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

Gian Ludovico Rapaccini, Antonio Gasbarrini, Fabio Farinati, Alessandro Vitale, Gaya Spolverato, Timothy M. Pawlik, Teh-La Huo, Yun-Hsuan Lee, Anna Chiara Frigo, Anna Giacomin, Edoardo G. Giannini, Francesca Ciccarese, Fabio Piscaglia, Mariella Di Marco, Eugenio Caturelli, Marco Zoli, Franco Borzio, Giuseppe Cabibbo, Martina Felder, Rodolfo SaccoFilomena Morisco, Elisabetta Biasini, Francesco Giuseppe Foschi, Gianluca Svegliati Baroni, Roberto Virdone, Alberto Masotto, Franco Trevisani, Umberto Cillo, Maurizio Biselli, Luigi Bolondi, Laura Bucci, Alessandro Cucchetti, Francesca Garuti, Annagiulia Gramenzi, Barbara Lenzi, Donatella Magalotti, Anna Pecorelli, Carla Serra, Laura Venerandi, Alessia Gazzola, Francesca Murer, Caterina Pozzan, Veronica Vanin, Paolo Del Poggio, Stefano Olmi, Claudia Balsamo, Elena Vavassori, Luisa Benvegnù, Alberta Capelli, Rita Golfieri, Cristina Mosconi, Matteo Renzulli, Paola Roselli, Serena Dell'Isola, Anna Maria Ialungo, Elena Rastrelli, Alessandro Moscatelli, Gaia Pellegatta, Antonino Picciotto, Vincenzo Savarino, Maria Rosa Barcellona, Calogero Cammà, Andrea Costantino, Andrea Affronti, Andrea Mega, Valeria Mismas, Anna Chiara Dall'Aglio, Valentina Feletti, Arianna Lanzi, Federica Mirici Cappa, Elga Neri, Giuseppe Francesco Stefanini, Stefano Tamberi, Gabriele Missale, Emanuela Porro, Maria Guarino, Laura Schiadà, Filiana Cuttone, Maria Chiaramonte, Fabiana Marchetti, Matteo Valerio

Risultato della ricerca: Contributo in rivistaArticolo in rivista

64 Citazioni (Scopus)

Abstract

Background: Prognostic 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 Findings: Prospective 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. Conclusions: The 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.
Lingua originaleEnglish
pagine (da-a)e1002006-N/A
RivistaPLoS Medicine
Volume13
DOI
Stato di pubblicazionePubblicato - 2016

Keywords

  • Aged
  • Biochemistry
  • Biotechnology
  • Carcinoma, Hepatocellular
  • Cell Biology
  • Databases, Factual
  • Decision Support Techniques
  • Female
  • Humans
  • Italy
  • Liver Neoplasms
  • Male
  • Middle Aged
  • Molecular Biology
  • Neoplasm Invasiveness
  • Neoplasm Staging
  • Neoplasms, Multiple Primary
  • Predictive Value of Tests
  • Reproducibility of Results
  • Retrospective Studies
  • Risk Assessment
  • Risk Factors
  • Survival Analysis
  • Taiwan
  • Time Factors
  • Tumor Burden
  • alpha-Fetoproteins

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