甲状腺髓样癌术后生存影响因素分析及列线图的构建
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四川省成都市第五人民医院 甲状腺乳腺外科,四川 成都 610000

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郭瑶,四川省成都市第五人民医院主治医师,主要从事甲状腺肿瘤及乳腺肿瘤方面的研究(

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Analysis of prognostic factors and nomogram construction for postoperative survival of medullary thyroid carcinoma
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Department of Thyroid and Breast Surgery, Chengdu Fifth People's Hospital, Chengdu 610000, China

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    摘要:

    背景与目的 目前用于评估甲状腺髓样癌(MTC)预后的主要方式采用TNM分期系统,但该系统不能个体化预测患者的预后。因此,需要建立专门针对MTC的精准预后指标体系。本研究分析影响MTC患者术后生存的因素,并构建MTC术后生存列线图。方法 选取2004—2015年SEER数据库MTC数据,共筛选出符合条件的1 884例患者纳入研究。将患者按3∶1随机分为训练集(1 413例)和验证集(471例),比较两组临床数据基线特征差异。采用单因素和多因素Cox回归模型筛选影响MTC生存的独立因素,Kaplan-Meier生存曲线分析其对预后的影响。基于Cox回归分析筛选出的结果建立MTC术后患者生存列线图。通过一致性指数(C-index)、ROC曲线、曲线下面积(AUC)、校准曲线和决策曲线分析(DCA)对列线图进行验证和评估。结果 单因素分析结果显示,性别、年龄、原发肿瘤分期、淋巴结转移、远处转移、是否甲状腺全切除、肿瘤是否侵犯甲状腺被膜、是否行放射治疗均影响患者预后(均P<0.05);Cox回归分析结果显示,性别、年龄、远处转移、侵犯甲状腺被膜、是否行甲状腺全切除术、是否放疗为MTC患者的独立预后因素(均P<0.05)。Kaplan-Meier生存曲线显示,男性患者、年龄≥49岁、伴远处转移、肿瘤侵犯甲状腺被膜、未行甲状腺全切除术、接收放疗患者预后更差。用患者性别、年龄、远处转移、甲状腺被膜受侵、手术方式构建了MTC患者2、5、10年的生存列线图。该列线图训练集的C-index为0.755(95% CI=0.741~0.769),验证集为0.725(95% CI=0.699~0.769)。ROC曲线用于评估列线图的区分度,在训练集2、5、10年的AUC值分别为0.79、0.779、0.766;在验证集分别为0.78、0.725、0.733。校准曲线结果显示该列线图预测的生存率和实际生存率具有一致性。DCA将列线图与AJCC第6版TNM分期的临床相比,该列线图的在5年和10年生存评估中均显示出更大的净收益。结论 性别、年龄、远处转移、甲状腺被膜侵犯、手术方式是影响MTC患者生存的独立因素;MTC术后生存列线图模型在一定程度上能够更准确地进行患者个体生存预测,帮助临床医师做出适当的个体化临床决策。

    Abstract:

    Background and Aims The current main approach for assessing the prognosis of medullary thyroid carcinoma (MTC) is the TNM staging system, but it cannot provide individualized prognosis prediction for patients. Therefore, there is a need to develop a precise prognostic indicator system specifically for MTC. This study was conducted to analyze the factors influencing postoperative survival in MTC patients and construct a postoperative survival nomogram for MTC.Methods MTC data from the SEER database from 2004 to 2015 were selected, and a total of 1 884 eligible patients were included in the study. The patients were randomly divided into a training set (1 413 cases) and a validation set (471 cases) at a ratio of 3∶1. The baseline clinical data and characteristics were compared between the two groups. Univariate and multivariate Cox regression models were used to identify independent factors for MTC survival, and Kaplan-Meier survival curves were used to analyze their impact on prognosis. A survival nomogram for postoperative MTC patients was established based on the results of Cox regression analysis. The nomogram was validated and evaluated using concordance index, ROC curve, area under the curve (AUC), calibration curve, and decision curve analysis (DCA).Results The results of univariate analysis showed that sex, age, primary tumor stage, lymph node metastasis, distant metastasis, total thyroidectomy, extrathyroidal. invasion, and radiotherapy were all associated with patients' prognosis (all P<0.05). The results of Cox regression analysis showed that sex, age, distant metastasis, extrathyroidal. invasion, total thyroidectomy, and radiotherapy were independent prognostic factors for MTC patients (all P<0.05). Kaplan-Meier survival curves demonstrated that male patients, age ≥49 years, presence of distant metastasis, extrathyroidal invasion, absence of total thyroidectomy, and receipt of radiotherapy had worse prognosis. Nomograms for 2-, 5-, and 10-year survival of MTC patients were constructed using variables that included sex, age, distant metastasis, and extrathyroidal invasion and surgical procedure. The concordance index for the training set of the nomogram was 0.755 (95% CI=0.741-0.769), and for the validation set, it was 0.725 (95% CI=0.699-0.769). The ROC curve was used to evaluate the discriminatory ability of the nomogram, with AUC values of 0.79, 0.779, and 0.766 for the training set at 2-, 5-, and 10-years, respectively, and 0.78, 0.725, and 0.733 for the validation set. The calibration curve showed good consistency between the predicted survival rates and actual survival rates. DCA demonstrated that the nomogram had greater net benefit compared to the AJCC 6th edition TNM staging system in 5- and 10-year survival assessment.Conclusion Sex, age, distant metastasis, extrathyroidal. invasion, and surgical approach are independent factors influencing the survival of MTC patients. The postoperative survival nomogram model for MTC can provide more accurate individual survival prediction to assist clinicians in making appropriate personalized clinical decisions.

    表 2 训练集患者预后的单因素及多因素分析Table 2 Univariate and multivariate Cox regression analysis based on OS (Training Cohort).
    图1 MTC患者筛选流程图Fig.1 Flowchart for the selection of MTC patients
    图2 X-tile确定年龄最佳分界 A:年龄的最优分组值出现;B:不同年龄分组直方图;C:不同年龄分组生存曲线Fig.2 Determination of the optimal age cutoff by X-tile analysis A: Appearance of the optimal grouping value for age; B: Histograms of different age groups; C: Survival curves for different age groups
    图3 不同预后因素分组MTC患者的Kaplan-Meier生存曲线 A:性别;B:诊断年龄;C:远处转移;D:被膜侵犯;E:手术情况;F:放疗情况Fig.3 Kaplan-Meier survival curves of MTC patients grouped by different prognostic factors A: Sex; B: Age at diagnosis; C: Distant metastasis; D: Extrathyroidal extension; E: Surgical procedure; F: Radiation
    图4 MTC患者2、5、10年生存列线图(例如:1例年龄≥49岁的男性MTC患者、肿瘤未侵犯甲状腺被膜、不伴远处转移且行甲状腺全切除术的患者其总得分为196分,其生存期<2、5、10年的概率分别为15.9%、35.4%、6.31%)Fig.4 Nomogram for 2-, 5-, and 10-year survival of MTC patients (For example, a male MTC patient aged ≥49 years, without tumor capsular invasion, without distant metastasis, and undergoing total thyroidectomy has a total score of 196; the probabilities of survival <2, 5, and 10 years are 15.9%, 35.4%, and 6.31% respectively)
    图5 MTC患者生存列线图ROC曲线 A:训练集的ROC曲线;B:验证集的ROC曲线Fig.5 ROC curves of the survival nomogram for MTC patients A: ROC curve of the training set; B: ROC curve of the validation set
    图6 MTC患者生存列线图校准曲线 A:训练集的校准曲线;B:验证集的校准曲线Fig.6 Calibration curves of the survival nomogram for MTC patients A: Calibration curve of the training set; B: Calibration curve of the validation set
    图7 列线图和TNM分期预测OS的DCA比较 A:5年OS;B:10年OSFig.7 Comparison of decision curve analysis between the nomogram and TNM staging for OS prediction A: 5-year OS; B: 10-year OS
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引用本文

郭瑶,但家强,袁智英.甲状腺髓样癌术后生存影响因素分析及列线图的构建[J].中国普通外科杂志,2023,32(5):698-706.
DOI:10.7659/j. issn.1005-6947.2023.05.009

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  • 收稿日期:2022-10-24
  • 最后修改日期:2023-04-12
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  • 在线发布日期: 2023-06-03