Irreversible Electroporation in Locally Advanced Pancreatic Cancer: Potential Improved Overall Survival

BackgroundIrreversible electroporation (IRE) has emerged as a viable consolidative therapy after induction chemotherapy, in which this combination has improved overall survival of locally advanced pancreatic cancer (LAPC). Optimal timing and patient selection for irreversible electroporation remains a clinically unmet need. The aim of this study was to investigate preoperative factors that may assist in predicting progression-free and overall survival following IRE.MethodsA multi-institutional, prospectively maintained database was reviewed for patients with LAPC treated with induction chemotherapy followed by open-technique irreversible electroporation from 7/2015-5/2019. RECIST 1.1 criteria were used to assess tumor response and radiological progression. Overall survival (OS) and progression-free survival (PFS) were recorded. Survival analyses were performed using Kaplan Meier and Cox multivariable regression analyses.Results187 LAPC patients (median age 62 years range, 21 – 91, 65% men, 35% women) were treated with IRE. Median PFS was 21.7 months and median OS from diagnosis was 25.5 months. On multivariable analysis, age ≤ 61 (HR 0.41, 95%CI 0.21-0.78, p<0.008) and no prior radiation (HR 0.49, 95%CI 0.26-0.94, p=0.03) were positive predictors of OS after IRE. Age ≤ 61(HR 0.53, 95%CI, 0.28-.99, p=0.046) and FOLFIRINOX followed by gemcitabine/abraxane induction chemotherapy (HR 0.37,95%CI 0.15-0.89, p=0.027) predicted prolonged PFS after IRE. Abnormal CA19-9 values at the time of surgery negatively impacted both OS (HR 2.46, 95%CI 1.28-4.72, p<0.007) and PFS (HR 2.192, 95%CI 1.143-4.201, p=0.018) following IRE.ConclusionsAge, CA 19-9 response, avoidance of pre-IRE radiation, and FOLFIRINOX plus gemcitabine/abraxane induction chemotherapy are prominent factors to consider when referring or selecting LAPC patients to undergo IRE.

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Irreversible electroporation for locally advanced pancreatic cancer

Annaly khirurgicheskoy gepatologii = Annals of HPB surgery ◽

10.16931/1995-5464.2018259-68 ◽

2018 ◽

Vol 23 (2) ◽

pp. 59-68

Author(s):

D. A. Astakhov ◽

D. N. Panchenkov ◽

Yu. V. Ivanov ◽

O. R. Shablovsky ◽

A. G. Kedrova ◽

...

Keyword(s):

Pancreatic Cancer ◽

Overall Survival ◽

Locally Advanced ◽

Irreversible Electroporation ◽

Advanced Pancreatic Cancer ◽

Pancreatic Head ◽

Locally Advanced Pancreatic Cancer ◽

Control Group ◽

Recurrence Free Survival ◽

Free Survival

Aim. To assess overall survival and recurrence-free period in patients with locally advanced pancreatic cancer who underwent irreversible electroporation of the tumor in combination with chemotherapy. Matherials and methods. It was performed a prospective analysis of overall survival in 23 patients who underwent irreversible electroporation of unresectable pancreatic cancer for the period from May 2012 to March 2017. Control group consisted of 35 patients with pancreatic cancer stage III who received standard chemotherapy alone. Results. Mean age of patients was 61 years (range 45–80). All procedures were successful. Fifteen patients had pancreatic head cancer, 8 – cancer of pancreatic body. Preoperative chemotherapy has been applied in 20 (86.9%) patients for 4 months prior to surgery on the average. Seventeen (73%) patients underwent chemotherapy after electroporation procedure. 90-day mortality was 4.3% (n = 1) in electroporation group. Surgery was followed by improved local recurrence-free survival (12 and 6 months, respectively, p = 0.01) and distant recurrence-free survival (15 and 8 months, respectively, p = 0.03). Overall survival was 18 and 11 months, respectively (p = 0.03). Conclusion. Irreversible electroporation of locally advanced pancreatic cancer is safe. Four-month chemotherapy followed by surgical procedure is associated with good local response and better overall survival compared with chemotherapy alone. These data will be validated in further multicenter study.

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

Journal of Clinical Medicine ◽

10.3390/jcm10081609 ◽

2021 ◽

Vol 10 (8) ◽

pp. 1609

Author(s):

Zainab L. Rai ◽

Roger Feakins ◽

Laura J. Pallett ◽

Derek Manas ◽

Brian R. Davidson

Keyword(s):

Pancreatic Cancer ◽

Mechanism Of Action ◽

Locally Advanced ◽

Irreversible Electroporation ◽

Advanced Pancreatic Cancer ◽

Standard Of Care ◽

Locally Advanced Pancreatic Cancer ◽

Animal Data ◽

Standard Of Care Treatment ◽

Apoptosis And Necrosis

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

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Estimation of Clinical Outcomes of Irreversible Electroporation Use During Locally Advanced Pancreatic Cancer: A Systematic Review and Meta-analysis

ADVANCED ULTRASOUND IN DIAGNOSIS AND THERAPY ◽

10.37015/audt.2018.180814 ◽

2018 ◽

Vol 2 (2) ◽

pp. 143

Author(s):

Jiang, PhD Tian’an ◽

Tian, MD Guo ◽

Wu, PhD Liming ◽

Zhao, PhD Qiyu

Keyword(s):

Systematic Review ◽

Pancreatic Cancer ◽

Clinical Outcomes ◽

Meta Analysis ◽

Locally Advanced ◽

Irreversible Electroporation ◽

Advanced Pancreatic Cancer ◽

Locally Advanced Pancreatic Cancer

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Locally Advanced Pancreatic Cancer: Work-Up, Staging, and Local Intervention Strategies

Cancers ◽

10.3390/cancers11070976 ◽

2019 ◽

Vol 11 (7) ◽

pp. 976 ◽

Cited By ~ 8

Author(s):

Eran van Veldhuisen ◽

Claudia van den Oord ◽

Lilly J. Brada ◽

Marieke S. Walma ◽

Jantien A. Vogel ◽

...

Keyword(s):

Pancreatic Cancer ◽

Stable Disease ◽

Tumor Regression ◽

Locally Advanced ◽

Irreversible Electroporation ◽

Advanced Pancreatic Cancer ◽

Locally Advanced Pancreatic Cancer ◽

Vascular Involvement ◽

Response To Chemotherapy ◽

Ablative Techniques

Locally advanced pancreatic cancer (LAPC) has several definitions but essentially is a nonmetastasized pancreatic cancer, in which upfront resection is considered not beneficial due to extensive vascular involvement and consequent high chance of a nonradical resection. The introduction of FOLFIRINOX chemotherapy and gemcitabine-nab-paclitaxel (gem-nab) has had major implications for the management and outcome of patients with LAPC. After 4–6 months induction chemotherapy, the majority of patients have stable disease or even tumor-regression. Of these, 12 to 35% are successfully downstaged to resectable disease. Several studies have reported a 30–35 months overall survival after resection; although it currently remains unclear if this is a result of the resection or the good response to chemotherapy. Following chemotherapy, selection of patients for resection is difficult, as contrast-enhanced computed-tomography (CT) scan is unreliable in differentiating between viable tumor and fibrosis. In case a resection is not considered possible but stable disease is observed, local ablative techniques are being studied, such as irreversible electroporation, radiofrequency ablation, and stereotactic body radiation therapy. Pragmatic, multicenter, randomized studies will ultimately have to confirm the exact role of both surgical exploration and ablation in these patients. Since evidence-based guidelines for the management of LAPC are lacking, this review proposes a standardized approach for the treatment of LAPC based on the best available evidence.

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Intraoperative Irreversible Electroporation in Locally Advanced Pancreatic Cancer: A Guide for the Interventional Radiologist

Seminars in Interventional Radiology ◽

10.1055/s-0039-1697640 ◽

2019 ◽

Vol 36 (05) ◽

pp. 386-391

Author(s):

Gregory T. Frey ◽

Carlos A. Padula ◽

John A. Stauffer ◽

Beau B. Toskich

Keyword(s):

Pancreatic Cancer ◽

Tertiary Care ◽

Multidisciplinary Treatment ◽

Locally Advanced ◽

Irreversible Electroporation ◽

Advanced Pancreatic Cancer ◽

Locally Advanced Pancreatic Cancer ◽

Locoregional Therapy ◽

Systemic Treatments ◽

Tertiary Care Institution

AbstractEfforts to improve mortality associated with locally advanced pancreatic cancer (LAPC) have shown minimal gains despite advances in surgical technique, systemic treatments, and radiation therapy. Locoregional therapy with ablation has not been routinely adopted due to the high risk of complications associated with thermal destruction of the pancreas. Irreversible electroporation (IRE) is an emerging, nonthermal, ablative technology that has demonstrated the ability to generate controlled ablation of LAPC while preserving pancreatic parenchymal integrity. IRE may be performed percutaneously or via laparotomy and will commonly involve multidisciplinary treatment teams. This article will describe the technical aspects of how multidisciplinary IRE is performed during laparotomy at a single tertiary care institution.

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Irreversible electroporation plus allogenic Vγ9Vδ2 T cells enhances antitumor effect for locally advanced pancreatic cancer patients

Signal Transduction and Targeted Therapy ◽

10.1038/s41392-020-00260-1 ◽

2020 ◽

Vol 5 (1) ◽

Author(s):

Mao Lin ◽

Xiaoyan Zhang ◽

Shuzhen Liang ◽

Haihua Luo ◽

Mohammed Alnaggar ◽

...

Keyword(s):

Pancreatic Cancer ◽

T Cells ◽

T Cell ◽

Locally Advanced ◽

Irreversible Electroporation ◽

Advanced Pancreatic Cancer ◽

Locally Advanced Pancreatic Cancer ◽

Antitumor Efficacy ◽

Γδ T Cell ◽

Group A

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

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