Electroporation Therapy Research Articles

Treatment Considerations to Overcome the Barriers Associated with Skin Cancer Targeting

: Skin cancer is a prevalent and diverse group of malignancies affecting the skin, with three primary types: basal cell carcinoma, squamous cell carcinoma, and melanoma. Each subtype varies in terms of its histological origin, behavior, and potential for metastasis. Despite advances in treatment, skin cancer poses challenges due to biological barriers that hinder drug delivery, multidrug resistance mechanisms that limit treatment effectiveness, and the complex interplay of genetic alterations driving tumorigenesis. Current treatment strategies encompass a spectrum of approaches, including chemotherapies, immunotherapies, gene therapies, and innovative techniques such as photothermal therapy, iontophoretic therapy, electroporation therapy, microneedle array therapy, and nanotechnology- based treatments. The latter involves liposomes, niosomes, carbon nanotubes, dendrimers, hydrogels, and gold nanoparticles, all tailored to enhance drug delivery and therapeutic efficacy. Additionally, herbal drug-based therapy harnesses the potential of natural compounds to target various aspects of skin cancer progression. This review provides an overview of skin cancer types, challenges in treatment, and an extensive exploration of current therapeutic strategies, highlighting the everevolving landscape of innovative approaches that promise to transform how skin cancer is managed.

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

Clinical efficacy and safety of irreversible electroporation combined with chemotherapy in stage IV pancreatic cancer treatment.

This study evaluates the clinical efficacy and safety of irreversible electroporation (IRE) therapy combined with chemotherapy in patients with stage IV pancreatic cancer. Between September 2021 and November 2023, we enrolled 38 patients with stage IV pancreatic cancer, with 20 receiving IRE plus chemotherapy and 18 receiving only chemotherapy. We recorded the general information of the patients and regularly followed up postoperative IRE-related adverse reactions. Progression-free survival (PFS) and overall survival (OS) were evaluated during follow-up. Median OS was longer in the IRE group than in the chemotherapy group. Median PFS was slightly extended with IRE compared to chemotherapy alone. The mean hospital stay for the IRE group was 5.90 ± 0.75 days. Four serious adverse events occurred after IRE. Postoperative pain scores were significantly lower than preoperative scores. IRE combined with chemotherapy showed clinical effectiveness in stage IV pancreatic cancer treatment, offering potential pain reduction benefits with fewer adverse effects and shorter hospital stays.

Recellularization via electroporation therapy of the duodenum combined with glucagon-like peptide 1 receptor agonist to replace insulin therapy in patients with type 2 diabetes: 12-month results of a first-in-human study

Studies have shown that hydrothermal duodenal mucosal ablation results in improved glycemic control. Recellularization via electroporation therapy (ReCET) is a novel endoscopic procedure that uses electroporation to induce cellular apoptosis and subsequent reepithelization. In this study, we aimed to eliminate exogenous insulin treatment in type 2 diabetes (T2D) patients through a single ReCET procedure combined with a glucagon-like peptide 1 receptor agonist. Feasibility, safety, and (dose) efficacy of ReCET were assessed. This first-in-human study included patients with T2D on basal insulin (age, 28-75 years; body mass index, 24-40 kg/m2; glycosylated hemoglobin,≤64mmol/mol; C-peptide,≥0.2 nmol/L). The electroporation dose was optimized during the study, starting with single 600 V and ending with double 750 V treatments. All patients underwent ReCET, after which insulin was discontinued and semaglutide (glucagon-like peptide-1 receptor agonist) was initiated. The primary endpoints were feasibility (procedure time [from catheter in to catheter out], technical success rate), safety, and efficacy (patients off insulin at 6 months; HbA1c,≤58mmol/mol). Fourteen patients underwent endoscopic ReCET. The median procedure time was 58 (interquartile range, 49-73) minutes. ReCET demonstrated a technical success rate of 100%. No device-related severe adverse events or severe hypoglycemic events were observed. At the 12-month follow-up, 12 (86%) patients remained off exogenous insulin therapy, with significant improvements in glycemic control and metabolic parameters. The 2 patients in whom insulin therapy was reintroduced both received ReCET at the lowest voltage (single 600 V). These results suggest that ReCET is feasible and safe. In combination with semaglutide, ReCET may be a promising therapeutic option to replace insulin therapy in selected T2D patients while improving glycemic control and metabolic health.

Endoscopic duodenal mucosa ablation techniques for diabetes and nonalcoholic fatty liver disease: A systematic review

Type 2 diabetes mellitus (T2DM) is increasing at an alarming rate, and only 50% of patients with T2DM achieve or maintain adequate glycemic control with pharmacological therapies. Metabolic surgery demonstrated superior efficacy compared to medical therapy but is unfeasible for most patients with T2DM. Duodenal mucosal resurfacing (DMR) by hydrothermal mucosal ablation, recellularization via electroporation therapy (ReCET), and photodynamic therapy are novel endoscopic procedures that use thermal, electrical, and photochemical energy, respectively, to ablate and reset dysfunctional duodenal mucosa. We assessed the data on the effects of these techniques on glycemic control and nonalcoholic fatty liver disease (NAFLD). We systematically searched independently and in duplicate English and non-English language publications through January 31st, 2024. Outcomes assessed were an improvement in different metabolic health parameters and the safety of duodenal mucosal ablation (DMA) procedures. Outcomes were presented descriptively. We selected 12 reports reporting results from 3 randomized and 6 uncontrolled trials (seven evaluating DMR, two evaluating ReCET, all with a low risk of bias) for a total of 317 patients enrolled. DMA reduced HbA1c, fasting plasma glucose, and liver fat. When combined with newer antidiabetic drugs, it allowed insulin discontinuation in up to 86% patients. No major safety signal emerged. All DMA techniques improve glucose homeostasis; DMR and ReCET appear to be safe in patients with T2DM. If confirmed by future randomized trials and by trials with histological endpoints in NAFLD, then DMA appears to be a promising alternative or complement option to medications for T2DM and NAFLD treatment. This study received no funding.

Endoscopic duodenal mucosa ablation: the future of diabetes treatment?

Duodenal mucosa ablation (DMA) is a novel approach to treat diabetes, consisting of endoscopic ablation of dysfunctional diabetic duodenal mucosa, which, following the healing response, is replaced by normally functioning mucosa. Two techniques, duodenal mucosal resurfacing (DMR) and recellularization via electroporation therapy (ReCET), recently showed promise in type 2 diabetes mellitus (T2DM) patients.

Abstract 490: Significant anti-proliferative effects of targeted magnetoelectric nanoparticles as potential theragnostic tools

Abstract Although current electroporation therapies have been demonstrated to be effective not only in ablating tumor tissue, but also in eliciting an anti-tumor immune response, they are limited in their application due to the strong risk factors associated with the high voltages required. Current methods of interacting with the body’s electrical currents are limited to traditional electrodes, which cause damage to surrounding tissue upon insertion, and require high voltages to create responses at the cellular level. Recent efforts at non-invasive interaction with the body’s electric fields have led to the fabrication of magnetoelectric nanoparticles (MENPs), a novel technology which has the ability to convert harmless magnetic fields into strong local electric fields, all while maintaining a diameter of ~70nm. These particles have been demonstrated to trigger neuronal firing under magnetic stimulation both in vitro and in vivo, and have been able to release chemotherapeutic agents on command in vitro and in vivo. This demonstrates the ability for MENPs to wirelessly generate electric fields within the body on demand with high temporal and spatial resolution. This suggests the potential for non-invasive electroporation therapy which could be triggered by external magnetic fields. Given the particles are themselves magnetic, this could show potential as a theragnostic tool as their magnetic properties suggest they may act simultaneously as an MRI contrast and an ablative therapy. To explore this possibility, we fabricated MENPs consisting of a magnetostrictive CoFe2O4 spinel core coupled with a piezoelectric BaTiO3 perovskite shell. These particles were then PEGylated to reduce agglomeration which is typical of magnetic nanoparticles. 50ul of a 1mg/ml PEG-MENP dispersion was deposited into a cell culture of SKOV-3 ovarian cancer cells. These cells were then stimulated by 120 10ms pulses of a 2kOe magnetic field over the course of 30 minutes. An cell-titre glo ATP assay was performed to indicate viability 24 hours after treatment. Treatment wells were compared to controls of no intervention, magnetic stimulation with no particles, and particles with no stimulation. The combination of particles and magnetic stimulation was the only group which showed significant decreases in viability, with a 32% reduction in viability. Particles on their own showed no effect on cell viability, neither did magnetic-only stimulation. This preliminary investigation into the use of MENPs as a non-invasive cancer treatment has shown some potential. The ability to wirelessly activate the particles provides an inherent targeting mechanism not found in traditional chemotherapeutics, while the nanometer diameter provides a non-invasive method to generate strong electric fields within the body. Citation Format: Max Shotbolt, Elric Zhang, Emily Zhu, Wael El-Rifai, John Bryant, Ping Liang, Sakhrat Khizroev. Significant anti-proliferative effects of targeted magnetoelectric nanoparticles as potential theragnostic tools [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 490.

Rapid estimation of electroporation-dependent tissue properties in canine lung tumors using a deep neural network

The efficiency of electroporation treatments depends on the application of a critical electric field over the targeted tissue volume. Both the electric field and temperature distribution strongly depend on the tissue-specific electrical properties, which both differ between patients in healthy and malignant tissues and change in an electric field-dependent manner from the electroporation process itself. Therefore, tissue property estimations are paramount for treatment planning with electroporation therapies. Ex vivo methods to find electrical tissue properties often misrepresent the targeted tissue, especially when translating results to tumors. A voltage ramp is an in situ method that applies a series of increasing electric potentials across treatment electrodes and measures the resulting current. Here, we develop a robust deep neural network, trained on finite element model simulations, to directly predict tissue properties from a measured voltage ramp. There was minimal test error (R2>0.94;p<0.0001) in three important electric tissue properties. Further, our model was validated to correctly predict the complete dynamic conductivity curve in a previously characterized ex vivo liver model (R2>0.93;p<0.0001) within 100 s from probe insertion, showing great utility for a clinical application. Lastly, we characterize the first reported electrical tissue properties of lung tumors from five canine patients (R2>0.99;p<0.0001). We believe this platform can be incorporated prior to treatment to quickly ascertain patient-specific tissue properties required for electroporation treatment planning models or real-time treatment prediction algorithms. Further, this method can be used over traditional ex vivo methods for in situ tissue characterization with clinically relevant geometries.

Treatment of Vulvovaginal Laxity by Electroporation: The Jett Plasma Medical for Her II Study.

Vaginal laxity is a widespread and undertreated medical condition associated especially with vaginal parity. To evaluate the efficacy and safety of electroporation therapy treatment of vulvovaginal laxity by the Jett Plasma for Her II device. The Jett Plasma for Her II Study is a multicentric, prospective, randomized, single-blinded, and controlled study. Women presenting with vaginal laxity were randomized to receive electroporation therapy delivered to the vaginal tissue (active-82 patients) vs. therapy with zero intensity (placebo-9 patients). A total of 91 subjects whose average age was 48.69 ± 10.89 were included. Due to the results of a one-way analysis of variance, it may be concluded that in the case of the vaginal laxity questionnaire (VLQ), there is a statistically significant difference between actively treated patients and the placebo group (F1,574 = 46.91; p < 0.001). In the case of the female sexual function index (FSFI), a one-way ANOVA test also showed a statistically significant difference between the actively treated patients and the placebo group (F1,278 = 7.97; p = 0.005). In the case of the incontinence impact questionnaire-7 (IIQ-7), a one-way ANOVA test showed a statistically significant difference between the actively treated patients and the placebo group (F1,384 = 15.51; p < 0.001). It confirms that improvement of vaginal laxity is conjoined with benefits in symptoms of urinary incontinence. Biopsy performed after the end of the treatment shows an increase in the vaginal mucosa thickness by an average of 100.04% in the active group. The treatment was well tolerated with no adverse events. No topical anesthetics were required. Treatments of vulvovaginal laxity by electroporation therapy achieved significant and sustainable 12-month effectiveness. Responses to the questionnaires also suggest subjective improvement in self-reported sexual function, incontinence, sexual satisfaction, and urogenital distress.

Tumor location on electroporation therapies by means of multi-electrode structures and machine learning

Electroporation is a phenomenon produced in the cell membrane when it is exposed to high pulsed electric fields that increases its permeability. Among other application fields, this phenomenon can be exploited in a clinical environment for tumor ablation therapies. In this context to achieve optimum results, it is convenient to focus the treatment on the tumor tissue to minimize side effects. In this work, a pre-treatment tumor location method is developed, with the purpose of being able to precisely target the therapy. This is done by taking different impedance measurements with a multi-output electroporation generator in conjunction with a multi-electrode structure. Data are processed by means of a vector of independent artificial neural networks, trained and tested with simulation data, and validated with phantom gels. This algorithm proved to provide suitable accuracy in spite of the low electrode count compared to the number of electrodes of a standard electrical impedance tomography device.

Piezoelectric Transformer-Based High-Voltage Pulse Generator Using Wide-Bandgap Semiconductors for Medical Electroporation Therapy.

In this paper, a new application of Piezoelectric Transformer (PT)-based power converters to generate high-voltage (HV) bipolar pulses for medical electroporation therapy is proposed. In particular, PT-based power conversion is investigated as an alternative to magnetics-based approaches of generating HV from a relatively low-voltage (LV)input source for application in electroporation therapy. The detailed PT-based system design and selection of wide bandgap semiconductor switches such as GaN FETs, high-voltage SiC diodes and SiC MOSFETs, as well as simulation results to demonstrate proof-of-concept using LTSpice are presented. Preliminary experimental results of the PT-based capacitor charger are shown, and work is ongoing to develop a complete hardware prototype of the proposed HV pulse generator.

835-P: First-in-Human Duodenal Endoscopic Recellularization via Electroporation Therapy for Type 2 Diabetes—An Interim Report

Background: We evaluated the feasibility and safety of endoscopic re-cellularization via electroporation therapy (ReCET) (Endogenex. Plymouth, MN) in restoring impaired duodenal signaling adversely impacting glucose control in type 2 diabetes (T2D). Method: We enrolled 30 adults with T2D: duration ≤10 years; HbA1c 7.5-11.0%; BMI of 24-40 kg/m2; C-peptide ≥333pmol/L; 1-4 non-insulin glucose-lowering medications (GLMs) at stable dose. Post-procedure GLMs were unchanged. Primary endpoint: Device or procedure-related serious adverse events (SAEs). Secondary endpoints: Changes in metabolic parameters at 24W. Results: The first 12 participants received single energy (Single Tx) then 18 received double energy application (Double Tx) with no device/procedure-related SAEs. Forty-five adverse events were reported in 23/30 participants (sore throat [17/30]; transient diarrhea [9/30]) and 80% were mild. HbA1c reduction at 24W was greater with double vs. single Tx (p&amp;lt;0.05). For double Tx vs. baseline: FPG was 7.5±1.7 mmol/L vs. 9.8±2.2 mmol/L (p&amp;lt;0.01), HOMA-IR 4.5±3.6 vs. 7.4±3.3 (p&amp;lt;0.01), Time-in-range 79.4±18.8 % vs. 59.0±24.2% (p&amp;lt;0.01), triglyceride 2.0±1.2mmol/L vs. 2.9±1.9mmol/L (P&amp;lt;0.05) and Δweight -5.1%±4.1% (p&amp;lt;0.01). Conclusions: Our data suggest that ReCET is safe and associated with clinically meaningful changes in metabolic control in T2D patients on GLMs. Disclosure C.Yuan: None. A.Sartoretto: Advisory Panel; Bariatek, Research Support; Endogenex, Erbe Electromedizin GMBH, Speaker's Bureau; Pfizer Inc., Stock/Shareholder; Apollo Endosurgery. B.Holt: None. G.Cameron: None. G.Marinos: None. F.E.Napier-flood: None. B.K.Abu dayyeh: Advisory Panel; Endogenex, Consultant; Apollo Endosurgery, Boston Scientific Corporation, Medtronic, Research Support; USGI, Endogastric Solutions. D.N.O'neal: None.

852-P: Duodenal Recellularization via Electroporation Therapy (ReCET) and GLP-1 RA to Replace Insulin in T2D Patients—EMINENT Study Six-Month Results

Introduction: Re-Cellularization via Electroporation Therapy (ReCET™), a novel endoscopic procedure using electroporation to elicit apoptosis of the duodenal mucosa. In this study we aimed to eliminate insulin in T2D patients using a single ReCET procedure combined with GLP-1RA. Safety, feasibility, and efficacy of ReCET using the Endogenex system were assessed. Methods: First in human study with 14 T2D patients on basal insulin (BMI 24-40 kg/m2; HbA1c ≤ 8.0%; C-peptide ≥ 0.2 nmol/l). All underwent ReCET after which semaglutide was titrated up to 1mg. Primary endpoints were: feasibility (technical success rate, procedure time [catheter in - out], % GLP-1RA tolerance); safety ((S)AE, hypoglycemic events); efficacy (off insulin at 6 mo; HbA1c ≤ 7.5%). Results: ReCET showed 100% technical success rate. Procedure time was 58 (IQR 49-79) min. Maximum semaglutide dosage was tolerated by 13 patients. No device related SAEs were observed. One non-severe hypoglycemic event occurred. At 6 mo, 12 patients were off insulin. A significant improvement in several glycemic and metabolic parameters was observed (Table 1); HbA1c decreased (7.2 to 6.6% p=0.003) and TIR increased (72 to 91% p=0.022). Conclusion: ReCET is safe and feasible. ReCET combined with semaglutide may effectively eliminate insulin in selected T2D patients, while improving glycemic control and metabolic health. Disclosure C.B.E.Busch: None. S.Meiring: None. A.C.G.Van baar: None. F.Holleman: None. M.Nieuwdorp: Advisory Panel; caelus health. J.J.Bergman: Consultant; Endogenex, Fractyl Health, Inc., Digma Medical, Research Support; Endogenex, Fractyl Health, Inc., Digma Medical.

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.

Tumor Ablation by Irreversible Electroporation Augments PD-1 Checkpoint Inhibitor Immunotherapy in Colon Adenocarcinoma

INTRODUCTION: Programmed Cell Death Protein 1 (PD-1) checkpoint inhibitors have recently been approved for microsatellite instability high (MSI-H) or mismatch repair deficient (dMMR) colorectal cancer (CRC). Response rates are promising in MSI-H-dMMR CRC but remain dismal for microsatellite-stable (MSS) or mismatch repair proficient (pMMR) CRC. >80% of CRCs are MSS-pMMR. Increasing tumor-infiltrating lymphocytes (TILs) may improve checkpoint inhibitor efficacy in CRC. New data suggest irreversible electroporation (IRE) therapy whereby electric pulses cause tumor necrosis and apoptosis; increase tumor-associated protein uptake by dendritic cells, subsequently boosting neoantigen presentation and TILs. We hypothesized that IRE combined with anti–PD-1 antibody, when compared with IRE or anti–PD-1 antibody alone, would increase survival, cause tumor regression by increasing TILs, and guard against secondary tumor challenge by increasing tumor antigen-specific CD8 T cells. METHODS: Using the MC38 cell line derived from murine colon adenocarcinoma, immunohistochemistry, and anti-CD8 antibodies, we evaluated antitumor immune responses in mice. RESULTS: IRE with anti–PD-1 antibody showed statistically significant survival, tumor regression, and increased TILs compared with IRE or anti–PD-1 antibody alone. Seventeen of 18 mice treated with IRE and anti–PD-1 antibody rejected a secondary tumor challenge. Conversely, IRE with anti–PD-1 antibody failed to protect against tumor rechallenge in mice that underwent CD8 T-cell depletion. Zero of 10 CD8 T-cell–depleted mice survived after secondary tumor challenge (Figure).FigureCONCLUSION: These data suggest IRE and anti–PD-1 antibody work in concert to bolster tumor-specific CD8 T-cell immune responses, serving as a pragmatic strategy for overcoming clinical challenges in checkpoint inhibitor immunotherapy for CRC.

1295TiP Investigation of calcium electroporation (CaEP) therapy in malignant cutaneous and subcutaneous tumours: A non-randomized phase II clinical trial of a novel palliative therapy

Skin metastases can occur from any tumour entity and often cause distress. Surgery or radiation are options, limitations arise from size or location and prior treatments. Electroporation (EP) creates transient pores in cell membranes by short high-voltage pulses allowing diffusion of molecules into the cells. EP with systemic chemotherapy is a standard therapy for cutaneous tumours, causing cell death of tumour cells and skin tissue recovering. Calcium-ions (Ca) are part of various signalling pathways. Intracellular Ca overload induces celldeath through ATP depletion as demonstrated in vitro and vivo, with healthy cells recovering. Intratumoural Ca-injection before EP-treament of affected areas is a new, promising palliative treatment reducing use of chemotherapy and interactions anti-tumour-therapies. The purpose of this trial was to investigate CaEP as therapy for cutaneous and subcutaneous tumours. Approval of German and Danish Drug Oversight Agencies and local Ethics Committees was obtained prior to the start of the trial. It was supported from the European Fund for Regional Development as part of the “Changing Cancer Care”-project. This multi-centre non-randomized single-arm phase II trial investigates the use of CaEP in cutaneous and subcutaneous tumours of any cancer histology. All included patients receive CaEP. Primary endpoint is clinical response rate at two months. Response rate is defined as number of responding to treated lesions, evaluated by reduction in size, documented with clinical photography. Secondary endpoints include: treatment response at time points month 1, 3, 4, 6 and 12; histological tissue changes in biopsies one year after treatment; response on MRI on a subset of patients; quality-of-life assessments before treatment, after 2 and 12 months using the EORTC QLQ-C15-PAL questionnaire; examining systemic immune response through routine scans; response due to tumour histology; response rate of all tumours treated; response rate per patient; current of applied pulses and qualitative interviews of one subset of patients. The study is conducted at three cancer centres in Germany and Denmark. EudraCT 2019-004314-34; NCT04225767. The authors.

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.

Electrochemotherapy in the head and neck area: an addition to the treatment armamentarium

Electrochemotherapy (ECT) is increasingly used in different settings in head and neck cancer patients when conventional treatment options are not available. Recent improvements of electroporation and ECT include new advanced electrode probes, the combination with intratumorally injected supraphysiological doses of calcium and an update of the standard operating procedures. ECT is a treatment modality that combines administration of a chemotherapeutic drug, for example, bleomycin, with electroporation therapy (EPT). EPT uses brief, high-intensity, pulsed electrical currents to enhance the uptake of cytotoxic drugs by producing a transient increase in cell wall permeability. ECT increases the effect of cytostatic drugs, is independent on histology of the lesion, enables treatment to previously treated areas, preserves healthy tissue, has no significant side effects (low-dose chemotherapy) and enables repeated treatments. ECT can be combined with other treatment modalities and is an addition to the current treatment options of head and neck cancer. ECT is not only able to palliate symptoms but can also provide complete responses and curation.

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.