Shanghai Score: A Prognostic and Adjuvant Treatment-evaluating System Constructed for Chinese Patients with Hepatocellular Carcinoma after Curative Resection
Hui-Chuan Sun1, Lu Xie2, Xin-Rong Yang1, Wei Li3, Jian Yu2, Xiao-Dong Zhu1, Yong Xia4, Ti Zhang5, Yang Xu1, Bo Hu1, Li-Ping Du6, Ling-Yao Zeng2, Jian Ouyang2, Wei Zhang5, Tian-Qiang Song5, Qiang Li5, Ying-Hong Shi1, Jian Zhou1, Shuang-Jian Qiu1, Qian Liu7, Yi-Xue Li8, Zhao-You Tang1, Yu Shyr6, Feng Shen4, Jia Fan1
1 Department of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai 200032, China
2 Shanghai Center for Bioinformation Technology, Shanghai Academy of Science and Technology, Shanghai 201203, China
3 Shanghai Center for Bioinformation Technology, Shanghai Academy of Science and Technology, Shanghai 201203; Britton Chance Center for Biomedical Photonics, Wuhan National Laboratory for Optoelectronics, Huazhong University of Science and Technology, Wuhan, Hubei 430074; Key Laboratory of Computational Biology, CAS-MPG Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China
4 Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai 200438, China
5 Department of Hepatobiliary Surgery, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300040, China
6 Center for Quantitative Sciences, Vanderbilt University School of Medicine, Nashville, TN 37232, USA
7 Britton Chance Center for Biomedical Photonics, Wuhan National Laboratory for Optoelectronics, Huazhong University of Science and Technology, Wuhan, Hubei 430074, China
8 Shanghai Center for Bioinformation Technology, Shanghai Academy of Science and Technology; Key Laboratory of Computational Biology, CAS-MPG Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China
Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai 200032
Source of Support: None, Conflict of Interest: None
Background: For Chinese patients with hepatocellular carcinoma (HCC), surgical resection is the most important treatment to achieve long-term survival for patients with an early-stage tumor, and yet the prognosis after surgery is diverse. We aimed to construct a scoring system (Shanghai Score) for individualized prognosis estimation and adjuvant treatment evaluation.
Methods: A multivariate Cox proportional hazards model was constructed based on 4166 HCC patients undergoing resection during 2001–2008 at Zhongshan Hospital. Age, hepatitis B surface antigen, hepatitis B e antigen, partial thromboplastin time, total bilirubin, alkaline phosphatase, γ-glutamyltransferase, α-fetoprotein, tumor size, cirrhosis, vascular invasion, differentiation, encapsulation, and tumor number were finally retained by a backward step-down selection process with the Akaike information criterion. The Harrell's concordance index (C-index) was used to measure model performance. Shanghai Score is calculated by summing the products of the 14 variable values times each variable's corresponding regression coefficient. Totally 1978 patients from Zhongshan Hospital undergoing resection during 2009–2012, 808 patients from Eastern Hepatobiliary Surgery Hospital during 2008–2010, and 244 patients from Tianjin Medical University Cancer Hospital during 2010–2011 were enrolled as external validation cohorts. Shanghai Score was also implied in evaluating adjuvant treatment choices based on propensity score matching analysis.
Results: Shanghai Score showed good calibration and discrimination in postsurgical HCC patients. The bootstrap-corrected C-index (confidence interval [CI]) was 0.74 for overall survival (OS) and 0.68 for recurrence-free survival (RFS) in derivation cohort (4166 patients), and in the three independent validation cohorts, the CI s for OS ranged 0.70–0.72 and that for RFS ranged 0.63–0.68. Furthermore, Shanghai Score provided evaluation for adjuvant treatment choices (transcatheter arterial chemoembolization or interferon-α). The identified subset of patients at low risk could be ideal candidates for curative surgery, and subsets of patients at moderate or high risk could be recommended with possible adjuvant therapies after surgery. Finally, a web server with individualized outcome prediction and treatment recommendation was constructed.
Conclusions: Based on the largest cohort up to date, we established Shanghai Score – an individualized outcome prediction system specifically designed for Chinese HCC patients after surgery. The Shanghai Score web server provides an easily accessible tool to stratify the prognosis of patients undergoing liver resection for HCC.