Effectiveness and Safety of Irreversible Electroporation when Used for the Ablation of Stage 3 Pancreatic Adenocarcinoma: Initial Results from the DIRECT Registry Study

Background/Objectives: Overall survival for patients with Stage 3 pancreatic ductal adenocarcinoma (PDAC) remains limited, with a median survival of 12 to 15 months. Irreversible electroporation (IRE) is a local tumor ablation method that induces cancerous cell death by disrupting cell membrane homeostasis. The DIRECT Registry study was designed to assess the effectiveness and safety of IRE when combined with standard of care (SOC) treatment for Stage 3 PDAC versus SOC alone in a real-world setting after at least 3 months of induction chemotherapy; Methods: Patients with Stage 3 PDAC treated with IRE plus SOC or SOC alone were prospectively enrolled in a multicenter registry study. Enrollment required 3 months of active multi-agent chemotherapy with no progression before enrollment. Endpoints were 30- and 90-day mortality and adverse events (AEs). Results: Eighty-seven IRE and 27 SOC subjects were enrolled in the registry. Mean ages were 64.0 ± 8.4 and 66.4 ± 9.9 years, and mean anterior/posterior tumor diameters were 2.2 ± 0.7 cm and 3.2 ± 1.3 for the IRE and SOC groups respectively (p = 0.0066). All IRE procedures were performed using an open approach. The 90-day all-cause mortality was 5/83 (6.0%) and 2/27 (7.4%) for the IRE and SOC groups, respectively. Two subjects in the IRE group died from treatment-related complications, and one patient in the SOC group died due to chemotherapy-related complications. Conclusions: Initial results from the DIRECT registry study indicate the use of IRE for curative intent tumor ablation in combination with induction chemotherapy has equivalent morbidity and mortality rates when compared to standard-of-care chemotherapy alone.