Circulating tumor DNA in peripheral blood may predict the efficacy of immune-targeted therapy in patients with hepatocellular carcinoma

Abstract

Background & Aims

Hepatocellular carcinoma (HCC) is a highly prevalent and fatal malignancy globally. Accurate prognosis prediction is crucial for developing personalized therapeutic strategies.

Methods

This study involved 28 HCC patients who received immune-targeted therapy at the Xiamen Branch of Zhongshan Hospital of Fudan University from April 2020 to June 2022. Next-generation sequencing (NGS) of circulating tumor DNA (ctDNA) was conducted at baseline and after two treatment cycles. The primary objective was to investigate the relationship between changes in variation allele frequency (VAF) during therapy and clinical outcomes.

Results

A total of 134 single nucleotide variants, 1 insertion-deletion mutation, and 5 copy number variations were detected across the cohort. A decrease in mean VAF (VAF_mean) after two cycles of immune-targeted therapy was associated with longer progression-free survival. The sensitivity and specificity of VAF_mean reduction in predicting partial response(PR) and complete response(CR) were 1.0 and 0.8125, respectively, which were higher than those of serum alpha-fetoprotein (AFP) levels (0.9167 and 0.4667). No significant correlation was observed between baseline mutation status and the efficacy of immune-targeted therapy.

Conclusions

This study highlights that advanced ctDNA analysis can detect somatic mutations in a substantial proportion of patients with advanced HCC. Monitoring ctDNA dynamics during immune-targeted therapy enables real-time assessment of disease status and provides a basis for optimizing treatment strategies.