Development and Validation of a New Prognostic System for Patients with Hepatocellular Carcinoma

Abstract

BackgroundPrognostic assessment in patients with hepatocellular carcinoma (HCC) remains controversial. Using the Italian Liver Cancer (ITA.LI.CA) database as a training set, we sought to develop and validate a new prognostic system for patients with HCC.Methods and FindingsProspective collected databases from Italy (training cohort, n = 3,628; internal validation cohort, n = 1,555) and Taiwan (external validation cohort, n = 2,651) were used to develop the ITA.LI.CA prognostic system. We first defined ITA.LI.CA stages (0, A, B1, B2, B3, C) using only tumor characteristics (largest tumor diameter, number of nodules, intra- and extrahepatic macroscopic vascular invasion, extrahepatic metastases). A parametric multivariable survival model was then used to calculate the relative prognostic value of ITA.LI.CA tumor stage, Eastern Cooperative Oncology Group (ECOG) performance status, Child–Pugh score (CPS), and alpha-fetoprotein (AFP) in predicting individual survival. Based on the model results, an ITA.LI.CA integrated prognostic score (from 0 to 13 points) was constructed, and its prognostic power compared with that of other integrated systems (BCLC, HKLC, MESIAH, CLIP, JIS). Median follow-up was 58 mo for Italian patients (interquartile range, 26–106 mo) and 39 mo for Taiwanese patients (interquartile range, 12–61 mo).The ITA.LI.CA integrated prognostic score showed optimal discrimination and calibration abilities in Italian patients. Observed median survival in the training and internal validation sets was 57 and 61 mo, respectively, in quartile 1 (ITA.LI.CA score ≤ 1), 43 and 38 mo in quartile 2 (ITA.LI.CA score 2–3), 23 and 23 mo in quartile 3 (ITA.LI.CA score 4–5), and 9 and 8 mo in quartile 4 (ITA.LI.CA score > 5). Observed and predicted median survival in the training and internal validation sets largely coincided. Although observed and predicted survival estimations were significantly lower (log-rank test, p < 0.001) in Italian than in Taiwanese patients, the ITA.LI.CA score maintained very high discrimination and calibration features also in the external validation cohort.The concordance index (C index) of the ITA.LI.CA score in the internal and external validation cohorts was 0.71 and 0.78, respectively. The ITA.LI.CA score’s prognostic ability was significantly better (p < 0.001) than that of BCLC stage (respective C indexes of 0.64 and 0.73), CLIP score (0.68 and 0.75), JIS stage (0.67 and 0.70), MESIAH score (0.69 and 0.77), and HKLC stage (0.68 and 0.75). The main limitations of this study are its retrospective nature and the intrinsically significant differences between the Taiwanese and Italian groups.ConclusionsThe ITA.LI.CA prognostic system includes both a tumor staging—stratifying patients with HCC into six main stages (0, A, B1, B2, B3, and C)—and a prognostic score—integrating ITA.LI.CA tumor staging, CPS, ECOG performance status, and AFP. The ITA.LI.CA prognostic system shows a strong ability to predict individual survival in European and Asian populations.

Longitudinal alterations in health-related quality of life and its impact on the clinical course of patients with advanced hepatocellular carcinoma receiving sorafenib treatment

“…Many studies associate preserved liver function with better survival [36], however, Child-Pugh score as an index of liver function was not chosen as a significant predictor for overall survival in this study. The reason for this discrepancy can be explained by the background of our cohort; liver function was well preserved in most patients (Child-Pugh score 5: 59 %, score 6: 32 %, and score 7: 9 %).…”

External validation of the ITA.LI.CA prognostic system for patients with hepatocellular carcinoma: A multicenter cohort study

“…Recently, a multicenter Italian study group proposed a new prognostic system for patients with HCC, the Italian Liver Cancer (ITA.LI.CA) system . Its main feature is to re‐establish the prognostic centrality of tumor staging.…”

A Simple Measure of Hepatocellular Carcinoma Burden Predicts Tumor Recurrence After Liver Transplantation: The Recurrent Hepatocellular Carcinoma–Initial, Maximum, Last Classification

“…Although delay in LT priority for HCC has been a part of official US policy since October 2015, UNOS only recently enacted a policy change excluding patients with AFP >1000 ng/mL from automatic MELD HCC exception points unless levels decreased to <500 ng/mL with LRT . This policy change was based on an abundance of data showing a strong correlation between elevated pre‐LT AFP levels and post‐LT rHCC and poor outcomes . In our multivariate competing risk model, we included, as binary covariates, waiting time <6 or ≥6 months and AFP <500 or ≥500 ng/mL.…”