RF ablation with adjuvant therapy: comparison of external beam radiation and liposomal doxorubicin on ablation efficacy in an animal tumor model.

Purpose: To determine the critical thermal dosimetry and relative efficacy for RF ablation combined with external beam radiation (XRT) or liposomal doxorubicin (LD), in an animal tumor model.

Materials And Methods: This study was performed in two phases, in 13-18 mm diameter R3230 tumors subcutaneously implanted into Fischer rats. In phase 1, tumors (n = 30) were randomized into six groups. RF energy (titrated to 70 degrees C tip temperature) was applied for either 2.5 or 5 min (n = 15, each group). For each duration, one of three adjuvant therapies was applied (n = 5, each): no therapy (control), LD (1 mg intravenously, 30 min post-RF), or XRT (20 Gy at 1 Gy min(-1), within 2 h post-RF), with sacrifice at 48 h for pathologic analysis. In phase 2, thermal mapping was performed in 20 tumors throughout RF application (70 degrees C; 5 min), at 1.5-7 mm distances from the active electrode tip. Temperature profiles throughout the tumor were constructed and were used to interpolate temperatures over time at the critical ablation margin, to derive maximum threshold temperature, AUC (area under the curve) and CEM(43) (cumulative equivalent minutes at 43 degrees C). Ablation sizes and all calculated values were compared within and across experimental groups using MANOVA statistics with pair-wise T-test for individual comparisons.

Results: RF/XRT produced the largest coagulation (11.7 +/- 1.5 mm at 2.5 min, >or=15 +/- 0.7 mm at 5 min), followed by RF/LD, and then RF alone (p < 0.001 for all comparisons). RF/XRT demonstrated temperature threshold decreases from RF alone of 11.7 +/- 0.01 degrees C and 12.7 +/- 0.38 degrees C at 2.5 and 5 min respectively (with absolute thresholds of 42 degrees C for XRT compared to 52 degrees C for RF alone). RF/LD had decreases of 4.0 degrees C at 2.5 min and 4.4 degrees C at 5 min. Thermal dose requirements (AUC) decreased by 7.79% or 9.28% for RF/LD compared to >or=19.36% or 25.82% for RF/XRT at 2.5 and 5 min (p < 0.001). CEM(43) values followed similar patterns (p < 0.001), but with a reduction of 10(1) and 10(4) in magnitude for RF/LD and RF/XRT therapies at 5 min, respectively.

Conclusions: For a standardized RF dose, the combination of high dose XRT and RF increased ablation size compared to RF and liposomal doxorubicin or RF alone. Increased ablation size is more closely associated with decreased temperature threshold necessary to induce coagulation, rather than the total thermal dose.