An internally validated new clinical and inflammation-based prognostic score for patients with advanced hepatocellular carcinoma treated with sorafenib

Clin Transl Oncol. 2018 Mar;20(3):322-329. doi: 10.1007/s12094-017-1720-4. Epub 2017 Aug 11.

Abstract

Background: Sorafenib is a standard treatment for patients (pts) with advanced hepatocellular carcinoma (aHCC), although the clinical benefit is heterogeneous between different pts groups. Among novel prognostic factors, a low baseline neutrophil-to-lymphocyte ratio (bNLR) and early-onset diarrhoea have been linked with a better prognosis.

Purpose: To identify prognostic factors in pts with aHCC treated with 1st-line sorafenib and to develop a new prognostic score to guide management.

Materials and methods: Retrospective review of 145 pts bNLR, overall toxicity, early toxicity rates and overall survival (OS) were assessed. Univariate and multivariate analysis of prognostic factors for OS was performed. The prognostic score was calculated from the coefficients found in the Cox analysis. ROC curves and pseudoR2 index were used for internal validation. Discrimination ability and calibration were tested by Harrel's c-index (HCI) and Akaike criteria (AIC).

Results: The optimal bNLR cut-off for the prediction of OS was 4 (AUC 0.62). Independent prognostic factors in multivariate analysis for OS were performance status (PS) (p < .0001), Child-Pugh (C-P) score (p = 0.005), early-onset diarrhoea (p = 0.006) and BNLR (0.011). The prognostic score based on these four variables was found efficient (HCI = 0.659; AIC = 1.180). Four risk groups for OS could be identified: a very low-risk (median OS = 48.6 months), a low-risk (median OS = 11.6 months), an intermediate-risk (median OS = 8.3 months) and a high-risk group (median OS = 4.4 months).

Conclusions: PS and C-P score were the main prognostic factors for OS, followed by early-onset diarrhoea and bNLR. We identified four risk groups for OS depending on these parameters. This prognostic model could be useful for patient stratification, but an external validation is needed.

Keywords: Cirrhosis; Hepatocellular carcinoma; Neutrophil activation; Prognostic factors; Sorafenib.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / therapeutic use*
  • Area Under Curve
  • Carcinoma, Hepatocellular / drug therapy*
  • Carcinoma, Hepatocellular / pathology
  • Diarrhea / chemically induced
  • Diarrhea / epidemiology
  • Female
  • Humans
  • Inflammation / pathology*
  • Liver Neoplasms / drug therapy*
  • Liver Neoplasms / mortality
  • Liver Neoplasms / pathology
  • Lymphocyte Count
  • Male
  • Middle Aged
  • Neutrophils
  • Niacinamide / analogs & derivatives*
  • Niacinamide / therapeutic use
  • Phenylurea Compounds / therapeutic use*
  • Prognosis
  • Proportional Hazards Models
  • ROC Curve
  • Retrospective Studies
  • Severity of Illness Index
  • Sorafenib
  • Treatment Outcome

Substances

  • Antineoplastic Agents
  • Phenylurea Compounds
  • Niacinamide
  • Sorafenib