Mathematical modeling of the thermal effects of irreversible electroporation for <i>in vitro</i>, <i>in vivo</i>, and clinical use: a systematic review

Agnass, Pierre; Veldhuisen, Eran van; Gemert, Martin J. C. van; Geld, C.W.M. van der; Lienden, Krijn P. van; Gulik, Thomas M. van; Meijerink, Martijn R.; Besselink, Marc G.; Kok, H. Petra; Crezee, J.

doi:10.1080/02656736.2020.1753828

Cited by 47 publications

(47 citation statements)

References 95 publications

(352 reference statements)

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“…Therefore, a higher number of pulses are needed to exert such action, which results in longer treatments [ 18 ]. Additionally, due to the higher number of pulses, IRE contains a nonnegligible thermal component, which can introduce additional safety concerns when treating targets near temperature-sensitive tissue, such as the central bile ducts [ 15 , 22 , 23 , 24 ]. In contrast, the advantage of ECT is the utilization of a smaller number of pulses for reversible electroporation of cells and the induction of apoptotic cell death with delayed action of cytotoxic agents and not electric pulses [ 18 ].…”

Section: Discussionmentioning

confidence: 99%

A Prospective Phase II Study Evaluating Intraoperative Electrochemotherapy of Hepatocellular Carcinoma

Djokić

Čemažar

Bošnjak

et al. 2020

Cancers

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The aim of this clinical study was to investigate the effectiveness and long-term safety of electrochemotherapy as an emerging treatment for HCC in patients not suitable for other treatment options. A prospective phase II clinical study was conducted in patients with primary HCC who were not suitable for other treatment options according to the Barcelona Clinic Liver Cancer classification. A total of 24 patients with 32 tumors were treated by electrochemotherapy. The procedure was effective, feasible, and safe with some procedure-related side effects. The responses of the 32 treated nodules were: 84.4% complete response (CR), 12.5% partial response (PR), and 3.1% stable disease (SD). The treatment was equally effective for nodules located centrally and peripherally. Electrochemotherapy provided a durable response with local tumor control over 50 months of observation in 78.0% of nodules. The patient responses were: 79.2% CR and 16.6% PR. The median progression-free survival was 12 months (range 2.7–50), and the overall survival over 5 years of observation was 72.0%. This prospective phase II clinical study showed that electrochemotherapy was an effective, feasible, and safe option for treating HCC in patients not suitable for other treatment options.

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Section: Discussionmentioning

confidence: 99%

A Prospective Phase II Study Evaluating Intraoperative Electrochemotherapy of Hepatocellular Carcinoma

Djokić

Čemažar

Bošnjak

et al. 2020

Cancers

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“…The irreversible aspect is a result of the number of pores created such that a cell cannot recover from the collapse of cell membrane function. Though presented as non-thermal, inclusion of IRE in this review is justified since significant temperature rises in the hyperthermic and in the thermal ablation range are reported to occur during IRE, significantly contributing to the ablation effect [284][285][286][287][288][289][290]. These significant temperature increases are a result of the excessively high SAR generated in a short time (1 -10 min) in the treatment area during IRE, particularly close to the electrodes.…”

Section: Electroporationmentioning

confidence: 99%

Heating technology for malignant tumors: a review

Kok

Cressman

Ceelen

et al. 2020

International Journal of Hyperthermia

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261

188

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The therapeutic application of heat is very effective in cancer treatment. Both hyperthermia, i.e., heating to 39-45 C to induce sensitization to radiotherapy and chemotherapy, and thermal ablation, where temperatures beyond 50 C destroy tumor cells directly are frequently applied in the clinic. Achievement of an effective treatment requires high quality heating equipment, precise thermal dosimetry, and adequate quality assurance. Several types of devices, antennas and heating or power delivery systems have been proposed and developed in recent decades. These vary considerably in technique, heating depth, ability to focus, and in the size of the heating focus. Clinically used heating techniques involve electromagnetic and ultrasonic heating, hyperthermic perfusion and conductive heating. Depending on clinical objectives and available technology, thermal therapies can be subdivided into three broad categories: local, locoregional, or whole body heating. Clinically used local heating techniques include interstitial hyperthermia and ablation, high intensity focused ultrasound (HIFU), scanned focused ultrasound (SFUS), electroporation, nanoparticle heating, intraluminal heating and superficial heating. Locoregional heating techniques include phased array systems, capacitive systems and isolated perfusion. Whole body techniques focus on prevention of heat loss supplemented with energy deposition in the body, e.g., by infrared radiation. This review presents an overview of clinical hyperthermia and ablation devices used for local, locoregional, and whole body therapy. Proven and experimental clinical applications of thermal ablation and hyperthermia are listed. Methods for temperature measurement and the role of treatment planning to control treatments are discussed briefly, as well as future perspectives for heating technology for the treatment of tumors.

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“…In IRE ablation, the cell death is predominantly a result of electroporation and not the temperature increase. However, local heating of tissue does occur, especially in the immediate vicinity of the electrodes and when large numbers of pulses are used [12,14,15]. IRE ablation has been used in clinical trials for treatment of tumors in internal organs such as liver, pancreas, kidneys and prostate [11,[16][17][18][19].…”

Section: Ire Ablation Therapymentioning

confidence: 99%

“…IRE ablation is usually considered a non-thermal method. However, several experimental in vivo and in silico studies have shown a significant increase in temperature during treatment [ 14 , 15 , 20 , 29 , 30 ]. Thermal coagulation has been observed a few millimeters from the electrodes in animal experimental studies [ 29 – 31 ].…”

Section: Introductionmentioning

confidence: 99%

Investigation of safety for electrochemotherapy and irreversible electroporation ablation therapies in patients with cardiac pacemakers

et al. 2020

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Background The effectiveness of electrochemotherapy of tumors (ECT) and of irreversible electroporation ablation (IRE) depends on different mechanisms and delivery protocols. Both therapies exploit the phenomenon of electroporation of the cell membrane achieved by the exposure of the cells to a series of high-voltage electric pulses. Electroporation can be fine-tuned to be either reversible or irreversible, causing the cells to either survive the exposure (in ECT) or not (in IRE), respectively. For treatment of tissues located close to the heart (e.g., in the liver), the safety of electroporation-based therapies is ensured by synchronizing the electric pulses with the electrocardiogram. However, the use of ECT and IRE remains contraindicated for patients with implanted cardiac pacemakers if the treated tissues are located close to the heart or the pacemaker. In this study, two questions are addressed: can the electroporation pulses interfere with the pacemaker; and, can the metallic housing of the pacemaker modify the distribution of electric field in the tissue sufficiently to affect the effectiveness and safety of the therapy? Results The electroporation pulses induced significant changes in the pacemaker ventricular pacing pulse only for the electroporation pulses delivered during the pacing pulse itself. No residual effects were observed on the pacing pulses following the electroporation pulses for all tested experimental conditions. The results of numerical modeling indicate that the presence of metal-encased pacemaker in immediate vicinity of the treatment zone should not impair the intended effectiveness of ECT or IRE even when the casing is in direct contact with one of the active electrodes. Nevertheless, the contact between the casing and the active electrode should be avoided due to significant tissue heating at the site of the other active electrode for the IRE protocol and may cause the pulse generator to fail to deliver the pulses due to excessive current draw. Conclusions The observed effects of electroporation pulses delivered in close vicinity of the pacemaker or its electrodes do not indicate adverse consequences for either the function of the pacemaker or the treatment outcome. These findings should contribute to making electroporation-based treatments accessible also to patients with implanted cardiac pacemakers.

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Mathematical modeling of the thermal effects of irreversible electroporation for in vitro, in vivo, and clinical use: a systematic review

Cited by 47 publications

References 95 publications

A Prospective Phase II Study Evaluating Intraoperative Electrochemotherapy of Hepatocellular Carcinoma

A Prospective Phase II Study Evaluating Intraoperative Electrochemotherapy of Hepatocellular Carcinoma

Heating technology for malignant tumors: a review

Investigation of safety for electrochemotherapy and irreversible electroporation ablation therapies in patients with cardiac pacemakers

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