon cancer (COLOPEC): a multicentre, open-label, randomised trial
- Author
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Ignace H. J. T. de Hingh, Erwin van der Harst, Victor J. Verwaal, Edwin S. van der Zaag, Karlijn van Woensdregt, R.T.J. Kortekaas, Bas Inberg, Sebastiaan Festen, Petur Snaebjornsson, Karin K. van Diepen, Anna A. W. van Geloven, Alexandra Brandt, Roderick F. Schmitz, Pieter J. Tanis, Koen C.M.J. Peeters, Cornelis J. A. Punt, Eva V. E. Madsen, Sanne C. Veltkamp, Charlotte E. L. Klaver, Johanne Bloemen, P.A. Neijenhuis, Eino B. van Duyn, Thomas J.M. Kootstra, Henderik L van Westreenen, Johannes H. W. de Wilt, T.C. van Sprundel, Emma C. E. Wassenaar, M. Westerterp, Philip R. de Reuver, Jennifer Demelinne, Dirkje W. Sommeijer, Loes van den Nieuwenhof, Marinus J. Wiezer, H.C.J. van der Mijle, Pauline Evers, Rogier M P H Crolla, Annette A van Zweeden, Joost T. Heikens, Daniel A. Hess, Marcel G. W. Dijkgraaf, Jan Jansen, D. J. A. Sonneveld, Anthony W. H. van de Ven, Frank W.H. Kloppenberg, Mandy Zournas, Patrick H. J. Hemmer, Koen P. Rovers, J. W. T. Dekker, Daniel D Wisselink, Jacobus W. A. Burger, Huib A. Cense, Esther D. van den Ende, David D. E. Zimmerman, Wilhelmina M U van Grevenstein, Frank C. den Boer, Jarmila D. W. van der Bilt, Sandra A Radema, Vivian P. Bastiaenen, Djamila Boerma, Johannes Crezee, Maarten Vermaas, Hans F. J. Fabry, Maartje Los, Floris Ferenschild, Lotte Schoonderwoerd, Walter J.A. Brokelman, Jeroen Heemskerk, Pieter Poortman, Jurriaan B. Tuynman, Johannes A. Wegdam, Marc J. van Det, Linda Mol, Bert van Ramshorst, Arend G. J. Aalbers, Marjolein Diepeveen, Gijsbert D. Musters, Arjen J. Witkamp, Daan ten Bokkel Huinink, Niels F. M. Kok, Simon W. Nienhuijs, Willem A. Bemelman, Geert-Jan Creemers, Jolien Pon, Caroline S. Andeweg, Sebastiaan W. Polle, Esther C. J. Consten, Nina R. Sluiter, Fennie Wit, A.J.A. Bremers, Surgery, AGEM - Re-generation and cancer of the digestive system, CCA - Cancer Treatment and quality of life, Robotics and image-guided minimally-invasive surgery (ROBOTICS), Graduate School, AGEM - Digestive immunity, CCA - Cancer Treatment and Quality of Life, Oncology, Radiotherapy, Epidemiology and Data Science, and APH - Methodology
- Subjects
Male ,SURGERY ,Colorectal cancer ,Kaplan-Meier Estimate ,COLORECTAL-CANCER ,law.invention ,Postoperative Complications ,0302 clinical medicine ,Randomized controlled trial ,law ,Antineoplastic Combined Chemotherapy Protocols ,Clinical endpoint ,Intraoperative Complications ,Laparoscopy ,Colectomy ,Peritoneal Neoplasms ,RISK ,education.field_of_study ,medicine.diagnostic_test ,Gastroenterology ,Middle Aged ,PERITONEAL CARCINOMATOSIS ,Oxaliplatin ,Chemotherapy, Adjuvant ,030220 oncology & carcinogenesis ,Colonic Neoplasms ,Female ,030211 gastroenterology & hepatology ,Hyperthermic intraperitoneal chemotherapy ,medicine.drug ,medicine.medical_specialty ,Perforation (oil well) ,Population ,Adenocarcinoma ,03 medical and health sciences ,All institutes and research themes of the Radboud University Medical Center ,SDG 3 - Good Health and Well-being ,Journal Article ,medicine ,Humans ,education ,Aged ,Neoplasm Staging ,Hepatology ,business.industry ,Hyperthermia, Induced ,Length of Stay ,medicine.disease ,Surgery ,Reconstructive and regenerative medicine Radboud Institute for Health Sciences [Radboudumc 10] ,METASTASES ,SYSTEMIC CHEMOTHERAPY ,business - Abstract
BACKGROUND: Nearly a quarter of patients with locally advanced (T4 stage) or perforated colon cancer are at risk of developing peritoneal metastases, often without curative treatment options. We aimed to determine the efficacy of adjuvant hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with locally advanced colon cancer.METHODS: This multicentre, open-label trial was done in nine hospitals that specialised in HIPEC in the Netherlands. Patients with clinical or pathological T4N0-2M0-stage tumours or perforated colon cancer were randomly assigned (1:1), with a web-based randomisation application, before resection of the primary tumour, to adjuvant HIPEC followed by routine adjuvant systemic chemotherapy (experimental group) or to adjuvant systemic chemotherapy alone (control group). Patients were stratified by tumour characteristic (T4 or perforation), age (FINDINGS: Between April 1, 2015, and Feb 20, 2017, 204 patients were randomly assigned to treatment (102 in each group). In the HIPEC group, two patients withdrew consent after randomisation. In this group, 19 (19%) of 100 patients were diagnosed with peritoneal metastases: nine (47%) during surgical exploration preceding intentional adjuvant HIPEC, eight (42%) during routine follow-up, and two (11%) during diagnostic laparoscopy at 18-months. In the control group, 23 (23%) of 102 patients were diagnosed with peritoneal metastases, of whom seven (30%) were diagnosed by laparoscopy at 18-months and 16 during regular follow-up (therefore making them ineligible for diagnostic laparoscopy). In the intention-to-treat analysis (n=202), there was no difference in peritoneal-free survival at 18-months (80·9% [95% CI 73·3-88·5] for the experimental group vs 76·2% [68·0-84·4] for the control group, log-rank one-sided p=0·28). 12 (14%) of 87 patients who received adjuvant HIPEC developed postoperative complications and one (1%) encapsulating peritoneal sclerosis.INTERPRETATION: In patients with T4 or perforated colon cancer, treatment with adjuvant HIPEC with oxaliplatin did not improve peritoneal metastasis-free survival at 18 months. Routine use of adjuvant HIPEC is not advocated on the basis of this trial.FUNDING: Organization for Health Research and Development and the Dutch Cancer Society.
- Published
- 2019