Abstract
Electrochemotherapy is an anticancer treatment based on applying electric field pulses that reduce cell membrane selectivity, allowing chemotherapy drugs to enter the cells. In parallel to electrochemotherapy clinical tests, in silico experiments have helped scientists and clinicians to understand the electric field distribution through anatomically complex regions of the body. In particular, these in silico experiments allow clinicians to predict problems that may arise in treatment effectiveness. The current work presents a metastatic case of a mast cell tumor in a dog. In this specific treatment planning study, we show that using needle electrodes has a possible pitfall. The macroscopic consequence of the electroporation was assessed through a mathematical model of tissue electrical conductivity. Considering the electrical and geometrical characteristics of the case under study, we modeled an ellipsoidal tumor. Initial simulations were based on the European Standard Operating Procedures for electrochemotherapy suggestions, and then different electrodes' arrangements were evaluated. To avoid blind spots, multiple applications are usually required for large tumors, demanding electrode repositioning. An effective treatment electroporates all the tumor cells. Partially and slightly overlapping the areas increases the session's duration but also likely increases the treatment's effectiveness. It is worth noting that for a single application, the needles should not be placed close to the tumor's borders because effectiveness is highly likely to be lost.
Highlights
IntroductionElectrochemotherapy is an anticancer treatment based on pulsed electric fields and chemotherapy drugs. e electric field reduces the cell membrane’s selectivity, promoting the cell’s intake of chemotherapy drugs [1,2,3]. is biophysical phenomenon of decreasing cell membrane selectivity through electric field imposition is called electropermeabilization.e most accepted theory to explain such permeabilization considers that pores are induced around the cell membrane [4]. is process is called electroporation and considers that the membrane permeabilization can be reversible or irreversible depending on the membrane’s capability of resealing the pores after the removal of the electric field [2, 5].e reversible or irreversible electroporation can lead to different treatment outcomes
We use a simple study case to demonstrate a treatment planning procedure based on numerical simulation. e presented results allowed us to highlight the loss of potential treatment effectiveness due to the electric field indentation between needles with the same polarity
The conclusions of this study still must be translated into in vitro and in vivo experiments, we showed that fundamental issues like a safe margin and effectiveness loss can be revealed using a validated numerical model
Summary
Electrochemotherapy is an anticancer treatment based on pulsed electric fields and chemotherapy drugs. e electric field reduces the cell membrane’s selectivity, promoting the cell’s intake of chemotherapy drugs [1,2,3]. is biophysical phenomenon of decreasing cell membrane selectivity through electric field imposition is called electropermeabilization.e most accepted theory to explain such permeabilization considers that pores are induced around the cell membrane [4]. is process is called electroporation and considers that the membrane permeabilization can be reversible or irreversible depending on the membrane’s capability of resealing the pores after the removal of the electric field [2, 5].e reversible or irreversible electroporation can lead to different treatment outcomes. Is process is called electroporation and considers that the membrane permeabilization can be reversible or irreversible depending on the membrane’s capability of resealing the pores after the removal of the electric field [2, 5]. Reversible electroporation facilitates the uptake of chemotherapy drugs (e.g., bleomycin and cisplatin) by the cells and the selective death of tumor cells [1, 3]. When this delivery method is used, the cytotoxicity of bleomycin increases 300–700 times [3]. Irreversible electroporation induces membrane disruption and indiscriminate cell death [2] In this sense, the ability to achieve the right parameters for targeting tumor cells has imposed challenges. E electric field distribution in biological tissues has been studied for decades, and recent in silico experiments have taken advantage of years of bioelectrical impedance analysis [6, 7] and powerful processors. rough in silico experiments, several different scenarios can be run, which
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