The Feasibility of Irreversible Electroporation for the Treatment of Breast Cancer and Other Heterogeneous Systems

Abstract

Developments in breast cancer therapies show potential for replacing simple and radical mastectomies with less invasive techniques. Localized thermal techniques encounter difficulties, preventing their widespread acceptance as replacements for surgical resection. Irreversible electroporation (IRE) is a non-thermal, minimally invasive focal ablation technique capable of killing tissue using electric pulses to create irrecoverable nano-scale pores in the cell membrane. Its unique mechanism of cell death exhibits benefits over thermal techniques including rapid lesion creation and resolution, preservation of the extracellular matrix and major vasculature, and reduced scarring. This study investigates applying IRE to treat primary breast tumors located within a fatty extracellular matrix despite IREs dependence on the heterogeneous properties of tissue. In vitro experiments were performed on MDA-MB-231 human mammary carcinoma cells to determine a baseline electric field threshold (1000 V/cm) to cause IRE for a given set of pulse parameters. The threshold was incorporated into a three-dimensional numerical model of a heterogeneous system to simulate IRE treatments. Treatment-relevant protocols were found to be capable of treating targeted tissue over a large range of heterogeneous properties without inducing significant thermal damage, making IRE a potential modality for successfully treating breast cancer. Information from this study may be used for the investigation of other heterogeneous tissue applications for IRE.

Irreversible electroporation of the pancreas: Definitive local therapy without systemic effects

“…The goal of electrode placement is to induce an IRE field that encompasses the entire tumor. The outcome of IRE is influenced by number of parameters including pulse shape, length, frequency, electrical field strength, voltage applied to the electrodes, electrode shape, electrode size, and tissue type [15][16][17]. However, accurate field prediction based on mathematical models and in vitro studies has been performed for IRE in some tumor types.…”

“…However, accurate field prediction based on mathematical models and in vitro studies has been performed for IRE in some tumor types. The predicted IRE parameters are designed to allow prediction of the ablation field, determine maximum ablation, and minimize the thermal effects [17][18][19]. Such studies have yet to be conducted for tumors of the pancreas.…”

Experimental characterization of intrapulse tissue conductivity changes for electroporation

“…The medulla of kidneys contains the collecting system and ureter for the organ, which will present a great deal of heterogeneities and possibly affect experimental results [10,16]. However, the bulk properties of the cortex are relatively homogeneous and suitable for characterizing the bulk changes resulting from the electric pulses.…”

“…The electric pulses in electroporation therapies will cause tissue heating due to Joule heating from bulk tissue resistance. These two factors will influence the electric field distribution that the tissue experiences, and therefore the treatment region [9][10][11] .…”

Irreversible Electroporation for the Ablation of Liver Tumors

“…Other groups have reported the ability of IRE to ablate prostate cancer cells in vitro, 61 breast cancer cells in vitro, 62 breast tumors orthotopically implanted in nude mice in vivo, 63 and pancreas ductal adenocarcinoma in vivo in a mouse model. 64 …”