Abstract B140: Irreversible electroporation and radiation therapy: Potential for combination therapy for locally advanced pancreatic cancer

Abstract Introduction: Irreversible electroporation (IRE) is a non-thermal ablative technology that uses short, high-voltage electric pulses to induce cell death. Stereotactic body radiotherapy (SBRT) is focused radiation therapy that is widely used for the control of locally advanced pancreatic cancer (LAPC). In this study, using an orthotopic murine PDAC model, we investigated how IRE and SBRT modulate the tumor immune microenvironment and correlated these changes with tumor control. We further examined if the combination of IRE and SBRT (2 days pre- or post-IRE) could exert synergistic effects. Methods: We injected the organoid cell line (KPC-46) into the tail of the pancreas and marked the site with a barium fiducial to generate orthotopic tumors in syngeneic mice. Tumors were treated with SBRT at a single fraction of 16 Gy when they reached 5–7 mm in diameter using a precision small animal irradiator (biologically equivalent to multi-fraction regimens used clinically) and/or IRE at 1500 V/cm, 100 µs pulses (100 pulses total) via repeat laparotomy. Mice that did not receive IRE underwent a sham laparotomy. Harvested tumors were analyzed by IHC and flow cytometry. Results: The doses of IRE and SBRT were intentionally selected to achieve comparable reductions (50–75%) in tumor size compared to sham/control. The addition of SBRT pre- or post-IRE led to numerically but not significantly greater reduction in tumor size. H&E staining showed distinct ablated zones in tumors treated with IRE, which were not observed in the SBRT-alone groups. A significant decrease in α-SMA positive fibroblasts was observed in the ablated zones in the IRE-treated groups compared to sham or SBRT alone. In lymph nodes, significant increases in the percentage of CD11c+ dendritic cells, CD19+ B cells, and MHC-II+ B cells were observed in SBRT-treated groups. Although IRE did not increase the number of tumor-infiltrating CD8+ T cells, the percentage of cytotoxic effector CD8+ T cells was significantly higher in IRE-treated groups compared to the sham and SBRT-alone groups. Conclusions: In summary, while both treatments were similarly effective in local tumor control, IRE decreased tumor fibrosis, accompanied by the infiltration of activated T cells. Analysis of lymph nodes suggested dendritic cell and B cell-mediated antigen presentation in response to SBRT. This study highlights the potential for additive immunomodulatory effects of IRE and SBRT and justifies further clinical exploration of how to optimally combine IRE and SBRT for the treatment of LAPC. Citation Format: Himangshu Sonowal, Kim Nguyen-Ta, Helene Lucie . Gros, Riley Jones, Jorge De la Torre. Medina, Utsav Joshi, Badri Narayanan . Narasimhan, Andrew Sharabi, Rebekah White. Irreversible electroporation and radiation therapy: Potential for combination therapy for locally advanced pancreatic cancer [abstract]. In: Proceedings of the AACR Conference on Pancreatic Cancer: New Frontiers in Biology and Therapeutic Development; 2026 Sep 25-28; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(18_Suppl_2):Abstract nr B140.