Introduction: When lenvatinib is administered to people with hepatocellular carcinoma (HCC), tumor blood flow is reduced due to the inhibition of the vascular endothelial growth factor receptor (VEGFR) and fibroblast growth factor receptor (FGFR). Few studies have examined the decrease in tumor blood flow with respect to changes in tumor blood vessels (TBVs) in clinical practice. We investigated the mechanism of tumor blood flow control by investigating changes in the diameter of relatively large TBVs in large-sized lesions with high blood flow. Methods: From January 2011 to October 2021, patients receiving lenvatinib for unresectable intrahepatic HCC at Toranomon Hospital, Tokyo, Japan were considered for inclusion. We investigated the TBV diameter in the arterial phase of dynamic computed tomography (dynamic CT) before treatment and its change over time 2-12 weeks after lenvatinib initiation. The relationship between changes in TBV diameter and prognosis was also examined. Results: Of 114 patients treated with lenvatinib for HCC, 26 patients who had intrahepatic lesions with a tumor diameter of 30 mm or more enrolled in the study. The median tumor and TBV diameters before treatment were 58 mm and 2.55 mm, respectively. Twenty-five patients (96%) had a shrinkage in TBV diameter 2 to 12 weeks after lenvatinib administration. The maximum TBV diameter shrinkage of 20% or more was observed in 19 patients (73%), and progression-free survival (PFS) was prolonged in these patients compared to the group with less than 20% TBV diameter shrinkage (P = 0.039). Discussion/Conclusion: Due to the antiangiogenic effect of lenvatinib, a shrinkage in the TBV diameter of HCC was observed. The shrinkage of TBV may be regarded as a process of normalization of TBVs. The shrinkage of tumor blood vessels in imaging analysis may be associated with improved prognosis; however, additional studies are still required.

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