Implications and considerations of thermal effects when applying irreversible electroporation tissue ablation therapy

Abstract

Irreversible electroporation (IRE) describes a cellular response to electric field exposure, resulting in the formation of nanoscale defects that can lead to cell death. While this behavior occurs independently of thermally-induced processes, therapeutic ablation of targeted tissues with IRE uses a series of brief electric pulses, whose parameters result in secondary Joule heating of the tissue. Where contemporary clinical pulse protocols use aggressive energy regimes, additional evidence is supplementing original studies that assert care must be taken in clinical ablation protocols to ensure the cumulative thermal effects do not induce damage that will alter outcomes for therapies using the IRE non-thermal cell death process for tissue ablation. In this letter, we seek to clarify the nomenclature regarding IRE as a non-thermal ablation technique, as well as identify existing literature that uses experimental, clinical, and numerical results to discretely address and evaluate the thermal considerations relevant when applying IRE in clinical scenarios, including several approaches for reducing these effects. Existing evidence in the literature describes cell response to electric fields, suggesting cell death from IRE is a unique process, independent from traditional thermal damage. Numerical simulations, as well as preclinical and clinical findings demonstrate the ability to deliver therapeutic IRE ablation without occurrence of morbidity associated with thermal therapies. Clinical IRE therapy generates thermal effects, which may moderate the non-thermal aspects of IRE ablation. Appropriate protocol development, utilization, and pulse delivery devices may be implemented to restrain these effects and maintain IRE as the vastly predominant tissue death modality, reducing therapy-mitigating thermal damage. Clinical applications of IRE should consider thermal effects and employ protocols to ensure safe and effective therapy delivery.

Focal Therapy in Primary Localised Prostate Cancer : The European Association of Urology Position in 2018

“…IRE applies electric current to ablate tissue with a small transition zone between treated and non-treated tissue (26…”

Multiparametric prostate magnetic resonance imaging in the evaluation of prostate cancer

“…This has enabled the use of mpMRI to guide focal therapy of prostate cancer through one of several minimally invasive techniques, such as high‐intensity focused ultrasound, cryotherapy, laser ablation, and irreversible electroporation . MRI technology not only allows physicians to reach the focal lesions for therapy but also allows them to monitor the status of treatment in real time via MRI thermometry, which results in accurate tumor damage estimation . The early and limited results for focal therapy are promising; however, these methods are still under development, and large‐scale, multiinstitutional studies are needed to determine their efficacy and side effects.…”

Numerical modelling challenges for clinical electroporation ablation technique of liver tumors

“…Interestingly it has been shown that this method selectively affects the cell membrane, which becomes permeable if the high voltage is high enough. It thus makes it possible to either introduce non permeant molecules (ions, cytotoxic drugs like bleomycin, DNA plasmids) into living cells, which is referred to as reversible electroporation [3,46] or to kill directly the cells in the targeted region (tumor) by a nonthermal mechanism (this is named irreversible electroporation [11,12,15]. cells (cancerous or not).…”