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 timeintensity 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 Â 10 À4 ± 2.94 Â 10 À4 , 3.07 Â 10 À4 ± 3.79 Â 10 À4 , and 10.0 Â 10 À4 ± 20.8 Â 10 À4 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 Â 10 À3 ± 4.58 Â 10 À3 , 1.16 Â 10 À3 ± 1.57 Â 10 À3 , and 6.39 Â 10 À3 ± 22.8 Â 10 À3 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.

Prediction of Therapeutic Response Using Contrast-Enhanced Ultrasound in Japanese Patients Treated with Atezolizumab and Bevacizumab for Unresectable Hepatocellular Carcinoma

“…CEUS is a simple tool that can predict the therapeutic response of chemotherapy for diverse malignancies such as HCC, renal cell carcinoma, gastric carcinoma, and gastrointestinal stromal tumor [25][26][27]. CEUS can evaluate tumor necrosis and decreased blood flow inside the tumor more accurately than CT and MRI, and it is useful as an early therapeutic response evaluation tool in u-HCC cases treated with SOR and LEN [16,17,[28][29][30]. In par- ticular, SOR and LEN are considered to be suitable drugs for early evaluation by CEUS, because anti-tumor effects due to antiangiogenic effects appear early after the start of administration.…”

Diagnosing Hepatocellular Carcinoma Using Sonazoid Contrast-Enhanced Ultrasonography: 2023 Guidelines From the Korean Society of Radiology and the Korean Society of Abdominal Radiology

“…Funaoka et al [ 87 ] reported that Sonazoid CEUS was helpful for evaluating HCC after radiation treatment. After treating HCC with systemic agents such as sorafenib, Sonazoid CEUS was helpful in predicting treatment response by examining perfusion parameters or evaluating enhancement architecture [ 88 89 90 91 ]. However, most studies considered fewer than 50 patients and had preliminary study designs in which evaluation parameters were not established.…”

Evaluation and Prediction of Treatment Response for Hepatocellular Carcinoma

“…51 As lenvatinib strongly decreases the blood perfusion early after administration, several studies have used the contrastenhanced ultrasound with high temporal resolution to assess the tumor hemodynamics and early response to treatment. [52][53][54] Dynamic contrast-enhanced MRI under free-breathing using a stack-of-stars technique was developed as a method to evaluate the blood perfusion over time, and may be applied in the future to evaluate the early therapeutic effect of HCC after lenvatinib administration. 55,56 Evaluation of Treatment Response after ICI (Fig.…”