Investigating the feasibility of a clinical trial to test using irreversible electroporation to treat locally advanced pancreatic cancer following initial chemotherapy

2021 ◽  
Author(s):  
Brian Davidson ◽  
Kellie Platt
Keyword(s):  
Pancreatic Cancer ◽  
Clinical Trial ◽  
Locally Advanced ◽  
Irreversible Electroporation ◽  
Advanced Pancreatic Cancer ◽  
Locally Advanced Pancreatic Cancer

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

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.

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

Cancers ◽  
2019 ◽  
Vol 11 (7) ◽  
pp. 976 ◽  
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.

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

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.

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

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.

scholarly journals Irreversible Electroporation for Locally Advanced Pancreatic Cancer

2020 ◽  
Vol 23 (2) ◽  
pp. 100675 ◽  
Author(s):  
Florentine E.F. Timmer ◽  
Bart Geboers ◽  
Alette H. Ruarus ◽  
Evelien A.C. Schouten ◽  
Sanne Nieuwenhuizen ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Locally Advanced ◽  
Irreversible Electroporation ◽  
Advanced Pancreatic Cancer ◽  
Locally Advanced Pancreatic Cancer

Pre-SBRT metabolic tumor volume and total lesion glycolysis to predict survival in patients with locally advanced pancreatic cancer receiving stereotactic body radiation therapy.

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 189-189
Author(s):  
Avani Satish Dholakia ◽  
Muhammad Ali Chaudhry ◽  
Jeffrey P. Leal ◽  
Daniel Tandel Chang ◽  
Siva P. Raman ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Clinical Trial ◽  
Overall Survival ◽  
Tumor Volume ◽  
Locally Advanced ◽  
Advanced Pancreatic Cancer ◽  
Metabolic Tumor Volume ◽  
Total Lesion Glycolysis ◽  
Pet Scan ◽  
Locally Advanced Pancreatic Cancer

189 Background: Though prior studies have demonstrated the prognostic value of pre- and post-treatment positron emission tomography (PET) parameters in other malignancies, the role of PET in pancreatic cancer is yet to be established. We analyzed the prognostic utility of PET for patients with locally advanced pancreatic cancer (LAPC) undergoing fractionated stereotactic body radiotherapy (SBRT). Methods: Thirty-two patients with LAPC received up to 3 doses of gemcitabine, followed by SBRT 6.6 Gy in 5 daily fractions, 33 Gy total, on a prospective clinical trial. All patients received a baseline PET scan prior to SBRT (pre-SBRT PET). Metabolic tumor volume (MTV), total lesion glycolysis (TLG), and maximum and peak standardized uptake values (SUVmax and SUVpeak) on pre-SBRT PET scans were calculated using an in-house software. Disease measurability was assessed at a threshold based on the liver standard uptake value (SUV) using the equation Livermean + (2 * Liversd). Median values of PET parameters were used as cutoffs when assessing their prognostic potential through univariate and multivariate Cox regression analyses. Results: Of the 32 patients in this study, the majority were male (N=19, 59%), 65 years or older (N=21, 66%), and had tumors located in the pancreatic head (N=27, 84%). Twenty-seven patients (85%) received induction gemcitabine prior to SBRT per protocol. Median overall survival for the entire cohort was 18.8 months (95% CI, 15.7-22.0). An MTV of 26.8 cm3 or greater (HR 4.46, 95% CI 1.64 to 5.88, p < 0.003) and TLG of 70.9 cm3 or greater (HR 3.08, 95% CI 1.18 to 8.02, p < 0.021) on pre-SBRT PET scan were associated with inferior overall survival on univariate analysis. Both pre-SBRT MTV (HR 5.13, 95% CI 1.19 to 22.21, p=0.029) and TLG (HR 3.34, 95% CI 1.07 to 10.48, p=0.038) remained independent prognostic factors for overall survival in separate multivariate analyses. Conclusions: Pre-SBRT MTV and TLG yield prognostic information on overall survival in patients with LAPC and may assist in tailoring therapy. Clinical trial information: NCT01146054.

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