胆管癌根治性切除术后患者预后相关因素分析和生存预测模型构建

Analysis on prognosis related factors of patients with cholangiocarcinoma after radical resection and establishment of survival prediction model

目的:探讨胆管癌(CCA)根治性切除术(根治术)后患者复发和生存的影响因素,建立列线图预测术后生存时间。方法:回顾性分析本院行CCA根治术的89例患者临床和病理资料,中位无病生存期(DFS)和总生存期(OS)分别为10和13个月。采用Kaplan-Meier生存分析和Cox回归模型分析临床病理特征对CCA患者DFS和OS的影响;采用R软件进行LASSO回归,评估CCA患者术后复发的相关影响因素。建立列线图预测患者术后OS,并通过一致性指数(C-index)、校准曲线和受试者工作特征曲线(ROC)下面积(AUC)评估列线图的预测效能。结果:单因素分析,糖尿病(χ^(2)=5.204,P=0.023)、糖类抗原19-9(CA19-9)(χ^(2)=7.694,P=0.006)、糖类抗原125(CA125)(χ^(2)=6.908,P=0.009)、糖类抗原242(CA242)(χ^(2)=10.712,P=0.001)、肿瘤大小(χ^(2)=4.310,P=0.038)和淋巴结转移(χ^(2)=16.883,P<0.001)是影响CCA患者术后DFS的独立危险因素。Kaplan-Meier生存分析,癌胚抗原(CEA)(χ^(2)=5.188,P=0.023)、CA19-9(χ^(2)=9.324,P=0.002)、CA125(χ^(2)=9.568,P=0.002)、CA242(χ^(2)=19.119,P<0.001)、前白蛋白(χ^(2)=4.370,P=0.037)、丙氨酸氨基转移酶(ALT)(χ^(2)=4.072,P=0.045)、天冬氨酸氨基转移酶(AST)(χ^(2)=6.401,P=0.011)、碱性磷酸酶(ALP)(χ^(2)=4.682,P=0.045)、淋巴结转移(χ^(2)=11.739,P<0.001)、脉管癌栓(χ^(2)=5.940,P=0.015)、血管侵犯(χ^(2)=4.892,P=0.027)和术后辅助治疗(χ^(2)=4.011,P=0.045)是影响CCA患者术后生存的危险因素。LASSO回归和Cox多因素分析,淋巴结转移是CCA根治术患者术后复发的独立危险因素(OR=3.067,95%CI=1.192~8.252,P=0.022),淋巴结转移(HR=2.094,95%CI=1.074~4.083,P=0.030)和术后辅助治疗(HR=0.374,95%CI=0.190~0.736,P=0.004)是影响CCA患者生存的独立因素。建立列线图预测CCA患者的OS,其C-index为0.697,第1、2和5年生存率的AUC分别为0.72(95%CI:0.68~0.88)、0.65(95%CI:0.63~0.81)和0.84(95%CI:0.77~0.91)。结论:CCA患者预后较差,术后生存率低,淋巴结转移是影响患者复发和生存的共同独立危险因素,结合有无术后辅助治疗构建的列线图对CCA患者术后的生存期有较好的预测效能。

Objective:To explore the influencing factors of recurrence and survival of the patients with cholangiocarcinoma(CCA)after radical resection,and to establish the nomogram to predict the postoperative survival time.Methods:The clinical and pathological data of 89 patients who underwent cholangiocarcinoma resection in our hospital were retrospectively collected.The median time of disease-free survival(DFS)and overall survival(OS)of the patients were 10 and 13 months,respectively.Kaplan Meier and Cox regression models were used to analyze the effects of clinical and pathological characteristics on DFS and OS.LASSO regression was performed by R software to evaluate the related influencing factors of recurrence of the patients after surgery.A nomogram was established to predict the OS of patients after operation,and the prediction efficiency was evaluated by the consistency index(C-index),calibration curve and area under receiver operaing characteristic(ROC)curve(AUC).Results:The postoperative univariate analysis showed that diabetes(χ^(2)=5.204,P=0.023),CA19-9(χ^(2)=7.694,P=0.006),CA125(χ^(2)=6.908,P=0.009),CA242(χ^(2)=10.712,P=0.001),tumor size(χ^(2)=4.310,P=0.038),lymph node metastasis(χ^(2)=16.883,P<0.001)were the independent risk factors of DFS after operation in the CCA patients.The Kaplan-Meier survival analysis results showed that CEA(χ^(2)=5.188,P=0.023),CA19-9(χ^(2)=9.324,P=0.002),CA125(χ^(2)=9.568,P=0.002),CA242(χ^(2)=19.119,P<0.001),prealbumin(χ^(2)=4.370,P=0.037),ALT(χ^(2)=4.072,P=0.045),AST(χ^(2)=6.401,P=0.011),ALP(χ^(2)=4.682,P=0.045),lymph node metastasis(χ^(2)=11.739,P<0.001),portal carcinoma(χ^(2)=5.940,P=0.015),vascular invasion(χ^(2)=4.892,P=0.027),postoperative adjuvant therapy(χ^(2)=4.011,P=0.045)were the risk factors affecting postoperative survival of the CCA patients.The LASSO regression analysis and COX multivariate analysis showed that lymph node metastasis was an independent risk factor of postoperative recurrence of the patients(OR=3.067,95%CI=1.192-8.252,P=0.022),lymph node metastasis(HR:2.094,95%CI=1.074-4.083,P=0.030)and postoperative adjuvant therapy(HR=0.374,95%CI=0.190-0.736,P=0.004)were the independent factors of survial of the CCA patients.A nomogram was established to predict the OS of CCA patients,Tte C-index was 0.697,and the AUC of the 1-year,2-year and 5-year survival rates were 0.72(95%CI:0.68-0.88),0.65(95%CI:0.63-0.81),and 0.84(95%CI:0.77-0.91),respectively.Conclusion:The prognosis of CCA patients is poor and the postoperative survival rate is low.Lymph node metastasis is a common independent risk factor for both recurrence and survival.Combined with postoperative adjuvant therapy,a nomogram is constructed,which has a good predictive efficiency in survival in the CCA patients after radical resection.