Circulating tumor cells as liquid biomarker for high HCC recurrence risk after curative liver resection

// Johann von Felden 1, * , Kornelius Schulze 1, * , Till Krech 2 , Florian Ewald 3 , Björn Nashan 3 , Klaus Pantel 4 , Ansgar W. Lohse 1 , Sabine Riethdorf 4 and Henning Wege 1 1 Department of Internal Medicine, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany 2 Institute of Pathology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany 3 Department for Hepatobiliary and Transplant Surgery, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany 4 Department of Tumor Biology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany * These authors have contributed equally to this work Correspondence to: Henning Wege, email: h.wege@uke.de Keywords: hepatocellular carcinoma, CTC, BCLC A, liquid biopsy, precision medicine Received: July 13, 2017 Accepted: July 31, 2017 Published: September 23, 2017 ABSTRACT Background: Early hepatocellular carcinoma (HCC) has a limited prognosis due to recurrence rates of more than 50% after liver resection. Recurrence within two years is believed to be caused by untraceable micro metastases at the time of resection. The objective of this study was to investigate EpCAM-positive circulating tumor cells (CTC) as liquid biomarker to identify patients with high risk of recurrence after liver resection. Methods: 61 patients undergoing resection between 2011 and 2015 were consecutively enrolled. Blood specimens were obtained prior to surgery and processed with the CellSearch TM system, detecting EpCAM-positive CTC. The primary endpoint was recurrence-free survival (RFS). Results: 13 women and 44 men (63.6 ± 11.1 years) were finally evaluated. CTC-positive patients had a significantly higher risk of recurrence with a hazard ratio (HR) of 2.3 (p=0.027), and a shorter RFS compared to CTC-negative patients (5.0 ± 1.5 vs. 12.0 ± 2.5 months, p=0.039). As expected, incomplete resection (R1) was also associated with shorter RFS (HR=2.6, p=0.035), but vascular invasion was not. However, the predictive power of CTC status was independent of R1. Conclusion: Bloodstream detection of CTC prior to curative-intended liver resection discloses an elevated risk of HCC recurrence and could identify patients, who might benefit from adjuvant treatment.