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Combination of Radiofrequency Ablation with Antiangiogenic Therapy for Tumor Ablation Efficacy: Study in Mice¹

¹ From the Laboratory for Minimally Invasive Tumor Therapy (A. Hakimé, A. Hines-Peralta, H.P., S.N.G.), Department of Radiology (A. Hines-Peralta, S.N.G.), and Department of Medicine (M.B.A., V.P.S., M.R.), Beth Israel Deaconess Medical Center, 1 Deaconess Rd, WCC 308B, Boston, MA 02215; and Department of Pathology, Brigham and Women's Hospital, Boston, Mass (S.S.). Received June 10, 2006; revision requested August 15; revision received September 27; accepted October 31; final version accepted November 21. Supported by National Cancer Institute Dana Farber/Harvard Cancer Center Renal Cancer SPORE grant 1 P50 CA10194-01. Address correspondence to S.N.G. (e-mail: sgoldber{at}caregroup.harvard.edu).

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.

© RSNA, 2007

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