Irreversible Electroporation Therapy Research Articles

Statistical property of absorbed energy in monolayer cell collectives with porous dielectric structure during irreversible electroporation therapy

Statistical property of absorbed energy in monolayer cell collectives with porous dielectric structure during irreversible electroporation therapy

Irreversible electroporation as a focal therapy for localized prostate cancer: A systematic review.

Irreversible electroporation (IRE) is a new and promising focal therapy for the treatment of localized prostate cancer. In this systematic review, we summarize the literature on IRE for prostate cancer published over the last decade. PubMed and EMBASE were searched with the end date of May 2023 to find relevant publications on prostate cancer ablation using IRE. Original studies with focal IRE as the primary curative treatment which reported on functional or oncological outcomes were included. The bibliography of relevant studies was also scanned to identify suitable articles. A total of 14 studies reporting on 899 patients treated with IRE for localized prostate cancer were included. Of all the studies reviewed, 77% reported on recurrence within the zone of ablation, and it ranged from 0% to 38.9% for in-field and 3.6% to 28% for out-of-field recurrence. Although, a standardised follow-up protocol was not followed, all the studies employed serial prostate-specific antigen monitoring, a multiparametric magnetic resonance imaging, and a biopsy (6-12 months post-treatment). Across all the studies, 58% reported that the urinary continence returned to the pretreatment levels and 25% reported a minor decrease in the continence from the baseline at 12-months of follow-up. Erections sufficient for intercourse varied from 44% to 75% at the baseline to 55% to 100% at 12-months of follow-up across all the studies. IRE, as a focal therapy, shows promising results with minimal complications and reasonably effective oncological control, but the data comparing it to the standard of care is still lacking. Future research should focus on randomized definitive comparisons between IRE, radical prostatectomy, and radiation therapy.

Abstract No. 158 Characterizing the Anti-Tumor Immune Response to IRE vs Thermal Ablation Therapy in an Immunocompetent Oncopig Model of Hepatocellular Carcinoma

Immunotherapies for cancer treatment are designed to mobilize a patient’s own immune system against their malignancy locally and systemically. Percutaneous ablation techniques have the potential to work in conjunction with modern immunotherapies by priming the patient’s own lymphocytes to attack previously untreated cancer cells. This phenomenon, known as the abscopal effect, has garnered interest because of the potential for locoregional therapies to induce local and systemic anti-tumor effects and shrinkage of distant tumors (Fionda, 2020). The goal of this study is to evaluate the anti-tumor immune response to irreversible electroporation (IRE) compared with microwave (MWA) and cryoablation in an immunocompetent Oncopig liver tumor model of hepatocellular carcinoma. In-situ liver tumors were induced in a transgenic immunocompetent porcine liver model (2-4 tumors in each liver) with Cre-recombinase induced TP53 and KRAS mutations (Oncopig). Oncopigs were separated into three treatment groups (n = 2), each undergoing either MWA, cryoablation or IRE treatment of a single liver tumor under US or CT guidance. Pre-, immediate post- and 1-week post ablation imaging was performed to evaluate treated and non-treated tumor growth. At each time point, venous blood was also drawn and assayed for critical cytokines related to anti- or pro-tumor immune response. Systemic cytokine levels were correlated to targeted and off-targeted tumor volumes after each time point. Liver tumors were induced at an 83.3% (20/24) success rate. Treated tumors decreased by an average 7% in volume across all treatment modalities on 1-week follow-up imaging. Off-target tumors increased by volume by 71.7% with IRE, 13.6% with MWA and 1.4% with cryoablation. On 1-week blood samples, IRE treated pigs demonstrated lower circulating concentrations of pro-inflammatory IL-2 cytokines when compared with cryoablation (10.9 vs 40.7 pg/mL; P = 0.051). There was no difference in IL-2 levels between MWA and cryoablation-treated pigs (40.7 vs 42.4 pg/mL; P = 0.97). The pro- and anti-tumor immune response is dependent on the type of ablation modality. IRE had the lowest levels of inflammatory marker IL-2 and the lowest degree of tumor control in off target tumors at the one-week time point. Modulating inflammatory pathways via these cytokines after IRE may potentially play a role in amplifying the abscopal effect in liver tumors.

Irreversible Electroporation-Assisted Resection for Locally Advanced Pancreas Cancer.

A significant number of patients with advanced pancreatic cancer are unable to undergo resection due to vascular involvement. Irreversible electroporation (IRE) has shown promise in improving survival. This study sought to assess a novel IRE application whereby IRE was performed pre-resection to alter tissue plasticity and assist tumor removal from underlying vasculature when surgical excision was otherwise precluded. After multidisciplinary evaluation appropriate patients were consented for IRE therapy. All IRE cases were tracked prospectively using an institutional review board-approved database that was retrospectively queried for patients undergoing IRE-assisted resection (IRE-AR) for pancreatic adenocarcinoma located in the head/uncinate process. Patients who underwent other IRE therapy or had disease location elsewhere were excluded. 5 patients met the study inclusion criteria with a mean tumor size of 3.2cm (range 2.4-4.1cm). Using IRE-AR median recurrence free survival was 10.6months, with 21.6month overall survival. The average comprehensive complication index score was 23.23. One patient had grade 3 [or higher] complications and there were no 90day mortalities. Employing a high-starting voltage for ablation along resection margins allows for resection when margins are anticipated to be positive. Patients with locally advanced pancreatic adenocarcinoma who underwent IRE-AR had promising outcomes. This study reports IRE-AR as a novel approach for resecting locally advanced pancreatic adenocarcinoma. A prospective trial of IRE-AR for inoperable pancreatic adenocarcinoma will provide additional data for the long-term application of this approach.

Expert recommendation on image-guided irreversible electroporation ablation treatment for renal carcinoma (2023 edition)

Irreversible electroporation ablation therapy can destroy tumor cells while retaining the integrity of the important surrounding physiological structures. It is suitable for patients with renal cell carcinoma who cannot be surgically resected or who do not want surgical resection, and can ensure the best postoperative renal function to the greatest extent, and has advantages that other thermal ablation treatments do not have. However, since irreversible electroporation therapy has high requirements for electrode needles and parameter settings, improper operation will directly affect the prognosis of patients. In order to improve the level of comprehensive treatment of renal cell cancer and standardize the operation technique of irreversible electroporation for renal cell carcinoma, the Committee of interventional minimally invasive therapy of the Chinese Medical Education Association took the lead in formulating the Expert Recommendation on image-guided irreversible electroporation ablation for Renal Cancer (2022 edition). The article introduces in detail the indications, contraindications, perioperative preparation, basic principles of operation, complications and related management and follow-up of irreversible electroporation for renal cell carcinoma, in order to provide reference for clinical practice.

Simultaneous Gemcitabine and Percutaneous CT-Guided Irreversible Electroporation for Locally Advanced Pancreatic Cancer.

Background Irreversible electroporation (IRE) is a new local ablation technique for pancreatic cancer. The aim of this study is to analyse the safety and effectiveness of simultaneous gemcitabine and percutaneous CT-guided IRE for locally advanced pancreatic cancer (LAPC). Materials and Methods From October 2016 to January 2018, 61 patients with LAPC who received simultaneous gemcitabine and IRE therapy (GEM-IRE group, n = 31) or IRE alone therapy (IRE group, n = 30). Routine intravenous gemcitabine chemotherapy was performed 2 weeks after IRE in both groups. Results Technical success rates were 90.0% (27/30) and 93.3% (28/30) in the GEM-IRE and IRE groups. Compared with the IRE group, the GEM-IRE group exhibited longer overall survival (OS), local tumor progression free survival (LTPFS), and distant disease free survival (DDFS) from IRE (OS, 17.1 vs. 14.2 months, p=0.031; LTPFS, 14.6 vs. 10.2 months, p=0.045; DDFS, 15.4 vs. 11.7 months, p=0.071). Multivariate Cox regression analysis results suggested that tumor volume ≤37 cm3 and simultaneous gemcitabine with IRE were significant independent prognostic factors of OS, LTPFS, and DDFS. Four major adverse reactions occurred; all of them were resolved after symptomatic treatment. Conclusions Simultaneous gemcitabine and percutaneous CT-guided IRE therapy model was effective and well-tolerated therapeutic strategy in LAPC patients.

Treatment of unresectable locally advanced pancreatic cancer with percutaneous irreversible electroporation (IRE) following initial systemic chemotherapy (LAP-PIE) trial: study protocol for a feasibility randomised controlled trial

BackgroundApproximately 30% of patients with pancreas cancer have unresectable locally advanced disease, which is currently treated with systemic chemotherapy. A new treatment option of irreversible electroporation (IRE) has been investigated...

Multimodal therapy with or without irreversible electroporation for unresectable locally advanced pancreatic adenocarcinoma: a systematic review and meta-analysis.

Irreversible electroporation (IRE) is used as a locoregional treatment modality for patients with locally advanced pancreatic cancer (LAPC), but is non-curative and is associated with postoperative morbidity and mortality. We performed a systematic review and meta-analysis comparing survival outcomes of multimodal therapy with or without IRE. Separate searches were performed for multimodal therapy+IRE and multimodal therapy alone given the lack of comparative literature using PubMed, SCOPUS, and Cochrane Library in 3/2021. We determined overall survival (OS) and progression-free survival (PFS) from diagnosis and time of IRE. Treatment-related morbidity and mortality was determined. Of 585 published articles, 48 met inclusion criteria for IRE (n=27) and without IRE (n=21) with data for 1420 (IRE) and 1348 (without IRE) patients. The 6/12/24 months OS with IRE was 99%/84%/28%. The 6/12/24 months OS without IRE was 99%/80%/12%. At 12 months from IRE, OS was 55% and PFS was 12%. The mean major complication and 90-day mortality rates for IRE were 17.95% and 2.65%. Multimodal therapy alone is associated with similar OS to multimodal therapy+IRE in patients with LAPC. Most patients progress and nearly half die within 1 year of the IRE procedure. Given the lack of quality prospective data, IRE should remain experimental and be used with caution in LAPC.

Local Release of TGF-β Inhibitor Modulates Tumor-Associated Neutrophils and Enhances Pancreatic Cancer Response to Combined Irreversible Electroporation and Immunotherapy.

Pancreatic cancer is a deadly disease with little response to standard therapies. Irreversible electroporation (IRE) has emerged as a novel ablative technique for the clinical treatment of pancreatic cancer. Combinations of IRE and immunotherapies, including anti‐programmed death 1 (αPD1) immune checkpoint blockade, have shown promising efficacy in both preclinical and clinical studies. However, tumor recurrence remains an obstacle that needs to be overcome. It herein is shown that IRE induces a substantial infiltration of neutrophils into pancreatic tumors. These neutrophils are then polarized into a protumor phenotype by immunosuppressive cues, in particular transforming growth factor β (TGF‐β). Using glutathione‐responsive degradable mesoporous silica nanoparticles loaded with SB525334, an inhibitor of TGF‐β1 receptor, it is demonstrated that local inhibition of TGF‐β within the tumor microenvironment promotes neutrophil polarization into an antitumor phenotype, enhances pancreatic cancer response to combined IRE and αPD1 therapy, and induces long‐term antitumor memory. The therapeutic efficacy is also attributed to tumor infiltration by CD8+ cytotoxic T cells, depletion of regulatory T cells, and maturation of antigen‐presenting dendritic cells. Thus, modulating neutrophil polarization with nanomedicine is a promising strategy for treating pancreatic cancer.

Evaluation of clinical and mpMRI findings of irreversible electroporation therapy for the treatment of localized prostate cancer: Preliminary results.

To evaluate early clinical and multiparametric prostate magnetic resonance imaging (mpMRI) results of irreversible electroporation (IRE) efficiency in treatment of localized prostate cancer. For the patients in whom IRE was performed for local ablation, mpMRI was used for the sixth month follow-up. These images were compared with the mpMRI images obtained before the procedure. We performed transperineal fusion biopsy to patients with diagnosis of localized prostate cancer. We treated the eligible ones with IRE. Six of them have completed their 6-month follow-up period. We compared preoperative prostate specific antigen (PSA), international prostate symptom score, international index of erectile function (IIEF), and mpMRI of these patients with those obtained at the sixth month of follow-up. Side effects experienced by the patients were evaluated as well. We had 10 patients who received IRE treatment. Six patients completed their sixth month-follow-up and came for control visits. At the end of 6 months, the mean decrease in PSA level was 73%. IIEF results were seen not to have changed significantly. On mpMRI, diffusion restriction was seen to have disappeared except for one patient, and Prostate Imaging Reporting Data System scores were decreased. We concluded that early clinical and mpMRI results for IRE in the focal ablative treatment of localized prostate cancer were gratifying. As an ambulatory procedure with a low incidence of side effects, we look forward to seeing the long-term results of IRE treatment.

Irreversible Electroporation (IRE) in Locally Advanced Pancreatic Cancer: A Review of Current Clinical Outcomes, Mechanism of Action and Opportunities for Synergistic Therapy.

Locally advanced pancreatic cancer (LAPC) accounts for 30% of patients with pancreatic cancer. Irreversible electroporation (IRE) is a novel cancer treatment that may improve survival and quality of life in LAPC. This narrative review will provide a perspective on the clinical experience of pancreas IRE therapy, explore the evidence for the mode of action, assess treatment complications, and propose strategies for augmenting IRE response. A systematic search was performed using PubMed regarding the clinical use and safety profile of IRE on pancreatic cancer, post-IRE sequential histological changes, associated immune response, and synergistic therapies. Animal data demonstrate that IRE induces both apoptosis and necrosis followed by fibrosis. Major complications may result from IRE; procedure related mortality is up to 2%, with an average morbidity as high as 36%. Nevertheless, prospective and retrospective studies suggest that IRE treatment may increase median overall survival of LAPC to as much as 30 months and provide preliminary data justifying the well-designed trials currently underway, comparing IRE to the standard of care treatment. The mechanism of action of IRE remains unknown, and there is a lack of data on treatment variables and efficiency in humans. There is emerging data suggesting that IRE can be augmented with synergistic therapies such as immunotherapy.

The role of irreversible electroporation in promoting M1 macrophage polarization via regulating the HMGB1-RAGE-MAPK axis in pancreatic cancer

ABSTRACT Irreversible electroporation (IRE) is an effective method for treating pancreatic ductal adenocarcinoma (PDAC). It remains unclear whether IRE can induce a specific immune response by stimulating macrophages. Here, the associated markers of macrophages were analyzed after exposure to tumor culture supernatant (TSN) of tumor cells treated with electroporation. Subcutaneous and orthotopic PDAC models were also used to evaluate the effect of macrophage polarization induced by IRE. Aside from its direct killing effect, IRE could induce the immunogenic cell death of tumor cells by increasing the synthesis and secretion of damage associated molecular patterns. Moreover, IRE could increase the release of HMGB1, which activates the MAPK-p38 pathway and leads to the increased expression of M1 markers in macrophages, through binding to the receptor of the advanced glycation end-product (RAGE) receptor. M1 polarization was inhibited by the inhibitors of HMGB1 release, the RAGE receptor, and the MAPK-p38 signaling pathway, but it was activated by rHMGB1 or the stimulator of MAPK-p38. In addition, the promotion of M1 macrophage polarization was enhanced by the positive-feedback release or expression of HMGB1 and RAGE through the MAPK-ERK pathway in macrophages. The promotion of M1 macrophage polarization induced by IRE provided a specific rationale for the combination of IRE and immune therapy in treating PDAC.

Irreversible electroporation plus allogenic V\u03b39V\u03b42 T cells enhances antitumor effect for locally advanced pancreatic cancer patients

Immunotherapy has limited efficacy against locally advanced pancreatic cancer (LAPC) due to the presence of an immunosuppressive microenvironment (ISM). Irreversible electroporation (IRE) can not only induce immunogenic cell death, but also alleviate immunosuppression. This study aimed to investigate the antitumor efficacy of IRE plus allogeneic γδ T cells in LAPC patients. A total of 62 patients who met the eligibility criteria were enrolled in this trial, then randomized into two groups (A: n = 30 and B: n = 32). All patients received IRE therapy and after receiving IRE, the group A patients received at least two cycles of γδ T-cell infusion as one course continuously. Group A patients had better survival than group B patients (median OS: 14.5 months vs. 11 months; median PFS: 11 months vs. 8.5 months). Moreover, the group A patients treated with multiple courses of γδ T-cell infusion had longer OS (17 months) than those who received a single course (13.5 months). IRE combined with allogeneic γδ T-cell infusion is a promising strategy to enhance the antitumor efficacy in LAPC patients, yielding extended survival benefits.ClinicalTrials.gov ID: NCT03180437.

Irreversible Electroporation For Hepatocellular Carcinoma: Longer-Term Outcomes At A Single Centre

Irreversible electroporation (IRE) is a non-thermal ablation technique for unresectable hepatocellular carcinoma (HCC) not amenable to standard thermal ablation. The aim of this study was to report our longer-term outcomes using this treatment modality. We identified all patients at our institution who underwent IRE for HCC between December 2008 and October 2019 as recommended after multi-disciplinary team review. Demographic, clinical, tumour response and survival data up until 1 March, 2020 were analysed. The primary outcome was local recurrence-free survival (LRFS) in patients who had a complete response (CR). Secondary outcomes included CR rates, procedure-related complications and the incidence of death or liver transplantation. A total of 23 patients (78% males, median age 65.2years) received IRE therapy to 33 HCC lesions during the study period with the median tumour size being 2.0cm (range 1.0-5.0cm). Twenty-nine (87.9%) lesions were successfully ablated after one (n = 26) or two (n = 3) procedures. The median follow-up time for these lesions was 20.4months. The median overall LRFS was 34.5 (95% CI 24.8 -) months with a 6- and 12-month LRFS of 87.9% (95% CI 75.8-100) and 83.6% (95% CI 70.2-99.7), respectively. Tumours < 2cm had a 12-month LRFS of 100% (95% CI 100-100). IRE appears to be an efficacious local ablative method for early stage HCC not amenable to standard ablative techniques, with very good CR rates and longer-term LRFS, particularly for smaller lesions. Further studies comparing this technique to more widely accepted ablative methods such as radiofrequency and microwave ablation are warranted.

Real-time prediction of patient immune cell modulation during irreversible electroporation therapy

Immunotherapies have demonstrated limited efficacy in pancreatic ductal adenocarcinoma (PDAC) patients despite their success in treating other tumor types. This limitation is largely due to the relatively immunosuppressive environment surrounding the tumor. A focal ablative technique called irreversible electroporation (IRE) has been shown to modulate this environment, enhancing the efficacy of immunotherapy. One enhancing factor related to improved prognosis is a decrease in regulatory T cells (Treg). This decrease has been previously unpredictable for clinicians using IRE, who currently have limited real-time metrics for determining the activation of the patient’s immune response. Here, we report that larger overall changes in output current are correlated with larger decreases in T cell populations 24 hours post-treatment. This result suggests that clinicians can make real-time decisions regarding optimal follow-up therapy based on the range of output current delivered during treatment. This capability could maximize the immunomodulating effect of IRE in synergy with follow-up immunotherapy. Additionally, these results suggest that feedback from a preliminary IRE treatment of the local tumor may help inform clinicians regarding the timing and choice of subsequent therapies, such as resection, immunotherapy, chemotherapy, or follow-up thermal or non-thermal ablation.

The interaction between irreversible electroporation therapy (IRE) and embolization material using a validated vegetal model: an experimental study.

Irreversible electroporation (IRE) is a nonthermal tumor ablation technique that induces cell apoptosis while preserving extracellular architecture. Surgical clips and embolic agents may lie adjacent to, or within, the target lesion. It is unknown to date if IRE causes degradation to the embolic agents or surgical clips that may have adverse effects to patients. We aimed to examine the effects of the IRE on the morphology of various embolic agents and the effects of these agents to the ablation field using a previously validated vegetal model. Metallic surgical clips and various metallic and nonmetallic embolic agents were inserted within the center of the tuber ablation field. Additionally, clips were inserted on the edge and outside the ablation field. One tuber was ablated as a control. Ablation settings were based on previous published experiments. Tubers were imaged with magnetic resonance imaging (MRI) 18-24 hours after ablation and the ablated field dimensions were measured. Nonmetallic embolic agents were examined microscopically by the pathologist. Nonmetallic agents did not affect the ablation pattern. Metallic implants, however, caused arcing of the ablation margins. There was no macroscopic or microscopic degradation to the agents after IRE. The ablation zone arced in the presence of surgical clips at the edge or outside the ablation margins; therefore, nearby critical structures may be susceptible to the effects of IRE. Furthermore, there was no physical degradation of the embolic agents or surgical clips, and this may have importance when considering IRE ablation of previously embolized lesions in vivo.

Quality of life assessment for patients undergoing irreversible electroporation (IRE) for treatment of locally advanced pancreatic cancer (LAPC)

BackgroundIRE is a non-thermal ablative modality that has been shown to be safe and efficacious in LAPC and liver tumors, but few studies have shown its effects on patients’ (QOL). The goal of this study is to evaluate quality-of-life (QOL) before and after irreversible electroporation (IRE) therapy for treatment of locally advanced pancreatic carcinoma (LAPC). MethodsBetween 11/2014 and 12/2016, patients scheduled for IRE therapy for LAPC were offered QOL questionnaires (EORTC QLQ-C30 V2.0) before surgery and 1,3 and 6-months after surgery. Descriptive statistics, one-way ANOVA and effect-size calculations were used in analysis of the 15 modules. ResultsEight-four prospective patients were enrolled with a median age of 59.08 years (range 27.38–75.72) all who completed 6 months QOL surveys. Global health status scale showed lower average score at 3 and 6 months(p = 0.001). Symptoms scales constipation and insomnia showed higher averages at 3 months (p = 0.007 and p = 0.003 respectively), while dyspnea had higher average at 6 months (p < 0.001). Finally, changes were noted with worse diarrhea symptoms scale at 1 and 3 months (p < 0.001). Otherwise all QOL side effects were normalized at 3 months after IRE. ConclusionsThe preponderance of symptoms at 3–6 months, symptom profile, and the use of additional therapy on majority of patients suggests other interrelated clinical factors influenced results (e.g. chemotherapy toxicity). This demonstrates that IRE therapy does not adversely affect QOL in the short term in patients with LAPC.

Cycled pulsing to mitigate thermal damage for multi-electrode irreversible electroporation therapy

Purpose: This study evaluates the effects of various pulsing paradigms, on the irreversible electroporation (IRE) lesion, induced electric current, and temperature changes using a perfused porcine liver model.Materials and methods: A 4-monopolar electrode array delivered IRE therapy varying the pulse length and inter-pulse delay to six porcine mechanically perfused livers. Pulse paradigms included six forms of cycled pulsing schemes and the conventional pulsing scheme. Finite element models provided further insight into the effects of cycled pulsing on the temperature and thermal injury distribution.Results: ‘Single pulse cycle with no interpulse delay’ deposited maximum average energy (2.34 ± 0.35 kJ) and produced the largest ratio of thermally damaged tissue area and IRE ablation area from all other pulse schemes (18.22% 8.11, p < .0001 all pairwise comparisons). These compared favorably to the conventional algorithm (2.09 ± 0.37 kJ, 3.49% 2.20, p < .0001, all comparisons). Though no statistical significance was found between groups, the ‘5 pulse cycle, 0 s delay’ pulse paradigm produced the largest average IRE ablation cross sectional area (11.81 ± 1.97 cm2), while conventional paradigm yielded an average of 8.90 ± 0.91 cm2. Finite element modeling indicated a ‘10 pulse cycle, 10 s delay’ generated the least thermal tissue damage and ‘1 pulse cycle, 0 s delay’ pulse cycle sequence the most (0.47 vs. 3.76 cm2), over a lengthier treatment time (16.5 vs. 6.67 minutes).Conclusions: Subdividing IRE pulses and adding delays throughout the treatment can reduce white tissue coagulation and electric current, while maintaining IRE treatment sizes.

Cancer Treatments of the Irreversible Electroporation

Irreversible electroporation (IRE) is a kind of non-thermal tumor treatment strategy. Based on this, Nanoknife emerged, which is approved by FDA in 2011. From then on, clinical application of nanosecond electrical pulsed have showed an explosive growth. At the cell level, the biophysical mechanism of nonthermal irreversible electroporation of electrical pulsed was studied. At the animal level, it has studied the safety of irreversible electroporation and preclinical animal experiments, also the clinical application of irreversible electroporation. We reviewed Animal studies of IRE and Clinical application of IRE. Also traditional medical imaging methods such as CT, magnetic resonance imaging (MRI) and ultra-sound imaging can be used in the IRE therapy. The evidences can prove the beneficial effects and safety of IRE in tumor treatment and verify the potential of IRE in clinical treatment to some extent. However, larger clinical trials are still needed to confirm these conclusions. Hopefully, as we go deeper into IRE, we get a more thorough understanding of it and the application will appear in various fields.

Cardiac impact of R-wave triggered irreversible electroporation therapy

Irreversible electroporation (IRE) is a novel tumor ablative therapy technique, using electric fields to induce apoptosis in target tissues. Whether these electric pulses of high field strength can cause cardiac damage and/or ablation-induced arrhythmias is unclear. The purpose of this study was to systematically evaluate the safety of electrocardiogram (ECG)-gated IRE with regard to cardiac side effects. In all patients, 12-lead ECG and signal-averaged ECG (SAECG) recordings were performed before and after IRE and 24-hour Holter recording on the day of the IRE procedure. Venous blood samples (N-terminal pro-brain-type natriuretic peptide [NT-proBNP], high-sensitive troponin I [hsTnI]) were obtained before and 4 and 16 hours after the procedure. Patients with abnormal findings were reevaluated after 3 months. In total, 26 patients with an oncologic indication for IRE (11 females, mean age 62.9 years) were prospectively enrolled. Nine patients (34.6%) showed an increase in hsTnI and 21 patients (80.8%) an increase in NT-proBNP after ablation. Fifteen patients (57%) developed arrhythmias related to the procedure. One patient, in whom hsTnI and NT-proBNP had increased, developed multiple, nonsustained ventricular tachycardia events. In another patient, atrial fibrillation was triggered twice in 2 separate procedures. Twelve patients had clinically benign arrhythmias. SAECG was negative in all patients. Subclinical myocardial injury and nonfatal cardiac arrhythmias can occur in the context of IRE treatment. Although no sustained cardiac injuries could be found at 3-month follow-up, we propose implementation of a cardiac safety algorithm consisting of cardiac biomarkers and ECG monitoring when IRE is conducted.