Yun-Fan Sun1,2, Peng-Xiang Wang1,2, Jian-Wen Cheng1,2, Zi-Jun Gong1,2, Ao Huang1,2, Kai-Qian Zhou1,2, Bo Hu1,2, Ping-Ting Gao1,2, Ya Cao3,4, Shuang-Jian Qiu1,2, Jian Zhou1,2,5, Jia Fan1,2,5, Wei Guo6, Xin-Rong Yang1,2. 1. Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China. 2. Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, China. 3. Cancer Research Institute, Xiangya School of Medicine, Central South University, Changsha, China. 4. Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Changsha, China. 5. Institute of Biomedical Sciences, Fudan University, Shanghai, China. 6. Department of Laboratory Medicine, Zhongshan Hospital, Fudan University, Shanghai, China.
Abstract
BACKGROUND: Postoperative extrahepatic metastases (EHM) contribute to a grim outcome in patients with hepatocellular carcinoma (HCC) who are undergoing curative surgical resection. The current study investigated the clinical value of circulating tumor cells (CTCs) in predicting EHM after curative surgery. METHODS: A total of 197 patients with HCC who were undergoing curative surgical resection were assigned to a retrospective training cohort (144 patients) or a prospective validation cohort (53 patients). The CELLSEARCH system was used for the detection of CTCs prior to surgical resection and 1 month thereafter. The cutoff value of CTCs was estimated using receiver operating characteristic analysis. Bonferroni correction was applied for multiple testing in a Cox proportional hazards regression model. RESULTS: In the training cohort, EHM was found to be associated with a higher postoperative CTC burden compared with no EHM (mean: 4.33 vs 0.52; P < .001). Receiver operating characteristic analysis demonstrated a postoperative CTC count ≥3 as the optimal cutoff value for the prediction of EHM. Patients with a postoperative CTC count ≥3 experienced a higher EHM risk (56.3% vs 5.5%) and a shorter median overall survival (31.25 months vs not reached) (all P < .001). The prognostic significance of a postoperative CTC count ≥3 also applied to patient subgroups with a low EHM risk, such as those with an α-fetoprotein level ≤400 ng/mL, absence of vascular invasion, well differentiation, and early tumor stage, and its predictive value was retained in patients with a continuous normal α-fetoprotein level during postoperative follow-up (all P < .05). The results were confirmed in the validation cohort. CONCLUSIONS: A postoperative CTC count ≥3 appears to be a surrogate marker for the prediction of EHM after curative surgical resection of HCC. More careful surveillance should be recommended to patients with a high CTC load to ensure the greater possibility of early interventions for postoperative EHM.
BACKGROUND:Postoperative extrahepatic metastases (EHM) contribute to a grim outcome in patients with hepatocellular carcinoma (HCC) who are undergoing curative surgical resection. The current study investigated the clinical value of circulating tumor cells (CTCs) in predicting EHM after curative surgery. METHODS: A total of 197 patients with HCC who were undergoing curative surgical resection were assigned to a retrospective training cohort (144 patients) or a prospective validation cohort (53 patients). The CELLSEARCH system was used for the detection of CTCs prior to surgical resection and 1 month thereafter. The cutoff value of CTCs was estimated using receiver operating characteristic analysis. Bonferroni correction was applied for multiple testing in a Cox proportional hazards regression model. RESULTS: In the training cohort, EHM was found to be associated with a higher postoperative CTC burden compared with no EHM (mean: 4.33 vs 0.52; P < .001). Receiver operating characteristic analysis demonstrated a postoperative CTC count ≥3 as the optimal cutoff value for the prediction of EHM. Patients with a postoperative CTC count ≥3 experienced a higher EHM risk (56.3% vs 5.5%) and a shorter median overall survival (31.25 months vs not reached) (all P < .001). The prognostic significance of a postoperative CTC count ≥3 also applied to patient subgroups with a low EHM risk, such as those with an α-fetoprotein level ≤400 ng/mL, absence of vascular invasion, well differentiation, and early tumor stage, and its predictive value was retained in patients with a continuous normal α-fetoprotein level during postoperative follow-up (all P < .05). The results were confirmed in the validation cohort. CONCLUSIONS: A postoperative CTC count ≥3 appears to be a surrogate marker for the prediction of EHM after curative surgical resection of HCC. More careful surveillance should be recommended to patients with a high CTC load to ensure the greater possibility of early interventions for postoperative EHM.
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Authors: Víctor Amado; Sandra González-Rubio; Javier Zamora; Rafael Alejandre; María Lola Espejo-Cruz; Clara Linares; Marina Sánchez-Frías; Gema García-Jurado; José Luis Montero; Rubén Ciria; Manuel Rodríguez-Perálvarez; Gustavo Ferrín; Manuel De la Mata Journal: Cancers (Basel) Date: 2021-05-19 Impact factor: 6.639