Quantitative assessment of thermal ablation in small animal tumor models: implications for pre-clinical studies of combination treatments

Background. Radiofrequency (RF) and other thermal ablation modalities in combination with systemic therapies are the subject of investigations for the treatment of tumors at risk of recurrence after first line therapies. The potential of combined therapeutic approaches is studied largely in small animals where size constraints and tumor-specific physical characteristics may significantly influence the local heating. Spatial-temporal analyses of tissue temperature profiles (i.e, thermal dosimetry) are largely neglected in preclinical studies, thus limiting the reliable assessment and interpretation of biological outcomes. Approach. Imaging-based information and complementary experimental reports of the 1) heat transfer conditions on the external surface of the tumor, 2) RF applicator position, 3) tumor shape and dimension, and 4) blood flow in major intra-tumoral vessels acquired from a total of N = 15 rat tumor models were used to build computational models of a local radiofrequency-hyperthermia system within a subcutaneous tumor. Analysis of the influence of each variable on 3D temperature profiles and on the percentage of tumor volume above lethal (50 °C) and below irreversible thermal damage (43 °C) thresholds, V50 and V43, were conducted at 15 min of coupled electromagnetic-thermal transfer simulations. Results: For each examined variable, changes in V50 values ranged between 1) 9 – 31%, 2) 9 – 18%, 3) 4 – 58%, and 4) 12 – 19% and those in V43 are between 1) 24 – 74%, 2) 51 – 78%, 3) 3 – 86%, and 4) 58 – 65% indicating sources of considerable variability in tissue thermal profiles. Conclusions. Information of ablation procedure parameters, i.e. estimates of the RF applicator location, and accessible measurements of tumor biophysical characteristics, i.e. tumor size, shape and blood flow profile in major arteries, should be consistently reported in experimental studies of local heating in small animals in order to study heat-induced bioeffects and compare the outcomes in combination approaches with systemic therapies.