Study on the Safety and Efficacy of Algorithmically Controlled Electroporation for Treating Spontaneous Equine Melanomas

In recent years, electroporation, specifically irreversible electroporation (IRE), has shown significant potential as a non-thermal ablation technique in tumor treatment. Compared to traditional thermal ablation methods, IRE can better preserve the extracellular matrix and major blood vessels, minimizing damage to surrounding tissues. However, the current electroporation techniques face several challenges in practical applications, particularly in effectively controlling temperature changes during treatment to avoid thermal injuries. This study explores the safety and efficacy of algorithmically controlled electroporation (ACE) for treating spontaneous equine melanomas based on this background.

Research Source

This study was co-authored by Christopher C. Fesmire, Ross A. Petrella, Robert Williamson, Kobi Derks, Jennifer Ruff, Thomas McParkland, Erin O’Neil, Callie Fogle, Timo Prange, and Michael B. Sano. The research team belongs to the joint Department of Biomedical Engineering of North Carolina State University and the University of North Carolina at Chapel Hill, as well as the College of Veterinary Medicine at North Carolina State University. This paper has been accepted by IEEE Transactions on Biomedical Engineering and is scheduled to be published in 2024.

Research Procedure

The main workflow of this study includes computer modeling and ex vivo experiments, the development and validation of electrode and temperature control systems, the implementation of clinical trials, and data analysis. These steps are detailed as follows:

Computer Modeling and Ex Vivo Experiments

First, the research team developed a coaxial electrode combined with a high-voltage pulse generation system, integrated with a temperature feedback control system. Using finite element modeling and ex vivo experiments, the system’s ability to achieve and maintain target temperatures was verified. The model simulated a cylindrical tumor tissue domain with a 5 cm radius and 5 cm height. The central needle of the coaxial electrode was set as the cathode, and the outer ring electrode as the anode. Using COMSOL Multiphysics software, the electric field distribution and temperature changes under different geometric parameters and treatment voltages were studied.

Development and Validation of Electrode and Temperature Control Systems

The research team designed and 3D printed an electrode handle structure with embedded fiber optic temperature sensors. Using an ex vivo pig liver model, internal and external temperature sensors were compared to calibrate and validate the temperature control algorithm. Additionally, the team developed a customized pulse generator to enable real-time collection of pulse parameters and temperature data.

Clinical Trials

Subsequently, the research team conducted ACE treatment clinical trials for equine melanomas at the North Carolina State University College of Veterinary Medicine. The study included five dogs with spontaneous melanomas, with each tumor receiving electroporation treatment durations of 0.005s, 0.01s, or 0.02s based on its volume. The treatments were conducted while the patients were awake and standing, under only mild sedation.

Research Results

Temperature Control Validation

Ex vivo experiment results showed that with a standard constant pulse rate, the externally measured highest temperature exceeded the internally measured temperature. As the energy transfer rate increased, the temperature difference between the two also increased. With active temperature control, the temperature difference between external and internal measurements significantly reduced to 8.3%. This indicates that the temperature control algorithm can effectively maintain the tumor temperature near the set value, preventing thermal injuries beyond the target temperature.

Computer Simulation Results

Simulation results demonstrated that the coaxial electrode could cover potential tumors with diameters ranging from 1cm to 2cm. Compared to traditional two-needle electrode configurations, the coaxial electrode had a larger treatment range. Time-dependent simulations showed that due to the transient temperature’s impact on tissue electrical conductivity, the electric field distribution changed over time. Temperature control significantly reduced the thermal damage zone while maintaining efficient tumor treatment volume.

Clinical Trial Results

In clinical trials, all treatments were successfully completed without adverse events. The average temperature was controlled at 42.2±5.2ºC, with treatment currents increasing from 14.6±8.3A to 20.4±9.2A. The study found that electroporation treatments of all durations led to tumor volume reduction or complete regression. Tumor volumes decreased by 100%, 98%, and 100% on average, respectively.

Safety and Efficacy

The ACE method exhibited excellent safety and efficacy in treating equine melanomas. The temperature control algorithm can adjust the energy transfer rate in real-time without prior knowledge of tissue electrical or thermal properties, providing non-thermal treatment. Furthermore, the algorithm’s flexibility allows clinicians to adjust temperature settings in real-time based on tumor location and treatment needs.

Significance and Value

This study is the first to validate the feasibility of using algorithmically controlled electroporation for treating live equine melanomas, providing new insights for subsequent cancer treatments. Compared to traditional methods, the ACE method can achieve effective tumor ablation without complex pre-treatment planning and knowledge of tissue properties, avoiding excessive heating and subsequent thermal injuries. This technology holds significant promise in tumor treatment applications, particularly in clinical scenarios where precise energy control is needed to avoid thermal injuries.

Future research should further expand clinical test samples, explore applications for various tumor types and deep-seated tumors, and optimize treatment parameters to improve therapeutic outcomes. Through this study, ACE technology has the potential to become a safer and more efficient tumor treatment method, offering more treatment options for cancer patients.