Abstract

We extend an agent-based multiscale model of vascular tumour growth and angiogenesis to describe transarterial chemoembolisation (TACE) therapies. The model accounts for tumour and normal cells that are both nested in a vascular system that changes its structure according to tumour-related growth factors. Oxygen promotes nutrients to the tissue and determines cell proliferation or death rates. Within the extended model TACE is included as a two-step process: First, the purely mechanical influence of the embolisation therapy is modelled by a local occlusion of the tumour vasculature. There we distinguish between partial and complete responders, where parts of the vascular system are occluded for the first and the whole tumour vasculature is destroyed for the latter. In the second part of the model, drug eluding beads (DEBs) carrying the chemotherapeutic drug doxorubicin are located at destroyed vascular locations, releasing the drug over a certain time-window. Simulation results are parameterised to qualitatively reproduce clinical observations. Patients that undergo a TACE-treatment are categorised in partial and complete responders one day after the treatment. Another 90 days later reoccurance or complete response are detected by volume perfusion computer tomography (VPCT). Our simulations reveal that directly after a TACE- treatment an unstable tumour state can be observed, where regrowth and total tumour death have the same likeliness. It is argued that this short time-window is favorable for another therapeutical intervention with a less radical therapy. This procedure can shift the outcome to more effectiveness. Simulation results with an oxygen therapy within the unstable time-window demonstrate a potentially positive manipulated outcome. Finally, we conclude that our TACE model can motivate new therapeutical strategies and help clinicians analyse the intertwined relations and cross-links in tumours.

Details

Title
Hybrid Modelling of Transarterial Chemoembolisation Therapies (TACE) for Hepatocellular Carcinoma (HCC)
Author
Perfahl, H 1 ; Jain, H V 2   VIAFID ORCID Logo  ; Joshi, T 1 ; Horger, M 3 ; Malek, N 4 ; Bitzer, M 4 ; Reuss, M 1 

 University Stuttgart, Stuttgart Research Center Systems Biology, Stuttgart, Germany (GRID:grid.5719.a) (ISNI:0000 0004 1936 9713) 
 Florida State University, Department of Mathematics, Tallahassee, United States of America (GRID:grid.255986.5) (ISNI:0000 0004 0472 0419) 
 Eberhard-Karls-University, Department of Diagnostic and Interventional Radiology, Tübingen, Germany (GRID:grid.10392.39) (ISNI:0000 0001 2190 1447) 
 Eberhard-Karls-University, Department of Internal Medicine I, University Department of Medicine, Tübingen, Germany (GRID:grid.10392.39) (ISNI:0000 0001 2190 1447) 
Publication year
2020
Publication date
2020
Publisher
Nature Publishing Group
e-ISSN
20452322
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2418450569
Copyright
© The Author(s) 2020. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.