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

The implications of neutropenia after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) treatment have never been investigated.


To evaluate the occurrence of neutropenia and its effect on the risk of increased Clavien-Dindo morbidity as well as its effect on overall or disease-free survival.


All patients with colorectal peritoneal metastases (1996-2015) completing cytoreductive surgery and oxaliplatin-based HIPEC treatment from a bi-institutional database (Uppsala and Sydney) were included in the study. Clavien-Dindo grade 3-4 morbidity differences between the neutropenia group vs non-neutropenia group were calculated and Kaplan-Meier curves with log rank test were rendered. Univariate and multivariable Cox regression models for disease-free survival were implemented.


Two hundred and forty-six patients were identified – 32 postoperative any-grade neutropenia patients and 214 non-neutropenia patients. The neutropenia group had more combination oxaliplatin + irinotecan treatment than the non-neutropenia group (66% vs 13%, P = 0.0001). The neutropenia group was not associated with increased Clavien-Dindo grade 3-4 morbidity. Median overall survival was 53 mo vs 37 mo for the neutropenia and non-neutropenia group, P = 0.07. Median disease-free survival was 16 mo vs 11 mo, respectively, P = 0.02. Neutropenia was an independent prognostic factor for disease-free survival with hazard ratio: 0.58, 95% confidence interval: 0.36-0.95, P = 0.03.


13% of patients developed neutropenia which was not associated with increased Clavien-Dindo grade 3-4 morbidity. Neutropenia was an independent positive prognostic factor for disease-free survival and was associated with more intense HIPEC treatment. This is in direct contrast to the current paradigm of decreasing the treatment intensity.

Keywords: Colorectal cancer, Peritoneal metastases, Cytoreductive surgery, Hyperthermic intraperitoneal chemotherapy, Oxaliplatin, Neutropenia

Core tip: We investigated neutropenia after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) treatment of colorectal cancer with peritoneal metastases. The frequency of neutropenia was 13%; however, it was much more common in the oxaliplatin + irinotecan HIPEC treatment than in the single oxaliplatin HIPEC treatment. Neutropenia did not increase the risk of Clavien-Dindo morbidity. Furthermore, it was found to be an independent prognostic factor for disease-free survival. In conclusion, we found that neutropenia doesn’t appear to be a toxicity limiting factor as it does not increase the postoperative morbidity, but rather a positive prognostic factor that may predict a better outcome.