Improved survival prediction and comparison of prognostic models for patients with hepatocellular carcinoma treated with sorafenib

Tim A Labeur, Sarah Berhane, Julien Edeline, Jean-Frederic Blanc, Dominik Bettinger, Tim Meyer, Jeroen L A Van Vugt, David W G Ten Cate, Robert A De Man, Ferry A L M Eskens, Alessandro Cucchetti, Laura J Bonnett, Otto M Van Delden, Heinz-Josef Klümpen, R Bart Takkenberg, Philip J Johnson

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11 Citations (Scopus)
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BACKGROUND: The 'Prediction Of Survival in Advanced Sorafenib-treated HCC' (PROSASH) model addressed the heterogeneous survival of patients with hepatocellular carcinoma (HCC) treated with sorafenib in clinical trials but requires validation in daily clinical practice. This study aimed to validate, compare and optimize this model for survival prediction.

METHODS: Patients treated with sorafenib for HCC at five tertiary European centres were retrospectively staged according to the PROSASH model. In addition, the optimized PROSASH-II model was developed using the data of four centres (training set) and tested in an independent dataset. These models for overall survival (OS) were then compared with existing prognostic models.

RESULTS: The PROSASH model was validated in 445 patients, showing clear differences between the four risk groups (OS 16.9-4.6 months). A total of 920 patients (n = 615 in training set, n = 305 in validation set) were available to develop PROSASH-II. This optimized model incorporated fewer and less subjective parameters: the serum albumin, bilirubin and alpha-foetoprotein, and macrovascular invasion, extrahepatic spread and largest tumour size on imaging. Both PROSASH and PROSASH-II showed improved discrimination (C-index 0.62 and 0.63, respectively) compared with existing prognostic scores (C-index ≤0.59).

CONCLUSIONS: In HCC patients treated with sorafenib, individualized prediction of survival and risk group stratification using baseline prognostic and predictive parameters with the PROSASH model was validated. The refined PROSASH-II model performed at least as good with fewer and more objective parameters. PROSASH-II can be used as a tool for tailored treatment of HCC in daily practice and to define pre-planned subgroups for future studies.

Original languageEnglish
Pages (from-to)215-228
Number of pages14
JournalLiver International
Issue number1
Early online date3 Oct 2019
Publication statusPublished - Jan 2020

Bibliographical note

Funding Information:
DB is supported by the Berta‐Ottenstein Programme, Faculty of Medicine, University of Freiburg. HJK has received an unrestricted research grant from Bayer. JE was partly funded by the Foundation de France for this work. RBT has received grants from the Netherlands Organization for Health Research and Development (ZonMw) and The Netherlands Society for Gastroenterology (NVGE). SB acknowledges support from the UK EPSRC grant EP/N014499/1. TM is part funded by the NIHR UCLH Biomedical Research Centre. TL was supported by travel grants from the Cancer Center Amsterdam and the Netherlands Society for Hepatology. These funding bodies had no role in the design of this study, collection, analysis and interpretation of data, or in writing of the manuscript. Lastly, TL would like to acknowledge the exceptional hospitality of Philip and Sue Johnson, and the Department of Molecular and Clinical Medicine, University of Liverpool, during his stay in Liverpool.

DB receives teaching and speaking fees from Bayer Healthcare and from the Falk Foundation, Germany. HJK is a member of the advisory board for Ipsen and Sirtex. JE receives speaking fees and travel grants from Bayer. JFB is a member of the advisory board for Bayer, IPSEN, ESAI. RBT served as a speaker for Gore WL, Bayer and Norgine. He is a member of the advisory board for Gilead and Norgine. RdM served as a speaker for Norgine and as a consultant for Cook Medical. OvD served as a consultant for Cook Medical. All other authors have declared no conflicts of interest. This study was designed and conducted by academic investigators.

Publisher Copyright:
© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd


  • hepatocellular carcinoma
  • model
  • prediction
  • prognosis
  • sorafenib
  • survival

ASJC Scopus subject areas

  • Hepatology


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