Compensatory Hypertrophy and Changes of Liver Function After Sequential Transarterial Chemoembolization, Stereotactic Body Radiation Therapy, and Immunotherapy (START-FIT) in Unresectable Hepatocellular Carcinoma.

Abstract

Sequential transarterial chemoembolization (TACE), stereotactic body radiation therapy (SBRT), and immunotherapy (START-FIT) has shown its promising potential as a downstaging therapy of unresectable hepatocellular carcinoma (HCC). This study aims to analyze the dynamic changes in liver volume and hepatic function following START-FIT. Thirty-three prospectively recruited patients with unresectable HCC received a single dose of TACE followed by SBRT at day 28, and immunotherapy every 2 weeks thereafter. Dynamic contrast magnetic resonance imaging and hepatic function were evaluated at baseline and 3-monthly intervals until disease progression, death, or end of the study. Future liver remnant (FLR), liver parenchymal, and tumor volumetric changes were assessed over time dynamically. Right lobe atrophy (P < .001), tumor shrinkage (P < .001), and left lobe hypertrophy (P < .001) were observed from 3 months, which continued throughout the study period. The maximal median %FLR hypertrophy is 27.8% and the fastest rate of percentage FLR hypertrophy occurred within first 3 months and plateaued at around 12 months, whereas the maximal tumor volume shrinkage was observed at 6 months and there was more than a triple decrease in median tumor volume as compared to baseline (78 mL; interquartile range [IQR], 43-309 mL vs 302 mL; IQR, 147-703 mL; P < .001). There was a trend suggesting a decrease in right portal vein size, and large planning target volumes were associated with FLR >30%. Child-Pugh score progression +2 was noted in 12%, 14%, 6%, and 4.3% at 3 months, 6 months, 12 months, and 24 months, respectively. There was no significant change in Child-Pugh score and albumin-bilirubin score at different time points. START-FIT can induce FLR hypertrophy while shrinking the primary tumor. Adding TACE and immunotherapy to SBRT did not hamper the process of FLR hypertrophy and liver function recovery. It has the potential to become a novel bridge-to-resection technique in patients with unresectable HCC.