Over the past years, image-guided tumor ablation, especially thermal ablation techniques, have gained ground clinically in the treatment arsenal for patients with surgically unresectable tumors. Ablation of these tumors using radiofrequency ablation (RFA) or microwave ablation (MWA) is currently considered common practice and has led to improved survival.1 Unfortunately, the suitability of RFA and MWA is limited when surgically unresectable tumors are located in proximity of heat- susceptible structures, such as large blood vessels, bile ducts and intestines. Thermal ablation of tumors adjacent to large blood vessels is associated with a higher incidence of incomplete eradication (heat-sink phenomenon).2-4 Because of the risk of biliary tract injury, including severe quality-of-life diminishing consequences such as biliary duct occlusion, haemobilia, cholangitis, leakage or the formation of fistulas or bilomas, ablation of tumors within 1 cm of the major bile ducts is not recommended.5-8 Until recently, these patients were designated to palliative chemotherapy. Irreversible electroporation (IRE) is a relatively new image-guided ablation technique based on electrical energy rather than thermal energy to eradicate the tumor. High-voltage electrical pulses are delivered through several needle electrodes placed in and around a tumor. These electrical pulses distorts the cellular membrane potential, leading to disruption of the membrane, eventually causing the cell to lose its homeostatic properties and become apoptotic.9 The main advantage of IRE over thermal ablation techniques is that IRE mostly affects cells, sparing the extracellular matrix, thus preserving the consistency of the previously mentioned vulnerable structures (bile ducts and large blood vessels).10-12 Furthermore, since the working mechanism is based on electrical energy rather than thermal energy, the technique efficacy is not impeded by heat-sink.13 The search towards novel therapies for patients with tumors unsuitable for surgical resection and thermal ablation and the (hypothetical) advantages of IRE, has led to the setup of several clinical studies on IRE for different tumor origins, including hepatic, pancreatic, renal and pulmonary tumors. In the preclinical part of this thesis, a better understanding of the exact working mechanism and electrical properties was intended. The clinical part of this thesis presented the results of the clinical studies in which IRE was performed: the PANFIRE-2 trial for locally advanced and post- resection pancreatic cancer, the COLDFIRE-2 trial for colorectal liver metastases, and the ALPACA trial for (recurrences of) perihilar cholangiocarcinoma.
|Qualification||Doctor of Philosophy|
|Award date||14 Sep 2021|
|Place of Publication||s.l.|
|Publication status||Published - 14 Sep 2021|