Hyperthermic intraperitoneal chemotherapy in colorectal cancer
Authors: Fisher Oliver M , Brown Chris , Esquivel Jesus , Larsen Stein G , Liauw Winston , Alzahrani Nayef A , Morris David L , Kepenekian Vahan , Sourrouille Isabelle , Dumont Frédéric , Tuech Jean-Jacques , Ceribelli Cécilia , Doussot Béranger , Sgarbura Olivia , Alhosni Mohammed , Quenet Francois , Glehen Olivier , Cashin Peter H ,   Peritoneal Surface Oncology Group International (PSOGI), Nordic Peritoneal Oncology Group (NPOG), American Society for Peritoneal Surface Malignancy (ASPSM) and BIG-RENAPE Groups, Flatmark Kjersti , Graf Wilhelm , Takala Heikki , Lowy Andrew M , Chua Terence , Pelz Joerg , Baratti Dario , Baumgartner Joel M , Berri Richard , Bretcha-Boix Pedro , Deraco Marcello , Flores-Ayala Guillermo , Gomez-Portilla Alberto , González-Moreno Santiago , Goodman Martin , Halkia Evgenia , Kusamura Shigeki , Moller Mecker , Passot Guillaume , Pocard Marc , Salti George , Sardi Armando , Senthil Maheswari , Spilioitis John , Torres-Melero Juan , Turaga Kiran , Bereder Jean-Marc , Bernard Jean-Louis , Bakrin Naoual , Carrère Sébastien , Coget Julien , Cotte Eddy , Facy Olivier , Gelli Maximiliano , Gilly François-Noël , Ortega-Deballon Pablo , Passot Guillaume , Rat Patrick , Rousset Pascal , Thibaudeau Emilie , Vaudoyer Delphine 
Published: May 2024

Abstract

Background
This study evaluated the efficacy of hyperthermic intraperitoneal chemotherapy (HIPEC) in colorectal cancer with peritoneal metastases (pmCRC) in a large international data set of patients.

Patients and Methods
Patients with pmCRC from 39 centres who underwent cytoreductive surgery with HIPEC between 1991 and 2018 were selected and compared for the HIPEC protocols received—oxaliplatin-HIPEC versus mitomycin-HIPEC. Following analysis of crude data, propensity-score matching (PSM) and Cox-proportional hazard modelling were performed. Outcomes of interest were overall survival (OS), recurrence-free survival (RFS) and the HIPEC dose–response effects (high versus low dose, dose intensification and double drug protocols) on OS, RFS and 90-day morbidity. Furthermore, the impact of the treatment time period was assessed.

Results
Of 2760 patients, 2093 patients were included. Median OS was 43 months (95% c.i. 41 to 46 months) with a median RFS of 12 months (95% c.i. 12 to 13 months). The oxaliplatin-HIPEC group had an OS of 47 months (95% c.i. 42 to 53 months) versus 39 months (95% c.i. 36 to 43 months) in the mitomycin-HIPEC group (P = 0.002), aHR 0.77, 95% c.i. 0.67 to 0.90, P &lt; 0.001. The OS benefit persisted after PSM of the oxaliplatin-HIPEC group and mitomycin-HIPEC group (48 months (95% c.i. 42 to 59 months) versus 40 months (95% c.i. 37 to 44 months)), P &lt; 0.001, aHR 0.78 (95% c.i. 0.65 to 0.94), P = 0.009. Similarly, matched RFS was significantly higher for oxaliplatin-HIPEC versus others (13 months (95% c.i. 12 to 15 months) versus 11 months (95% c.i. 10 to 12 months, P = 0.02)). High-dose mitomycin-HIPEC protocols had similar OS compared to oxaliplatin-HIPEC. HIPEC dose intensification within each protocol resulted in improved survival. Oxaliplatin + irinotecan-HIPEC resulted in the most improved OS (61 months (95% c.i. 51 to 101 months)). Ninety-day mortality in both crude and PSM analysis was worse for mitomycin-HIPEC. There was no change in treatment effect depending on the analysed time period.

Conclusions
Oxaliplatin-based HIPEC provided better outcomes compared to mitomycin-based HIPEC. High-dose mitomycin-HIPEC was similar to oxaliplatin-HIPEC. The 90-day mortality difference favours the oxaliplatin-HIPEC group. A trend for dose–response between low- and high-dose HIPEC was reported.