Electroporation for the Treatment of Pancreatic Ductal Adenocarcinoma: A Systematic Review of Preclinical and Clinical Studies.

Abstract

Introduction: Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy with poor prognosis and limited treatment options. Electroporation-based therapies, such as electrochemotherapy (ECT) and irreversible electroporation (IRE), could be promising alternatives. ECT combines reversible electroporation with chemotherapy, enhancing intracellular drug uptake, while IRE leads to nonthermal tumor ablation. Both have been suggested as immunotherapy potentiators (electroimmunotherapy) in some tumor locations. We conducted a systematic review to evaluate the efficiency and safety of ECT, IRE, and immunoelectroporation in PDAC treatment.

Methods: We searched Medline, Embase, Cochrane, and Google-Scholar for ECT, IRE, and electroimmunotherapy following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. For ECT and electroimmunotherapy, regarding the scarcity of the data, we described independently each study protocol and results. For IRE, we collected protocol, efficiency, and safety data to provide a global analysis.

Results: Fifteen studies described the effects of ECT for PDAC treatment: Safety and efficiency were promising in both preclinical and human models. Thirty-eight clinical studies including 2,245 patients were analyzed for IRE, with patients mostly treated for locally advanced pancreatic cancer and a median overall survival of 17.2 months at the expanse of a 36% adverse event rate, half of which severe. Seven (preclinical and clinical) studies investigated electroimmunotherapy suggesting significant potentiation of immunotherapy in both preclinical and human models.

Discussion: In the largest systematic review to date regarding electroporation in PDAC treatment, analysis of study results plead against the use of IRE but highlight the potential benefits of ECT and electroimmunotherapy.