Department of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai 200032, China.
Shanghai Center for Bioinformation Technology, Shanghai Academy of Science and Technology, Shanghai 201203, China.
Chin Med J (Engl). 2017 Nov 20;130(22):2650-2660. doi: 10.4103/0366-6999.218019.
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.
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.
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.
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.
对于中国的肝细胞癌(HCC)患者,手术切除是实现早期肿瘤患者长期生存的最重要治疗方法,但手术后的预后各不相同。我们旨在构建一种评分系统(上海评分),用于个体化预后评估和辅助治疗评价。
基于 2001 年至 2008 年中山医院接受切除术的 4166 例 HCC 患者,构建了多变量 Cox 比例风险模型。最终,通过向后逐步选择过程,使用赤池信息量准则(Akaike information criterion)保留了年龄、乙型肝炎表面抗原、乙型肝炎 e 抗原、部分凝血活酶时间、总胆红素、碱性磷酸酶、γ-谷氨酰转肽酶、甲胎蛋白、肿瘤大小、肝硬化、血管侵犯、分化、包膜和肿瘤数量。哈雷尔一致性指数(C 指数)用于衡量模型性能。上海评分通过将 14 个变量值乘以每个变量的相应回归系数的乘积相加来计算。来自中山医院 2009 年至 2012 年接受切除术的 1978 例患者、2008 年至 2010 年东方肝胆外科医院的 808 例患者和 2010 年至 2011 年天津医科大学肿瘤医院的 244 例患者被纳入外部验证队列。还根据倾向评分匹配分析,使用上海评分来评估辅助治疗选择。
上海评分在术后 HCC 患者中表现出良好的校准和区分能力。Bootstrap 校正的 C 指数(置信区间 [CI])为总体生存(OS)的 0.74 和无复发生存(RFS)的 0.68(来自 4166 例患者的推导队列),在三个独立的验证队列中,OS 的 CI 范围为 0.70-0.72,RFS 的 CI 范围为 0.63-0.68。此外,上海评分还为辅助治疗选择(经导管动脉化疗栓塞或干扰素-α)提供了评估。低风险组的患者可以成为根治性手术的理想候选者,而中高风险组的患者可以在手术后推荐可能的辅助治疗。最后,构建了一个具有个体化预后预测和治疗建议的网络服务器。
基于迄今为止最大的队列,我们建立了上海评分-一种专门为中国 HCC 患者术后设计的个体化预后预测系统。上海评分网络服务器提供了一种易于访问的工具,可对接受 HCC 肝切除术的患者的预后进行分层。