Shanghai Score: A Prognostic and Adjuvant Treatment-evaluating System Constructed for Chinese Patients with Hepatocellular Carcinoma after Curative Resection

Abstract

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.

Conflict of interest statement

There are no conflicts of interest.

Figures

Figure 1

Calibration curves of the Shanghai Score in patient cohorts. The X-axis represents the estimated 3-year overall survival probability and the Y-axis represents the observed 3-year overall survival probability in Cohort 1 (a), Cohort 2 (b), Cohort 3 (c), and Cohort 4 (d).

Figure 2

Identification of the cutoffs at which patients in Cohort 1 can be classified into different groups using the Shanghai Score. (a) The log-rank statistics distribution between groups based on different cutoffs. A Shanghai Score cutoff of 4.922 identified two groups (higher and lower) with the overall survival difference reaching the maximum. (b) The log-rank statistics distribution among lower risk patients. A Shanghai Score cutoff of 4.129 subtyped the lower risk patients into moderate- and low-risk patients, with the overall survival difference between the two groups reaching the maximum. (c and d) Kaplan–Meier curves for overall survival and recurrence-free survival according to the Shanghai Score.

Figure 3

The survival benefit for postoperative transcatheter arterial chemoembolization (TACE) using the Shanghai Score for Cohort 1. Overall survival and recurrence-free survival in low-risk patients (a and b), moderate-risk patients (c and d), and high-risk patients (e and f); n = 4166 patients.

Figure 4

The survival benefit for postoperative interferon (IFN) using the Shanghai Score for Cohort 1. Overall survival and recurrence-free survival in low-risk patients (a and b), moderate-risk patients (c and d), and high-risk patients (e and f); n = 4166 patients.

Figure 5

The Shanghai Score web server interface. (a) Clinical indexes included in the Shanghai Score are listed in the first page, and should either be selected or inputted, and submitted to back stage model calculation. (b and c) Two examples of results predicted by the Shanghai Score. An individualized estimate of survival probability and recurrence rate for each case is calculated for 6 months, and 1, 2, 3, 5, and 9 years after surgery, and personalized treatment recommendations are provided based on the survival benefit estimation.