Non-thermal Ablation Technique Research Articles

Advances in Tumor Management: Harnessing the Potential of Histotripsy.

Tissue ablation techniques have long been used in clinical settings to treat various oncologic diseases. However, many of these techniques are invasive and can cause substantial adverse effects. Histotripsy is a noninvasive, nonionizing, nonthermal tissue ablation technique that has the potential to replace surgical interventions in various clinical settings. Histotripsy works by delivering high-intensity focused ultrasound waves to target tissue. These waves create cavitation bubbles within tissues that rapidly expand and collapse, thereby mechanically fractionating the tissue into acellular debris that is subsequently absorbed by the body's immune system. Preclinical and clinical studies have demonstrated the efficacy of histotripsy in treating a range of diseases, including liver, pancreatic, renal, and prostate tumors. Safety outcomes of histotripsy have been generally favorable, with minimal adverse effects reported. However, further studies are needed to optimize the technique and understand its long-term effects. This review aims to discuss the importance of histotripsy as a noninvasive tissue ablation technique, the preclinical and clinical literature on histotripsy and its safety, and the potential applications of histotripsy in clinical practice. Keywords: Tumor Microenvironment, Ultrasound-High-Intensity Focused (HIFU), Ablation Techniques, Abdomen/GI, Genital/Reproductive, Nonthermal Tissue Ablation, Histotripsy, Clinical Trials, Preclinical Applications, Focused Ultrasound © RSNA, 2024.

Effects of bipolar irreversible electroporation with different pulse durations in a prostate cancer mouse model.

Irreversible electroporation (IRE) is a non-thermal ablation technique for local tumor treatment known to be influenced by pulse duration and voltage settings, affecting its efficacy. This study aims to investigate the effects of bipolar IRE with different pulse durations in a prostate cancer mouse model. The therapeutic effectiveness was assessed with in vitro cell experiments, in vivo tumor volume changes with magnetic resonance imaging, and gross and histological analysis in a mouse model. The tumor volume continuously decreased over time in all IRE-treated groups. The tumor volume changes, necroptosis (%), necrosis (%), the degree of TUNEL-positive cell expression, and ROS1-positive cell (%) in the long pulse duration-treated groups (300μs) were significantly increased compared to the short pulse duration-treated groups (100μs) (all p < 0.001). The bipolar IRE with a relatively long pulse duration at the same voltage significantly increased IRE-induced cell death in a prostate cancer mouse model.

Abstract 6640: Zap! Irreversible electroporation in pancreatic cancer cells induces proinflammatory cell death and improves progression free survival

Abstract Pancreatic cancer is the third leading cause of cancer-related death due to its late diagnosis, few treatment options, and extremely low survival rates due to its immunosuppressive microenvironment. Irreversible electroporation (IRE),is a tumor non-thermal ablation technique that applies high-voltage electrical pulses to permeabilize the cell membrane that is irreversible and leads to necrotic cell death. IRE has had strong success in clinical trials nevertheless, little is known about the effect of IRE beyond the initiation of cell death in the tumor tissue. We hypothesize that IRE can not only induce cell death by membrane disruption to facilitate a proinflammatory microenvironment but also causes death via cell cycle arrest. We utilized in-vitro, and immunocompetent in-vivo murine models to investigate changes to pancreatic cancer and the tumor microenvironment. Our findings show that treating the cells with an increasing voltage of IRE induces more cell death. We observed cell cycle arrest in the G1 phase which may have been caused by DNA damage. There was upregulation of DNA damage repair machinery in the treated samples. Our histopathology data suggests increased necrosis on the tumor treated with IRE, as also PCR array analysis showed more proinflammatory cell death caused by pyroptosis. Finally, we demonstrated a reduction in the tumor size and a better survival rate aftertreatment. Our data suggest that Irreversible electroporation has a promising future in inducing proinflammatory type of cell death in the tumor and benefits increased patient survival. More investigation is needed to define ideal parameters for the electrical pulses and device development for tumor ablation in larger animals like porcine models. Citation Format: Manali Powar, Khan Mohammad Imran, Irving C. Allen, Rafael V. Davalos, Zaid Salamah, Kenneth Aycock, Rebecca M. Brock, Sheryl Coutermarsh-Ott, Katie Orr. Zap! Irreversible electroporation in pancreatic cancer cells induces proinflammatory cell death and improves progression free survival [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 6640.

Pulsed field versus cryoballoon ablation for atrial fibrillation: areal-world observational study on procedural outcomes and efficacy.

Atrial fibrillation often necessitates catheter ablation when antiarrhythmic drug therapy fails. Single-shot technologies using thermal energy, such as cryoballoon ablation, are commonly used, but pulsed field ablation (PFA), an innovative non-thermal ablation technique, is apotential alternative. This retrospective observational study aimed to compare the safety and efficacy of cryoballoon ablation and PFA in patients undergoing their first pulmonary vein isolation (PVI) procedure for atrial fibrillation treatment. We utilised real-world data from patients who underwent PVI using cryoballoon ablation or PFA. The primary outcome encompassed procedural complications, including phrenic nerve palsy, cardiac tamponade, thromboembolic complications, bleeding complications and mortality. Secondary outcomes were procedural characteristics including procedure duration, length of hospital admission, and re-do ablation rates within 6months. Atotal of 1714 procedures were analysed: 1241 in the cryoballoon group and 473 in the PFA group. Gender distribution (p = 0.03) and estimated glomerular filtration rate (p = 0.01) differed significantly. With regard to the primary outcome, the cryoballoon group demonstrated ahigher incidence of phrenic nerve palsy compared with the PFA group (15 vs0; p = 0.02). The procedure duration was shorter in the PFA group, even after adjusting for baseline characteristics (95.0 vs 74.0 min; p < 0.001). After adjustment for baseline characteristics, admission duration differed between the groups as well (p = 0.04). The study results supported the safety and efficacy of PFA over cryoballoon ablation for PVI, highlighting advantages such as shorter procedure duration and absence of phrenic nerve palsy.

Sequential Irreversible Electroporation for Locally Advanced Pancreatic Cancer.

Pancreatic cancer is a lethal disease, with locally advanced pancreatic cancer (LAPC) having a dismal prognosis. For patients with LAPC, gemcitabine-based regimens, with or without radiation, have long been the standard of care. Irreversible electroporation (IRE), a non-thermal ablative technique, may potentially prolong the survival of patients with LAPC. In this article, the authors present a case of LAPC of the uncinate process (biopsy proven pancreatic neuroendocrine carcinoma) with duodenal invasion. The patient had a combination of chemotherapy and radiation therapy but was found to have stable disease. He then underwent intra-operative IRE with cholecystectomy, Roux-en-Y gastrojejunostomy and hepaticojejunostomy. He subsequently underwent percutaneous IRE 13 months post open IRE. The patient also completed peptide receptor radionuclide therapy and has been started on Lanreotide. Following combination therapy, the pancreatic tumor showed significant reduction in size, with patient survival at 53 months post-diagnosis at the time of writing.

New Developments in Image-Guided Percutaneous Irreversible Electroporation of Solid Tumors.

This review will describe the various applications, benefits, risks, and approaches of conventional irreversible electroporation (IRE), as well as highlight the new technological developments of this procedure along with their clinical applications. Minimally invasive image-guided percutaneous IRE ablation has emerged as a newer, non-thermal ablation technique for tumors in the solid organs, particularly within the liver, pancreas, kidney, and prostate. IRE allows for ablation near heat-sensitive structures, including major blood vessels and nerves, and is not susceptible to the heat sink effect. However, it is limited by certain requirements, such as the need for precise parallel placement of at least two probes with a maximum inter-probe distance of 2.5 cm to reduce the risk of arching phenomenon, the requirement for general anesthesia with muscle relaxant, and the need for cardiac synchronization. However, new technological advancements in the ablation system and image guidance tools have been introduced to improve the efficiency and efficacy of IRE. IRE is a safe and effective treatment option for solid tumor ablation within the liver, pancreas, kidney, and prostate. Compared with other ablation techniques, IRE has several advantages, such as the absence of heat sink effect and minimal injury to blood vessels and bile ducts while activating the immune system. Novel techniques such as H-FIRE, needle placement systems, and robotics have enhanced the accuracy and performance in placement of IRE probes. IRE can be especially beneficial when combined with chemotherapy, immunomodulation, and immunotherapy.

Enhanced Electrical Injury Using Triangular Interdigitated Electrodes for Catheter-Based Irreversible Electroporation

Irreversible electroporation (IRE) is a promising nonthermal ablation technique that uses high-voltage electrical pulses to create permanent pores in the cell membrane of target tissue. Recently, endoscopic IRE with catheter-based electrodes has attracted significant attention as a potential alternative tool for gastrointestinal tumors, but it has been challenged owing to the limited electric field distribution in an in-plane electrode configuration, in which rectangular interdigitated electrodes (IDEs) are commonly used. Herein, we report an enhanced electrical injury in tissue using triangular IDEs that cause strong electric fields to be induced at the tip of the electrode fingers. A set of 10 pulses with a duration of 100 μs and a frequency of 1 Hz were delivered to the tissue, and a finite element method was used to calculate the electrical injury in the gastrointestinal model. The probability of cell death by electrical injury at the triangular IDEs increases by approximately 10 times compared to that of conventional rectangular IDEs at the same electrode distance. These results could potentially pave the way toward designing electrodes in catheter-based IRE devices.

Irreversible electroporation: Beyond the limits of tumor ablation

Irreversible Electroporation (IRE) is a non-thermal tumor ablation technique. High-voltage electrical pulses are applied between pairs of electrodes inserted around and/or inside a tumor. The generated electric current induces the creation of nanopores in the cell membrane, triggering apoptosis. As a result, IRE can be safely used in areas near delicate vascular structures where other thermal ablation methods are contraindicated.Currently, IRE has demonstrated to be a successful ablation technique for pancreatic, renal, and liver tumors and is widely used as a focal therapeutic option for prostate cancer.The need for specific anesthetic management and accurate parallel placement of multiple electrodes entails a high level of complexity and great expertise from the interventional team is required. Nevertheless, IRE is a very promising technique with a remarkable systemic immunological capability and may impact on distant metastases (abscopal effect).

Electroporación irreversible: ampliando las fronteras de la ablación

Irreversible electroporation (IRE) is a non-thermal tumor ablation technique. High-voltage electrical pulses are applied between pairs of electrodes inserted around and/or inside a tumor. The generated electric current induces the creation of nanopores in the cell membrane, triggering apoptosis. As a result, IRE can be safely used in areas near delicate vascular structures where other thermal ablation methods are contraindicated.Currently, IRE has demonstrated to be a successful ablation technique for pancreatic, renal, and liver tumors and is widely used as a focal therapeutic option for prostate cancer.The need for specific anesthetic management and accurate parallel placement of multiple electrodes entails a high level of complexity and great expertise from the interventional team is required. Nevertheless, IRE is a very promising technique with a remarkable systemic immunological capability and may impact on distant metastases (abscopal effect).

Histotripsy Ablation of Spontaneously Occurring Canine Bone Tumors In Vivo.

Osteosarcoma (OS) is a devastating primary bone tumor in dogs and humans with limited non-surgical treatment options. As the first completely non-invasive and non-thermal ablation technique, histotripsy has the potential to significantly improve the standard of care for patients with primary bone tumors. Standard of care treatment for primary appendicular OS involves surgical resection via either limb amputation or limb-salvage surgery for suitable candidates. Biological similarities between canine and human OS make the dog an informative comparative oncology research model to advance treatment options for primary OS. Evaluating histotripsy for ablating spontaneous canine primary OS will build a foundation upon which histotripsy can be translated clinically into a standard of care therapy for canine and human OS. Five dogs with suspected spontaneous OS were treated with a 500 kHz histotripsy system guided by real-time ultrasound image guidance. Spherical ablation volumes within each tumor (1.25-3 cm in diameter) were treated with single cycle histotripsy pulses applied at a pulse repetition frequency of 500 Hz and a dose of 500 pulses/point. Tumor ablation was successfully identified grossly and histologically within the targeted treatment regions of all subjects. Histotripsy treatments were well-tolerated amongst all patients with no significant clinical adverse effects. Conclusion & Significance: Histotripsy safely and effectively ablated the targeted treatment volumes in all subjects, demonstrating its potential to serve as a non-invasive treatment modality for primary bone tumors.

Enhanced Therapeutic Potential of Irreversible Electroporation under Combination with Gold-Doped Mesoporous Silica Nanoparticles against EMT-6 Breast Cancer Cells

Irreversible electroporation (IRE) is a non-thermal tumor ablation technique that delivers short pulses of strong electric fields to cancer tissues and induces cell death through the destruction of cell membranes. Here, we synthesized gold-doped mesoporous silica nanoparticles (Au-MSNs) via incipient wetness impregnation and evaluated the therapeutic potentials of combination therapy with IRE. The fabricated Au-MSNs had around 80-100 nm of particle size and were successfully end-doped with Au nanoparticles. Combination treatment of IRE (800 V/cm) and Au-MSNs (100 μg/mL) increased cell membrane permeability by 25-fold compared with single IRE treatment. Cellular reactive oxygen species (ROS) and lipid peroxidation of EMT-6 cells were significantly increased by 14- and 265-fold, respectively, under combination treatment of IRE (800 V/cm) and Au-MSNs (100 µg/mL). Cytotoxic cell death increased by 28% under a combination treatment of IRE (800 V/cm) and Au-MSNs (100 ug/mL) over single IRE. Our studies suggest that the combination treatment of IRE with Au-MSNs can enhance the therapeutic efficacy of IRE for breast cancer.

Irreversible electroporation: present and future in the treatment of hepatocellular carcinoma

Currently, among the possible treatments for hepatocellular carcinoma there is group of minimally invasive ablation techniques with wide clinical ac-ceptance due to their greater efficacy and safety in comparison to traditional therapies, low cost, and no need of being admitted to hospital (outpatient treatment program). Irreversible electroporation is a non-thermal abla-tion technique in which electrical fields are used to create nanopores in the cell membrane that induce tumor cell death. Irreversible electroporation has shown promising results in numerous clinical trials; however, its control on long-term tumor growth and recurrence is inferior in comparison to that of radiofrequency. Combining irreversible electroporation with immunological agents may increase its efficacy in the treatment of focal lesions and metastases. In this work, we present an update on IRE including procedure, mechanism of action, application as a treatment for HCC, and the improvements that have been made in the past few years.

A Multi-centre, Single Arm, Non-randomized, Prospective European Trial to Evaluate the Safety and Efficacy of the HistoSonics System in the Treatment of Primary and Metastatic Liver Cancers (#HOPE4LIVER)

PurposeImage-guided thermal ablation are established treatment options for non-surgical patients with primary and metastatic liver cancers. However, there are limitations with nonuniformity of cancer tissue destruction, heat sink effect and the risk of thermal ablative injury. The current non-thermal ablative techniques have high risk of local recurrence and are not widely adopted. Histotripsy is a treatment technology that destroys targeted tissue under ultrasound visualization via mechanical destruction through the precise application of acoustic cavitation and can offer the potential of non-invasive, non-thermal and non-ionizing radiation cancer treatment. The aim of this multi-centre non-randomized phase I/II trial is to assess the initial safety and efficacy of the prototype investigational ‘System’ in the treatment of primary and metastatic liver cancers.Methods/DesignAll non-surgical patients with primary/metastatic liver cancers having had previous liver directed therapy, radiation therapy or image-guided ablation may be offered image-guided Histotripsy as per trial protocol. The co-primary endpoints are technical success and procedural safety. Technical success is determined, at ≤ 36 h post procedure, by evaluating the histotripsy treatment size and coverage. The procedural safety is defined by procedure related major complications, defined as Common Terminology Criteria for Adverse Events (CTCAE version 5) grade 3 or higher toxicities, up to 30 days post procedure. This phase I/II trial has intended to recruit up to 45 patients to show safety and efficacy of image-guided histotripsy in liver cancers.Trail RegistrationClinicaltrials.gov identifier-NCT04573881; NIHR CRN CPMS-ID 47572.

Irreversible electroporation for stage III locally advanced pancreatic cancer: Single-center experience

Introduction: Irreversible Electroporation (IRE) is a non-thermal ablation technique with promising results for treating locally advanced pancreatic cancer (LAPC). This study was conducted to evaluate safety and efficacy of IRE in the management of LAPC. Methods: This was e retrospective single center study of ten patients with radiographic and biopsy proven stage III pancreatic head or body cancer that received open IRE with intraoperative ultrasound imaging. Perioperative complications at 90 days, tumor volume measurements, local recurrence and survival were recorded. Results: 20 patients, with a median age of 62, underwent IRE for locally advanced pancreatic head cancer (n=11) and body cancer (n=9). All patients were treated successfully with an open IRE approach. Nine patients experiences grade II (Clavien-Dindo) procedure related complications. There were no grade 3 to 5 complications. Median follow up was 30 monts. Tumor volume decrease at 6 months imaging follow up was found in 70% of patients (n=14). Local disease progression was observed in two patients, and there was evidence of metastatic disease in 7 patients. 8 patients died with a mean of 15, 2 months and 12 patients are still alive with a mean of 17,3 months. Median overall survival was 16,5 months. Conclusion: Our initial experience with IRE showed encouraging results regarding safety, feasibility and efficacy in patients with locally advanced pancreatic head or body cancer. Further investigation is needed.

Safety and feasibility of irreversible electroporation for the pancreatic head in a porcine model

BACKGROUNDIrreversible electroporation (IRE) is a local non-thermal ablative technique which has been suggested as a potential cancer therapy. However, the specific anatomic characteristics of the pancreatic head make it challenging to perform any local ablation in this region. Therefore, the safety and feasibility of IRE in the pancreatic head region should be further explored.AIMTo evaluate the safety of IRE in pancreatic head region including its effects on pancreatic ducts, vessels, and adjacent gastrointestinal organs.METHODSEight landrace miniature pigs underwent IRE of pancreatic head tissue successfully, with a total of 16 lesions created. Laboratory testing including white blood cell (WBC) count and serum amylase before IRE with follow-up laboratory analysis and pathological examination at 1, 7, 14, and 28 d postablation were performed. RESULTSAll pigs tolerated the ablation procedure without serious perioperative complications. Transiently elevated WBC count and amylase were observed at 24 h post-IRE, suggesting an acute pancreatic tissue damage which was confirmed by pathological observations. Vascular endothelial cells and pancreatic duct epithelial cells in ablation zone were also positive in terminal deoxynucleotidyl transferase dUTP nick end labeling staining. There was extensive duodenum mucosa damage with local hemorrhage 24 h after ablation, while regeneration of new villous structures were observed at 7 and 28 d post-IRE. Masson’s trichromatic staining showed that the extracellular matrix was still intact in vessels and pancreatic ducts, and even in the duodenum.CONCLUSIONIRE ablation to the pancreatic head may be safe and feasible without long-term damage to the surrounding vital structures. However, risks of stress injuries in acute phase should be taken into consideration to prevent severe perioperative complications.

Irreversible electroporation versus radiofrequency ablation for malignant hepatic tumor: A prospective single-center double-arm trial

ObjectiveIrreversible electroporation (IRE) is a nonthermal ablation technique for the treatment of malignant liver tumors. IRE has demonstrated efficacy and safety in the treatment of malignant liver tumors and its unique advantages in the treatment of nearby vascular lesions. This study aimed to compare the efficacy, safety, and intermediate-term outcomes of IRE and radiofrequency (RF) therapy in malignant liver tumors. MethodsTwenty-four patients with primary or secondary liver malignancies were included in this prospective, double-arm clinical trial. Patients were randomly divided into the IRE and RF groups. The primary outcome was the efficacy (local ablation control evaluation at 90 days). The secondary outcomes were safety (procedure-related complications at ​≤ ​90 days) and intermediate-term survival (at 24 months). ResultsThe ablation assessment at 90 days after surgery with mRECIST for IRE versus RF were 70%, 20%, 0%, and 10% versus 92.9%, 7.1%, 0%, and 0% (CR, PR, SD, and PD, respectively). The complication rates of IRE versus RF with Clavien-Dindo classification were 16.7%, 25%, 0%, 8.3%, and 8.3% versus 8.3%, 50%, 0%, 0%, and 0% (Grade I, II, III, IV, and V, respectively). The average overall survival (OS) was 17.55 months in the IRE group (95% CI 15.13-22.37) and 18.75 months in the RF group (95% CI 12.48-22.61). There was no statistical difference between the IRE and RF groups in terms of efficacy (p ​= ​0.48), safety(p ​= ​0.887), or 24-month OS (p ​= ​0.959). ConclusionsIRE ablation revealed similar efficacy and safety in a short-term follow-up, and similar OS in mid-term survival as RF ablation in treating malignant hepatic tumors.

Exploration of Novel Pathways Underlying Irreversible Electroporation Induced Anti-Tumor Immunity in Pancreatic Cancer.

Advancements in medical sciences and technologies have significantly improved the survival of many cancers; however, pancreatic cancer remains a deadly diagnosis. This malignancy is often diagnosed late in the disease when metastases have already occurred. Additionally, the location of the pancreas near vital organs limits surgical candidacy, the tumor’s immunosuppressive environment limits immunotherapy success, and it is highly resistant to radiation and chemotherapy. Hence, clinicians and patients alike need a treatment paradigm that reduces primary tumor burden, activates systemic anti-tumor immunity, and reverses the local immunosuppressive microenvironment to eventually clear distant metastases. Irreversible electroporation (IRE), a novel non-thermal tumor ablation technique, applies high‐voltage ultra-short pulses to permeabilize targeted cell membranes and induce cell death. Progression with IRE technology and an array of research studies have shown that beyond tumor debulking, IRE can induce anti-tumor immune responses possibly through tumor neo-antigen release. However, the success of IRE treatment (i.e. full ablation and tumor recurrence) is variable. We believe that IRE treatment induces IFNγ expression, which then modulates immune checkpoint molecules and thus leads to tumor recurrence. This indicates a co-therapeutic use of IRE and immune checkpoint inhibitors as a promising treatment for pancreatic cancer patients. Here, we review the well-defined and speculated pathways involved in the immunostimulatory effects of IRE treatment for pancreatic cancer, as well as the regulatory pathways that may negate these anti-tumor responses. By defining these underlying mechanisms, future studies may identify improvements to systemic immune system engagement following local tumor ablation with IRE and beyond.

Irreversible electroporation in renal tumours: A systematic review of safety and early oncological outcomes.

We review the safety and early oncological outcomes of irreversible electroporation (IRE), a novel non-thermal ablation technique, in small renal masses (SRMs). Following PROSPERO registration (CRD42020197943), a systematic search of MEDLINE, EMBASE and SCOPUS databases according to PRISMA guidelines was performed. Critical appraisal of the included studies was performed using the Newcastle-Ottawa Scale. Of 224 articles screened, 10 met the inclusion criteria. In total, 83 patients were identified. Except for one cohort study (n = 41), the remaining studies were case series of n < 10. Follow up was <12 months in 7/10 articles (range 3–34 months). About 10/10 articles reported safety outcomes. There were no 30-day mortalities. The most frequently reported adverse events were transient haematuria (11/83) and asymptomatic perirenal haematomas (7/83). About 62/63 patients with reported length of stay were discharged within 24 h. No significant long-term changes in renal function were reported. About 7/10 articles reported oncological outcomes. Only one article assessed histopathological outcomes, whilst the remaining studies used cross-sectional imaging modalities to assess efficacy, recurrence or disease progression. About 4/7 patients with histopathology outcomes, showed complete response (CR). About 43/55 patients with radiological outcomes showed CR. No mortalities were reported due to SRMs. These initial findings support IRE as safe and feasible in managing SRMs. However, results from larger studies with longer follow-up are needed to evaluate oncological outcomes and compare these with other ablation methods.

Irreversible Electroporation: An Emerging Immunomodulatory Therapy on Solid Tumors.

Irreversible electroporation (IRE), a novel non-thermal ablation technique, is utilized to ablate unresectable solid tumors and demonstrates favorable safety and efficacy in the clinic. IRE applies electric pulses to alter the cell transmembrane voltage and causes nanometer-sized membrane defects or pores in the cells, which leads to loss of cell homeostasis and ultimately results in cell death. The major drawbacks of IRE are incomplete ablation and susceptibility to recurrence, which limit its clinical application. Recent studies have shown that IRE promotes the massive release of intracellular concealed tumor antigens that become an “in-situ tumor vaccine,” inducing a potential antitumor immune response to kill residual tumor cells after ablation and inhibiting local recurrence and distant metastasis. Therefore, IRE can be regarded as a potential immunomodulatory therapy, and combined with immunotherapy, it can exhibit synergistic treatment effects on malignant tumors, which provides broad application prospects for tumor treatment. This work reviewed the current status of the clinical efficacy of IRE in tumor treatment, summarized the characteristics of local and systemic immune responses induced by IRE in tumor-bearing organisms, and analyzed the specific mechanisms of the IRE-induced immune response. Moreover, we reviewed the current research progress of IRE combined with immunotherapy in the treatment of solid tumors. Based on the findings, we present deficiencies of current preclinical studies of animal models and analyze possible reasons and solutions. We also propose possible demands for clinical research. This review aimed to provide theoretical and practical guidance for the combination of IRE with immunotherapy in the treatment of malignant tumors.

Early Differentiation of Irreversible Electroporation Ablation Regions With Radiomics Features of Conventional MRI

Irreversible electroporation (IRE) is a promising non-thermal ablation technique for the treatment of patients with hepatocellular carcinoma. Early differentiation of the IRE zone from surrounding reversibly electroporated (RE) penumbra is vital for the evaluation of treatment response. In this study, an advanced statistical learning framework was developed by evaluating standard MRI data to differentiate IRE ablation zones, and to correlate with histological tumor biomarkers. Fourteen rabbits with VX2 liver tumors were scanned following IRE ablation and forty-six features were extracted from T1w and T2w MRI. Following identification of key imaging variables through two-step feature analysis, multivariable classification and regression models were generated for differentiation of IRE ablation zones, and correlation with histological markers reflecting viable tumor cells, microvessel density, and apoptosis rate. The performance of the multivariable models was assessed by measuring accuracy, receiver operating characteristics curve analysis, and Spearman correlation coefficients. The classifiers integrating four radiomics features of T1w, T2w, and T1w+T2w MRI data distinguished IRE from RE zones with an accuracy of 97%, 80%, and 97%, respectively. Also, pixelwise classification models of T1w, T2w, and T1w+T2w MRI labeled each voxel with an accuracy of 82.8%, 66.5%, and 82.9%, respectively. Regression models obtained a strong correlation with behavior of viable tumor cells (0.62 ≤ r2 ≤ 0.85, p < 0.01), apoptosis (0.40 ≤ r2 ≤ 0.82, p < 0.01), and microvessel density (0.48 ≤ r2 ≤ 0.58, p < 0.01). MRI radiomics features provide descriptive power for early differentiation of IRE and RE zones while observing strong correlations among multivariable MRI regression models and histological tumor biomarkers.