The research of sorafenib in combination with microwave ablation on rabbit orthotopic VX2 liver tumor model

Abstract

Objective To evaluate the value of sorafenib as an adjuvant therapy in combination with microwave (MW) ablation on rabbit VX2 liver tumor model. Methods Thirty-seven rabbits with orthotic VX2 liver tumors were randomly divided into MW group (n=11), combination treatment group (n=14) and control group (n=12). MW therapy was performed with an output power of 20 W for one minute, achieving a maxim ablation diameter of about 1 cm. Sorafenib was given with a dosage of 30 mg/kg per day, while saline were given to the control group and the MW group. Tumor growth-curve in each group was drawn according to tumor volumes before and after treatment. The therapeutic efficacy was evaluated by contrast enhanced ultrasound (CEUS), magnetic resonance imaging (MRI), pathological and immunohistochemical examinations. The independent samples t-test and One-way ANOVA test were used to analyze the quantitative data. Chi-square test and fisher exact test were used to analyze the classified data. Two-tailed P<0.05 was considered statistically significant. Results The tumor growth was accelerated in MW group compared with control group and combination treatment group. The mean tumor volume in MW group at 3 d, 7 d and 14 d was significantly larger than those in two other groups (P=0.007, 0.001, 0.001), whereas no significant differences were found in tumor volume between control group and combination treatment group (P=0.381, 0.069, 0.328). A low metastases rate was shown in combination treatment group compared with other two groups. In combination treatment group, CEUS showed short rod-like and rim-like hypo-enhancement mainly detected in the periphery of lesion. However, conglomerate and latticed hyper-enhancement were the most patterns in MW group, with enhanced areas both in peripheral and internal of tumors. The apparent diffusion coefficient (ADC) value on diffused weighted image (DWI) was higher compared with that of the control and MW group, with statistical significance (1.845±0.503 vs. 1.102±0.149, 0.979±0.235). With adjuvant therapy of sorafenib after insufficient ablation, the microvessel density (MVD) was lower than that of control group (5.33±3.11 vs. 12.63±6.88), whereas in MW group the MVD was higher than that of control group (18.20±2.30 vs. 12.63±6.88), with statistical significance. Conclusion Insufficient thermal ablation promotes residual tumor progression. While the adjuvant therapy of sorafenib serves as an effective way to suppress the overgrowth and neovasculation of residual tumor after insufficient thermal ablation. Key words: Microwave ablation; Sorafenib; Orthotopic VX2 liver tumor model; Contrast enhanced ultrasound; Microvessel density; Apparent diffusion coefficient