scholarly journals Physical and Chemical Enhancement of and Adaptive Resistance to Irreversible Electroporation of Pancreatic Cancer

2017 ◽  
Vol 46 (1) ◽  
pp. 25-36 ◽  
Author(s):  
Qi Shao ◽  
Feng Liu ◽  
Connie Chung ◽  
Kianna Elahi-Gedwillo ◽  
Paolo P. Provenzano ◽  
...  
2021 ◽  
Vol 10 (1) ◽  
pp. 1875638
Author(s):  
Jia Yang ◽  
Aydin Eresen ◽  
Junjie Shangguan ◽  
Quanhong Ma ◽  
Vahid Yaghmai ◽  
...  

Cancers ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2862
Author(s):  
Rasmus V. Flak ◽  
Rune V. Fisker ◽  
Niels H. Bruun ◽  
Mogens T. Stender ◽  
Ole Thorlacius-Ussing ◽  
...  

(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.


2021 ◽  
Vol 10 (8) ◽  
pp. 1609
Author(s):  
Zainab L. Rai ◽  
Roger Feakins ◽  
Laura J. Pallett ◽  
Derek Manas ◽  
Brian R. Davidson

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.


2020 ◽  
Vol 1 (8) ◽  
pp. 100131
Author(s):  
Wells S. Brown ◽  
Paul C. McDonald ◽  
Oksana Nemirovsky ◽  
Shannon Awrey ◽  
Shawn C. Chafe ◽  
...  

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

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Alissa Hendricks-Wenger ◽  
Kenneth N. Aycock ◽  
Margaret A. Nagai-Singer ◽  
Sheryl Coutermarsh-Ott ◽  
Melvin F. Lorenzo ◽  
...  

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.


2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Chelsea M. Edelblute ◽  
James Hornef ◽  
Niculina I. Burcus ◽  
Thomas Norman ◽  
Stephen J. Beebe ◽  
...  

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 410-410
Author(s):  
Emanuel Boyer ◽  
Russell Palm ◽  
Jessica M. Frakes ◽  
Sarah E. Hoffe ◽  
Mokenge Peter Malafa

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]


Sign in / Sign up

Export Citation Format

Share Document