Effects of hyperthermic temperatures induced during irreversible electroporation in pancreatic cancer The benefit of mild hyperthermia in IRE treatments

This thesis investigates thermal effects induced during irreversible electroporation (IRE) treatments for pancreatic cancer and their impact on cell permeabilization.
Pancreatic cancer has a poor prognosis, with most patients ineligible for surgical resection due to metastatic or locally advanced pancreatic cancer (LAPC). For patients with LAPC, systemic chemotherapy is standardly used for treatment, sometimes followed by local ablation techniques if the tumor becomes stable. However, standard thermal ablation modalities risk damaging surrounding tissues and have reduced efficacy near blood vessels due to cooling effects. IRE aims to avoid thermal damage by using high-voltage pulses to create nanopores in tumor cell membranes, disrupting homeostasis and inducing cell death. Nonetheless, IRE pulses inevitably cause some temperature rise in the target region. Mild hyperthermia (≤45°C) may enhance permeabilization, while higher temperatures (>45°C) could cause thermal ablation. Therefore, this thesis aims to determine the contribution of thermal effects to permeabilization effect during pancreatic cancer treatment with IRE, and to establish the extent of the induced thermal effects in the IRE treated region.
The key findings were that thermally ablative effects occur in small regions, mainly neighboring the electrodes, while mild-hyperthermic effects are present in a large part of the IRE treated region, predicting the significant presence of hyperthermia in IRE. Also, the impact of both effects is particularly strongly visible for the electric-field strength range that results in 50% cell viability. Future IRE treatment protocols should aim to maximize the synergy between irreversible permeabilization and mild-hyperthermic effects in the target volume while minimizing thermal ablation.