Does doxorubicin survive thermal ablation? Results of an ex vivo bench top study

Abstract

C ombined transarterial chemoembolization (TACE) and percutaneous thermal ablation has shown clinical efficacy in the treatment of hepatocellular carcinoma (1). Not only do the embolic effects of TACE potentiate ablative heating by reducing vascular heat sink effects, but it is purported that TACE-mediated local chemotherapy delivery facilitates cytotoxic killing of any tumor cells that survive thermal destruction. When TACE precedes thermal ablation, such cytotoxic effects are contingent on the survival of chemotherapeutic drugs through the ablative heating period. However, the thermal effects of ablation on the structural integrity of locally delivered chemotherapeutic drugs are unknown. This bench top study was undertaken to test the hypothesis that doxorubicin (DOX) chemotherapy survives thermal ablative heating in a simple ex vivo model of combined TACE and thermal ablation. MethodsThis ex vivo bench top study did not require institutional review board approval. Sample preparation and treatmentThree fresh porcine psoas major muscle specimens (15 cm length × 10 cm width × 3 cm thickness) were submerged in aqueous DOX solution (empirically selected concentra- PURPOSEWe aimed to test the hypothesis that doxorubicin (DOX) survives thermal ablative heating in an ex vivo model of combined transarterial chemoembolization (TACE) and thermal ablation. METHODSFresh porcine psoas major muscle (3 samples, 15×10×3 cm) was submerged in aqueous DOX solution (60 µg/mL, 0.1 M) for 24 hours to passively saturate tissue. DOX-infused tissue was then dried and treated with microwave ablation (MWA) using a 2.45 GHz antenna at 65 W for 2, 5, and 10 minutes. Ablations were repeated in triplicate (9 total). Tissue was then sampled at both ablated and unablated control sites, and DOX concentration was quantified via ultra-high performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS), with samples analyzed in triplicate. Tissue DOX levels in ablation and control groups were compared using one-way ANOVA. RESULTSHomogeneous DOX uptake into porcine tissue was evident in all three samples. Mean DOX concentration in unablated tissue was 8.0±2.2 µg/mL. MWA was technically successful in all 9 procedures (100%), with tissue heating to 95-100°C. Mean tissue DOX concentration showed progressive reduction with increasing ablation time, measuring 6.7±1.3, 4.9±0.9, and 4.8±1.3 µg/ mL in MWA-treated tissue after 2, 5, and 10 minutes, respectively. Differences in tissue DOX levels between unablated tissue and MWA groups were statistically significant (P < 0.001). CONCLUSIONContrary to the initial hypothesis, tissue DOX concentration progressively decreased after MWA of longer ablation times. These results suggest that TACE followed by ablation may result in lower intratumoral DOX than would otherwise be anticipated for TACE alone.You may cite this article as: Morrison JD, Schlager CK, Lee AE, van Breemen RB, Gaba RC. Does doxorubicin survive thermal ablation? Results of an ex vivo bench top study. Diagn Interv Radiol 2018; 24: 28-30.