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

ABSTRACT: 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.

SUBMITTER: Labeur TA

PROVIDER: S-EPMC6973249 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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

Labeur Tim A TA Berhane Sarah S Edeline Julien J Blanc Jean-Frederic JF Bettinger Dominik D Meyer Tim T Van Vugt Jeroen L A JLA Ten Cate David W G DWG Ten Cate David W G DWG De Man Robert A RA Eskens Ferry A L M FALM Cucchetti Alessandro A Bonnett Laura J LJ Van Delden Otto M OM Klümpen Heinz-Josef HJ Takkenberg R Bart RB Johnson Philip J PJ

Liver international : official journal of the International Association for the Study of the Liver 20191118 1

<h4>Background</h4>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.<h4>Methods</h4>Patients treated with sorafenib for HCC at five tertiary European centres were retrospectively staged according to the PR ...[more]

PMID: 31579990

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Project description:Background and aimsInflammation affects progression of hepatocellular carcinoma (HCC). We therefore postulate that systemic inflammatory markers could help to predict prognosis in HCC patients receiving sorafenib therapy.MethodsOverall survival (OS) of HCC patients receiving palliative sorafenib treatment was correlated with the neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), C-reactive protein to albumin ratio (CAR), Glasgow prognostic score (GPS) and the modified GPS (mGPS) along with clinicopathological parameters. Predictors of OS were assessed by multivariable Cox regression and receiver operating characteristics and area under the curve (ROC-AUC) analyses.ResultsPatients receiving sorafenib (n = 120) for advanced HCC (Barcelona Clinic Liver Cancer stage C) were explored by retrospective analysis. Findings were subsequently validated by a second HCC cohort (n = 113) receiving sorafenib at two independent treatment centers. Multivariable assessment across these HCC cohorts confirmed a stable association of CAR (p ≤ 0.001), GPS (p ≤ 0.01) and mGPS (p ≤ 0.004) with OS. This study also identified Eastern Cooperative Oncology Group (ECOG) performance score (p < 0.001) and portal thrombosis (p = 0.002) as prognostic factors and uncovered an inconsistent OS association of NLR and PLR in HCC patients. Additional combined analysis of ECOG, portal thrombosis and GPS within an extended score (GPS-EP) was associated with OS (p = 0.021), which was confirmed within the validation cohort (p = 0.001). In sorafenib-treated HCC, the ROC-AUC value for the prediction of 12-month survival was 0.761 (CAR >/≤0.37 cut-off, p < 0.001), 0.766 (GPS, p < 0.001) and 0.754 (mGPS, p < 0.001), respectively. In comparison to this, GPS-EP achieved a higher AUC of 0.826 (0.746-0.907) for the 12-month survival prediction, resulting in a 64.4% sensitivity and 83.3% specificity at a > 2 point cut-off.ConclusionsInflammatory scores obtained before sorafenib treatment initiation are associated with OS in advanced HCC. Their combination with other risk factors improves prediction of 3- and 12-month survival, which could guide treatment decisions in selected patient subgroups.

Project description:To investigate in greater detail the efficacy and safety of sorafenib for the treatment of hepatocellular carcinoma (HCC) in patients with established cirrhosis.From October 2009 to July 2012 patients with an established diagnosis of cirrhosis and HCC treated with sorafenib were consecutively enrolled. According to the Barcelona Clinic Liver Cancer (BCLC) classification, patients were in the advanced stage (BCLC-C) or in the intermediate stage (BCLC-B) but unfit or unresponsive to other therapeutic strategies. Treatment was evaluated performing a 4-phase computed tomography or magnetic resonance imaging scan every 2-3 mo, and analyzed according to the modified Response Evaluation Criteria in Solid Tumors. Sorafenib was administered at 800 mg/d, until radiological progression or occurrence of unacceptable adverse events (AEs). Univariate and multivariate analyses identified predictors of 16-wk clinical benefit and overall survival.Forty-four patients were enrolled, 15 had intermediate HCC and 14 a Child-Pugh score of B7. AEs caused treatment interruption in 19 patients (43%), and median treatment duration was shorter in this subset (5 wk vs 19 wk, P < 0.001) and in the BCLC-C subgroup (13 wk vs 40 wk, P = 0.015). No significant differences in the reason for treatment interruption or in treatment duration were found comparing patients in Child-Pugh class A vs B or in patients older or younger than 70 years. After 16 wk of treatment, 18 patients (41%) had stable disease or partial response. Patients with viral infection or BCLC-C were at higher risk of disease progression. ECOG, extrahepatic spread, macrovascular invasion, alpha-fetoprotein or alkaline phosphatase levels at admission were independent predictors of overall survival.In patients with cirrhosis and HCC treated with sorafenib, AEs are a common cause of early treatment withdrawal. Vascular invasion and extrahepatic spread condition early response to treatment and survival. Baseline biochemical parameters may be helpful to identify patients at higher risk of shorter overall survival.

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

Publications

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

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