First Human Trial of High-Frequency Irreversible Electroporation Therapy for Prostate Cancer

Dong, Shoulong; Wang, Haifeng; Zhao, Yajun; Sun, Yinghao; Yao, Chenguo

doi:10.1177/1533033818789692

Cited by 67 publications

(42 citation statements)

References 37 publications

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“…observed no evidence of muscle or nerve excitation or cardiac arrhythmia during any pulse delivery when treating intracranial meningioma in dogs 35. In a first human study on high-frequency irreversible electroporation of prostate cancer, only a small amount of muscle relaxant was needed, and there were no visible muscle contractions during the pulse delivery process 36. Additionally, the histological analysis in in vivo porcine experiments indicates that with HF-IRE rapid and reproducible ablation in the liver can be achieved, while preserving gross vascular/biliary architecture 60.…”

Section: Discussionmentioning

confidence: 98%

“…Drawbacks of the application of 100 μs long monopolar, high-voltage electric pulses at repetition frequency 1 Hz are pain, muscle contractions26, 27, 28, the need to use muscle relaxants and general anesthesia29 and to synchronize pulses with the heart rhythm 30, 31. These problems can be alleviated for example by applying pulses at higher frequency26, by using special designs of electrodes32, 33, or, as it was recently demonstrated, by delivering bursts of short high-frequency bipolar pulses, i.e the so-called high-frequency irreversible electroporation (H-FIRE) pulses 33, 34, 35, 36, 37. Treatment with H-FIRE pulses, however, comes at the expense of delivering pulses of considerably higher amplitudes 38…”

Section: Introductionmentioning

confidence: 99%

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The use of high-frequency short bipolar pulses in cisplatin electrochemotherapy in vitro

Scuderi

Reberšek

Miklavčič

et al. 2019

Radiology and Oncology

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Background In electrochemotherapy (ECT), chemotherapeutics are first administered, followed by short 100 μs monopolar pulses. However, these pulses cause pain and muscle contractions. It is thus necessary to administer muscle relaxants, general anesthesia and synchronize pulses with the heart rhythm of the patient, which makes the treatment more complex. It was suggested in ablation with irreversible electroporation, that bursts of short high-frequency bipolar pulses could alleviate these problems. Therefore, we designed our study to verify if it is possible to use high-frequency bipolar pulses (HF-EP pulses) in electrochemotherapy. Materials and methods We performed in vitro experiments on mouse skin melanoma (B16-F1) cells by adding 1–330 μM cisplatin and delivering either (a) eight 100 μs long monopolar pulses, 0.4–1.2 kV/cm, 1 Hz (ECT pulses) or (b) eight bursts at 1 Hz, consisting of 50 bipolar pulses. One bipolar pulse consisted of a series of 1 μs long positive and 1 μs long negative pulse (0.5–5 kV/cm) with a 1 μs delay in-between. Results With both types of pulses, the combination of electric pulses and cisplatin was more efficient in killing cells than cisplatin or electric pulses only. However, we needed to apply a higher electric field in HF-EP (3 kV/cm) than in ECT (1.2 kV/cm) to obtain comparable cytotoxicity. Conclusions It is possible to use HF-EP in electrochemotherapy; however, at the expense of applying higher electric fields than in classical ECT. The results obtained, nevertheless, offer an evidence that HF-EP could be used in electrochemotherapy with potentially alleviated muscle contractions and pain.

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Section: Discussionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

The use of high-frequency short bipolar pulses in cisplatin electrochemotherapy in vitro

Scuderi

Reberšek

Miklavčič

et al. 2019

Radiology and Oncology

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“…The examination proved its structural integrity with no evidence of necrosis in the submucosa. Sexual function and continence were preserved by all patients [ 75 ].…”

Section: Irementioning

confidence: 99%

Electroporation-Based Treatments in Urology

Szlasa

Saczko

Kulbacka

2020

Cancers

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The observation that an application of a pulsed electric field (PEF) resulted in an increased permeability of the cell membrane has led to the discovery of the phenomenon called electroporation (EP). Depending on the parameters of the electric current and cell features, electroporation can be either reversible or irreversible. The irreversible electroporation (IRE) found its use in urology as a non-thermal ablative method of prostate and renal cancer. As its mechanism is based on the permeabilization of cell membrane phospholipids, IRE (as well as other treatments based on EP) provides selectivity sparing extracellular proteins and matrix. Reversible EP enables the transfer of genes, drugs, and small exogenous proteins. In clinical practice, reversible EP can locally increase the uptake of cytotoxic drugs such as cisplatin and bleomycin. This approach is known as electrochemotherapy (ECT). Few in vivo and in vitro trials of ECT have been performed on urological cancers. EP provides the possibility of transmission of genes across the cell membrane. As the protocols of gene electrotransfer (GET) over the last few years have improved, EP has become a well-known technique for non-viral cell transfection. GET involves DNA transfection directly to the cancer or the host skin and muscle tissue. Among urological cancers, the GET of several plasmids encoding prostate cancer antigens has been investigated in clinical trials. This review brings into discussion the underlying mechanism of EP and an overview of the latest progress and development perspectives of EP-based treatments in urology.

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“…A recent trial in China was the first to use high‐frequency bipolar IRE in men with prostate cancer . This aims to reduce muscle contractions that occur during monopolar IRE therapy.…”

Section: Clinical Trials Of Ire In Prostate Cancermentioning

confidence: 99%

Irreversible electroporation (IRE): a narrative review of the development of IRE from the laboratory to a prostate cancer treatment

et al. 2019

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Introduction Whilst whole‐gland radical treatment is highly effective for prostate cancer control, it has significant impact on quality of life and is unnecessary ‘over‐treatment’ in many men with screening‐detected prostate cancer. Improvements in prostate biopsy and imaging have led to increased interest in partial gland ablation to reduce treatment‐related morbidity. Several energies for focal ablation have been trialled. Irreversible electroporation (IRE) is a novel technology that ablates tissue by delivering direct current between electrodes. This narrative review documents the history of electroporation including its scientific basis, early data from pre‐clinical animal studies, and contemporary clinical outcomes from the use of IRE in prostate cancer. Methods A literature search using the Medical Literature Analysis and Retrieval System Online (MEDLINE), the Excerpta Medica dataBASE (EMBASE), PubMed and Google Scholar was undertaken to identify historical perspectives and current clinical data relating to IRE for prostate cancer. Results The history of electroporation and its implementation as a prostate cancer treatment was following the basic scientific principles, in vitro data, then animal studies, and now short‐ to medium‐term clinical cohorts in humans. The results of IRE on >283 patients have been published in several papers, with preserved rates of (pad‐free) continence in 91–100% of men and preserved erectile function in 79–100% of men. In‐field recurrence rates range from 0% to 33%. The current state of evidence for IRE for the treatment of primary and salvage prostate cancer is considered as Idea, Development, Exploration, Assessment, Long‐term follow‐up (IDEAL) stage 2B. Conclusions IRE is a new focal ablative technology for the treatment of localised prostate cancer in carefully selected men. Published cohorts report encouraging short‐term oncological and functional outcomes; however, longer‐term data are needed to validate this treatment before it can be recommended for widespread clinical use.

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First Human Trial of High-Frequency Irreversible Electroporation Therapy for Prostate Cancer

Cited by 67 publications

References 37 publications

The use of high-frequency short bipolar pulses in cisplatin electrochemotherapy in vitro

The use of high-frequency short bipolar pulses in cisplatin electrochemotherapy in vitro

Electroporation-Based Treatments in Urology

Irreversible electroporation (IRE): a narrative review of the development of IRE from the laboratory to a prostate cancer treatment

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