Novel biomarker-based model for the prediction of sorafenib response and overall survival in advanced hepatocellular carcinoma: a prospective cohort study.

Abstract

BACKGROUND:

Prediction of the outcome of sorafenib therapy using biomarkers is an unmet clinical need in patients with advanced hepatocellular carcinoma (HCC). The aim was to develop and validate a biomarker-based model for predicting sorafenib response and overall survival (OS).

METHODS:

This prospective cohort study included 124 consecutive HCC patients (44 with disease control, 80 with progression) with Child-Pugh class A liver function, who received sorafenib. Potential serum biomarkers (namely, hepatocyte growth factor [HGF], fibroblast growth factor [FGF], vascular endothelial growth factor receptor-1, CD117, and angiopoietin-2) were tested. After identifying independent predictors of tumor response, a risk scoring system for predicting OS was developed and 3-fold internal validation was conducted.

RESULTS:

A risk scoring system was developed with six covariates: etiology, platelet count, Barcelona Clinic Liver Cancer stage, protein induced by vitamin K absence-II, HGF, and FGF. When patients were stratified into low-risk (score ≤ 5), intermediate-risk (score 6), and high-risk (score ≥ 7) groups, the model provided good discriminant functions on tumor response (concordance [c]-index, 0.884) and 12-month survival (area under the curve [AUC], 0.825). The median OS was 19.0, 11.2, and 6.1 months in the low-, intermediate-, and high-risk group, respectively (P < 0.001). In internal validation, the model maintained good discriminant functions on tumor response (c-index, 0.825) and 12-month survival (AUC, 0.803), and good calibration functions (all P > 0.05 between expected and observed values).

CONCLUSIONS:

This new model including serum FGF and HGF showed good performance in predicting the response to sorafenib and survival in patients with advanced HCC.

• Authors: Hwi Young Kim, Dong Hyeon Lee, Jeong-Hoon Lee, Young Youn Cho, Eun Ju Cho, Su Jong Yu, Yoon Jun Kim, Jung-Hwan Yoon
• Journal: BMC cancer (BMC Cancer) Vol. 18 Issue 1 Pg. 307 (03 20 2018) ISSN: 1471-2407 [Electronic] England
• PMID: 29558905 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Biomarkers
• Phenylurea Compounds
• Niacinamide
• Sorafenib

Topics

• Antineoplastic Agents (therapeutic use)
• Biomarkers (blood)
• Carcinoma, Hepatocellular (blood, drug therapy, mortality, pathology)
• Disease Progression
• Female
• Follow-Up Studies
• Humans
• Liver Neoplasms (blood, drug therapy, mortality, pathology)
• Male
• Middle Aged
• Models, Statistical
• Niacinamide (analogs & derivatives, therapeutic use)
• Phenylurea Compounds (therapeutic use)
• Prognosis
• Prospective Studies
• Sorafenib
• Survival Rate