Combination of radiofrequency ablation with antiangiogenic therapy for tumor ablation efficacy:: Study in mice

Purpose: To prospectively determine whether modulation of renal cell carcinoma (RCC) tumor microvasculature by using the antiangiogenic drug sorafenib could increase the extent of radiofrequency (RF)-induced coagulation in an RCC animal tumor model. Materials and Methods: All investigations received animal care and utilization committee approval. RCC (human 786-0) was implanted subcutaneously into 27 nude mice. Sixteen mice were randomly assigned into one of three groups when tumors reached 12 mm in diameter: Six mice received 80 mg of sorafenib, a Raf kinase and vascular endothelial growth factor receptor inhibitor, per kilogram of body weight; five mice received 20 mg/ kg sorafenib; and five mice received a control carrier vehicle alone. Antiangiogenic therapy was administered until a mean 1-mm reduction in tumor diameter was noted in one group. These 16 mice received a standard dose of RF ablation. Ablation size was visualized by using 2% triphenyltetrazolium chloride. An additional 11 tumors in mice treated with sorafenib alone were stained with CD31 to determine microvascular density ( MVD). Resultant size of ablation was compared among groups; statistical significance was determined with analysis of variance. Differences in MVD were assessed with the Kruskal- Wallis test. Results: Over the 9-day administration of sorafenib, mean tumor size in the control group reached 15.2 mm +/- 0.8 (standard deviation). Tumors in mice receiving 20 mg/ kg and 80 mg/ kg sorafenib measured 12.2 mm +/- 0.6 and 11.1 mm +/- 0.5, respectively (P <.05). RF- induced coagulation diameter was 8.5 mm +/- 0.4 and 11.1 mm +/- 0.3 in the 20 mg/ kg and 80 mg/ kg sorafenib groups, respectively, but was only 6.7 mm +/- 0.7 for animals that underwent RF ablation alone (P <.01). Likewise, significant decreases in MVD were noted in the sorafenib-treated animals (P <.01). Conclusion: Treatment of RCC in nude mice with the antiangiogenic agent sorafenib resulted in markedly decreased MVD and significantly larger zones of RF-induced coagulation necrosis.