Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2021 Jul 8;13(14):3430.
doi: 10.3390/cancers13143430.

Preclinical In Vivo-Models to Investigate HIPEC; Current Methodologies and Challenges

Roxan F C P A Helderman  1   2 , Daan R Löke  2 , Pieter J Tanis  3 , Jurriaan B Tuynman  4 , Wim Ceelen  5 , Ignace H de Hingh  6   7 , Kurt van der Speeten  8 , Nicolaas A P Franken  1   2 , Arlene L Oei  1   2 , H Petra Kok  2 , Johannes Crezee  2
Affiliations
Review

Preclinical In Vivo-Models to Investigate HIPEC; Current Methodologies and Challenges

Roxan F C P A Helderman et al. Cancers (Basel). .

Abstract

Hyperthermic intraperitoneal chemotherapy (HIPEC) is a treatment modality for patients with peritoneal metastasis (PM) of various origins which aims for cure in combination with cytoreductive surgery (CRS). Efficacy of CRS-HIPEC depends on patient selection, tumor type, delivery technique, and treatment parameters such as temperature, carrier solution, type of drug, dosage, volume, and treatment duration. Preclinical research offers a powerful tool to investigate the impact of these parameters and to assist in designing potentially more effective treatment protocols and clinical trials. The different methodologies for peritoneal disease and HIPEC are variable. This study aims to review the objectives, methods, and clinical relevance of in vivo preclinical HIPEC studies found in the literature. In this review, recommendations are provided and possible pitfalls are discussed on the choice of type of animal and tumor model per stratified parameters and study goal. The guidelines presented in this paper can improve the clinical relevance and impact of future in vivo HIPEC experiments.

Keywords: cytoreductive surgery (CRS); hyperthermic intraperitoneal chemotherapy (HIPEC); peritoneal carcinomatosis; peritoneal metastasis.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Overview of important parameters for performing HIPEC in preclinical models. The preclinical model consists of a suitable animal model with a corresponding tumor model. The delivery technique, flow rate, tubing setup, temperature, and temperature control are relevant for the HIPEC model. The research categories are HIPEC treatment parameters with an impact on the treatment outcome; i.e., temperature, carrier solution, dosage, volume, type of drug, and duration.
Figure 2
Figure 2
Schematic overview of the type of animals to present the size, weight, and perfusate volume applied during the HIPEC procedures.
Figure 3
Figure 3
Schematic representation of the different tumor models with the according animal strains and their advantages and disadvantages.
Figure 4
Figure 4
Possible enhancement curves, varying per chemotherapy/cell line combination. The green shaded areas depict the region in the thermal enhancement where the increasing temperature might yield a significantly more effective treatment. The red region on the right visualizes regions where adverse effects such as thermal damage do not outweigh the added thermal enhancement, whereas the left red region visualizes regions where no increased effect or damage is expected. Note that these are simplified curves and that behavior is strongly dependent on the chemotherapy agent and cell line. We assumed that the amount of thermal damage is linear with temperature.
Figure 5
Figure 5
Recommendations for determination of treatment parameters.
See this image and copyright information in PMC

References

    1. Desai J.P., Moustarah F. Cancer, Peritoneal Metastasis. StatPearls; Treasure Island, FL, USA: 2020.
    1. Verwaal V.J., Bruin S., Boot H., Van Slooten G., Van Tinteren H. 8-Year Follow-up of Randomized Trial: Cytoreduction and Hyperthermic Intraperitoneal Chemotherapy Versus Systemic Chemotherapy in Patients with Peritoneal Carcinomatosis of Colorectal Cancer. Ann. Surg. Oncol. 2008;15:2426–2432. doi: 10.1245/s10434-008-9966-2. - DOI - PubMed
    1. Elias D., Lefevre J., Chevalier J., Brouquet A., Marchal F., Classe J.-M., Ferron G., Guilloit J.-M., Meeus P., Goéré D., et al. Complete Cytoreductive Surgery Plus Intraperitoneal Chemohyperthermia With Oxaliplatin for Peritoneal Carcinomatosis of Colorectal Origin. J. Clin. Oncol. 2009;27:681–685. doi: 10.1200/JCO.2008.19.7160. - DOI - PubMed
    1. Franko J., Ibrahim Z., Gusani N.J., Holtzman M.P., Bartlett D.L., Zeh H.J. Cytoreductive surgery and hyperthermic intraperitoneal chemoperfusion versus systemic chemotherapy alone for colorectal peritoneal carcinomatosis. Cancer. 2010;116:3756–3762. doi: 10.1002/cncr.25116. - DOI - PubMed
    1. Van Driel W.J., Koole S.N., Sikorska K., Schagen van Leeuwen J.H.S., Schreuder H.W., Hermans R.H., de Hingh I.H., van der Velden J., Arts H.J., Massuger L.F., et al. Hyperthermic Intraperitoneal Chemotherapy in Ovarian Cancer. N. Engl. J. Med. 2018;378:230–240. doi: 10.1056/NEJMoa1708618. - DOI - PubMed

LinkOut - more resources