Retrospective Cohort Study
Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Aug 15, 2020; 12(8): 903-917
Published online Aug 15, 2020. doi: 10.4251/wjgo.v12.i8.903
Comparison of hyperthermic intraperitoneal chemotherapy regimens for treatment of peritoneal-metastasized colorectal cancer
Julia Spiegelberg, Hannes Neeff, Philipp Holzner, Mira Runkel, Stefan Fichtner-Feigl, Torben Glatz
Julia Spiegelberg, Hannes Neeff, Philipp Holzner, Mira Runkel, Stefan Fichtner-Feigl, Torben Glatz, Department of General and Visceral Surgery, Medical Center – University of Freiburg, Freiburg 79106, Germany
Torben Glatz, Department of Surgery, Marien Hospital Herne, Ruhr-University Bochum, Herne 44625, Germany
Author contributions: All authors solely contributed to the preparation of this manuscript.
Institutional review board statement: The study was approved by the Medical Ethics Committee of the University of Freiburg (EK-FR 4/20).
Informed consent statement: All study participants or their legal guardian provided informed written consent about personal and medical data collection prior to study enrolment.
Conflict-of-interest statement: All the authors have no conflict of interest related to the manuscript.
Data sharing statement: The original anonymous dataset is available on request from the corresponding author at torben.glatz@uniklinik-freiburg.de.
STROBE statement: The guidelines of the STROBE Statement have been adopted.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Torben Glatz, MD, Surgeon, Department of Surgery, Marien Hospital Herne, Ruhr-University Bochum, Hölkeskampring 40, Herne 44625, Germany. torben.glatz@uniklinik-freiburg.de
Received: December 30, 2019
Peer-review started: December 30, 2019
First decision: February 20, 2020
Revised: May 29, 2020
Accepted: June 14, 2020
Article in press: June 14, 2020
Published online: August 15, 2020
ARTICLE HIGHLIGHTS
Research background

Cytoreductive Surgery (CRS) in combination with hyperthermic intraperitoneal chemotherapy (HIPEC) improves patient survival in colorectal cancer (CRC) with peritoneal carcinomatosis (PC). Commonly used cytotoxic agents nowadays include mitomycin C (MMC) and oxaliplatin. Evidence for the choice of the HIPEC agent and uniform procedure protocols is scarce, with studies reporting varying results.

Research motivation

There’s a severe lack of evidence regarding comparison of survival benefits for most commonly utilized chemotherapeutic agents for HIPEC oxaliplatin and MMC. At present there is no prospective study that compares these two HIPEC regimens for treatment of peritoneal metastasized CRC, thus leading to the reassessment of HIPEC and the need for structured treatment protocols. In this retrospective clinical analysis, we evaluated the outcome of patients undergoing CRS HIPEC at the university medical centre of Freiburg. Furthermore, this study is one of a few to focus on prognostic factors and treatment strategies after the development of peritoneal metastasis.

Research objectives

The aim of the study was to evaluate therapeutic benefits and operative and postoperative complications of CRS + MMC vs oxaliplatin HIPEC in patients with peritoneal metastasized CRC as well as prognostic factors for overall survival (OS).

Research methods

One hundred two patients who had undergone CRS and HIPEC for CRC PC between 2007 and 2019 at the Medical Center of the University Freiburg regarding interdisciplinary cancer conference decision were retrospectively analysed. Oxaliplatin and MMC were used in 68 and 34 patients, respectively. Each patient’s demographics and tumour characteristics, operative details, postoperative complications and survival were noted and compared. Complications were stratified and graded using Clavien/Dindo analysis. Prognostic outcome factors were identified using univariate and multivariate analysis of survival.

Research results

The two groups did not differ significantly regarding baseline characteristics. We found no difference in median OS. Patients treated with oxaliplatin HIPEC suffered increased postoperative complications (66.2% vs 35.3%; P = 0.003), particularly intestinal atony, intraabdominal infections and urinary tract infections, and had a prolonged intensive care unit (ICU) stay compared to the MMC group (7.2 d vs 4.4 d; P = 0.035). Regarding univariate analysis of survival, we found primary tumour factors, nodal positivity and resection margins to be of prognostic value as well as PC index (PCI)-score and the completeness of cytoreduction regarding peritoneal carcinomatosis. Multivariate analysis of survival confirmed primary distant metastasis and primary tumour resection status to have a significant impact on survival and likewise PCI-scoring regarding peritoneal carcinomatosis.

Research conclusions

We could not show any survival advantage for neither HIPEC regimens. Oxaliplatin showed an increased complication rate. Increased postoperative complication rates, especially severe complications (grade IIIb and IV according to Clavien-Dindo analysis), were also associated with prolonged ICU stay for the Oxaliplatin group compared to MMC (7.2 d vs 4.4 d; P = 0.035), which improves evidence to choose MMC for CRS-HIPEC.

Primary distant metastasis and primary tumour resection seem to have a significant impact on survival and likewise PCI-scoring regarding peritoneal carcinomatosis.

Research perspectives

For this special collective of patients with PC based on a colorectal primary tumour, several outcome predictors could be identified. We were also able to show comparable outcome results for CRS/HIPEC with oxaliplatin and MMC. Nevertheless, increased complication rates for oxaliplatin were demonstrated, which, according to literature, significantly affects OS, indicating that patients should be treated favourably with MMC-HIPEC. Further studies, in particular a phase III clinical trial comparing both HIPEC regimens would improve evidence-based decision-making.