Treatment of 200 Locally Advanced (Stage III) Pancreatic Adenocarcinoma Patients With Irreversible Electroporation

Martin, Robert C.G.; Kwon, David S.; Chalikonda, Sricharan; Sellers, Marty T.; Kotz, Eric; Scoggins, Charles R.; McMasters, Kelly M.; Watkins, Ken W.

doi:10.1097/sla.0000000000001441

Cited by 347 publications

(315 citation statements)

References 38 publications

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“…One treatment option for PDAC is IRE, which is an emerging, nonthermal, image-guided tumor ablation technique. IRE has been proven to be feasible and safe to locally advanced pancreatic cancer (LAPC), [3][4][5][6] and is approved in latest pancreatic cancer (PC) treatment guidelines.…”

Section: Introductionmentioning

confidence: 99%

Circulating Tumor DNA as a Sensitive Marker in Patients Undergoing Irreversible Electroporation for Pancreatic Cancer

Lin

Alnaggar

Liang

et al. 2018

Cell Physiol Biochem

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Background/Aims: Pancreatic ductal adenocarcinoma (PDAC) is often diagnosed at an advanced stage, resulting in extremely poor 5-year survival. Late diagnosis of PDAC is mainly due to lack of a reliable method of early detection. Carbohydrate antigen (CA) 19-9 is often used as a tumor biomarker in PDAC; however, the test lacks sensitivity and specificity. Therefore, new sensitive and minimally invasive diagnostic tools are required to detect pancreatic cancer. Methods: Here, we investigated circulating tumor DNA (ctDNA) which contained KRAS-mutated as a potential diagnostic tool for PDAC patients who underwent irreversible electroporation (IRE). We used droplet digital polymerase chain reaction (ddPCR) to detect the expression of KRAS-mutated genes in plasma samples of 65 PDAC patients who underwent IRE. Results: In these 65 cases, ctDNA was detected in 20 (29.2%) samples. The median overall survival (OS) was 11.4 months with ctDNA+ patients and 14.3 months for ctDNA- patients. ctDNA+ patients had a obviously poorer prognosis associated to overall survival (P < 0.001). Conclusion: Our results suggested that the existence of ctDNA was a predictor of survival for PDAC patients. Therefore, ctDNA may be a new sensitive biomarker for monitoring treatment outcome in PDAC.

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Section: Introductionmentioning

confidence: 99%

Circulating Tumor DNA as a Sensitive Marker in Patients Undergoing Irreversible Electroporation for Pancreatic Cancer

Lin

Alnaggar

Liang

et al. 2018

Cell Physiol Biochem

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“…PEF treatment has dramatically improved gene-transfer efficiencies in tissues such as liver, skin, and skeletal muscle [22,38,39,40]. IRE technology has been used to treat tumors in canine brain tissue [41], human and porcine liver tissue [42,43,44,45], and and human and porcine pancreatic tissue [46,47,48]. By destroying malignant cells while mitigating damage to critical stromal tissue components [49,50], it enables the treatment of tissues around critical structures that would otherwise render the site untreatable.…”

Section: Introductionmentioning

confidence: 98%

Quantification of cell membrane permeability induced by monopolar and high-frequency bipolar bursts of electrical pulses

Sweeney

Reberšek

Dermol

et al. 2016

Biochimica et Biophysica Acta (BBA) - Biomembranes

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High-frequency bipolar electric pulses have been shown to mitigate undesirable muscle contraction during irreversible electroporation (IRE) therapy. Here, we evaluate the potential applicability of such pulses for introducing exogenous molecules into cells, such as in electrochemotherapy (ECT). For this purpose we develop a method for calculating the time course of the effective permeability of an electroporated cell membrane based on real-time imaging of propidium transport into single cells that allows a quantitative comparison between different pulsing schemes. We calculate the effective permeability for several pulsed electric field treatments including trains of 100μs monopolar pulses, conventionally used in IRE and ECT, and pulse trains containing bursts or evenly-spaced 1μs bipolar pulses. We show that shorter bipolar pulses induce lower effective membrane permeability than longer monopolar pulses with equivalent treatment times. This lower efficiency can be attributed to incomplete membrane charging. Nevertheless, bipolar pulses could be used for increasing the uptake of small molecules into cells more symmetrically, but at the expense of higher applied voltages. These data indicate that high-frequency bipolar bursts of electrical pulses may be designed to electroporate cells as effectively as and more homogeneously than conventional monopolar pulses.

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“…This process is called irreversible electroporation (IRE) and is an emergent non-thermal cell ablation modality that is increasingly used clinically to treat solid tumors [1–3]. Recent studies (including human trials) suggest that IRE can be used as adjuvant treatment for various solid malignancies such as: prostate [4], pancreas [5] [6] and liver [7]. Due to its simplicity of use, its non-thermal nature, and its ability not to damage extra-cellular components such as blood vessels [8–10], it is being evaluated in pre-clinical studies as a new approach for cardiovascular tissue ablation [11–13].…”

Section: Introductionmentioning

confidence: 99%

Optimization of Irreversible Electroporation Protocols for In-vivo Myocardial Decellularization

et al. 2016

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BackgroundIrreversible electroporation (IRE) is a non-thermal cell ablation approach that induces selective damage to cell membranes only. The purpose of the current study was to evaluate and optimize its use for in-vivo myocardial decellularization.MethodsForty-two Sprague-Dawley rats were used to compare myocardial damage of seven different IRE protocols with anterior myocardial infarction damage. An in-vivo open thoracotomy model was used, with two-needle electrodes in the anterior ventricular wall. IRE protocols included different combinations of pulse lengths (70 vs. 100 μseconds), frequency (1, 2, 4 Hz), and number (10 vs. 20 pulses), as well as voltage intensity (50, 250 and 500 Volts). All animals underwent baseline echocardiographic evaluation. Degree of myocardial ablation was determined using repeated echocardiography measurements (days 7 and 28) as well as histologic and morphometric analysis at 28 days.ResultsAll animals survived 28 days of follow-up. Compared with 50V and 250V, electroporation with 500V was associated with significantly increased myocardial scar and reduction in ejection fraction (67.4%±4% at baseline vs. 34.6%±20% at 28 days; p <0.01). Also, compared with pulse duration of 70 μsec, pulses of 100 μsec were associated with markedly reduced left ventricular function and markedly increased relative scar area ratio (28%±9% vs. 16%±3%, p = 0.02). Decreasing electroporation pulse frequency (1Hz vs. 2Hz, 2Hz vs. 4Hz) was associated with a significant increase in myocardial damage. Electroporation protocols with a greater number of pulses (20 vs. 10) correlated with more profound tissue damage (p<0.05). When compared with myocardial infarction damage, electroporation demonstrated a considerable likeness regarding the extent of the inflammatory process, but with relatively higher levels of extra-cellular preservation.ConclusionsIRE has a graded effect on the myocardium. The extent of ablation can be controlled by changing pulse length, frequency and number, as well as by changing electric field intensity.

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Treatment of 200 Locally Advanced (Stage III) Pancreatic Adenocarcinoma Patients With Irreversible Electroporation

Abstract: For patients with LAPC (stage III), the addition of IRE to conventional chemotherapy and radiation therapy results in substantially prolonged survival compared with historical controls. These results suggest that ablative control of the primary tumor may prolong survival.

Cited by 347 publications

References 38 publications

Circulating Tumor DNA as a Sensitive Marker in Patients Undergoing Irreversible Electroporation for Pancreatic Cancer

Circulating Tumor DNA as a Sensitive Marker in Patients Undergoing Irreversible Electroporation for Pancreatic Cancer

Quantification of cell membrane permeability induced by monopolar and high-frequency bipolar bursts of electrical pulses

Optimization of Irreversible Electroporation Protocols for In-vivo Myocardial Decellularization

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