Evaluating the therapeutic effect of lenvatinib against advanced hepatocellular carcinoma by measuring blood flow changes using contrast-enhanced ultrasound

Abstract

Background: The antitumor effect of a drug is considered to be associated with a decrease in tumor blood flow. Aims: We investigated whether the efficacy of lenvatinib (LEN) could be accurately assessed by measuring blood flow in hepatocellular carcinoma (HCC) during early treatment stages. Methods and results: Blood flow changes and treatment results of 19 patients who underwent contrast-enhanced ultrasound (CEUS), before and after LEN administration, in Kurume University Hospital from July 2018 to June 2020 were examined. Blood flow was evaluated after the intravenous administration of perflubutane (0.015 ml/kg). The vascular phase was photographed and used as RAW data, and time-intensity curve analysis was used to obtain the region of interest (ROI) on the entire tumor nodule and quantify tumor blood flow. The evaluation was performed before and 1 and 4 weeks after LEN administration. Mean ± standard deviation (SD) values of the brightness of blood flow in the background liver before and 1 and 4 weeks after LEN administration were 2.84 × 10−4 ± 2.94 × 10−4, 3.07 × 10−4 ± 3.79 × 10−4, and 10.0 × 10−4 ± 20.8 × 10−4 dB, respectively. Blood flow in the background liver did not significantly decrease at 1 and 4 weeks compared with that before treatment. Mean ± SD values of the brightness of blood flow in HCC before and 1 and 4 weeks after administration were 3.49 × 10−3 ± 4.58 × 10−3, 1.16 × 10−3 ± 1.57 × 10−3, and 6.39 × 10−3 ± 22.8 × 10−3 dB, respectively. Blood flow in HCC after 1 week was significantly lower than that before administration (p =.0192). The therapeutic effects were significantly higher in the group with ≥50% blood flow reduction in HCC at 1 week after administration (p =.0038) and the group with reduced blood flow in HCC at 4 weeks after administration (p =.0051) than those before administration. Conclusion: Early blood flow evaluation by CEUS may be useful in predicting the therapeutic effect of LEN for unresectable advanced HCC.