Predictive value of baseline peripheral blood inflammatory biomarkers for prognosis in patients with advanced hepatocellular carcinoma treated with immunotherapy combined with targeted therapy / 国际肿瘤学杂志

ABSTRACT

Objective:To investigate the prognostic value of baseline peripheral blood inflammatory biomarkers for prognosis in patients with advanced hepatocellular carcinoma (HCC) receiving immunotherapy combined with targeted therapy.Methods:The clinical data of a total of 120 patients with advanced HCC who received immunotherapy combined with targeted therapy at Cancer Center of Renmin Hospital of Wuhan University from December 2019 to March 2022 were analyzed retrospectively. Receiver operating characteristic (ROC) curve was used to calculate the optimal cut-off values of neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), systemic immune inflammation index (SII) and prognostic nutritional index (PNI). According to the optimal cut-off values, the study objects were divided into high value group and low value group. The Kaplan-Meier method was used for survival analysis. Cox proportional hazard regression model was applied to analyze the factors associated with prognosis.Results:By the end of follow-up, 74 patients died and 46 survived. The median follow-up time was 23.0 months, the median overall survival (mOS) was 15.6 months, and the median progression-free survival (mPFS) was 13.1 months. ROC curve analysis showed that the optimal cut-off values of NLR, PLR, SII, LMR and PNI were 3.45, 131.87, 626.21, 2.12 and 43.30, respectively. The mPFS (18.3 months vs. 8.7 months) and mOS (26.6 months vs. 10.9 months) of patients in the low-NLR group ( n=75) were longer than those of the high-NLR group ( n=45), and there were statistically significant differences ( χ2=55.64, P<0.001; χ2=64.14, P<0.001). The mPFS (17.9 months vs. 10.9 months) and mOS (24.5 months vs. 13.5 months) of patients in the low-PLR group ( n=55) were longer than those of the high-PLR group ( n=65), and there were statistically significant differences ( χ2=5.27, P=0.023; χ2=11.84, P<0.001). The mPFS (18.0 months vs. 10.7 months) and mOS (25.7 months vs. 12.8 months) of patients in the low-SII group ( n=75) were longer than those of the high-SII group ( n=45), and there were statistically significant differences ( χ2=24.46, P<0.001; χ2=25.42, P<0.001). The mPFS (18.2 months vs. 10.9 months) and mOS (26.6 months vs. 13.2 months) of patients in the high-LMR group ( n=56) were longer than those of the low-LMR group ( n=64), and there were statistically significant differences ( χ2=19.25, P<0.001; χ2=19.92, P<0.001). The mPFS (17.9 months vs. 10.9 months) and mOS (25.4 months vs. 13.4 months) of patients in the high-PNI group ( n=62) were longer than those of the low-PNI group ( n=58), and there were statistically significant differences ( χ2=13.69, P<0.001; χ2=19.07, P<0.001). Univariate analysis showed that Barcelona clinic liver cancer (BCLC) stage ( HR=1.83, 95% CI: 1.17-2.87, P=0.008), Child-Pugh grade ( HR=2.21, 95% CI: 1.47-3.34, P<0.001), modified albumin-bilirubin (mALBI) grade ( HR=1.35, 95% CI: 1.01-1.81, P=0.045), extrahepatic metastases ( HR=2.18, 95% CI: 1.47-3.25, P<0.001), NLR ( HR=1.40, 95% CI: 1.28-1.54, P<0.001), PLR ( HR=1.00, 95% CI: 1.00-1.01, P=0.001), SII ( HR=1.00, 95% CI: 1.00-1.00, P<0.001), LMR ( HR=0.64, 95% CI: 0.51-0.79, P<0.001) and PNI ( HR=0.95, 95% CI: 0.93-0.98, P=0.001) were correlated with PFS; BCLC stage ( HR=2.18, 95% CI: 1.21-3.91, P=0.009), Child-Pugh grade ( HR=2.57, 95% CI: 1.61-4.09, P<0.001), Eastern Cooperative Oncology Group performance status score ( HR=1.59, 95% CI: 1.01-2.51, P=0.044), mALBI grade ( HR=1.60, 95% CI: 1.17-2.17, P=0.003), extrahepatic metastasis ( HR=2.51, 95% CI: 1.59-3.96, P<0.001), NLR ( HR=1.45, 95% CI: 1.32-1.60, P<0.001), PLR ( HR=1.01, 95% CI: 1.01-1.01, P<0.001), SII ( HR=1.01, 95% CI: 1.01-1.01, P<0.001), LMR ( HR=0.57, 95% CI: 0.40-0.72, P<0.001) and PNI ( HR=0.92, 95% CI: 0.89-0.96, P<0.001) were correlated with OS. Multivariate analysis showed that extrahepatic metastasis ( HR=1.78, 95% CI: 1.10-2.87, P=0.018) and NLR ( HR=1.46, 95% CI: 1.24-1.73, P<0.001) were independent influencing factors for PFS; extrahepatic metastasis ( HR=2.09, 95% CI: 1.21-3.61, P=0.009), NLR ( HR=1.56, 95% CI: 1.29-1.88, P<0.001), SII ( HR=1.00, 95% CI: 1.00-1.00, P=0.025), LMR ( HR=0.59, 95% CI: 0.45-0.78, P=0.008) and PNI ( HR=0.93, 95% CI: 0.88-0.99, P=0.013) were independent influencing factors for OS. Conclusion:NLR and extrahepatic metastasis can be regarded as important indicators to predict PFS in patients with advanced HCC receiving immunotherapy combined with targeted therapy, and NLR, SII, LMR, PNI and extrahepatic metastasis can be regarded as important indicators to predict OS in patients with advanced HCC receiving immunotherapy combined with targeted therapy. High NLR, high SII, low LMR, low PNI and extrahepatic metastasis indicate poor prognosis of HCC patients.