Abstract：
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.
摘要：
循环肿瘤细胞(CTCs)与肝胆管肿瘤预后不良有关,包括肝细胞癌和胆囊癌，但它们在肝内胆管癌（ICC）中的价值是模糊的。本研究旨在探讨化疗期间CTC的变化及其与临床特征的相关性。晚期ICC患者的治疗反应和生存状况。51不可切除，我们连续纳入接受化疗的晚期ICC患者.在诊断时和化疗开始后2个月（M2）收集外周血样品，通过ISET方法进行CTC检测。诊断时的平均和中位CTC计数为7.4±12.2和4.0（范围：0.0-68.0），分别,92.2%的患者有一个以上的CTC。诊断时较高的CTC计数与淋巴结转移升高相关（p=0.005），远处转移（p=0.005）和TNM分期（p=0.001），但没有其他特征。此外,非客观反应患者诊断时的CTC计数高于客观反应患者(p=0.002)，诊断为3以上的CTC计数与无进展生存期（PFS）（p=0.007）和总生存期（OS）（p=0.036）相关。在M2时,CTC计数显著降低(p<0.001)。M2时的CTC计数也与较低的治疗反应相关(p<0.001)，CTC计数高于3与不良PFS（p=0.003）和OS（p=0.017）相关。经过多变量Cox分析，诊断高于3时的CTC计数和CTC计数从诊断增加到M2独立地预测了PFS和OS(p<0.05)。在化疗之前和期间检测CTC对于晚期ICC患者的预后是有用的。
