Improved Prediction of Survival by a Risk Factor-Integrating Inflammatory Score in Sorafenib-Treated Hepatocellular Carcinoma

Martin F Sprinzl; Martha M Kirstein; Sandra Koch; Marie-Luise Seib; Julia Weinmann-Menke; Hauke Lang; Christoph Düber; Gerrit Toenges; Daniela Zöller; Jens U Marquardt; Marcus-Alexander Wörns; Peter R Galle; Arndt Vogel; Matthias Pinter; Arndt Weinmann

doi:10.1159/000492628

Improved Prediction of Survival by a Risk Factor-Integrating Inflammatory Score in Sorafenib-Treated Hepatocellular Carcinoma

Liver Cancer. 2019 Oct;8(5):387-402. doi: 10.1159/000492628. Epub 2018 Oct 4.

Authors

Martin F Sprinzl^{1

2}, Martha M Kirstein³, Sandra Koch^{1

2}, Marie-Luise Seib¹, Julia Weinmann-Menke^{1

2}, Hauke Lang⁴, Christoph Düber⁵, Gerrit Toenges⁶, Daniela Zöller^{6

7}, Jens U Marquardt¹, Marcus-Alexander Wörns¹, Peter R Galle¹, Arndt Vogel³, Matthias Pinter⁸, Arndt Weinmann^{1

2}

Affiliations

¹ Department of Internal Medicine I, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.
² Clinical Registry Unit, Department of Internal Medicine I, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.
³ Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.
⁴ Department of General, Visceral and Transplant Surgery, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.
⁵ Department of Diagnostic and Interventional Radiology, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.
⁶ Institute of Medical Biostatistics, Epidemiology and Informatics (IMBEI), University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.
⁷ Institute for Medical Biometry and Statistics, Faculty of Medicine and Medical Center, University of Freiburg, Freiburg, Germany.
⁸ Department of Gastroenterology, Department of Internal Medicine III, Medical University, Vienna, Austria.

Abstract

Background and aims: Inflammation affects progression of hepatocellular carcinoma (HCC). We therefore postulate that systemic inflammatory markers could help to predict prognosis in HCC patients receiving sorafenib therapy.

Methods: Overall 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.

Results: Patients 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.

Conclusions: Inflammatory 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.

Keywords: Hepatocellular carcinoma; Inflammation; Prognostic prediction; Sorafenib; Systemic chemotherapy.