The Efficacy and Safety of Irreversible Electroporation for the Ablation of Renal Masses: A Prospective, Human, In-Vivo Study.

The past decades have shown an increase in the incidence of small renal masses
(SRM). At the moment laparoscopic partial nephrectomy is the *golden standard*
in treatment of SRMs. Thermal ablation techniques are indicated in patients who
are poor surgical candidates or who have a predisposition to develop multiple
tumours. Recent studies have shown thermal ablation techniques to have similar
long-term oncologic results. Downsides to thermal ablation are the possible
damage to vital structures in the vicinity of the ablation zone, e.g.
collecting system or intestine, and unpredictable results due to difficulty in
monitoring the ablation zone and *thermal sink*.

Electroporation or electropermeabilisation is a novel technique with the
potential to overcome the main disadvantages of thermal ablation. It utilizes
electric pulses, traveling between two or more electrodes, to create
*nanopores* in the cell membrane. If the applied current reaches a certain
threshold these *nanopores* become permanent resulting in cell death. The use
of electric current means that IRE is not susceptible to *thermal sink* leading
to consistent ablation results. IRE ablation targets the cell membrane, sparing
tissue architecture and minimizing damage to blood vessels, nerves and the
renal collecting system.

The first in human studies have proven the safety of IRE for the ablation of
small renal masses. However the efficacy of IRE through histopathological
examination of an ablated renal tumour has not yet been studied, compromising
the correct and scientific evaluation of a new technology. This is the primary
objective of this research project.

Primary Objectives:
- To determine the efficacy of IRE ablation of renal masses, measured by
histopathologic examination of the targeted tumour.
- To determine the safety of IRE ablation of small renal masses, by evaluating
device and procedural adverse events.

Secondary Objective:
- To evaluate the efficacy of MRI in the imaging of ablation success, extend of
the ablation zone, one and three weeks post IRE ablation.
- To evaluate the efficacy of CEUS in the imaging of ablation success, extend
of the ablation zone, one and three weeks post IRE ablation.

This is a prospective, human, in-vivo pilot study. Patients will receive IRE
ablation of the SRM, performed under general anaesthesia, 4 weeks before
radical nephrectomy. Follow-up at one and three weeks post IRE will be
performed using MRI and CEUS imaging. After radical nephrectomy
histopathological examination will be performed to evaluate IRE ablation
success.

Patients will undergo IRE ablation of a renal tumour. The IRE procedure will
take place at the Intervention Radiology room at the OR complex under general
anesthesia with aditional muscle relaxation. ECG monitoring and synchronization
of IRE pulses will be performed. Needle electrodes will be placed under
ultrasound guidance using an external spacer for fixation during pulse
administration, between 3 and 5 electrodes will be used to adjust the ablation
zone. Device settings will be kept at fixed settings while electrode number and
placement will be adjusted for specific tumour shape and size. Pulses will be
administered in sets of 10 after which the device will recharge for 3.5
seconds. The IRE treatment cycle will take several minutes, total operating
time is estimated at 2 hours.

There are no benefits for patients that participate in this study.

Study participants will be exposed to additional risk when compared to standard
treatment. They will have to undergo an additional procedure under general
anaesthesia with muscle relaxation. Patients have to be informed about the
risks of procedural complications as noted in paragraph 6.4. The exposure to
ionizing radiation during the procedure has been estimated at 32 mSv.

Information on the efficacy of IRE, proven histopathologically, is a vital step
in order to progress to long term follow-up studies without tumour excision. So
far no study has investigated the efficacy of IRE for the ablation of renal
tumours in this manner.