Effect of Tissue Inhomogeneity in Soft Tissue Sarcomas: From Real Cases to Numerical and Experimental Models

Abstract

Electrochemotherapy is an established treatment option for patients with superficially metastatic tumors, mainly malignant melanoma and breast cancer. Based on preliminary experiences, electrochemotherapy has the potential to be translated in the treatment of larger and deeper neoplasms, such as soft tissue sarcomas. However, soft tissue sarcomas are characterized by tissue inhomogeneity and, consequently, by variable electrical characteristic of tumor tissue. The inhomogeneity in conductivity represents the cause of local variations in the electric field intensity. Crucially, this fact may hamper the achievement of the electroporation threshold during the electrochemotherapy procedure. In order to evaluate the effect of tissue inhomogeneity on the electric field distribution, we first performed ex vivo analysis of some clinical cases to quantify the inhomogeneity area. Subsequently, we performed some simulations where the electric field intensity was evaluated by means of finite element analysis. The results of the simulation models are finally compared to an experimental model based on potato and tissue mimic materials. Tissue mimic materials are materials where the conductivity can be suitably designed. The coupling of computation and experimental results could be helpful to show the effect of the inhomogeneity in terms of variation in electric field distribution and characteristics.

Numerical mesoscale tissue model of electrochemotherapy in liver based on histological findings

“…The electric field distribution depends on the electrical properties of the medium. This is especially important when treating target volumes that contain tissues with significantly different conductivities, as the majority of voltage drop, and consequently electric field strength, occurs in tissues with low conductivity 18 , 27 , 31 , 32 . The natural heterogeneity of the liver structure may have an impact on the electric field distribution and consequently on the outcome of electroporation-based treatments in liver.…”

Multi-Electrode Architecture Modeling and Optimization for Homogeneous Electroporation of Large Volumes of Tissue

“…The proposed structure allows the application of a uniform electric field like the current flat plates but also allows the application of several electric field vectors with different orientations. Applying electric field vectors in different orientations can improve the homogeneity an the efficacy of the treatment [33][34][35] as is done with needle multielectrodes [23][24][25]36,37], but unlike these the proposed electrode does not need to be repositioned. Although the use of flat plate electrodes is not very common in internal tissues, some experiments have been carried out, and it is believed that with a suitable support the proposed multi-electrodes could be better in some cases.…”

“…This direction changes due to tissue heterogeneity, conductivity variations, and the different cell geometry, among other factors. Nowadays, the most extended method to apply more than one electric field vector is to physically reposition them [22][23][24][25]. This procedure is not always available, and in the case of needle electrodes, repositioning the electrodes increases the damage and extend the treatment.…”

Biological factors of the tumour response to electrochemotherapy: Review of the evidence and a research roadmap

“…Cell shape, size and density also affect tumour cell permeabilization and drug distribution and thus ECT effectiveness [66,67]. In addition to drug availability, the extracellular matrix affects the electric field distribution and conductivity [68,69]. Additionally, dense desmoplastic stroma can also interfere with the antitumour immune response, directly by acting as a physical barrier to immune cell infiltration or indirectly by establishing an immunosuppressive microenvironment [70].…”