scholarly journals Irreversible electroporation ablation overcomes tumor-associated immunosuppression to improve the efficacy of DC vaccination in a mice model of pancreatic cancer

2021 ◽  
Vol 10 (1) ◽  
pp. 1875638
Author(s):  
Jia Yang ◽  
Aydin Eresen ◽  
Junjie Shangguan ◽  
Quanhong Ma ◽  
Vahid Yaghmai ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Irreversible Electroporation ◽  
Mice Model

scholarly journals Usefulness of Imaging Response Assessment after Irreversible Electroporation of Localized Pancreatic Cancer—Results from a Prospective Cohort

Cancers ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2862
Author(s):  
Rasmus V. Flak ◽  
Rune V. Fisker ◽  
Niels H. Bruun ◽  
Mogens T. Stender ◽  
Ole Thorlacius-Ussing ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Irreversible Electroporation ◽  
Response Assessment ◽  
Time Intervals ◽  
Patient Level ◽  
Positron Emission ◽  
Included Patient ◽  
Before And After ◽  
Lesion Level ◽  
Level Analysis

(1) Background: Irreversible electroporation (IRE) is a nonthermal ablation technique that is being studied in nonmetastatic pancreatic cancer (PC). Most published studies use imaging outcomes as an efficacy endpoint, but imaging interpretation can be difficult and has yet to be correlated with survival. The aim of this study was to examine the correlation of imaging endpoints with survival in a cohort of IRE-treated PC patients. (2) Methods: Several imaging endpoints were examined before and after IRE on 18F-fluorodeoxyglucose positron emission tomography (PET) with computed tomography. Separate analyses were performed at the patient and lesion levels. Mortality rate (MR) ratios for imaging endpoints after IRE were estimated. (3) Results: Forty-one patients were included. Patient-level analysis revealed that progressive disease (PD), as defined by RECIST 1.1, is correlated with a higher MR at all time intervals, but PD, as defined by EORTC PET response criteria, is only correlated with the MR in the longest interval. No correlation was found between PD, as defined by RECIST, and the MR in the lesion-level analysis. (4) Conclusions: Patient-level PD, as defined by RECIST, was correlated with poorer survival after IRE ablation, whereas no correlations were observed in the lesion-level analyses. Several promising lesion-level outcomes were identified.

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 An Efficient Photodynamic Therapy Treatment for Human Pancreatic Adenocarcinoma

2020 ◽  
Vol 9 (1) ◽  
pp. 192 ◽  
Author(s):  
Alexandre Quilbe ◽  
Olivier Moralès ◽  
Martha Baydoun ◽  
Abhishek Kumar ◽  
Rami Mustapha ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Photodynamic Therapy ◽  
Immune System ◽  
Cancer Cells ◽  
Pancreatic Adenocarcinoma ◽  
Cell Lines ◽  
Folate Receptor ◽  
Mice Model ◽  
Gene And Protein Expression ◽  
The Impact

To date, pancreatic adenocarcinoma (ADKP) is a devastating disease for which the incidence rate is close to the mortality rate. The survival rate has evolved only 2–5% in 45 years, highlighting the failure of current therapies. Otherwise, the use of photodynamic therapy (PDT), based on the use of an adapted photosensitizer (PS) has already proved its worth and has prompted a growing interest in the field of oncology. We have developed a new photosensitizer (PS-FOL/PS2), protected by a recently published patent (WO2019 016397-A1, 24 January 2019). This photosensitizer is associated with an addressing molecule (folic acid) targeting the folate receptor 1 (FOLR1) with a high affinity. Folate binds to FOLR1, in a specific way, expressed in 100% of ADKP or over-expressed in 30% of cases. The first objective of this study is to evaluate the effectiveness of this PS2-PDT in four ADKP cell lines: Capan-1, Capan-2, MiapaCa-2, and Panc-1. For this purpose, we first evaluated the gene and protein expression of FOLR1 on four ADKP cell lines. Subsequently, we evaluated PS2’s efficacy in our cell lines and we assessed the impact of PDT on the secretome of cancer cells and its impact on the immune system. Finally, we evaluate the PDT efficacy on a humanized SCID mouse model of pancreatic cancer. In a very interesting way, we observed a significant increase in the proliferation of activated-human PBMC when cultured with conditioned media of ADKP cancer cells subjected to PDT. Furthermore, to evaluate in vivo the impact of this new PS, we analyzed the tumor growth in a humanized SCID mice model of pancreatic cancer. Four conditions were tested: Untreated, mice (nontreated), mice with PS (PS2), mice subjected to illumination (Light only), and mice subjected to illumination in the presence of PS (PDT). We noticed that the mice subjected to PDT presented a strong decrease in the growth of the tumor over time after illumination. Our investigations have not only suggested that PS2-PDT is an effective therapy in the treatment of PDAC but also that it activates the immune system and could be considered as a real adjuvant for anti-cancer vaccination. Thus, this new study provides new treatment options for patients in a therapeutic impasse and will provide a new arsenal in the fight against PDAC.

Single-Institution Experience with Irreversible Electroporation for T4 Pancreatic Cancer: First 50 Patients

2015 ◽  
Vol 23 (5) ◽  
pp. 1736-1743 ◽  
Author(s):  
Michael D. Kluger ◽  
Irene Epelboym ◽  
Beth A. Schrope ◽  
Krishnaraj Mahendraraj ◽  
Elizabeth M. Hecht ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Irreversible Electroporation ◽  
Single Institution

scholarly journals Establishing an immunocompromised porcine model of human cancer for novel therapy development with pancreatic adenocarcinoma and irreversible electroporation

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Alissa Hendricks-Wenger ◽  
Kenneth N. Aycock ◽  
Margaret A. Nagai-Singer ◽  
Sheryl Coutermarsh-Ott ◽  
Melvin F. Lorenzo ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Electrical Properties ◽  
Pancreatic Adenocarcinoma ◽  
Mouse Models ◽  
Tumor Tissue ◽  
Irreversible Electroporation ◽  
Human Pancreatic Cancer ◽  
Large Animal Model ◽  
Preclinical Model ◽  
Large Animal

AbstractNew therapies to treat pancreatic cancer are direly needed. However, efficacious interventions lack a strong preclinical model that can recapitulate patients’ anatomy and physiology. Likewise, the availability of human primary malignant tissue for ex vivo studies is limited. These are significant limitations in the biomedical device field. We have developed RAG2/IL2RG deficient pigs using CRISPR/Cas9 as a large animal model with the novel application of cancer xenograft studies of human pancreatic adenocarcinoma. In this proof-of-concept study, these pigs were successfully generated using on-demand genetic modifications in embryos, circumventing the need for breeding and husbandry. Human Panc01 cells injected subcutaneously into the ears of RAG2/IL2RG deficient pigs demonstrated 100% engraftment with growth rates similar to those typically observed in mouse models. Histopathology revealed no immune cell infiltration and tumor morphology was highly consistent with the mouse models. The electrical properties and response to irreversible electroporation of the tumor tissue were found to be similar to excised human pancreatic cancer tumors. The ample tumor tissue produced enabled improved accuracy and modeling of the electrical properties of tumor tissue. Together, this suggests that this model will be useful and capable of bridging the gap of translating therapies from the bench to clinical application.

scholarly journals Controllable Moderate Heating Enhances the Therapeutic Efficacy of Irreversible Electroporation for Pancreatic Cancer

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Chelsea M. Edelblute ◽  
James Hornef ◽  
Niculina I. Burcus ◽  
Thomas Norman ◽  
Stephen J. Beebe ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Therapeutic Efficacy ◽  
Irreversible Electroporation

Early outcomes of irreversible electroporation after stereotactic body radiation therapy for the treatment of locally advanced pancreatic adenocarcinoma (LAPC): A matched pair analysis.

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 410-410
Author(s):  
Emanuel Boyer ◽  
Russell Palm ◽  
Jessica M. Frakes ◽  
Sarah E. Hoffe ◽  
Mokenge Peter Malafa
Keyword(s):  
Pancreatic Cancer ◽  
Radiation Therapy ◽  
Pancreatic Adenocarcinoma ◽  
Cohort Analysis ◽  
Locally Advanced ◽  
Irreversible Electroporation ◽  
Advanced Pancreatic Cancer ◽  
Matched Pair ◽  
Optimal Timing ◽  
Entire Cohort

410 Background: Outcomes remain poor for those diagnosed with unresectable pancreatic cancer. SBRT and IRE have independently demonstrated high rates of local control and minimal toxicity for patients with locally advanced pancreatic cancer (LAPC). Data is limited regarding safety and efficacy in the sequential use of both therapies. Materials and Methods: A single institution retrospective matched cohort analysis was performed for patients with non-metastatic pancreatic cancer treated with induction chemotherapy and SBRT followed by IRE, compared with patients of the same cohort who did not receive IRE. Patients were paired based on age, tumor stage, GTV D95, CA19-9 prior to SBRT, and chemotherapy type to mitigate selection bias in surgical candidates. Overall survival (OS), progression free survival (PFS), freedom from local failure (FFLF) and freedom from distant failure (FFDF) were the primary outcomes compared via Kaplan-Meier survival analysis with log-rank methods. Results: From July, 2014 to February, 2020 17 patients received SBRT followed by IRE. These patients were matched with 17 patients who received SBRT from January, 2012 to March, 2019. Most patients received neoadjuvant FOLFIRINOX (82.4%) and were AJCC 8 stage III (79.4%). Median age of the overall cohort was 65.5 years and 50% were male. Median dose delivered to 95% of gross tumor volume was 32.61 Gy, and median pre SBRT CA19-9 value was 70.5 U/mL. There were no statistically significant differences in matched characteristics between the two cohorts. Among the SBRT+IRE, the median time between IRE and SBRT was 66 days (range:49-467 days). The median OS, PFS, FFLF, and FFDF for IRE+SBRT vs. SBRT alone from SBRT was 10.8 vs 15.1 months, 9.6 vs. 15.3 months, 15.7 vs. 15.3 months, 15.9 vs. 14.4 months respectively (all P > .10). 11 patients in the entire cohort experienced toxicity as a result of their radiation therapy (35%), with one G3 GIB and one patient experiencing G3 abdominal pain. Among the 17 patients who underwent IRE, nine patients experienced toxicity (53%). Most of these events were G3, with two G4 intestinal bleeds. There was zero mortality in the 90 day period post operatively. Conclusions: In a retrospective cohort,non-selective delivery ofIRE afterSBRT demonstrated no oncological benefit for patients with unresectable pancreatic adenocarcinoma compared to only SBRT. Compared to historical experiences of IRE alone, there was no increase in overall toxicity with the combination of SBRT and IRE. The optimal timing, sequencing, and indications for IRE and SBRT in LAPC remain unknown and are best assessed prospectively. [Table: see text]

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.

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