Circulating tumor DNA as a potential prognostic and predictive biomarker during interventional therapy of unresectable primary liver cancer

Abstract

Background: Imaging and alpha fetoprotein (AFP) measurement are used as surveillance methods during interventional therapy in patients with unresectable liver cancer, but their accuracy has been challenged in patients receiving drug perfusion therapy. Circulating tumor DNA (ctDNA) can reflect tumor load and treatment efficacy. Studies of the prognostic value of ctDNA in unresectable liver cancer are needed. Methods: Forty-two patients with unresectable liver cancer were prospective enrolled in this study. Pretreatment, in-treatment plasma samples and available matched tissue samples were collected. Targeted-capture sequencing of 1,021 genes that are frequently mutated in solid tumors. Results: Targeted-capture sequencing of 1,021 genes that are frequently mutated in solid tumors revealed that the most frequently mutated genes in ctDNA were TP53 (52.4%) and TERT (35.7%). The ctDNA abundance was more closely correlated with tumor size than the AFP level and was also related to BCLC stage (P<0.001). Gene mutations profile in ctDNA with progressed disease. PD patients were enriched in TP53 mutation group compared with TP53 wildtype group (P=0.0221). Moreover, interventional therapy was more effective in patients without TP53 mutation (OS: P=0.0589; PFS: 0.0411). The dynamic change of ctDNA showed consistent or more sensitivity than imaging for evaluating treatment response. The tumor mutation burden was highly consistent between tissue and blood samples (P<0.0001). Conclusions: ctDNA was a reliable biomarker to assist in diagnosis and evaluation of prognosis and treatment efficacy in advanced liver cancer. Considering that biopsy is unnecessary when advanced liver cancer is diagnosed, ctDNA may be an ideal biomarker for evaluating tumor mutation burden prior to immunotherapy.