High Epithelial Cell Adhesion Molecule–Positive Circulating Tumor Cell Count Predicts Poor Survival of Patients with Unresectable Hepatocellular Carcinoma Treated with Transcatheter Arterial Chemoembolization
The detection of peripheral blood circulating tumor cells (CTCs) has been used to develop the association between recurrence and prognosis after surgical resection or liver transplantation in patients with hepatocellular carcinoma (HCC). Through a prospective analysis, the authors sought to assess the role of epithelial cell adhesion molecule (EpCAM)–positive CTC count in predicting survival outcomes of chemoembolization in patients with unresectable HCC. 89 patients with a pathologic or clinical diagnosis of HCC had peripheral blood samples analyzed through the CellSearch system for EpCAM positive CTCs 1-2 days prior to chemoembolization and were stratified into three groups for analysis (0-1 CTC, 2-5 CTCs, and ≥ 6 CTCs) based on the Cox proportional-hazards model. Chemoembolization was performed using oxaliplatin, pirarubicin, and fluorouridine; disease progression was evaluated per modified Response Evaluation Criteria In Solid Tumors as identified by 2 senior radiologists who were blinded to the clinical information.
After controlling for Child-Pugh class, ECOG status, presence of vascular invasion, number of tumors, tumor size, and AFP, the authors found that a CTC was an independent predictor of overall survival (OS) in patients with HCC treated with chemoembolization (P = .049). The risk of death in the high-level and moderate-level groups was 2.819 fold (P = .016) and 1.301 fold (P = .477) higher, respectively, than in the low-level group. The median OS times of patients with high, middle, and low CTC levels were 5.3 months, 10.5 months, and 19 months, respectively (P < .001). Analysis regarding progression free survival (PFS) showed that the risk of progression was 4.745 fold greater (P <.0001) in the high-level group and 1.525 fold greater (P =.201) in the moderate-level group compared with the low level group. High EpCAM-positive CTC counts appear to be associated with poor survival of patients with unresectable HCC treated with chemoembolization.
Note–Groups 0, 1, and 2 represent low level group (CTC count 0/1), moderate level group (CTC count 2–5), and high level group (CTC count ≥ 6). Variable CTC was compared vs group 0 in Cox analysis.
AFP = a-fetoprotein; CTC = circulating tumor cell; ECOG = Eastern Cooperative Oncology Group; HR = hazard ratio; OS = overall survival; PS = performance status.
*Refers to imaging diagnosis, not pathologic diagnosis.
The results of the present study are in accordance with previous studies with regard to EpCAM-positive CTC counts correlating with tumor recurrence and survival, particularly in patients with high-level counts (CTC ≥ 6). The association between higher CTC counts and malignant features of HCC including satellite foci, vascular invasion, and poorly differentiated tumors is the suggested explanation for these findings.
However, the findings of the study must be interpreted with caution as 63 of the included patients had previously received treatment with 50 of those patients undergoing previous chemoembolization. The variation between primary chemoembolization and repeat chemoembolization on CTC counts and patient responsiveness is unknown. Further, the implications of added cost and potential for false positive results (0.6 %– 5.3%) must be considered when implementing this prognostic tool. As CTC counts seem to correlate with malignant HCC features and late BCLC stage, the value added by this test to prognostication for unresectable HCC beyond that already established by previous staging/imaging findings appears limited. Despite these reservations, using CTCs to detect and predict the responsiveness of various oncologic treatments appears to be a promising field of investigation.
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Shen J, Wang W-S, Zhu X-L, Ni C-F. High Epithelial Cell Adhesion Molecule–Positive Circulating Tumor Cell Count Predicts Poor Survival of Patients with Unresectable Hepatocellular Carcinoma Treated with Transcatheter Arterial Chemoembolization. Journal of Vascular and Interventional Radiology [Internet]. 2018 Nov 1;0(0).
Jacob Bundy, MD, MPH
Department of Surgery
University of Michigan Health System