肝细胞癌患者肝切除术后预后列线图的建立与验证

Establishment and verification of a nomogram for predicting patient prognosis after hepatectomy for hepatocellular carcinoma

目的旨在建立和验证预测肝细胞癌肝切除术后患者总生存期(OS)的列线图。方法选取广西医科大学附属肿瘤医院2004年2月-2013年10月肝细胞癌肝切除术患者1013例。随机分为训练队列(n=710)和验证队列(n=303),在训练队列中,通过Cox比例风险模型确定独立危险因素,并构建训练队列的列线图预测1、3、5年的生存率。通过训练队列内部验证与验证队列的外部验证,并采用C指数、受试者工作特征曲线(ROC曲线)以及校准曲线对模型的性能进行评价。连续变量2组间比较采用独立样本t检验。分类变量2组间比较采用χ^2检验或Fisher检验。通过Cox比例风险模型进行单因素和多因素分析。结果训练队列中1、3、5年总生存率分别为0.72、0.48、0.34;验证队列中1、3、5年总生存率分别为0.66、0.45、0.32。单因素和多因素分析确定影响肝细胞癌肝切除术后患者OS的危险因素为年龄、肿瘤数目、肿瘤大小、肿瘤包膜、血管侵犯、微卫星灶、AST、AFP(P值均<0.05),并将其构建列线图模型。训练队列中,预测OS的C指数为0.748[95%可信区间(95%CI):0.712~0.784]。1、3、5年生存率的校准曲线显示列线图的预测值和实际观察值结果一致;1、3、5年生存率ROC曲线下面积分别为0.81(95%CI:0.76~0.87)、0.82(95%CI:0.77~0.88)、0.79(95%CI:0.71~0.88)。在验证队列中,C指数为0.712(95%CI:0.685~0.739)。1、3、5年生存率的校准曲线显示列线图预测值与实际观察值结果一致。1、3、5年生存率的ROC曲线下面积分别是0.75(95%CI:0.71~0.79)、0.77(95%CI:0.73~0.81)、0.74(95%CI:0.68~0.80)。结论建立的列线图可以有效的预测肝细胞癌肝切除术后患者的OS。

Objective To establish and validate a nomogram for overall survival (OS) of patients after hepatectomy for hepatocellular carcinoma (HCC).Methods A retrospective analysis was performed for the clinical data of 1013 patients who underwent hepatectomy for HCC in The Affiliated Tumor Hospital of Guangxi Medical University from February 2004 to October 2013.These patients were randomly divided into training cohort with 710 patients and validation cohort with 303 patients.For the training cohort,the Cox proportional hazards model was used to determine independent risk factors and a nomogram was established to predict 1-,3-,and 5-year survival rates.The performance of this nomogram was evaluated by internal verification within the training cohort and external verification of the validation cohort,as well as C-index,receiver operating characteristic (ROC) curve,and calibration curve.The independent samples t -test was used for comparison of continuous variables between groups,and the chi-square test or the Fisher's exact test was used for comparison of categorical variables between groups.The Cox proportional hazards model was used for univariate and multivariate analyses.Results The 1-,3-,and 5-year OS rates in the training cohort were 0.72,0.48,and 0.34,respectively,and those in the validation cohort were 0.66,0.45,0.32,respectively.The univariate and multivariate analyses showed that age,number of tumors,tumor diameter,tumor capsule,vascular invasion,microsatellite lesion,aspartate aminotransferase (AST),and alpha-fetoprotein (AFP) were the influencing factors for OS in patients after hepatectomy for HCC (all P <0.05),and such factors were used to establish a nomogram model.In the training cohort,the C-index for predicting OS was 0.748 (95% confidence interval [CI]: 0.712-0.784);the calibration curve of 1-,3-,and 5-year survival rates showed that the predicted value of the nomogram was in good consistency with the actual values observed;this nomogram model had an area under the ROC curve of 0.81 (95%CI: 0.76-0.87),0.82 (95%CI: 0.77-0.88),and 0.79 (95%CI: 0.71-0.88),respectively,in predicting the 1-,3-,and 5-year survival rates.In the validation cohort,the C-index was 0.712 (95%CI: 0.685-0.739);the calibration curve of 1-,3-,and 5-year survival rates showed that the predicted value of the nomogram was in good consistency with the actual values observed;this nomogram model had an area under the ROC curve of 0.75 (95%CI: 0.71-0.79),0.77 (95%CI: 0.73-0.81),and 0.74 (95%CI: 0.68-0.80),respectively,in predicting the 1-,3-,and 5-year survival rates.Conclusion The nomogram established in this study can effectively predict OS in patients after hepatectomy for HCC.