Longitudinal change of circulating tumour cell count and its relation to prognosis in advanced intrahepatic cholangiocarcinoma patients

Circulating tumour cells (CTCs) are related to poor prognosis in hepatobiliary cancers, including hepatocellular carcinoma and gallbladder carcinoma, but their value in intrahepatic cholangiocarcinoma (ICC) is obscure. This study aimed to investigate the change in CTCs during chemotherapy and its correlation with clinical features, treatment response and survival profile in advanced ICC patients. Fifty-one unresectable, advanced ICC patients who underwent chemotherapy were consecutively enrolled. Peripheral blood samples were collected at diagnosis and 2 months (M2) after chemotherapy initiation for CTC detection via the ISET method. The mean and median CTC counts at diagnosis were 7.4 ± 12.2 and 4.0 (range: 0.0-68.0), respectively, with 92.2% of patients having more than one CTC. A higher CTC count at diagnosis was correlated with elevated lymph node metastasis (p = 0.005), distant metastasis (p = 0.005) and TNM stage (p = 0.001) but no other characteristics. In addition, the CTC count at diagnosis was higher in nonobjective-response patients than in objective-response patients (p = 0.002), and a CTC count at diagnosis above 3 correlated with worse progression-free survival (PFS) (p = 0.007) and overall survival (OS) (p = 0.036). At M2, the CTC count was greatly decreased (p < 0.001). CTC count at M2 also correlated with lower treatment response (p < 0.001), and CTC counts above 3 were associated with poor PFS (p = 0.003) and OS (p = 0.017). After multivariate Cox analyses, CTC counts at diagnosis above 3 and CTC count increase from diagnosis to M2 independently predicted PFS and OS (p < 0.05). Detection of CTCs before and during chemotherapy is useful for prognostication in advanced ICC patients.