Role of monocyte-to-lymphocyte ratio in predicting sorafenib response in patients with advanced hepatocellular carcinoma

Abstract

Purpose: Sorafenib is the first-line treatment for patients with unresectable hepatocellular carcinoma (HCC), and its clinical response rate is only about 10%. In clinical practice, some HCC patients obtain favorable overall survival (OS) to the treatment of sorafenib while some patients do not demonstrate a sensitive response to sorafenib. Therefore, it is valuable to determine the subgroups of patients who respond well as well as poorly to sorafenib. Thus, clinical variables of advanced HCC patients with sorafenib treatment were compiled to investigate whether monocyte-to-lymphocyte ratio (MLR) could be a biomarker for predicting sorafenib response.

Patients and methods: In this study, a total of 142 patients with advanced HCC were enrolled from January 1, 2013 to December 31, 2016 at the Fudan University Shanghai Cancer Center. MLR was analyzed using a ROC curve. A Cox regression model and log-rank test were performed to analyze the relationship between clinical factors and OS, as well as progression free survival (PFS).

Results: The optimal cut-off point for MLR was 0.35, and MLR level had no significant correlation with age, gender, hepatitis B infection, grade, alpha-fetoprotein (AFP) level and state of portal vein tumor thrombus. Multivariate Cox regression model showed that grade (HR: 0.608, 95% CI: 0.409-0.904, P=0.014), AFP (HR: 0.445, 95% CI: 0.307-0.645, P=0.0001), MLR (HR: 0.445, 95% CI: 0.301-0.658, P=0.0001) and aspartate aminotransferase (AST) (HR: 1.005, 95% CI: 1.001-1.009, P=0.007) may serve as independent prognostic predictors for OS, and MLR maintained significant correlation with PFS in HCC patients (HR: 0.457, 95% CI: 0.308-0.678, P=0.0001). By log-rank test, there was longer PFS and OS in patients with low MLR than in those with high MLR (both P=0.0001).

Conclusion: MLR can predict sorafenib response and a high MLR is correlated with poor prognosis in patients with advanced HCC.

Keywords: hepatocellular carcinoma; monocyte-to-lymphocyte ratio; prognosis; sorafenib.

Figure 1

The ROC curve was performed to test the specificity and sensitivity of MLR and SIRI in HCC patients. MLR and SIRI at baseline, along with the progression time, were analyzed by Independent-samples t-test. Notes: (A) ROC curve of MLR. The area under the curve was 0.6918. The sensitivity and specificity were 55.6% and 77.8%, respectively. (B) ROC curve of SIRI. The area under the curve was 0.6859. The sensitivity and specificity were 65.3% and 72.2%, respectively. (C) MLR at baseline and the progression time were compared by t-test. Abbreviations: AUC, area under the curve; HCC, hepatocellular cancer; MLR, monocyte to lymphocyte ratio; ROC, receiver operating characteristic; SIRI, systemic inflammation response index.

Figure 2

Index parameters of liver function, including TBIL (A), DBIL (B), ALB (C), LDH (D), ALT (E) and AST (F) levels, were analyzed in the low and high MLR groups of patients with HCC by Independent-samples t-test. Note: P>0.05. Abbreviations: ALB, albumin; ALT, alanine aminotransferase; AST, aspartate aminotransferase; DBIL, direct bilirubin; HCC, hepatocellular cancer; LDH, lactic dehydrogenase; MLR, monocyte-to-lymphocyte ratio; TBIL, total bilirubin.

Figure 3

Log-rank tests were used to compare OS in different groups of HCC patients receiving sorafenib therapy, including grade (A), MLR levels (B), AFP levels (C) and AST levels (D). Abbreviations: AFP, alpha-fetoprotein; AST, aspartate aminotransferase; BCLC, Barcelona Clinic Liver Cancer; HCC, hepatocellular cancer; OS, overall survival; MLR, monocyte-to-lymphocyte ratio.

Figure 3

Log-rank tests were used to compare OS in different groups of HCC patients receiving sorafenib therapy, including grade (A), MLR levels (B), AFP levels (C) and AST levels (D). Abbreviations: AFP, alpha-fetoprotein; AST, aspartate aminotransferase; BCLC, Barcelona Clinic Liver Cancer; HCC, hepatocellular cancer; OS, overall survival; MLR, monocyte-to-lymphocyte ratio.

Figure 4

Progression free survival was compared between two groups of patients with advanced HCC receiving sorafenib therapy. Notes: Patients with BCLC C (A), higher MLR (B), higher AFP (C) and higher AST (D) show significantly shorter PFS. Abbreviations: AFP, alpha-fetoprotein; AST, aspartate aminotransferase; BCLC, Barcelona Clinic Liver Cancer; HCC, hepatocellular cancer; MLR, monocyte-to-lymphocyte ratio; PFS, progression free survival.