Electroporation for the treatment of pancreatic ductal adenocarcinoma, a systematic review of preclinical and clinical studies

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 non-thermal tumor ablation. Both have been suggested as immunotherapy potentiators (electro-immunotherapy) in some tumor locations. We conducted a systematic review to evaluate the efficiency and safety of ECT, IRE and immuno-electroporation in PDAC treatment. We searched Medline, Embase, Cochrane and Google-Scholar for ECT, IRE and electro-immunotherapy following the PRISMA guidelines. For ECT and electro-immunotherapy, 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. 15 studies described the effects of ECT for PDAC treatment: safety and efficiency were promising in both pre-clinical and human models. 38 clinical studies including 2245 patients were analyzed for IRE, with patients mostly treated for LAPC and a median overall survival of 17.2 months at the expanse of a 36% adverse event rate, half of which severe. 7 (preclinical and clinical) studies investigated electro-immunotherapy suggesting significant potentiation of immunotherapy in both pre-clinical and human models. 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 electro-immunotherapy.