基于SEER数据的原发性小肝癌肝切除术后生存率列线图模型的构建及验证

唐豪佑; 刘胜; 曾新; 黄孝彬; 杨洋; 邓大炜; 李建水

doi:10.3969/j.issn.1001-5256.2022.01.017

基于SEER数据的原发性小肝癌肝切除术后生存率列线图模型的构建及验证

DOI: 10.3969/j.issn.1001-5256.2022.01.017

川北医学院附属医院肝胆外二科，四川南充 637000

基金项目:

四川省科技计划项目 (2018JY0489);

四川省教育厅科研项目 (18ZB0217);

四川省卫健委普及应用项目 (20PJYY2695);

川北医学院科研项目 (CBY18-A-YB37)

利益冲突声明：本研究不存在研究者、伦理委员会成员、受试者监护人以及与公开研究成果有关的利益冲突。

作者贡献声明：唐豪佑、刘胜、李建水负责课题设计，资料分析，撰写论文；曾新、黄孝彬、杨洋参与收集数据，修改论文；李建水、邓大炜负责拟定写作思路，指导撰写文章并最后定稿。

详细信息

通信作者:
李建水，ljs2005doctor@126.com

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出版历程
- 收稿日期: 2021-06-09
- 录用日期: 2021-06-29
- 出版日期: 2022-01-20

Establishment of a nomogram for survival rate after liver resection for primary small hepatocellular carcinoma based on SEER data and external validation

Second Department of Hepatobiliary Surgery, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan 637000, China

Research funding:

Sichuan Science and Technology Program Project (2018JY0489);

Sichuan Education Department Scientific Research Project (18ZB0217);

Sichuan Health Care Commission Popular Application Project (20PJYY2695);

North Sichuan Medical College Scientific Research Project (CBY18-A-YB37)

摘要

摘要: 目的基于SEER数据和中国数据建立并验证原发性小肝癌肝切除术后总生存率列线图模型。方法提取2004年—2015年美国国立癌症研究所SEER数据库所登记的原发性小肝癌接受肝切除术治疗的1809例患者资料作为建模组；收集2010年—2017年在川北医学院附属医院接受肝切除术治疗的小肝癌患者158例为验证组。采用单因素Cox风险回归、lasso回归、多因素Cox风险回归分析小肝癌患者肝切除术后OS的影响因素。根据OS的独立影响因素构建列线图模型，利用一致性指数(C-index)、绘制校准曲线及ROC曲线检验模型的预测能力。利用Kaplan-Meier生存分析和log-rank检验分析高、低风险组间的生存差异。结果多因素Cox风险回归分析发现性别(HR=1.22, 95%CI：1.05~1.41, P=0.010)、Seer分期(HR=1.51, 95%CI：1.23~1.85, P＜0.001；HR=10.31, 95%CI：2.53~42.04, P=0.001)、肿瘤直径(HR=1.22，95%CI：1.06~1.39，P=0.004)、脉管侵犯或转移(HR=1.43，95%CI：1.24~1.65，P＜0.001)、AFP(HR=1.33，95%CI：1.16~1.54，P＜0.001)是小肝癌患者肝切除术后OS的独立危险因素。建模组C指数为0.621，其1、2、3年ROC曲线下面积分别为0.666(95%CI：0.628~0.704)，0.678(95%CI：0.647~0.708)，0.663(95%CI：0.635~0.690)；验证组C指数为0.718；其1、2、3年ROC曲线下面积分别为0.695(95%CI：0.593~0.797)，0.781(95%CI：0.706~0.856)，0.759(95%CI：0.669~0.848)。根据列线图模型进行风险分层，Kaplan-Meier生存分析显示：建模组和验证组的低风险组的预后均明显优于高风险组(P＜0.01)。结论建立的原发性小肝癌肝切除术后生存率模型可以用于预测1、2、3年OS，可以使用于国内临床工作。
- 癌, 肝细胞 /
- 肝切除术 /
- 列线图
Abstract: Objective To establish a nomogram for overall survival rate after liver resection for primary small hepatocellular carcinoma based on SEER data and external validation of Chinese data. Methods The data of 1809 patients, registered in National Cancer Institute SEER database in 2004-2015, who underwent hepatectomy for primary small hepatocellular carcinoma were extracted as modeling group, and 158 patients with small hepatocellular carcinoma who underwent hepatectomy in Affiliated Hospital of North Sichuan Medical College from 2010 to 2017 were collected as validation group. The univariate Cox risk regression analysis, lasso regression analysis, and multivariate Cox hazard regression analysis were used to investigate the influencing factors for OS after hepatectomy in patients with small hepatocellular carcinoma. A nomogram was established based on the independent influencing factors for OS, and index of concordance (C-index), calibration curves, and receiver operating characteristic (ROC) curve were used to analyze the predictive ability of the nomogram. The Kaplan-Meier survival analysis and the log-rank test were used to investigate the difference in survival between the high- and low-risk groups. Results The multivariate Cox hazard regression analysis showed that sex (hazard ratio [HR]=1.22, 95% confidence interval [CI]: 1.05-1.41, P=0.010), Seer stage (HR=1.51, 95%CI: 1.23-1.85, P < 0.001; HR=10.31, 95%CI: 2.53-42.04, P=0.001), tumor diameter (HR=1.22, 95%CI: 1.06-1.39, P=0.004), vascular invasion or metastasis (HR=1.43, 95%CI: 1.24-1.65, P < 0.001), and alpha-fetoprotein (HR=1.33, 95%CI: 1.16-1.54, P < 0.001) were independent risk factors for OS after hepatectomy for small hepatocellular carcinoma. The modeling group had a C-index of 0.621, and its area under the ROC curve at 1, 2, and 3 years was 0.666(95%CI 0.628-0.704), 0.678(95%CI 0.647-0.708), and 0.663(95%CI: 0.635-0.690), respectively; the validation group had a C-index of 0.718, and its area under the ROC curve at 1, 2, and 3 years was 0.695(95%CI: 0.593-0.797), 0.781(95%CI: 0.706-0.856), and 0.759(95%CI 0.669-0.848), respectively. Risk stratification was performed based on the nomogram, and the Kaplan-Meier survival analysis showed that for both the modeling group and the validation group, the low-risk group had a significantly better prognosis than the high-risk group (P < 0.01). Conclusion The model established for survival rate after liver resection for primary small hepatocellular carcinoma can predict the 1-, 2-, and 3-year OS rates and can thus be used in clinical practice in China.
- Carcinoma, Hepatocellular /
- Hepatectomy /
- Nomograms

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图 1 lasso回归分析及交叉验证

注：a，lasso回归路径图；b，交叉验证图。

下载: 全尺寸图片幻灯片

图 2 小肝癌患者肝切除术后OS列线图预测模型

下载: 全尺寸图片幻灯片

图 3 建模组和验证组预测小肝癌患者肝切除术后1、2、3生存率的校准曲线

注：a、b、c为建模组；d、e、f为验证组。

下载: 全尺寸图片幻灯片

图 4 模型预测1、2、3年OS的ROC曲线及高风险组和低风险组生存分析

注：a、b分别为建模组和验证组模型预测1、2、3年OS的ROC曲线；c、d分别为建模组和验证组模型的高风险组及低风险组生存分析。

下载: 全尺寸图片幻灯片

表 1 建模组和验证组一般资料

指标	建模组(n=1809)	验证组(n=158)
年龄[例(%)]
＜60岁	695(38.4)	114(72.2)
≥60岁	1114(61.6)	44(27.8)
性别[例(%)]
女	527(29.1)	26(16.5)
男	1282(70.9)	132(83.5)
分化程度[例(%)]
高	368(20.3)	9(5.7)
中	991(54.8)	89(56.3)
低/未	450(24.9)	60(38.0)
Seer分期[例(%)]
L	1613(89.2)	139(88.0)
R	179(9.9)	18(11.4)
D	17(0.9)	1(0.6)
N分期[例(%)]
N0	1799(99.4)	152(96.2)
N1	10(0.6)	6(3.8)
M分期[例(%)]
M0	1794(99.2)	157(99.4)
M1	15(0.8)	1(0.6)
肿瘤直径[例(%)]
＜3 cm	724(40.0)	46(29.1)
≥3 cm	1085(60.0)	112(70.9)
脉管侵犯或转移[例(%)]
无	1185(65.5)	115(72.8)
有	624(34.5)	43(27.2)
AFP[例(%)]
阴性	698(38.6)	75(47.5)
阳性	1111(61.4)	83(52.5)
肿瘤个数[例(%)]
单发	1369(75.7)	139(88.0)
多发	440(24.3)	19(12.0)
注：AFP＜20 ng/ml为阴性。

下载: 导出CSV

表 2 建模组OS的单因素及多因素Cox分析结果

变量	单因素分析			多因素分析
变量	HR	95%CI	P值	HR	95%CI	P值
年龄
＜60岁
≥60岁	1.13	0.99~1.30	0.066
性别
女
男	1.19	1.03~1.38	0.022	1.22	1.05~1.41	0.010
分化程度
高
中	0.82	0.70~0.97	0.018
低/未	0.76	0.63~0.92	0.005
Seer分期
L
R	1.97	1.63~2.38	＜0.001	1.51	1.23~1.85	＜0.001
D	3.98	2.39~6.65	＜0.001	10.31	2.53~42.04	0.001
N分期
N0
N1	1.43	0.68~3.02	0.342
M分期
M0
M1	3.35	1.93~5.80	＜0.001
肿瘤直径
＜3 cm
≥3 cm	1.25	1.09~1.42	0.001	1.22	1.06~1.39	0.004
脉管侵犯或转移
无
有	1.68	1.48~1.92	＜0.001	1.43	1.24~1.65	＜0.001
AFP
阴性
阳性	1.40	1.22~1.60	＜0.001	1.33	1.16~1.54	＜0.001
肿瘤个数
单发
多发	1.01	0.87~1.18	0.866

下载: 导出CSV

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