Tumor DNA Index and α-Fetoprotein Level Define Outcome following Liver Transplantation for Advanced Hepatocellular Carcinoma

Abstract

Background: Patients with hepatocellular carcinoma (HCC) beyond the Milan criteria are expected to have inferior outcome after liver transplantation (LT) and are therefore currently not considered for LT in many countries. The purpose of this study was to identify predictive factors for overall survival following LT for HCC that may support the Milan criteria in the selection of appropriate transplant candidates. Methods: Clinicopathological data on 364 patients with HCC who underwent LT between 1989 and 2010 were retrospectively evaluated. Predictors of overall survival in the entire cohort as well as in subsets of patients within (n = 214) and beyond (n = 150) the Milan criteria were analyzed. Results: Multivariate analysis in the entire cohort identified DNA index >1.5 (p < 0.0001), α-fetoprotein level (AFP) >200 ng/ml (p = 0.005), and HCC beyond the Milan criteria (p = 0.002) to be associated with worse overall survival. In patients within the Milan criteria (median survival: 170 months), DNA index >1.5 (p < 0.0001) was the only predictor of worse overall survival in multivariate analysis. In patients beyond the Milan criteria (median survival: 44 months), DNA index >1.5, AFP >200 ng/ml, microvascular invasion, patient age >60 years, and DNA index >1.5 concomitant with AFP >200 ng/ml were associated with worse overall survival in univariate analysis. Multivariate analysis identified DNA index >1.5 concomitant with AFP >200 ng/ml (p < 0.0001) as the only independent predictor of worse overall survival. Consequently, patients beyond the Milan criteria with a combined favorable DNA index ≤1.5 and AFP ≤200 ng/ml had a median survival (147 months) comparable to that of patients within the Milan criteria. Conclusions: DNA index and AFP level predict overall survival following LT in patients with advanced HCC beyond the Milan criteria. A combined assessment of these markers during the evaluation of transplant candidates can contribute to the selection of patients with HCC who may benefit from LT independently of their tumor burden.

Hepatocellular carcinoma: when is liver transplantation oncologically futile?

“…Therefore AFP is a well-established surrogate of tumor biology as it correlates with histologic grading and vascular invasion (14,(41)(42)(43). Not surprisingly, a large number of studies have highlighted the importance of increased AFP values for the recurrence risk after LT (3,23,(25)(26)(27)39,(41)(42)(43)(44)(45)(46)(47)(48). It is important to note that increased AFP values are not only a risk factor in patients beyond but also in patients within the Milan criteria.…”

Liver transplantation for hepatocellular carcinoma - non-cancer factors and implications for improving outcome beyond standard tumor criteria

“…The identification of patients with aggressive tumor behavior is one important clinical practice to safely expand the pool of eligible liver transplant recipients beyond the MC [27][28][29] . Different surrogate markers of tumor biology were shown to improve the selection process beyond the MC, such as alpha-fetoprotein (AFP) [30,31] , protein induced by Vitamin K absence II (PIVKA-II) [32,33] , serological inflammatory markers [C-reactive protein (CRP); neutrophil lymphocyte ratio (NLR), platelet lymphocyte ratio (PLR)] [34] , 18F-fluorodeoxyglucose (FDG) uptake on positron emission tomography (PET) [35,36] and tumor downstaging under locoregional treatments [37,38] . Apart from that, there is increasing evidence that not only tumor-specific characteristics, but also non-cancer factors may decisively influence cancer-specific outcome.…”