Abstract

We developed a novel systemic immune-inflammation index (SII) based on lymphocyte, neutrophil, and platelet counts and explored its prognostic value in hepatocellular carcinoma (HCC). The SII was developed based on a retrospective study of 133 patients with HCC undergoing resection between 2005 and 2006, and validated in a prospective study of 123 patients enrolled from 2010 to 2011. The circulating tumor cell (CTC) level in the validation cohort was measured using the CellSearch system. Prediction accuracy was evaluated with area under the receiver operating characteristic curve (AUC). An optimal cutoff point for the SII of 330 × 10(9) stratified the patients with HCC into high (≥330) and low SII (<330) groups in the training cohort. Univariate and multivariate analyses revealed the SII was an independent predictor for overall survival and relapse-free survival, and prognostic for patients with negative α-fetoprotein and Barcelona Clinic Liver Cancer stage 0+A. The AUCs of the SII for survival and recurrence were higher than other conventional clinical indices. An SII ≥ 330 was significantly associated with vascular invasion, large tumors, and early recurrence. CTC levels were significantly higher in the SII ≥ 330 group (1.71 ± 0.34 vs. 4.37 ± 1.04, P = 0.029). In patients with detectable CTCs, those with SII ≥ 330 had higher recurrence rates and shorter survival time than patients with SII < 330. The SII was a powerful prognostic indicator of poor outcome in patients with HCC and is a promising tool for HCC treatment strategy decisions. The dismal outcome in patients with high SII scores might be related to higher CTC levels.

Highlights

  • Hepatocellular carcinoma (HCC) is the fifth most common cancer and has the third highest mortality rate in the world [1, 2]

  • Univariate and multivariate analyses revealed the systemic immune-inflammation index (SII) was an independent predictor for overall survival and relapse-free survival, and prognostic for patients with negative a-fetoprotein and Barcelona Clinic Liver Cancer stage 0þA

  • circulating tumor cell (CTC) levels were significantly higher in the SII ! 330 group (1.71 Æ 0.34 vs. 4.37 Æ 1.04, P 1⁄4 0.029)

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Summary

Introduction

Hepatocellular carcinoma (HCC) is the fifth most common cancer and has the third highest mortality rate in the world [1, 2]. Surgery remains the main treatment for patients with HCC. In spite of "curative" resection, approximate 60% to 70% patients experience recurrence or distant metastasis within 5 years [3]. It is important to identify patient subpopulations with. Note: Supplementary data for this article are available at Clinical Cancer Research Online (http://clincancerres.aacrjournals.org/).

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