Irreversible electroporation of locally advanced pancreatic cancer

Locally advanced pancreatic cancer (LAPC) constitutes approximately one-third of all pancreatic cancer, with standard of care inconsistently defined and achieving modest outcomes at best. While resection after downstaging offers the chance for cure, only a fraction of patients with LAPC become candidates for resection. Chemotherapy remains the mainstay of treatment for the remainder. In these patients, ablative therapy may be given for local control of the tumor. Irreversible electroporation (IRE) is an attractive ablative technique. IRE changes the permeability of tumor cell membranes to induce apoptosis. Unlike other ablative therapies, IRE causes little thermal injury to the target area, making it ideal for LAPC involving major vessels. Compared to systemic chemotherapy alone, IRE seems to offer some survival benefit. Although early studies reported notable morbidity and mortality rates, IRE presents opportunities for those who cannot undergo resection and who otherwise have limited options. Another role of IRE is to extend the margins of resected tumors when there is a concern for R1 resection. Perhaps most exciting, IRE is thought to have effects beyond local ablation. IRE has immunomodulatory effects, which may induce in vivo vaccination and may potentially synergize with immunotherapy. Through electrochemotherapy, IRE may enhance drug delivery to residual tumor cells. Ultimately the role of IRE in the treatment of LAPC still needs to be validated through well designed randomized trials. Investigations of its future possibilities are in the early stages. IRE offers the potential to provide more options to LAPC patients.