Evaluación oncológica mediante células tumorales circulantes, PET-TC y AFP de pacientes con hepatocarcinoma sometidos a trasplante hepático

Resumo

Introduction Hepatocellular carcinoma (HCC) is one of the most prevalent malignancies worldwide. Liver transplantation (LT) is the best potentially curative therapeutic option in selected cirrhotic patients (Milan criteria). Nevertheless, the shortage of organ donors lengthens the wait time and promotes tumor progression. What is more, the recurrence rate after LT is high, around 10 to 20%. Nowadays, there are not efficient markers of biological pretransplant activity that could predict early recurrence. In this context, the investigation of circulating tumor cells (CTCs) in peripheral blood, also termed liquid biopsy, could play a major role. The aim of this work is 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). Patients and method Peripheral blood was obtained from 30 patients on the waiting list for LT and after 1 month, 6 months and one and two 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., Chicago, Ill, USA). Results A total of 30 patients with HCC within Milan criteria were included. Ninety percent were male, with a median age of 57 years. The median follow-up was 57 months (IQR: 45-62). During follow-up, 4 patients (13.3%) had a recurrence. A blood sample was taken from all patients for the determination of CTCs before LT, and in 24 of them (80%) at least one CTC was counted. Statistically significant differences were found between the pre-LT levels and the CTC levels at one year (p=0.018) and at 2 years (p=0.038). Throughout follow-up, CTC levels were similar in patients with and without recurrence. Pre-LT levels of CTC were associated with a prolonged waiting time on the list (p=0.002), positive PET-CT (p=0.024), larger tumor size (p=0.001), increase in the sum of the diameters of viable tumors (p=0.006) and presence of microvascular invasion (p=0.033). No significant correlation was found between pre-LT CTC levels and recurrence. In patients with positive PET-CT, the presence of microvascular invasion was more frequent (p=0.03) and was associated with higher levels of pre-LT CTCs (p=0.028) and an increase in the sumsum of viable tumors diameter (p=0.034). Patients with recurrence presented a higher SUVmax (5.2 vs 1.1; p=0.013), larger tumor size (5 cm vs 2 cm, p=0.036), and greater sum of the diameters of viable tumors (8, 3 cm vs 2.8 cm; p = 0.031), higher frequency of microvascular invasion (50% vs 3.8%; p=0.039), lower recurrence-free survival (8 months vs 59.5 months, p = 0.003) and lower overall survival (22 months vs 59.5 months; p=0.017). Also, a downward trend was observed in CTC levels. The recurrence-free survival was lower in patients with SUVmax ≥ 3.5 (p<0.001) and pre-LT CTC levels ≥ 9 (p=0.040). Conclusion CTC levels decrease significantly after LT. CTC levels and PET-CT uptake in patients with HCC undergoing LT is associated with clinical and pathological factors of poor prognosis and lower recurrence-free survival. Therefore, the determination of these markers before transplantation is useful to predict recurrence