Single-needle electroporation and interstitial electrochemotherapy: in vivo safety and efficacy evaluation of a new system

Pedersoli, Federico; Ritter, Andreas; Zimmermann, Markus; Schulze-Hagen, Maximilian; Liebl, Martin; Dethlefsen, Ebba; Stillfried, Saskia von; Pfeffer, Joachim; Kuhl, Christiane K.; Bruners, Philipp; Isfort, Peter

doi:10.1007/s00330-019-06251-3

Cited by 6 publications

(4 citation statements)

References 23 publications

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“…The third large area of preclinical research is dealing with different types of electrodes that can be used in vitro, in vivo, or in humans, that is, grid, single needle, or endoscopic, [59][60][61][62][63][64] with different types (e.g., sine wave pulses, pulsed electromagnetic field, and high-frequency short bipolar pulses), and parameters of electric pulses (amplitude and frequency). [65][66][67][68][69] The overall aim of these studies is to provide new electrodes that will be able to reach/treat the tumors that are not accessible with the current electrodes that are on the market and to provide electrodes that will not induce pain, muscle contraction, and/or skin burns, that is, undesired side effects that are commonly reported in clinical studies on electrochemotherapy.…”

Section: Electrochemotherapy: New Electrodes and Numerical Modelingmentioning

confidence: 99%

Recent Advances in Electrochemotherapy

Čemažar

Serša

2019

Bioelectricity

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Electrochemotherapy is gaining recognition as an effective local therapy that uses systemically or intratumorally injected bleomycin or cisplatin with electroporation as a delivery system that brings drugs into the cells to exert their cytotoxic effects. Preclinical work is still ongoing, testing new drugs, seeking the best treatment combination with other treatment modalities, and exploring new sets of pulses for effective tissue electroporation. The applications of electrochemotherapy are being fully exploited in veterinary oncology, where electrochemotherapy, because of its simple execution, has a relatively good cost-benefit ratio and is used in the treatment of cutaneous tumors. In human oncology, electrochemotherapy is fully recognized as a local therapy for cutaneous tumors and metastases. Its effectiveness is being explored in combination with immunomodulatory drugs. However, the development of electrochemotherapy is directed into the treatment of deepseated tumors with a percutaneous approach. Because of the vast number of reports, this review discusses the articles published in the past 5 years.

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Section: Electrochemotherapy: New Electrodes and Numerical Modelingmentioning

confidence: 99%

Recent Advances in Electrochemotherapy

Čemažar

Serša

2019

Bioelectricity

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“…We introduce the biophysical model for a case of IRE with an expandable applicator 20 . This specific applicator design was chosen for this study due to its low number of insertions (single insertion to place five electrodes), thereby reducing treatment time and misplacement errors.…”

Section: Methodsmentioning

confidence: 99%

“…We introduce the biophysical model for a case of IRE with an expandable applicator. 20 This specific applicator design was chosen for this study due to its low number of insertions (single insertion to place five electrodes), thereby reducing treatment time and misplacement errors. A scenario with colorectal liver metastasis (CRLM) was considered due to the lack of standard therapies other than resection and the associated high mortality rate, killing more than two thirds of patients.…”

Section: Biophysical Modelingmentioning

confidence: 99%

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

et al. 2023

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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 treatmentThis is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

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“…10 Working closely with radiologists, our department focusses on developing an improved electroporation probe, which enables the combination of IRE with ECT treatment for liver cancer. [5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23] In both IRE and ECT, the success of the treatment is dependent on application of the appropriate electric field. The electric field can be affected by the following parameters: tissue-specific electrical properties, geometry and positions of electrodes, and electric pulse parameters.…”

Section: Introductionmentioning

confidence: 99%

Pulse Parameters and Thresholds for (ir)Reversible Electroporation on Hepatocellular Carcinoma Cells in Vitro

Lindelauf

Baragona

Baumann

et al. 2023

Technol Cancer Res Treat

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Hepatocellular carcinoma is a leading cause of cancer-related death in many parts of the world. Traditional treatment options are not always effective. During the promising minimally invasive electroporation-based therapies, biological cell membranes are exposed to an external, sufficiently high, pulsed electric field which creates so-called nanopores into the lipid bilayer of the cell membrane. These pores can either be permanent (irreversible electroporation (IRE)), leading to apoptosis, or repairable (reversible electroporation (RE)), with continued cell function. In tumor therapy, RE is used to increase the diffusion of a chemotherapeutic drug during electrochemotherapy. For both IRE and RE, the success of the treatment is dependent on application of the appropriate electric field. Therefore, this study aims to define the pulse parameters and thresholds for IRE and RE on hepatocellular carcinoma (HepG2) cells in-vitro. In a custom-made in-vitro setup, HepG2 cell viability (0, 5, 10, and 15 min), and the peak temperature were measured after electroporation with the different IRE and RE pulsing protocols, to determine the most successful settings for IRE and RE. A CAM/PI flow cytometric assay was performed to confirm cell permeabilization for the RE pulsing protocols with the highest cell viability. The results indicated that an IRE pulsing protocol (70 pulses, 100 µs pulse length, and 100 ms interval) with an electric field strength of 4000 V/cm was needed as threshold for almost complete cell death of HepG2 cells. A RE pulsing protocol (8 pulses, 100 µs pulse length, and 1000 ms interval) with an electric field strength of 1000 V/cm was needed as threshold for viable and permeabilized HepG2 cells. The low peak temperatures (max 30.1°C for IRE, max 23.1°C for RE) within this study indicated that the reduction in HepG2 cell viability was caused by the applied electric field and was not a result of Joule heating.

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Single-needle electroporation and interstitial electrochemotherapy: in vivo safety and efficacy evaluation of a new system

Cited by 6 publications

References 23 publications

Recent Advances in Electrochemotherapy

Recent Advances in Electrochemotherapy

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

Pulse Parameters and Thresholds for (ir)Reversible Electroporation on Hepatocellular Carcinoma Cells in Vitro

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