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Background: The aims of this study were to identify useful predictors of early tumor response to lenvatinib, and to evaluate the utility of estimation of tumor differentiation from pretreatment image analysis. Methods: We evaluated 37 consecutive patients with unresectable hepatocellular carcinoma (HCC) diagnosed by dynamic computed tomography (CT) who received lenvatinib. Pretreatment arterial- and portal-phase dynamic CT images were classified into three enhancement patterns: Type-2 is a homogeneous enhancement pattern with increased arterial blood flow; Type-3 is a heterogeneous enhancement pattern with a septum-like structure; and Type-4 is a heterogeneous enhancement pattern with irregularly shaped ring structures. Generally, macroscopic classification of the nodular type of SNEG and CMN types strongly relates to the Type-3 enhancement pattern, and histologically, the Type-1 enhancement pattern represents well-differentiated HCC, while the Type-2 and -3 patterns represent moderately-differentiated HCC; the Type-4 enhancement pattern is a significantly specific feature for predicting poorly-differentiated HCC.　Treatment response was evaluated using mRECIST at 8–12 weeks after initiation of lenvatinib. Results: In early treatment response evaluation, 6 of 37 patients (16%) achieved a complete response (CR), 22 (59%) experienced a partial response (PR), 6 (16%) had stable disease (SD), and 3 (8%) had progressive disease (PD); therefore, 28 of 37 patients (76%) experienced an objective response (OR). By dynamic CT enhancement pattern using mRECIST, the objective response rate (ORR) was significantly elevated along with increasing heterogeneity of enhancement pattern from Type-2 (54%) to Type-4 pattern (89%; P=0.046). Multivariate logistic regression analysis revealed that a pretreatment dynamic CT heterogeneous enhancement pattern (Type-3 and -4) (hazard ratio, 6.12; P=0.040) is a useful predictor of early OR. Conclusion: Lenvatinib provided a good early treatment response in patients with unresectable HCC. Estimation of tumor differentiation using image analysis was also useful for predicting early tumor response.

Objective

Background: Although DC Bead has been useful in treatment of multiple and large hepatocellular carcinoma, loading time of doxorubicin into the DC Bead takes a long time of 30-120 minutes. Epirubicin is also used as an antitumor agent together with DC Bead, but its loading efficiency was not sufficiently elucidated. Methods: To shorten loading time of epirubicin into DC Bead (100-300µm, 300-500µm, 500-700µm), we examined the following three methods after mixing the drug: (a) let stand in room temperature, (b) agitated for 30 seconds with Vortex mixer, and (c) sonicated for 30 seconds with ultrasonic cleaner. After loading of epirubicin by each method, supernatant concentration for epirubicin was assayed at 5, 10, 30, 60, and 120 minutes. Results: Epirubicin loading rates for small bead (100-300µm) at 5 minutes were 82.9 % in group a, 93.8% in group b, and 79.9 % in group c. Similarly, medium bead (300-500µm), 40.1% in group a, 65.7% in group b and 45.5% in group c, respectively. In large-sized bead (500-700µm), loaded rates of epirubicin were 38.8% in group a, 59.0% in group b and 48.0% in group c. Agitation of mixture of epirubicin and DC Bead with Vortex mixer significantly shortened the loading time, but sonication did not affect the time required. Microscopic examination did not lead to any morphological change of microspheres in all the methods. Conclusions: Short time of agitation with Vortex mixer reduced the necessary time for loading of epirubicin in every standard of DC Bead.

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