Liver-Directed Irreversible Electroporation Therapy: Longitudinal Efficacy Studies in a Rat Model of Hepatocellular Carcinoma

• Published in: Cancer research (Chicago, Ill.) Vol. 70; no. 4; p. 1555
• Main Authors: Guo, Yang, Zhang, Yue, Klein, Rachel, Nijm, Grace M., Sahakian, Alan V., Omary, Reed A., Yang, Guang-Yu, Larson, Andrew C.
• Format: Journal Article
• Language: English
• Published: 02.02.2010
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/0008-5472.CAN-09-3067

Irreversible electroporation (IRE) is an innovative local-regional therapy that involves delivery of intense electrical pulses to induce nano-scale cell membrane defects for tissue ablation. The purpose of this study was to investigate the feasibility of using irreversible electroporation as a liver-directed ablation technique for the treatment of hepatocellular carcinoma (HCC) in the N1-S1 rodent model. N1-S1 rat hepatoma was grown in 30 Sprague-Dawley rats; these animals were divided into treatment and control groups. For treatment groups, IRE electrodes were inserted and 8 100 µs 2500V pulses applied to ablate the targeted tumor tissues. For both treatment and control groups (6 rats/group), MRI scans were performed at base-line and 15-day follow-up intervals to measure tumor sizes (1D maximum diameter, Dmax, and estimated 2D cross-sectional area, Cmax) to determine longitudinal outcomes based upon observed size changes. Additional groups of treated animals were sacrificed at 1, 3, and 7-day intervals post-therapy for pathology assessment of treatment response. MR images demonstrated significant tumor size reductions within 15 days post-therapy (32±31% Dmax and 52±39% Cmax decreases compared to 110±35% Dmax and 286±125% Cmax increases for untreated tumors). Pathology correlation studies showed a clear progression from poorly differentiated viable HCC tissues pre-therapy to extensive tumor necrosis and complete regression in 9 out of 10 treated rats 7–15 days after treatment. Our findings suggest that IRE was effective for targeted ablation of liver tumors in the N1-S1 rodent model; IRE may offer a promising new approach for liver-directed treatment of HCC.