Pulsed Electrical Field Ablation Plus Intratumoral Immunotherapy for Hepatocellular Carcinoma

The fourth leading cause of cancer death worldwide, hepatocellular carcinoma, is known to progress relentlessly and recur despite treatment. Given the high tumor mutational burden, hepatocellular carcinoma is an attractive target for immunotherapy. Early trials of systemic checkpoint inhibitors have produced promising results, although complete and durable immunologic tumor eradication remains elusive. Pulsed electrical field ablation is a nonthermal ablation technology that causes apoptosis of diseased cells, while preserving the neoantigens for subsequent immune recognition by antigen-presenting cells and effectors. The neoantigens are released when the membrane is permeabilized. Furthermore, pulsed electrical field ablation was shown to induce the formation of tertiary lymphoid structures, congregations of immune cells that form inside the tumor at the ablation site, analogous to a lymph node. We present a novel treatment regimen with pulsed electrical field ablation combined with intratumoral immunotherapy injection. Treatments were performed using computed tomography guidance in a percutaneous manner. Pulsed electrical field ablation was performed within the tumor using the Aliya pulsed electrical field system (Galvanize, Redwood City, CA). After ablation was performed, the immunotherapy was administered into the tumor, mixed with iodinated contrast for visibility and gelfoam slurry for local retention. Three patients underwent treatment, and all treated tumors responded favorably with a decrease in size and a marked decrease in postcontrast enhancement. There were no treatment-related complications or high-grade toxicities. Pulsed electrical field ablation plus intratumoral immunotherapy may be safe and effective for the treatment of advanced hepatocellular carcinoma.