Efficacy Of Irreversible Electroporation Research Articles

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.

Irreversible Electroporation in Pancreatic Cancer-An Evolving Experimental and Clinical Method.

Pancreatic cancer has no symptoms until the disease has advanced and is aggressive cancer with early metastasis. Up to now, the only curative treatment is surgical resection, which is possible in the early stages of the disease. Irreversible electroporation treatment offers new hope for patients with unresectable tumors. Irreversible electroporation (IRE) is a type of ablation therapy that has been explored as a potential treatment for pancreatic cancer. Ablation therapies involve the use of energy to destroy or damage cancer cells. IRE involves using high-voltage, low-energy electrical pulses to create resealing in the cell membrane, causing the cell to die. This review summarizes experiential and clinical findings in terms of the IRE applications. As was described, IRE can be a non-pharmacological approach (electroporation) or combined with anticancer drugs or standard treatment methods. The efficacy of irreversible electroporation (IRE) in eliminating pancreatic cancer cells has been demonstrated through both in vitro and in vivo studies, and it has been shown to induce an immune response. Nevertheless, further investigation is required to assess its effectiveness in human subjects and to comprehensively understand IRE's potential as a treatment option for pancreatic cancer.

Safety and Efficacy of Irreversible Electroporation in Locally Advanced Pancreatic Cancer: An Evaluation from a Surgeon's Perspective.

Irreversible electroporation (IRE) has emerged as a promising treatment for patients with locally advanced pancreatic cancer (LAPC). Therefore, in this study, we evaluate the safety and efficacy of IRE against LAPC, as well as exploring its impact on anti-tumor immunity. A retrospective analysis was conducted in consecutive patients at a single institution. Eligible patients were assigned to IRE, palliative surgery (PS), or vascular resection (VR) groups, according to their respective treatments. The IRE group consisted of LAPC patients. One-to-one propensity score matching was performed, in order to compare the incidence of complications and median overall survival (mOS). Serum and intratumoral cytokines, as well as intratumoral immune cells, were analyzed in order to identify changes in immunity after IRE. A total of 210 patients were included. After matching, the rate of major complications (Clavien-Dindo III-V), intra-abdominal hemorrhage, and re-intervention in the IRE group were similar to those in the VR group (p > 0.05). The mOS of the IRE group (13.0 months) was shorter than that of the VR group (15.0 months), but longer than that of the PS group (8.0 months) (p < 0.05). Patients in the IRE group had elevated serum levels of immunogenic cytokines, including IL-2, IL-6, and TNF-α, which were related to anti-tumor immunity. The survival advantage in IRE-treated patients was attributed to tumor ablation and immune modulation effects. Overall, IRE can be considered a feasible treatment for patients with LAPC.

Novel irreversible electroporation ablation (Nano-knife) versus radiofrequency ablation for the treatment of solid liver tumors: a comparative, randomized, multicenter clinical study.

Irreversible electroporation (IRE) is a soft tissue ablation technique that uses short electrical fields which induce the death of target cells. To evaluate the safety and efficacy of an IRE-based device compared to regular radiofrequency ablation (RFA) of solid liver tumors, in this multicenter, randomized, parallel-arm, non-inferiority study, 152 patients with malignant liver tumors were randomized into IRE (n = 78) and RFA (n = 74) groups. The primary endpoint was the success rate of tumor ablation; the secondary endpoints included the tumor ablation time, complications, tumor recurrence rates and treatment-related adverse events (TRAE). The success rate of tumor ablation using IRE was 94.9% and was non-inferior to the RFA group (96.0%) (P = 0.761). For the secondary endpoints, the average ablation time was 34.29 ± 30.38 min for the IRE group, which was significantly longer than for the RFA group (19.91 ± 16.08 min) (P < 0.001). The incidences of postoperative complications after 1 week (P = 1.000), 1 month (P = 0.610) and 3 months (P = 0.490) were not significantly different between the 2 groups. The recurrence rates of liver tumor at 1, 3 and 6 months after ablation were 0 (0.0%), 10 (13.9%) and 10 (13.3%) in the IRE group and 2.9%, 7.3% and 19.7% in the RFA control group (all P > 0.05), respectively. For safety assessments, 51 patients experienced 191 AEs (65.4%) in the IRE group, which was not different from the RFA group (73.0%, 54/184) (P = 0.646). In 7 IRE patients, 8 TRAEs (7.9%) occurred, the most common being edema of the limbs (mild grade) and fever (severe grade), while no TRAEs occurred in the RFA group. This study proved that the excellent safety and efficacy of IRE was non-inferior to the regular radiofrequency device in ablation performance for the treatment of solid liver tumors. Clinical trial registration: Chinese Clinical Trial Registry: ChiCTR1800017516

Irreversible Electroporation Balloon Therapy for Palliative Treatment of Obstructive Urethral Transitional Cell Carcinoma in Dogs.

Progression of transitional cell carcinoma (TCC) in dogs often leads to urinary obstruction. This observational pilot study aimed to evaluate the safety and efficacy of irreversible electroporation (IRE) balloon therapy for the palliative treatment of TCC with partial urethral obstruction. Three client-owned dogs diagnosed with TCC causing partial urethral obstruction were enrolled. After ultrasonographic and cystoscopic examination, IRE pulse protocols were delivered through a balloon catheter device inflated within the urethral lumen. After the procedure, the patients were kept overnight for monitoring and a recheck was planned 28 days later. No complication was observed during the procedure and postprocedural monitoring. After 28 days, one dog had a complete normalization of the urine stream, one dog had stable stranguria, and one dog was presented with a urethral obstruction secondary to progression of the TCC. On recheck ultrasound, one dog had a 38% diminution of the urethral mass diameter whereas the other two dogs had a mass stable in size. IRE balloon therapy seems to be a feasible and apparently safe minimally invasive novel therapy for the palliative treatment of TCC causing urethral obstruction. Further studies are needed to better characterize the safety, efficacy, and outcome of this therapy.

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.

Is irreversible electroporation (IRE) an effective and safe ablation method for local advanced pancreatic cancer: A meta-analysis

To evaluate the safety and efficacy of irreversible electroporation (IRE) for treating local advanced pancreatic carcinoma. Relevant literature published from January 1, 2010, to July 1, 2021, was retrieved from PubMed and EMBASE databases. The following keywords were applied: " IRE, "Irreversible electrophoresis, "pancreatic cancer, "ablation, "and " ablation therapy. "The primary outcomes was IRE related significant complications rate. 19 studies were included, a total of 984 patients had undergone IRE. The probability of IRE-related major (Grade 3–5) complications rate was 17% (95% CI: 10–28%). 2 deaths related to IRE procedure were reported. The median overall survival time since IRE ranged from 6.1 to 27 months. Patients treated with IRE combined with surgical resection or standard chemotherapy showed a longer overall survival. IRE can benefit the survival of patients with locally advanced pancreatic cancer, but related adverse events should be treated with caution.

Comparison between high-frequency irreversible electroporation and irreversible electroporation ablation of small swine liver: follow-up of DCE-MRI and pathological observations.

Background:High-frequency irreversible electroporation (H-FIRE) is a novel, next-generation nanoknife technology with the advantage of relieving irreversible electroporation (IRE)-induced muscle contractions. However, the difference between IRE and H-FIRE with distinct ablation parameters was not clearly defined. This study aimed to compare the efficacy of the two treatments in vivo.Methods:Ten Bama miniature swine were divided into two group: five in the 1-day group and five in the 7-day group. The efficacy of IRE and H-FIRE ablation was compared by volume transfer constant (Krans), rate constant (Kep) and extravascular extracellular volume fraction (Ve) value of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), size of the ablation zone, and histologic analysis. Each animal underwent the IRE and H-FIRE. Temperatures of the electrodes were measured during ablation. DCE-MRI images were obtained 1, 4, and 7 days after ablation in the 7-day group. All animals in the two groups were euthanized 1 day or 7 days after ablation, and subsequently, IRE and H-FIRE treated liver tissues were collected for histological examination. Student's t test or Mann-Whitney U test was applied for comparing any two groups. One-way analysis of variance (ANOVA) test and Welch's ANOVA test followed by Holm-Sidak's multiple comparisons test, one-way ANOVA with repeated measures followed by Bonferroni test, or Kruskal-Wallis H test followed by Dunn's multiple comparison test was used for multiple group comparisons and post hoc analyses. Pearson correlation coefficient test was conducted to analyze the relationship between two variables.Results:Higher Ve was seen in IRE zone than in H-FIRE zone (0.14 ± 0.02 vs. 0.08 ± 0.05, t = 2.408, P = 0.043) on day 4, but no significant difference was seen in Ktrans or Kep between IRE and H-FIRE zones at all time points (all P > 0.05). For IRE zone, the greatest Ktrans was seen on day 7, which was significantly higher than that on day 1 (P = 0.033). The ablation zone size of H-FIRE was significantly larger than IRE 1 day (4.74 ± 0.88 cm2vs. 3.20 ± 0.77 cm2, t = 3.241, P = 0.009) and 4 days (2.22 ± 0.83 cm2vs. 1.30 ± 0.50 cm2, t = 2.343, P = 0.041) after treatment. Apoptotic index (0.05 ± 0.02 vs. 0.73 ± 0.06 vs. 0.68 ± 0.07, F = 241.300, P < 0.001) and heat shock protein 70 (HSP70) (0.03 ± 0.01 vs. 0.46 ± 0.09 vs. and 0.42 ± 0.07, F = 64.490, P < 0.001) were significantly different between the untreated, IRE and H-FIRE zones, but no significant difference was seen in apoptotic index or HSP70 between IRE and H-FIRE zone (both P > 0.05). Electrode temperature variations were not significantly different between the two zones (18.00 ± 3.77°C vs. 16.20 ± 7.45°C, t = 0.682, P = 0.504). The Ktrans value (r = 0.940, P = 0.017) and the Kep value (r = 0.895, P = 0.040) of the H-FIRE zone were positively correlated with the number of hepatocytes in the ablation zone.Conclusions:H-FIRE showed a comparable ablation effect to IRE. DCE-MRI has the potential to monitor the changes of H-FIRE ablation zone.

Irreversible electroporation versus radiofrequency ablation for hepatocellular carcinoma: a single centre propensity-matched comparison

Background and aims Irreversible electroporation (IRE) is a relatively new non-thermal ablative method for unresectable hepatocellular carcinoma (HCC). We aimed to compare the longer-term efficacy of IRE to the standard thermal technique of radiofrequency ablation (RFA) in HCC. Methods All patients who underwent IRE or RFA for HCC in our centre were identified and demographic and clinical data were analysed up until 1st March, 2020. Local recurrence-free survival (LRFS) was compared between groups after propensity score matching for age, gender, Child–Pugh grade, BCLC stage, lesion size and alpha-fetoprotein (AFP) level. Results A total of 190 HCC ablations (31 IRE and 159 RFA) were identified. After propensity score matching, we compared 25 IRE procedures (76% males, median age 62.4 years, median tumour size 20 mm) to 96 RFA procedures (84.4% males, median age 64.3 years, median tumour size 18.5 mm). LRFS did not differ between groups, with a 1-, 2- and 5-year LRFS of 80.4% (95% CI 55.8–92.2), 69.1% (95% CI 43.3–84.9) and 44.9% (95% CI 18.9–68.1%), respectively for IRE and 84.8% (95% CI 75.2–90.9), 71.3% (95% CI 58.3–81.0) and 52.1% (95% CI 35.4–66.4%), respectively for RFA (p = .63). There were no major procedure-related complications or deaths in either group. Conclusions Whilst IRE remains a relatively novel therapy for HCC cases where standard thermal ablation is contraindicated, the LRFS in our centre is comparable to that of RFA. IRE should therefore be considered as a treatment option in such cases when available before stage-migration to non-curative therapies such as transarterial chemoembolization (TACE).

Clinical impact of irreversible electroporation ablation for unresectable hilar cholangiocarcinoma

Irreversible electroporation (IRE) is a non-thermal ablation modality that has been shown to be safe and effective in its application to tumors that are close to risky areas. This study aims to assess the safety and efficacy of IRE for unresectable hilar cholangiocarcinoma. Nine patients from two medical centers in Asia received IRE treatment between June 2015 and July 2017. Before IRE treatment, percutaneous biliary decompressions had been performed on eight patients, and internal stenting had been performed on one patient. All patients tolerated the procedure well without high-grade complications. The ablated tumors had constant size without contrast enhancement for more than three months in eight patients and the level of CA19-9 decreased significantly in all patients. The percutaneous biliary drainage tube was removed from two patients with recanalization of the bile duct. The internal stent in one patient was removed without further stenting. The median overall survival period was 26 months, and the progression-free survival was 18 months. Bile ducts remained narrow in the majority (2/3) of the treated patients. Nevertheless, IRE ablation of unresectable hilar cholangiocarcinoma involving vital structures is a safe and feasible primary treatment for local tumor control and is effective in prolonging survival.

Recent progress in pulsed electric field ablation for liver cancer.

The number of liver cancer patients is likely to continue to increase in the coming decades due to the aging of the population and changing risk factors. Traditional treatments cannot meet the needs of all patients. New treatment methods evolved from pulsed electric field ablation are expected to lead to breakthroughs in the treatment of liver cancer. This paper reviews the safety and efficacy of irreversible electroporation in clinical studies, the methods to detect and evaluate its ablation effect, the improvements in equipment and its antitumor effect, and animal and clinical trials on electrochemotherapy. We also summarize studies on the most novel nanosecond pulsed electric field ablation techniques in vitro and in vivo. These research results are certain to promote the progress of pulsed electric field in the treatment of liver cancer.

Ultrasound-guided Percutaneous Irreversible Electroporation for Treatment of Locally Recurrent Pancreatic Cancer After Surgical Resection.

Irreversible electroporation (IRE) has recently been used as an experimental treatment for cancers including locally advanced pancreatic cancer. There is very limited data on IRE in pancreatic cancer that is locally recurrent after surgical resection. The aim of this study was to evaluate the safety and efficacy of IRE in this setting. Ten patients with locally recurrent pancreatic cancer without distant metastases after surgical resection were included and treated with ultrasound-guided percutaneous IRE. Two patients had severe complications, of whom one died. Median disease-free survival was 3.3 months and overall median survival after IRE and resection was 16.5 and 42.7 months, respectively. Two patients are alive 42.1 and 23.9 months after the IRE without signs of local recurrence. Percutaneous IRE in locally recurrent pancreatic cancer following curative resection is feasible, but should be regarded as a high-risk procedure that, at present, cannot be recommended outside of clinical trials. Further research is needed to select patients who might benefit from this treatment.

Irreversible electroporation and adjuvant chemoradiotherapy for locally advanced pancreatic carcinoma

The safety and efficacy of irreversible electroporation (IRE) for locally advanced pancreatic carcinoma (LAPC) are well established. However, whether adjuvant chemoradiotherapy after IRE increases, the survival rate remains unknown. Therefore, this study evaluated the effect of chemoradiotherapy combined with IRE in patients with LAPC. We retrospectively analyzed 42 patients with LAPC between July 2015 and December 2016 at PLA General Hospital treated with IRE or IRE combined with radiation and/or chemotherapy. These patients were divided into the IRE group and the combined-therapy group. All patients underwent computed tomography (CT), magnetic resonance imaging, and positron-emission tomography-CT and no signs of metastases were found. The prognosis of these patients was observed. The times after operation and after diagnosis in the combined-therapy group (304.20 ± 118.54) and (334.40 ± 114.07) days, respectively, were better those than in the IRE group (214.36 ± 95.68) and (244.68 ± 110.61) days, respectively. Moreover, patients in the combined-therapy group had a significantly better survival rate than the IRE group (80 vs. 45.45%, P < 0.05). IRE combined with radiotherapy or chemotherapy was superior to IRE alone for the treatment of LAPC, as it prolonged the survival time and improved the survival rate, making it worthy of wide dissemination and clinical application.

Irreversible electroporation versus radiotherapy after induction chemotherapy on survival in patients with locally advanced pancreatic cancer: a propensity score analysis

BackgroundLocally advanced pancreatic cancer (LAPC) represents more than one third of pancreatic cancers and owns poor survival after the standard chemotherapy. Irreversible electroporation (IRE) is a novel method and has been recently used in LAPC. The aim of this study was to compare the efficacy of IRE and radiotherapy after induction chemotherapy for patients with LAPC.MethodsFrom August 2015 to August 2017, a total of 76 patients with biopsy proven LAPC and who had received IRE or radiotherapy after chemotherapy were included. Thirty-two pairs of patients were selected through propensity score matching (PSM) analysis and the efficacy of two treatments was compared.ResultsBefore PSM analysis, after induction chemotherapy, patients with LAPC benefited more in terms of overall survival (OS) and progression free survival (PFS) from IRE, compared with radiotherapy (2-year OS rates, 53.5% vs 26.9%, p = 0.039; 2-year PFS rates, 28.4% vs 13.3%, p = 0.045). After PSM analysis, the survival benefits of OS and PFS of patients after induction chemotherapy followed by IRE were more obvious than those of patients treated with radiotherapy (2-year OS rates, 53.5% vs 20.7%, p = 0.011; 2-year PFS rates, 28.4% vs 5.6%, p = 0.004). Multivariate Cox regression analysis indicated that IRE after induction chemotherapy was identified as a significant favourable factor for both OS and PFS in both the whole and matched cohort.ConclusionsInduction chemotherapy followed by IRE is superior to induction chemotherapy followed by radiotherapy for treating LAPC. A randomized clinical trial comparing the efficacy of IRE and radiotherapy after the induction chemotherapy is therefore considerable.

Normal and fibrotic liver parenchyma respond differently to irreversible electroporation

BackgroundThe safety and efficacy of irreversible electroporation (IRE) in treating hepatic, biliary, and pancreatic malignancies are active areas of clinical investigation. In addition, recent studies have shown that IRE may enable regenerative surgery and in vivo tissue engineering. To use IRE effectively in these clinical applications, it is important to understand how different tissue microenvironments impact the response to IRE. In this study, we characterize the electrical and histological properties of non-fibrotic and fibrotic liver parenchyma before and after IRE treatment. MethodsElectrical resistivity and histology of fibrotic liver from C57BL/6 mice fed a 0.1% 3,5-diethylcarbonyl-1,4-dihydrocollidine (DDC) diet were compared to those of non-fibrotic liver from matched control mice before and after IRE treatment. ResultsAt baseline, the electrical resistivity of fibrotic liver was lower than that of non-fibrotic liver. Post-IRE, resistivity of non-fibrotic liver declined and then recovered back to baseline with time, correlating with hepatocyte repopulation of the ablated parenchyma without deposition of fibrotic scar. In contrast, resistivity of fibrotic liver remained depressed after IRE treatment, correlating with persistent inflammation. ConclusionNon-fibrotic and fibrotic liver respond to IRE differently. The underlying tissue microenvironment is an important modifying factor to consider when designing IRE protocols for tissue ablation.

Irreversible electroporation combined with chemotherapy for unresectable pancreatic carcinoma: a prospective cohort study.

ObjectiveWe aimed to determine the safety and efficacy of irreversible electroporation (IRE) combined with chemotherapy for unresectable pancreatic carcinoma (stage III/IV).MethodsWe prospectively enrolled 54 patients (30 men; median age 61.0 years; range 41–73 years) undergoing IRE with or without chemotherapy for pancreatic cancer between July 2015 and August 2016. Kaplan–Meier estimates were used to analyze progression-free survival (PFS) and overall survival (OS). Safety was assessed based on the occurrence of adverse events.ResultsAll patients successfully underwent IRE. Major IRE-related complications were observed in four patients (7.4%). Gastrointestinal hemorrhage only developed in cases undergoing IRE via the open method, and was successfully managed with interventional embolization and/or vascular ligation. Any minor complications in the cases were alleviated within 14 days after symptomatic treatment. Overall, the performance status score decreased from 1.06 to 0.89 at 3 months after IRE (P<0.05). Among those with stage III disease, after a median follow-up of 18.8 months (range 9.6–28.7 months), the median OS from diagnosis was 16.2 and 20.3 months in the IRE and IRE + Chemo groups, respectively. Among those with stage IV disease, after a median follow-up of 13.3 months (range 3.7–23.1 months), the median OS from diagnosis was 11.6 and 13.56 months in the IRE and IRE + Chemo groups, respectively. The OS was significantly poorer in the IRE group than in the IRE + Chemo group (log-rank test, P=0.0398).ConclusionPatients with pancreatic carcinoma could benefit from IRE, which improved the OS in certain patients who had also undergone chemotherapy. Although some severe complications were noted, IRE was generally well tolerated.

Irreversible Electroporation for Unresectable Hepatocellular Carcinoma: Initial Experience.

To evaluate the efficacy and safety of irreversible electroporation (IRE) in the treatment of unresectable hepatocellular carcinoma (HCC). A retrospective study was conducted from September 2014 to June 2017. A total of 21 HCCs in 21 patients with cirrhosis were treated with IRE. There were eight subcapsular or exophytic, ten perivascular and three peribiliary tumors. The median tumor size was 26mm (range 14-40mm). The technical success of the procedure was recorded. Median follow-up, median time to local recurrence, median local tumor progression-free survival (PFS) and complications were recorded. Technical success was achieved in all the patients. The median follow-up was 10months (range 2-30months). The median time to local recurrence and local tumor PFS were 4months (range 3-4months) and 7months (range 3-30months), respectively. The tumor-related factor that was significantly associated with local PFS was the size. Maximum tumor diameter < 25mm was significantly associated with local tumor PFS (p = 0.045). Other parameters including tumor location, segmental portal vein thrombosis, baseline alpha-fetoprotein level and underlying etiology did not affect local tumor PFS. Complications were noted in nine patients and were classified as grades 1 and 2. No procedure-related mortality was encountered. IRE is an effective treatment for ablation of small HCCs. Larger prospective studies with strict selection criteria will establish the safety and efficacy of IRE in the treatment of unresectable HCC in patients who cannot undergo thermal ablation.

Safety and Efficacy of Irreversible Electroporation for Gastric Tissue Ablation with Magnetic Anchoring Electrodes in a Rabbit Model

Safety and Efficacy of Irreversible Electroporation for Gastric Tissue Ablation with Magnetic Anchoring Electrodes in a Rabbit Model

Safety and efficacy of irreversible electroporation in the treatment of obstructive jaundice in advanced hilar cholangiocarcinoma

BackgroundIrreversible electroporation (IRE) has successfully been used for palliation of pancreatic and liver cancers due to its ability to ablate tumors without destroying nearby vital structures. To date, it has not been evaluated in patients with advanced hilar cholangiocarcinoma (AHC). This study presents a single-institution experience with IRE for management of obstructive jaundice in AHC. MethodsA single-institution database was queried for patients undergoing IRE for AHC after PTBD placement for relief of obstructive jaundice from 2010 to 2017 and compared to a control group treated with standard of care only (No IRE). ResultsTwenty-six patients underwent IRE for AHC after PTBD replacement. Three patients experienced complications, with two experiencing severe (≥ grade 3) complications. After IRE, median time to PTBD removal was 122 days (range 0–305 days) and median catheter-free time before requiring PTBD replacement was 305 days (range 92–458 days). In comparison, the 137 control patients had an admission rate of 59% (N = 80 patients) for PTBD infection, occlusion, or catheter related problem. ConclusionIRE safely achieves biliary decompression via tumor electroporation and allows PTBD removal for an extended period of time. In appropriately selected patients with obstructive jaundice in the setting of AHC, IRE can be used to increase catheter-free days and optimize overall quality of life.

Abstract 3722: Efficacy of irreversible electroporation in combination with liposome-nvp-bez235 for head and neck cancer

Abstract Introduction: Irreversible electroporation (IRE) is an emerging, minimally invasive ablation technique with the advantage of not being affected by heat sink effect and the ability of ablation in close vicinity of major blood vessels. One limitation is local recurrence at the original ablated site. We hypothesize that combining IRE with a chemotherapeutic drug could prevent recurrence. NVP-BEZ235 (BEZ) is a dual PI3K/mTOR inhibitor that has shown promise for treating advanced solid malignancies, including sensitizing head and neck squamous cell carcinoma to radiotherapy. However, clinical trials revealed low bioavailability and high toxicity due to high dose oral administration over a long period of time. Thus, we formulated a liposomal BEZ (L-BEZ) and studied its antitumor effect in combination with IRE and compared the results with orally delivered BEZ (oral-BEZ). Methods: IRE was performed using ECM 830 (BTX Harvard Apparatus) at various field strengths. BEZ was loaded into liposome (L-BEZ) by hydration-sonication method. The in vitro and in vivo efficacy was tested against head and neck cancer cell line, HN5 cells and in nude mice bearing HN5 xenografts (n=4/group). Mice were divided into control (no treatment), IRE (2500 V/cm for 99 pulses), IRE + L-BEZ (IRE at 2500 V/cm for 99 pulses and 7 doses of L-BEZ) and IRE + oral-BEZ (IRE at 2500 V/cm for 99 pulses and 21 doses of oral-BEZ) groups. Tumor size was monitored for 60 days. Results: The hydrodynamic volume of NVP-BEZ ranged from 100-500nm. Maximum drug loading was achieved at 2.7mg/mL of BEZ. Electroporation disrupted nanoparticle's integrity even at the lowest tested field strength (250 V/cm) and released BEZ. At the highest field strength (2500 V/cm), approximately 5% of cells survived with IRE, while cells electroporated at 500 V/cm increased cell viability (114%) as compared to the untreated group (100 %). Combination of electroporation and L-BEZ significantly decreased cell viability at 500 V/cm (p&amp;lt;0.05). In vivo, IRE + L-BEZ suppressed tumor growth the longest, as compared with control (no treatment), IRE, and IRE + oral-BEZ. It was also the only group that resulted in no palpable tumor from day 30 to day 60. Survival studies show a significant difference between IRE + L-BEZ and the other groups. IRE + L-BEZ group had 100% animal survival on day 60. IRE + oral-BEZ had 50%, while IRE and control groups had 0% animal survival, on day 60. Also, the total administered BEZ amount in IRE + L-BEZ group was only 6.6% of that in IRE + oral-BEZ group. Conclusion: Incomplete electroporation increases the viability of surviving cells both in vitro and in vivo. Co-delivery of L-BEZ enhances the antitumor efficacy of IRE alone. L-BEZ also decreases BEZ exposure compared to oral-BEZ. Thus, L-BEZ in combination with IRE potentially ensures complete eradication of surviving cells left after IRE. Citation Format: Li Tian, Lucas Wang, Yang Qiao, Saisree Ravi, Ashley Chang, Thomas Alexander Rogers, Linfeng Lu, Adam D. Melancon, Marites Pasuelo Melancon. Efficacy of irreversible electroporation in combination with liposome-nvp-bez235 for head and neck cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3722.