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Identification and monitoring of mutations in circulating cell-free tumor DNA in hepatocellular carcinoma treated with lenvatinib

藤井 康智 広島大学

2022.03.23

概要

Background: There has been a recent surge in interest in predicting biological effects associated with genomic
alterations in order to implement personalized cancer treatment strategies. However, no reports have yet evaluated
the utility of profiling blood-based circulating tumor DNA (ctDNA) in hepatocellular carcinoma (HCC) patients
treated with lenvatinib (LEN).
Method: We retrospectively performed ctDNA next-generation sequencing (NGS) analysis in 24 patients with
advanced HCC at baseline and 4 weeks after initiation of LEN. Association of the changes in variant allele
frequencies (VAFs) during treatment and clinical outcome were evaluated.
Results: In total, 131 single nucleotide variants, 17 indels, and 23 copy number variations were detected as somatic
alterations in 28, 6, and 12 genes, respectively in 23 of 24 patients. The most frequently altered genes were TP53
(54%), CTNNB1 (42%), TERT (42%), ATM (25%), and ARID1A (13%). The reduction in the mean frequency of variants
(VAFmean) following 4 weeks of LEN treatment was associated with longer progression-free survival. The specificity
and sensitivity of the reduction of VAFmean for predicting partial response were 0.67 and 1.0, respectively, which
were higher than those of serum α-fetoprotein level (0.10 and 0.93, respectively). No association between the
mutation status at baseline and the effectiveness of LEN was observed.
Conclusion: Our study demonstrated that somatic alterations could be detected in the majority of advanced HCC
patients by ctDNA profiling and that ctDNA-kinetics during LEN treatment was a useful marker of disease
progression. These results suggest that ctDNA profiling is a promising method that provides valuable information in
clinical practice. ...

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