J Cancer 2017; 8(3):378-387. doi:10.7150/jca.16786

Research Paper

Predictive factors in patients with hepatocellular carcinoma receiving sorafenib therapy using time-dependent receiver operating characteristic analysis

Hiroki Nishikawa1*, Norihiro Nishijima2*, Hirayuki Enomoto1✉, Azusa Sakamoto2, Akihiro Nasu2, Hideyuki Komekado2, Takashi Nishimura1, Ryuichi Kita2, Toru Kimura2, Hiroko Iijima1, Shuhei Nishiguchi1, Yukio Osaki2

1. Division of Hepatobiliary and Pancreatic disease, Department of Internal Medicine, Hyogo College of Medicine, Hyogo, Japan;
2. Department of Gastroenterology and Hepatology, Osaka Red Cross Hospital, Osaka, Japan.
* Hiroki Nishikawa and Norihiro Nishijima contributed equally to this work.

Abstract

Aims: To investigate variables before sorafenib therapy on the clinical outcomes in hepatocellular carcinoma (HCC) patients receiving sorafenib and to further assess and compare the predictive performance of continuous parameters using time-dependent receiver operating characteristics (ROC) analysis.

Patients and methods: A total of 225 HCC patients were analyzed. We retrospectively examined factors related to overall survival (OS) and progression free survival (PFS) using univariate and multivariate analyses. Subsequently, we performed time-dependent ROC analysis of continuous parameters which were significant in the multivariate analysis in terms of OS and PFS. Total sum of area under the ROC in all time points (defined as TAAT score) in each case was calculated.

Results: Our cohort included 175 male and 50 female patients (median age, 72 years) and included 158 Child-Pugh A and 67 Child-Pugh B patients. The median OS time was 0.68 years, while the median PFS time was 0.24 years. On multivariate analysis, gender, body mass index (BMI), Child-Pugh classification, extrahepatic metastases, tumor burden, aspartate aminotransferase (AST) and alpha-fetoprotein (AFP) were identified as significant predictors of OS and ECOG-performance status, Child-Pugh classification and extrahepatic metastases were identified as significant predictors of PFS. Among three continuous variables (i.e., BMI, AST and AFP), AFP had the highest TAAT score for the entire cohort. In subgroup analyses, AFP had the highest TAAT score except for Child-Pugh B and female among three continuous variables.

Conclusion: In continuous variables, AFP could have higher predictive accuracy for survival in HCC patients undergoing sorafenib therapy.

Keywords: Hepatocellular carcinoma, Sorafenib, Clinical outcomes, Predictive factor, Time-dependent ROC analysis.

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How to cite this article:
Nishikawa H, Nishijima N, Enomoto H, Sakamoto A, Nasu A, Komekado H, Nishimura T, Kita R, Kimura T, Iijima H, Nishiguchi S, Osaki Y. Predictive factors in patients with hepatocellular carcinoma receiving sorafenib therapy using time-dependent receiver operating characteristic analysis. J Cancer 2017; 8(3):378-387. doi:10.7150/jca.16786. Available from http://www.jcancer.org/v08p0378.htm