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中华介入放射学电子杂志

中华介入放射学电子杂志 ›› 2022, Vol. 10 ›› Issue (02) : 169 -178. doi: 10.3877/cma.j.issn.2095-5782.2022.02.009

肿瘤介入

不可切除胆道癌致梗阻性黄疸患者行介入术后的生存预测模型建立
王加雷1, 周海峰1, 杨魏1, 刘圣1, 施海彬1, 周卫忠1,†()   
  1. 1. 210029　江苏南京，南京医科大学第一附属医院介入放射科
  • 收稿日期:2022-01-03 出版日期:2022-05-25
  • 通信作者: 周卫忠

Establishment of a survival prediction model for patients with obstructive jaundice caused by unresectable biliary tract cancer undergoing interventional therapy

Jialei Wang1, Haifeng Zhou1, Wei Yang1, Sheng Liu1, Haibin Shi1, Weizhong Zhou1,†()   

  1. 1. Department of Interventional Radiology, the First Affiliated Hospital, Nanjing Medical University, Jiangsu Nanjing 210029, China
  • Received:2022-01-03 Published:2022-05-25
  • Corresponding author: Weizhong Zhou
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引用本文：

王加雷, 周海峰, 杨魏, 刘圣, 施海彬, 周卫忠. 不可切除胆道癌致梗阻性黄疸患者行介入术后的生存预测模型建立[J]. 中华介入放射学电子杂志, 2022, 10(02): 169-178.

Jialei Wang, Haifeng Zhou, Wei Yang, Sheng Liu, Haibin Shi, Weizhong Zhou. Establishment of a survival prediction model for patients with obstructive jaundice caused by unresectable biliary tract cancer undergoing interventional therapy[J]. Chinese Journal of Interventional Radiology(Electronic Edition), 2022, 10(02): 169-178.

目的

探讨因不可切除胆道癌致阻黄患者行介入治疗后预后生存的影响因素，并构建列线图个体化预测患者总生存期（OS）。

方法

回顾性分析我院2015年6月至2021年7月收治的261例胆道癌行经皮介入降黄患者的资料。总体划分为训练组（n = 188）及验证组（n = 73）。单因素和多因素Cox回归分析筛选患者OS的独立影响因素，并以此构建列线图，个体化预测不可切除胆道癌伴有阻黄患者介入治疗术后生存情况。绘制AUC曲线及一致性曲线评估模型预测性能。通过K-M曲线评估分类预测因子的危险分层能力。

结果

在261例患者中，训练组中位OS为244 d（IQR：213，275）。验证组中位OS为236 d（IQR：186，285）。单因素及多因素回归分析显示，总胆红素、总胆固醇、血红蛋白、血清钠、糖类抗原199水平和肿瘤亚型为预测不可切除胆道癌伴阻黄患者3、6个月和1年的OS的独立相关因素，并建立诺模图。ROC曲线下面积显示，该模型在训练组（0.817、0.825和0.796）和验证组（0.921、0.880和0.904）对3、6个月和1年的OS预测具有良好的分辨能力，可以较准确地预测患者的总体生存情况。

结论

本模型能够较好预测不可切除胆道癌伴阻黄患者3、6个月、1年的生存机会，为临床治疗策略选择提供一定的帮助。

关键词: 胆道癌, 梗阻性黄疸, 预后模型, 介入治疗
Objective

To explore the factors affecting the prognosis and survival of patients with unresectable biliary tract cancer caalignant biliary obstruction after interventional therapy, and to construct an individualized nomogram to predict the overall survival time (overall survival, OS).

Methods

From June 2015 to July 2021, a total of 261 patients with obstructive jaundice caused by unresectable biliary tract cancer treated with interventional decompression in our center were retrospectively analyzed. The patients were divided into two groups: a training group (n = 188) and a validation group (n = 73). The univariate and multivariate Cox proportional hazard regression analyses were used to determine the independent factors related to OS, and an individual nomogram was constructed to visualize the new model and predict 3-month, 6-month, and 1-year survival. The area under the curves (AUC) and the calibration curves were drawn to evaluate predictive performance in total patients . The risk stratification ability of each categorical predictors was evaluated by Kaplan-Meier curves.

Results

For the enrolled patients, the median OS was 244 days (IQR: 213, 275) in the training group and 236 days (IQR: 186, 285) in the validation group. The univariate and multivariate regression analyses showed that the independent factors were total bilirubin, total cholesterol, hemoglobin, serum sodium, carbohydrate antigen-9 and subtypes of tumor. A nomogram was successfully established to predict 3-months, 6-month and 1-year survival probability. The AUCs showed that the new model had good discrimination for 3-month, 6-month and 1-year OS prediction in the training group (0.817, 0.825 and 0.796, respectively) and the calibration group (0.921, 0.880 and 0.904, respectively).

Conclusions

The new model could effectively predict 3 months, 6 months and 1 year OS for patients with unresectable biliary tract cancer caused obstructive jaundice undergoing interventional decompression, which may help for clinical decision making.

Key words: Biliary tract cancer, Jaundice, Prognostic model, Interventional therapy
表1 晚期胆道癌伴阻黄患者训练组及验证组基线资料（n，%）
指标 总数(n = 261) 训练组(n = 188) 验证组(n = 73) P值
性别       0.288
  女 101(38.7%) 69(36.7%) 32(43.8%)  
  男 160(61.3%) 119(63.3%) 41(56.2%)  
年龄 66.1(10.6) 65.6(10.6) 67.4(10.6) 0.239
Bismuth分型       0.167
  Ⅰ 39(14.9%) 28(14.9%) 11(15.1%)  
  Ⅱ 108(41.4%) 70(37.2%) 38(52.1%)  
  Ⅲ 106(40.7%) 83(44.2%) 23(33.5%)  
  Ⅳ 8(3.1%) 7(3.7%) 1(1.4%)  
介入策略       0.206
  外引流管 147(56.3%) 104(55.3%) 43(58.9%)  
  金属支架 90(34.5%) 63(33.5%) 27(37.0%)  
  支架联合碘粒子条 24(9.2%) 21(11.2%) 3(4.1%)  
肿瘤亚型       0.889
  肝内胆管癌 51(19.5%) 36(19.1%) 15(29.4%)  
  肝门部胆管癌 134(51.3%) 96(51.1%) 38(52.1%)  
  远端胆管癌 54(20.7%) 41(21.8%) 13(17.8%)  
  胆囊癌 22(8.4%) 15(8.0%) 7(9.6%)  
M分期       0.674
  0 212(81.2%) 154(81.9%) 58(79.5%)  
  1 49(18.8%) 34(18.1%) 15(20.5%)  
外科切除史       0.758
  无 193(73.9%) 140(74.5%) 53(72.6%)  
  有 68(26.1%) 48(25.5%) 20(27.4%)  
后续化疗       0.792
  无 231(88.5%) 167(88.8%) 64(27.7%)  
  有 30(11.5%) 21(11.2%) 9(12.3%)  
后续放疗       0.649
  无 221(84.7%) 158(84.0%) 63(86.3%)  
  有 40(15.3%) 30(16.0%) 10(13.7%)  
胸腔积液       0.295
  无 235(90.0%) 167(88.8%) 68(93.2%)  
  有 26(10.0%) 21(11.2%) 5(6.8%)  
腹腔积液       0.578
  无 220(84.3%) 157(83.5%) 63(86.3%)  
  有 41(15.7%) 31(16.5%) 10(13.7%)  
胸腹腔积液       0.388
  无 213(81.6%) 151(80.3%) 62(84.9%)  
  有 48(18.4%) 37(19.7%) 11(15.1%)  
ALT (IU/L) 117(102) 116(102) 118(105) 0.865
AST (IU/L) 125(110) 124(112) 127(110) 0.831
γ-GT (IU/L) 510(370) 518(377) 492(355) 0.624
AKP (IU/L) 633(422) 620(406) 666(461) 0.440
ALB (g /L) 31.8(5.04) 32.1(5.14) 31.0(4.70) 0.124
GLB (g/L) 27.7(6.7) 27.5(7.41) 28.0(5.21) 0.612
TB (μmol/L) 239(153) 242(159) 231(138) 0.603
DB (μmol/L) 170(108) 172(112) 164(98) 0.621
TB/DB比值 1.44(0.23) 1.44(0.18) 1.46(0.32) 0.555
TC (mmol/L) 5.90(4.04) 6.00(4.37) 5.63(3.00) 0.513
TG (mmol/L) 2.40(1.92) 2.26(1.11) 2.78(3.18) 0.053
BUN (mmol/L) 5.42(4.81) 5.53(5.40) 5.14(2.76) 0.558
Cr (μmol/L) 62.6(38.9) 63.6(43.5) 60.2(23.1) 0.540
K (mmol/L) 3.70(0.50) 3.70(0.50) 3.72(0.52) 0.676
Na (mmol/L) 135(8.99) 136(4.05) 134(15.8) 0.205
Cl (mmol/L) 101(5.06) 101(5.46) 101(3.95) 0.571
Ca (mmol/L) 2.38(3.04) 2.45(3.58) 2.19(0.15) 0.535
Glu (mmol/L) 5.85(2.00) 5.83(2.11) 5.90(1.68) 0.806
WBC (×109/L) 8.22(3.89) 7.95(3.56) 8.91(4.60) 0.072
N% 73.6(12.6) 73.2(12.2) 74.5(13.4) 0.446
L% 16.1(9.19) 16.5(9.27) 14.9(8.94) 0.220
NLR 7.76(13.2) 7.70(14.8) 7.92(7.86) 0.901
Hb (g/L) 109(18.0) 109(19.1) 108(14.7) 0.716
PLT (×109g/L) 261(97.5) 225(101) 229(88) 0.744
CEA (ng/mL)       0.199
  < 5 132(53.7%) 100(56.2%) 32(47.1%)  
  ≥5 114(46.3%) 78(43.8%) 36(52.9%)  
CA19-9 (U/mL)       0.648
  < 1 000 136(55.3%) 100(56.2%) 36(52.9%)  
  ≥1 000 110(44.7%) 78(43.8%) 32(47.1%)  
ECOGPS评分       0.066
  0 24(9.2%) 19(10.1%) 5(6.8%)  
  1 192(73.6%) 131(69.7%) 61(83.6%)  
  2 or 3 45(17.2%) 38(20.2%) 7(9.6%)  
图1 训练组（n = 188，A，B和C）和验证组（n = 73，D，E和F）中3个肿瘤相关预测因子的Kaplan-Meier曲线
表2 训练组患者OS相关因素的单因素及多因素分析
指标 单因素分析 多因素分析
HR (95%CI) P值 HR (95%CI) P值
性别   0.492    
  女        
  男 1.124(0.804~1.570)      
年龄 1.018（1.002~1.034) 0.030    
Bismuth分型   0.136    
  Ⅰ        
  Ⅱ 0.499(0.066~3.761)      
  Ⅲ 0.639(0.088~4.641)      
  Ⅳ 0.766(0.106~5.553)      
介入策略   0.816    
  外引流管        
  金属支架 0.896(0.530~1.515)      
  碘粒子条 0.838(0.483~1.455)      
肿瘤亚型   0.015   0.002
  肝内胆管癌        
  肝门部胆管癌 0.847(0.451~1.591)   0.788(0.401~1.548)  
  远端胆管癌 0.496(0.279~0.881)   0.416(0.222~0.780)  
  胆囊癌 0.471(0.249~0.892)   0.390(0.198~0.766)  
M分期   0.093    
  0        
  1 1.412(0.945~2.111)      
手术切除史   0.661    
  无        
  有 1.087(0.750~1.576)      
后续化疗   0.001    
  无        
  有 0.350(0.189~0.650)      
后续放疗   0.040    
  无        
  有 0.626(0.390~1.003)      
胸腔积液   0.244    
  无        
  有 1.341(0.818~2.199)      
腹腔积液   0.016    
  无        
  有 1.648(1.096~2.476)      
ALT (IU/L) 1.000(0.998~1.001) 0.598    
AST (IU/L) 1.002(1.000~1.003) 0.059    
γ-GT (IU/L) 1.000(0.999~1.000) 0.243    
AKP (IU/L) 1.000(1.000~1.001) 0.222    
ALB (g/L) 0.930(0.900~0.961) < 0.001    
GLB (g/L) 1.004(0.981~1.028) 0.714    
TB (μmol/L) 1.002(1.001~1.003) < 0.001 1.002(1.001~1.004) < 0.001
DB (μmol/L) 1.003(1.002~1.004) < 0.001    
TB/DB比值 0.612(0.265~1.413) 0.250    
TC (mmol/L) 0.952(0.904~1.002) 0.057 0.918(0.861~0.978) 0.008
TG (mmol/L) 1.005(0.879~1.149) 0.942    
BUN (mmol/L) 1.050(1.018~1.083) 0.002    
Cr (μmol/L) 1.005(1.001~1.008) 0.006    
K (mmol/L) 0.655(0.451~1.954) 0.027    
Na (mmol/L) 0.906(0.867~0.946) < 0.001 0.923(0.879~0.969) 0.001
Cl (mmol/L) 0.939(0.904~0.976) 0.001    
Ca (mmol/L) 0.227(0.073~0.707) 0.011    
Glu (mmol/L) 0.951(0.862~1.049) 0.317    
WBC (×109/L) 1.095(1.046~1.146) < 0.001    
N% 1.014(0.999~1.030) 0.072    
L% 0.972(0.952~0.992) 0.006    
NLR 1.007(0.999~1.015) 0.101    
Hb (g/L) 0.987(0.979~0.994) 0.001 0.983(0.973~0.993) 0.001
PLT (×109g/L) 1.000(0.998~1.001) 0.697    
CEA (ng/mL)   0.001    
  < 5        
  ≥5 1.780(1.276~2.484)      
CA19-9 (U/mL)   < 0.001   0.001
  < 1 000        
  ≥1 000 2.777(1.973~3.908)   1.985(1.342~2.936)  
ECOG PS评分   0.006    
  0        
  1 0. 357(0.181~0.702)      
  2 or 3 0.604(0.402~0.907)      
图2 生存预测模型的诺模图，该模型基于6个临床预测因子。要使用这些诺模图，需要在每个变量轴上定位单个患者的值，并画一条线来确定每个变量值所接收的点数。这些数字的总和位于总分的轴上，向下画三条线到风险轴，以确定3、6个月和1年的生存概率。
图3 预测表现的校准曲线。3、6个月和1年生存预测模型的校准曲线在训练集（A、B和C）内评估，外部在验证集（D、E和F）评估，临近45度线周围，表明模型具有较好的准确性和区分性。
图4 ROC曲线与AUC的预测表现（n = 261）。在训练集（A、B、C）内评估COMBO-BaS模型（蓝线）、M期（红线）和CA19-9（绿线）预测3、6个月和1年生存的AUC，外部评估（D、E、F）。
图5 不同介入治疗策略亚组ROC曲线与AUC的预测表现（n = 261）。5A：引流管（n = 147）；5B：支架（n = 90）；5C：粒子支架（n = 24），蓝线指3个月，红线指6个月，绿线指1年。
图6 ROC曲线与AUC对不同亚型肿瘤患者（A：ICC，n = 51；B：PCC，n = 134；C：DCC，n = 54；D：GBC，n = 22）的预测性能。在全部患者中对3个月（蓝线）、6个月（红线）和1年（绿线）生存预测模型的AUC进行内部评估。
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