Global sensitivity study for irreversible electroporation: Towards treatment planning under uncertainty

Prashanth Lakshmi Narasimhan (Corresponding author), Zoi Tokoutsi, Davide Baroli, Marco Baragona, Karen Veroy, Ralph Maessen, Andreas Ritter

Research output: Contribution to journalArticleAcademicpeer-review

1 Citation (Scopus)
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Abstract

Background: Electroporation-based cancer treatments are minimally invasive, nonthermal interventional techniques that leverage cell permeabilization to ablate the target tumor. However, the amount of permeabilization is susceptible to the numerous uncertainties during treatment, such as patient-specific variations in the tissue, type of the tumor, and the resolution of imaging equipment. These uncertainties can reduce the extent of ablation in the tissue, thereby affecting the effectiveness of the treatment. Purpose: The aim of this work is to understand the effect of these treatment uncertainties on the treatment outcome for irreversible electroporation (IRE) in the case of colorectal liver metastasis (CRLM). Understanding the nature and extent of these effects can help us identify the influential treatment parameters and build better models for predicting the treatment outcome. Methods: This is an in silico study using a static computational model with a custom applicator design, spherical tissue, and tumor geometry. A nonlinear electrical conductivity, dependent on the local electric field, is considered. Morris analysis is used to identify the influential treatment parameters on the treatment outcome. Seven treatment parameters pertaining to the relative tumor location with respect to the applicator, the tumor growth pattern, and the electrical conductivity of tissue are analyzed. The treatment outcome is measured in terms of the relative tumor ablation with respect to the target ablation volume and total ablation volume. Results: The Morris analysis was performed with 800 model evaluations, sampled from the seven dimensional input parameter space. Electrical properties of the tissue, especially the electrical conductivity of the tumor before ablation, were found to be the most influential parameter for relative tumor ablation and total ablation volume. This parameter was found to be about 4–15 times more influential than the least influential parameter, depending on the tumor size. The tumor border configuration was identified as the least important parameter for treatment effectiveness. The most desired treatment outcome is obtained by a combination of high healthy liver conductivity and low tumor conductivity. This information can be used to tackle worst-case scenarios in treatment planning. Finally, when the safety margins used in the clinical applications are accounted for, the effects of uncertainties in the treatment parameters reduce drastically. Conclusions: The results of this work can be used to create an efficient surrogate estimator for uncertainty quantification in the treatment outcome, that can be utilized in optimal real-time treatment planning solutions.

Original languageEnglish
Pages (from-to)1290-1304
Number of pages15
JournalMedical Physics
Volume50
Issue number3
DOIs
Publication statusPublished - Mar 2023

Bibliographical note

Funding Information:
This work is a part of the ElectroPros project and has received funding from the European Union's Horizon 2020 research and innovation programme, under the Marie Sklodowska‐Curie Grant Agreement No. 813192. Furthermore, the authors would like to express our appreciation to Prof. Dr. med. Peter Isfort and Dr. Nada Cvetkovic for helpful discussions while writing this work. Finally, we would like to thank the editor and the anonymous reviewers for their valuable suggestions.

Publisher Copyright:
© 2023 The Authors. Medical Physics published by Wiley Periodicals LLC on behalf of American Association of Physicists in Medicine.

Keywords

  • global sensitivity analysis
  • irreversible electroporation
  • Morris method
  • treatment planning

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