Modeling a Freeze-Thaw Cycle to Treat Lung Cancer
Dugard, Lauren; Hayes, Scott; Holter, Tara; Leviter, Julie
This study examines the effects of pre-freezing on the RF ablation of lung cancer, a widespread disease in the United States. While current treatments utilize cryosurgery or RF ablation to destroy lung tumors, neither method ensures the tumor destruction. Sun et al. (2008) describes an alternative treatment combining both cryosurgery and RF heating techniques, consisting of 10 minutes of pre-freezing with a -150 degrees C probe followed by 30 minutes of RF heating (1). Pre-freezing acts to lower the inactivation energy of the tissue, resulting in an increased radius of tumor death for the same duration of resistive heating. The study aims to examine the effects of pre-freezing on RF ablation surgery of a lung tumor, verify the findings of Sun et al. using COMSOL, and examine the sensitivity of the freeze-thaw procedure to tumor and tissue material properties. COMSOL Multiphysics was used to model the freeze-thaw procedure for a lung tumor with a 16.7 mm radius, in comparison with simple RF heating. Pre-freezing was simulated as heat transfer by conduction with a constant -150 degrees C temperature probe with a 2.5 mm probe radius, and accounted for latent heat in tabulated data for apparent specific heat of the tissue. RF heating was simulated by implementing the voltage equation to account for resistive heat generation in the tissue. Cell radius of tumor death was calculated using an equation for cell death due to heating formulated by Sun et al. (2008). The COMSOL model was verified by comparing the cell death radius to values reported by Sun (2008). The applied voltage was first set to 17.6 V to destroy a tumor radius of 8.7 mm with simple RF heating as observed by Sun et al. (2008). The freeze-thaw procedure was implemented for a range of inactivation energy values from 136 to150 kcal/mol. The energy of inactivation energy required for a tumor death radius of 12.7 mm was143200 cal/mol, a 0.0485% difference from the literature reported of 143,898 cal/mol. For the tumor we modeled in COMSOL, the voltage was adjusted to 20 V to destroy the entire area of tumor and minimize damage to normal tissue. A sensitivity analysis was conducted for thermal conductivity, density, and specific heats of the tissue and tumor, and inactivation energy. The model demonstrated that ten minutes of pre-freezing can increase the effectiveness of RF ablation. This resulted in a larger area of tumor destruction and allows for a lower voltage or reduced duration of probe contact. Furthermore, the material properties of the tumor and surrounding tissue had a minimal effect on the radius of tumor death, suggesting variation between patients and tumor composition would have little effect on the effectiveness of the freeze-thaw treatment. Before the procedure could be used for animal trials or human use, the required voltage for the freeze-thaw treatment of various tumor sizes and geometries must be calculated, and the model should be run using all biologically probable parameters. Nonetheless, the freeze-thaw procedure combines cryosurgical and RF ablation surgical techniques that have already been proven safe and effective for human use. Therefore, the freeze-thaw procedure may improve the outcome of lung cancer cases with minimal cost to develop and comparable patient risk to current treatment procedures.
BEE 4530 Project
cryosurgery; lung cancer; pre-freezing; COMSOL