Retrospective Cohort Study
Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. May 15, 2020; 12(5): 549-558
Published online May 15, 2020. doi: 10.4251/wjgo.v12.i5.549
Neutropenia in colorectal cancer treated with oxaliplatin-based hyperthermic intraperitoneal chemotherapy: An observational cohort study
Peter H Cashin, Lana Ghanipour, Malin Enblad, David L Morris
Peter H Cashin, Lana Ghanipour, Malin Enblad, Department of Surgical Sciences, Section of Surgery, Uppsala University, Akademiska Sjukhuset, Uppsala 75185, Sweden
David L Morris, Department of Surgery, University of New South Wales, Sydney 2217, New South Wales, Australia
Author contributions: Cashin PH designed research and wrote the paper; Cashin PH, Ghanipour L, Enblad M and Morris DL did data acquisition, data interpretation, manuscript editing for intellectual content.
Institutional review board statement: The study was reviewed and approved for publication by the Uppsala County Ethical Review Board.
Informed consent statement: No informed consent was required by the ethical review board due to the retrospective nature of the study and the anonymous data used for the study.
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
STROBE statement: The authors have read the STROBE Statement-checklist of items, and the manuscript was prepared and revised according to the STROBE Statement-checklist of items.
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:
Corresponding author: Peter H Cashin, MD, PhD, Director, Surgeon, Department of Surgical Sciences, Uppsala University, Akademiska Sjukhuset, Uppsala 75185, Sweden.
Received: February 3, 2020
Peer-review started: February 3, 2020
First decision: February 25, 2020
Revised: April 14, 2020
Accepted: April 24, 2020
Article in press: April 24, 2020
Published online: May 15, 2020
Research background

Neutropenia after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) treatment of colorectal cancer with peritoneal metastases is poorly studied.

Research motivation

Neutropenia is currently a treatment limiting toxicity in HIPEC. Its association with the combination treatment of oxaliplatin and irinotecan HIPEC caused this intensified HIPEC regimen to be stopped. However, the implications of the neutropenia was never investigated as it was assumed to be an unwanted side-effect. More research in neutropenia is needed if more intense HIPEC treatment are to be investigated.

Research objectives

The objective of this study was to report on the frequency of neutropenia and its effect on Clavien-Dindo morbidity, reoperation rate, disease-free and overall survival.

Research methods

An observational cohort study design was implemented using two prospectively maintained databases – Uppsala and Sydney. Kaplan-Meier and log rank tests were used as well as Cox proportional hazard models.

Research results

Neutropenia occurs in 13% of colorectal cancer patients being treated with HIPEC and is more common in the oxaliplatin + irinotecan HIPEC regimen. Neutropenia is not associated with increased Clavien-Dindo morbidity nor increased reoperation rate. It is a positive prognostic factor for disease-free survival with a clear benefit in disease-free survival (P = 0.02) as well as a trend towards a benefit in overall survival (P = 0.07).

Research conclusions

Neutropenia may not be a treatment limiting toxicity. HIPEC intensification is possible without increasing morbidity or the reoperation rate. Unexpectedly, neutropenia was a positive prognostic factor for disease-free survival. Future studies need to confirm this unexpected finding. It suggests that neutropenia should be viewed with a different perspective – not as an unwelcomed complication, but rather as a possible predictor of treatment efficacy.