Patients and study design

We screened patients with unresectable HCC who were treated with lenvatinib at Hokkaido University Hospital and related hospitals between April 2018 and January 2020. Patients were included if they were treated with lenvatinib, were followed for more than 2 months, underwent dynamic computed tomography (CT) at baseline and every 2 to 3 months for evaluation of the treatment response, and had baseline preserved serum samples for the evaluation of serum growth factors as biomarkers and adequate clinical data available. Patients were excluded if they were followed for less than 2 months, received lenvatinib in conjunction with other treatments, had insufficient clinical data or no baseline preserved serum samples available, or lacked proper treatment response evaluation by dynamic CT.

Baseline clinical data, including sex; age; etiology of HCC; laboratory data, including alpha-fetoprotein (AFP) and des-gamma-carboxyprothrombin; Barcelona Clinic Liver Cancer (BCLC) stage; Child-Pugh score; and serum levels of FGF19, FGF21, ANG2, and VEGF, were collected. The patients were evaluated using laboratory tests and physical examination every 2 weeks after lenvatinib initiation. The treatment response was evaluated based on enhanced CT every 2 to 3 months after lenvatinib initiation.

This study was approved by the ethics committee of Hokkaido University Hospital (approval number: 017–0521). All patient’s data were fully anonymized, and were obtained from Hokkaido University Hospital and JCHO Hokkaido Hospital. The date range during which patients’ medical records were accessed, was April 2018-January 2020. All patients provided written informed consent to participate in the study and were provided the option to decline participation. This study conformed to the ethics guidelines of the Declaration of Helsinki.