Improved Prediction of Survival by a Risk Factor-Integrating Inflammatory Score in Sorafenib-Treated Hepatocellular Carcinoma

Abstract

<b><i>Background and Aims:</i></b> Inflammation affects progression of hepatocellular carcinoma (HCC). We therefore postulate that systemic inflammatory markers could help to predict prognosis in HCC patients receiving sorafenib therapy. <b><i>Methods:</i></b> Overall survival (OS) of HCC patients receiving palliative sorafenib treatment was correlated with the neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), C-reactive protein to albumin ratio (CAR), Glasgow prognostic score (GPS) and the modified GPS (mGPS) along with clinicopathological parameters. Predictors of OS were assessed by multivariable Cox regression and receiver operating characteristics and area under the curve (ROC-AUC) analyses. <b><i>Results:</i></b> Patients receiving sorafenib (<i>n</i> = 120) for advanced HCC (Barcelona Clinic Liver Cancer stage C) were explored by retrospective analysis. Findings were subsequently validated by a second HCC cohort (<i>n</i> = 113) receiving sorafenib at two independent treatment centers. Multivariable assessment across these HCC cohorts confirmed a stable association of CAR (<i>p</i> ≤ 0.001), GPS (<i>p</i> ≤ 0.01) and mGPS (<i>p</i> ≤ 0.004) with OS. This study also identified Eastern Cooperative Oncology Group (ECOG) performance score (<i>p</i> < 0.001) and portal thrombosis (<i>p</i> = 0.002) as prognostic factors and uncovered an inconsistent OS association of NLR and PLR in HCC patients. Additional combined analysis of ECOG, portal thrombosis and GPS within an extended score (GPS-EP) was associated with OS (<i>p</i> = 0.021), which was confirmed within the validation cohort (<i>p</i> = 0.001). In sorafenib-treated HCC, the ROC-AUC value for the prediction of 12-month survival was 0.761 (CAR >/≤0.37 cut-off, <i>p</i> < 0.001), 0.766 (GPS, <i>p</i> < 0.001) and 0.754 (mGPS, <i>p</i> < 0.001), respectively. In comparison to this, GPS-EP achieved a higher AUC of 0.826 (0.746–0.907) for the 12-month survival prediction, resulting in a 64.4% sensitivity and 83.3% specificity at a > 2 point cut-off. <b><i>Conclusions:</i></b> Inflammatory scores obtained before sorafenib treatment initiation are associated with OS in advanced HCC. Their combination with other risk factors improves prediction of 3- and 12-month survival, which could guide treatment decisions in selected patient subgroups.

Platelet-to-lymphocyte and neutrophil-to-lymphocyte ratios predict tumor size and survival in HCC patients: Retrospective study

“…Although a large literature already exists on the use of various common blood tests that reflect systemic inflammation and prognosis, and to a lesser extent reflecting in turn the extent of the disease [ [6] , [7] , [8] , [9] , [10] , [11] , [12] , [13] , [14] , [15] , [16] , [17] , [18] , [19] , [20] , [21] , [22] , [23] , [24] , [25] , [26] ], the precise relationship of inflammatory markers to tumor extent has not been well defined. The current work attempts to do this by use of the commonly used PLR and NLR ratios, to assess their relationship to MTD and to try to find their ability to predict small tumor size (MTD).…”

“…Inflammation-based prognostic scores have been shown to be associated with survival [ 3 ] and with various parameters of tumor aggressiveness [ 4 ]. This may be related to the involvement in tumor growth of a variety of easily measurable indices of inflammation [ 5 ] in routine clinical blood tests, including levels of neutrophils, lymphocytes, monocytes, platelets, albumin, C-reactive protein (CRP), as well as marker ratios, such as albumin and CRP (Glasgow Index), neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) and monocyte-to-lymphocyte ratios, amongst others [ [6] , [7] , [8] , [9] , [10] , [11] , [12] , [13] , [14] , [15] , [16] , [17] , [18] , [19] , [20] , [21] , [22] , [23] , [24] , [25] , [26] ]. In the current study, NLR and PLR were evaluated with reference to maximum tumor diameter (MTD) and also to survival in a large Turkish HCC cohort.…”

Role of Pre-Operative of Neutrophil/Lymphocyte and Platelet/Lymphocyte Ratio in Prognosis of Hepatocellular Carcinoma

“…Mean survival was shorter if PLR ≥ 254 in our series. It is an evidence that either higher NLR or PLR were significantly asso-International Journal of Clinical Medicine ciated with lymph node metastasis, and poor overall survival in most studies [6] [38] [51]. Taken together, either increased neutrophil and platelet, or decreased lymphocyte will elevate either NLR or PLR.…”

“…Most oncologists try to get a good survival due to the improvement of care program in the world [2] [3]. Pretreatment imaging and assessment remain the main methods used to evaluate prognosis in liver cancer patients after treatments [4] [5] [6]. The relationship of the prognosis of HCC patients and inflammation was noted in recent decade [4] [7] [8].…”

Development and Assessment of Novel Predictive Nomograms Based on APRI for Hepatitis B Virus-associated Small Solitary Hepatocellular Carcinoma with Stereotactic Body Radiotherapy

“…The predictive role of serum inflammatory markers in cancer has been paid more and more attention. The prognostic value of serum inflammation indicators before treatment for liver cancer has been confirmed by studies focus on surgical resection, liver transplantation, target therapy, radiofrequency ablation (RFA),transcatheter arterial chemoembolization (TACE) and selective internal radiation therapy (SIRT) [16][17][18][19][20][21]. However, studies about cases of liver cancer treated with SBRT rarely reported prognostic inflammatory markers, instead, most of which merely focused on NLR and PLR [22].…”