Abstract
Simple SummaryHepatocellular carcinoma is the most common liver malignancy. In the population with an advanced stage of the disease, outcomes could be disappointed by treating with molecular targeting agents because of low treatment response rates. It has gained improving effects of immune checkpoint inhibitor as an emerging treatment for advanced HCC (Hepatocellular carcinoma). However, this novel treatment regimen is quite expensive; to select suitable patients prior to treatment is crucial in daily practice. Here, we intend to present the effect of immunotherapy in treating advanced hepatocellular carcinoma in the real world and to assess potential factors predicting treatment responses for patient selection.Immune checkpoint inhibitors (ICI) have been applied to treat advanced stage hepatocellular carcinoma (HCC) and obtain promising effects. However, tumor response to treatment was unpredictable. A predicting biomarker of objective response or disease-control is an unmet need for patient selection. In this study, 45 advanced HCC patients who failed to sorafenib treatment and received nivolumab, 3 mg/kg bi-weekly, were included. Tumor responses to nivolumab treatment were assessed by the modified response evaluation criteria in solid tumors (mRECIST) criteria. Tumor responses were correlated to clinical characteristics to find out response predictors. In this small series, the prevalence of extrahepatic nodal metastasis, distant metastasis, and portal vein thrombus among the patients were 22.2% (n = 10), 48.9% (n = 22), and 42.2% (n = 19), respectively. The pre-treatment tumor size was 7.2 ± 4.2 cm in maximal diameter, and the calculated total tumor volume was 619.0 ± 831.1 cm3. Among 45 patients, 3 patients had partial response (PR), 11 had stable disease (SD), and the other 31 had progression of disease. By correlating clinical data to the patients with PR and SD, serum neutrophil-to-lymphocyte ratio (NLR) (hazard ratio (HR) = 2.04) and patient-generated subjective global assessment (PG-SGA) score (HR = 2.30) were the independent factors in multivariate analysis. By receiver operating characteristic curve analysis, pre-treatment NLR ≤ 2.5 and PG-SGA score < 4 were the cutoff points to predict tumor response to ICI treatment. In conclusion, biomarkers to predict tumor response for HCC are still lacking in this costly ICI therapy. In this study, NLR ≤ 2.5 and PG-SGA score < 4 indicated disease-control, and can be applied as biomarkers to select the right patients to receive this costly therapy.
Highlights
Hepatocellular carcinoma (HCC) is the major primary tumor in the liver [1]
We retrospectively reviewed the clinical profiles of the advanced HCC patients who received
A total of 45 patients who received nivolumab for advanced HCC were included in this study; 41 (91.1%) patients had liver cirrhosis but none of them was categorized as CTP
Summary
Hepatocellular carcinoma (HCC) is the major primary tumor in the liver [1]. Because tumors in the liver are always silent, many HCCs are already at advanced stage and inoperable once the tumors are found. Staging and therapeutic strategies, the patients at stage C should be treated systemically with molecular targeting agents or immune checkpoint inhibitors [2]. Molecular targeting agents have been applied to treat advanced HCC for many years and can prolong patients’. Survival; tumor response rate to the treatment is only 1–3% [3,4,5]. Molecular targeting therapy is not enough for BCLC stage C patients. Immune checkpoint inhibitor (ICI) is an emerging treatment for advanced HCC with promising effects [6]
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