Oncological Evaluation Using Circulating Tumor Cells and PET-CT of Patients with Hepatocellular Carcinoma Undergoing Liver Transplantation

Abstract

Introduction: Hepatocellular carcinoma (HCC) is one of the most prevalent malignancies. Liver transplantation (LT) is potentially the best curative therapeutic option in selected cirrhotic patients (Milan criteria). Nevertheless, the recurrence rate is high (10-20%) and there are not efficient markers of biological pretransplant activity. Aim: to determine the number of CTCs in patients with HCC awaiting for LT, to study its possible association with AFP levels, positivity of PET-CT and clinical variables (vascular invasion, tumor size, waiting list time, post-LT recurrence…) and to compare CTC levels before and after LT (one and six months and one and two years). Method: Peripheral blood was obtained from 30 patients included in the waiting list and after 1 and 6 months and 1 and 2 years of the LT. CTCs immunomagnetic isolation was performed with anti-EpCAM antibodies by IsoFlux™ system. Statistical analysis: Rho Spearman test, Mann-Whitney U test and Wilcoxon test were used when appropriate (SPSS 22.0;Inc;USA). Results: A total of 30 patients with HCC within Milan criteria were included. The median follow-up was 57 months (IQR: 45-62). Four patients (13.3%) had a recurrence. Before LT, at least one CTC was counted in 24 patients (80%). The average concentration of CTCs before LT was 9(IR:0-93) CTCs/10 ml. At 1 and 6 months, 1 and 2 years of LT, CTC levels were 4(IR:1-22), 3(IR:0-20), 2(IR:0-6) and 3(RI:1-9) CTCs/10 ml respectively. Statistically significant differences were found between pre-LT levels and CTC levels at one year (Z = - 2.375;p = 0.018) and at 2 years (Z = - 2.076;p = 0.038).Pre-LT levels of CTC were associated with a prolonged time on the waiting list (rs = 0.550;p = 0.002), positive PET-CT (U = 25;z = - 2.250;p = 0.024), larger tumor size (rs = 0.570;p = 0.001), increase in the sum of the diameters of viable tumors (rs = 0.487;p = 0.006) and presence of microvascular invasion (U = 10;z = - 2.130;p = 0.033). The recurrence-free survival was lower in patients with SUVmax≥3.5 (log-rank 14.6;p<0.001) and pre-LT CTC levels≥9 (log-rank 4.2; p = 0.040). A correlation was found between CTC levels and the days on waiting list (p = 0.002), tumor size (p = 0.001), positive PET-CT (p = 0.024) and presence of microvascular invasion (p = 0.033). Recurrence-free survival was lower in patients with CTCs ≥ 9 (p = 0.040). Conclusion: CTC levels in patients with HCC undergoing LT are associated with clinical and pathological factors of poor prognosis.CTC levels decrease significantly after LT.