Correlation between circulating tumor cell levels and tumor response in patients with advanced hepatocellular carcinoma undergoing immunotherapy and molecular targeted therapy

Circulating tumor cells (CTCs) are closely associated with the progression of hepatocellular carcinoma (HCC). However, the clinical value of CTC detection in patients receiving systemic therapy for advanced HCC remains to be fully elucidated. A total of 125 patients with advanced HCC who underwent systemic therapy were enrolled in this study. Five milliliters of peripheral blood were collected at five time points: before treatment initiation, and 1 month, 3 months, 6 months, and 1 year after treatment. CTCs were isolated and captured using the Isolation by Size of Epithelial Tumor Cells (ISET) method. Tumor response to systemic treatment was evaluated according to the modified Response Evaluation Criteria in Solid Tumors (mRECIST). We further analyzed the correlation between dynamic changes in peripheral blood CTC levels and tumor response to systemic therapy. The overall objective response rate (ORR) and disease control rate (DCR) were 39.2% (49/125) and 82.4% (103/125), respectively. Dynamic monitoring of CTCs revealed that CTC levels remained persistently high and gradually increased in patients with progressive disease (PD). In patients with complete response (CR) or partial response (PR), CTC levels decreased progressively during treatment and stayed at low levels thereafter. For patients with stable disease (SD), CTC counts began to decline 3 months after treatment but remained higher than those in patients with CR or PR. Baseline CTC levels were negatively correlated with treatment efficacy: patients with higher baseline CTC counts exhibited poorer tumor responses. Patients with baseline CTC counts < 15, CTC counts < 13 at 1 month post-treatment, and CTC counts < 10 at 3 months post-treatment were more likely to achieve an objective tumor response and obtained better therapeutic outcomes. Additionally, these patients had significantly longer progression-free survival (PFS) and overall survival (OS) compared with those who exceeded the above cut-off values. Peripheral blood CTC counts are correlated with tumor treatment response in patients with advanced HCC. Serial CTC detection serves as a valuable tool for evaluating the efficacy of systemic therapy in advanced HCC.