Combination therapy of radiofrequency ablation and bevacizumab monitored with power Doppler ultrasound in a murine model of hepatocellular carcinoma.

ABSTRACT

PURPOSE: The purpose of this study was to monitor tumour blood flow with power Doppler ultrasound following antiangiogenic therapy with bevacizumab in order to optimally time the application of radiofrequency (RF) ablation to increase ablation diameter. MATERIALS AND METHODS: Athymic nude mice bearing human hepatocellular carcinoma xenografts were treated with bevacizumab and imaged daily with power Doppler ultrasound to quantify tumour blood flow. Mice were treated with RF ablation alone or in combination with bevacizumab at the optimal time, as determined by ultrasound. Ablation diameter was measured with histology and tumour microvascular density was calculated with immunohistochemistry. A computational thermal model of RF ablation was used to estimate ablation volume. RESULTS: A maximum reduction of 27.8 ± 8.6% in tumour blood flow occurred on day 2 following antiangiogenic therapy, while control tumours increased 29.3 ± 17.1% (p < 0.05). Tumour microvascular density was similarly reduced by 45.1 ± 5.9% on day 2 following antiangiogenic therapy. Histology demonstrated a 13.6 ± 5.6% increase in ablation diameter (40 ± 21% increase in volume) consistent with a computational model. CONCLUSION: Quantitative power Doppler ultrasound is a useful biomarker to monitor tumour blood flow following antiangiogenic treatment and to guide the application of RF ablation as a drug plus device combination therapy.