Abstract
The present study aimed to determine the usefulness of contrast-enhanced ultrasonography (CEUS) with Sonazoid in evaluating the therapeutic response to sorafenib for hepatocellular carcinoma (HCC). In total, 26 patients with advanced HCC who received sorafenib and were followed up by CEUS were enrolled in the present study. CEUS was performed prior to and within 2-4 weeks of treatment, and the images of the target lesion in the post-vascular phase with a re-injection method were analyzed. The presence (+) or absence (-) of intratumoral necrosis and the intratumoral vascular architecture on micro-flow imaging (MFI) were compared prior to and subsequent to treatment. Target lesions that exhibited non-enhancement after re-injection were considered to indicate intratumoral necrosis. The intratumoral vascular architecture was classified into three groups, as follows: Vd, the intratumoral vessels visually narrowed or decreased; Vnc, the vessels remained unchanged; and Vi, the vessels were thickened or increased. Survival curves were estimated using the Kaplan-Meier method and compared using the log rank test between the intratumoral necrosis (+) and (-) groups, and among the Vd, Vnc and Vi groups. P<0.05 was considered to indicate a statistically significant difference. The number of patients in the intratumoral necrosis (+) and (-) groups was 8 and 18 patients, respectively, and the median survival time (MST) was 7.2 months [95% confidence interval (CI), 2.2-12.2] and 9.5 months (95% CI, 5.1-13.8), respectively (P=0.44). The MFI findings were observed in 11 patients in the Vd group, 10 patients in the Vnc group and 5 patients in the Vi group. The MSTs in the Vd, Vnc and Vi groups were 15.6 months (95% CI, 5.0-23.3), 11.0 months (95% CI, 3.5-17.6) and 3.6 months (95% CI: 1.2-6.0), respectively. The P-value for the differences between the Vd and Vnc groups, Vd and Vi groups, and Vnc and Vi groups were 0.78, 0.016 and 0.047, respectively, which indicated that the survival time decreased significantly in the Vi group. Evaluation of intratumoral vascular architecture using MFI demonstrates promise for assessing the therapeutic response to sorafenib in patients with HCC.
Highlights
Hepatocellular carcinoma (HCC) is the third most common cause of cancer‐associated mortality worldwide [1]
Of the 26 patients, 8 patients showed intratumoral necrosis and 18 patients did not, and the median survival time (MST) was 7.2 months and 9.5 months in the patient with and without intratumoral necrosis, respectively
Based upon the micro‐flow imaging (MFI) findings, the MST in the Vd, Vnc and Vi groups was 15.6 months, 11.0 months and 3.6 months, respectively
Summary
Hepatocellular carcinoma (HCC) is the third most common cause of cancer‐associated mortality worldwide [1]. Sorafenib (Nexavar; Bayer, Leverkusen, Germany) is an oral multi‐targeted tyrosine kinase inhibitor [4,5,6] that is indicated for unresectable advanced HCC and significantly improves the progression‐free and overall survival times of patients [7,8]. Sorafenib has been widely used for the treatment of unresectable advanced HCC, but it is an expensive drug that has certain adverse effects, such as hand-foot skin reaction and diarrhea [7]. Sorafenib is characterized by antitumor effects, including tumor growth inhibition and antiangiogenic effects, which makes it challenging to evaluate the therapeutic effects using the conventional Response Evaluation Criteria in Solid Tumors (RECIST) [9]. Alternative evaluation criteria, including tumor necrosis and intratumoral hemodynamics, such as the modified RECIST [10], Response Evaluation Criteria in Cancer of the Liver [11] and Choi criteria [12], have been recommended
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