Prognostic Roles of Blood Inflammatory Markers in Hepatocellular Carcinoma Patients Taking Sorafenib. A Systematic Review and Meta-Analysis

Abstract

The purpose of this meta-analysis is to investigate the effectiveness of the prognostic roles of blood inflammatory markers in hepatocellular carcinoma (HCC) patients receiving sorafenib. Methods: We carried out a comprehensive literature search in four databases. Study endpoints, hazard ratios (HRs) and the associated 95% confidence intervals (CI) for clinical outcomes, which were to assess therapeutic efficacy, were extracted. This meta-analysis was conducted by Review Manager 5.3. Results: We summarized the available evidence from 18 studies with a total of 2,745 cases. The pooled results showed that the synthesized HR favored patients with low pretreatment NLR (neutrophil-to-lymphocyte ratio), which also indicated that HCC patients with a lower baseline NLR may have a better response to sorafenib than those with higher NLR (HR = 1.76, 95% CI [1.44, 2.15], P < 0.00001, I² = 68%). Significance was also observed for the prognostic function of the PLR (platelet-to-lymphocyte ratio) of HCC patients treated with sorafenib (HR = 1.49, 95% CI [1.16, 1.93], P = 0.002, I² = 0%, P = 0.65). The subgroup analysis revealed that different gene backgrounds play a prominent role in the source of heterogeneity. Interestingly, the predictive effect on OS (overall survival) was more pronounced as the NLR cutoff value increased. Notably, a significant predictive effect of NLR on the clinical outcome was detected in HCC patients treated with sorafenib compared to those treated with tivantinib. Conclusion: In conclusion, the present study reported promising predictive biomarkers for HCC patients and notably indicated that HCC patients with a lower baseline NLR and PLR may have a better response to sorafenib than those with higher ones. Further large-scale prospective studies are required to determine the optimal NLR and PLR cutoff values, which are important for identifying the dominant populations for sorafenib treatment.

A Nomogram-Based Prognostic Model for Advanced Hepatocellular Carcinoma Patients Treated with Sorafenib: A Multicenter Study

“…Our study has several limitations. First, we were not able to compute and test the predictive value of immune–inflammatory scores such as PLR [ 60 ], NLR [ 61 ] and SII [ 62 ] since the recording in the ITA.LI.CA database of variables forming these scores started in 2017. Second, we a priori excluded patients’ symptoms as potential prognosticators in order to provide models relying only on standardized parameters.…”

Pretreatment peripheral neutrophils, lymphocytes and monocytes predict long-term survival in hepatocellular carcinoma

“…There are many previous studies that peripheral inflammatory cell-based combination scores like NLR, LMR and PLR have a promising prognostic values in predicting patient survival for HCC in various treatment modalities [55][56][57][58]. In addition, several reports focusing on individual cell types to evaluated the prognostic value in predicting survival for HCC have been published, but these studies investigated patients who performed specific treatment [59,60].…”

Neutrophil-to-Lymphocyte and Platelet-to-Lymphocyte Ratios as Predictors of Outcomes in Patients With Unresectable Hepatocellular Carcinoma Undergoing Transarterial Chemoembolization Plus Sorafenib

“…More recently, a meta-analysis including 5280 HCC patients treated by TACE reported that evaluated NLR and PLR at baseline were significantly correlated with poor OS (HR: 1.81, 95% CI: 1.66-1.97, p < 0.00001; HR: 1.56, 95% CI: 1.13-2.16, p 0.007, respectively) (Li et al, 2020). In addition, another meta-analysis indicated that HCC patients with lower NLR at baseline could have a better response to sorafenib than those with higher pretreatment NLR (HR 1.76, 95% CI: 1.44-2.15, p < 0.00001) (Liu et al, 2019). As shown in the present (Bruix et al, 2017).…”

“…In the present study, the OS and PFS curve showed a cut-off value of median NLR and PLR of 2.42 and 100, which significantly patients' OS and PFS stratified based on NLR and PLR (p < 0.001 for all). A recent meta-analysis indicated that 3 was the minimum cut-off value for NLR to play a prognostic value (Liu et al, 2019). However, different ethnic populations and the heterogeneity of the enrolled studies had a greater impact on the consistency of the results.…”