High Frequency Irreversible Electroporation (H-FIRE) as a Therapeutic Modality for Liver Cancer Treatment and Its Effect on the systemic Extracellular Vesicle Population

High-frequency irreversible electroporation (H-FIRE) is a non-thermal ablation technique that uses intense, short, bipolar electrical pulses to induce cell death in cancerous tissues. It's being studied for treating hepatocellular carcinoma (HCC) in dogs. Previous in vitro research suggests H-FIRE may impact the release of extracellular vesicles (EVs).

This study aims to explore how H-FIRE affects peripheral extracellular vesicle (EV) dynamics, potentially providing insights into its broader systemic effects and implications for biomarker development in canine liver cancer treatment.

Dogs diagnosed with HCC were enrolled in a clinical trial. H-FIRE was applied to tumors, followed by surgical resection at three different time points. Peripheral blood samples were collected before and immediately after H-FIRE treatment. Plasma was isolated, aliquoted, and stored at -20°C. EVs were enriched from plasma via filtration and ultracentrifugation. Nanoparticle Tracking Analysis (NTA) quantified EV concentration and size distribution.

Ten patients provided pre- and post-treatment plasma samples. The median EV concentration in peripheral blood increased from 2.56 x 10^11 particles/ml pre-treatment to 2.68 x 10^11 particles/ml post-treatment (p = 0.0048). The mean EV size decreased from 99.32 nm pre-treatment to 87.82 nm post-treatment (p = 0.007). The mode of EV size decreased from 83 nm pre-treatment to 70.5 nm post-treatment (p = 0.0076).

The results of this study raise intriguing questions on the significance of changes in extracellular vesicle size and concentration post-treatment, as well as the potential clinical implications of these changes.