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基于列线图的肺癌住院患者静脉血栓栓塞症新型风险评估模型的推导、验证与评估:一项回顾性病例对照研究

Derivation, validation and assessment of a novel nomogram-based risk assessment model for venous thromboembolism in hospitalized patients with lung cancer: A retrospective case control study.

作者信息

Li Huimin, Tian Yu, Niu Haiwen, He Lili, Cao Guolei, Zhang Changxi, Kaiweisierkezi Kaiseer, Luo Qin

机构信息

Department of Respiratory and Neurology, The Affiliated Tumor Hospital of Xinjiang Medical University, Urumqi, China.

出版信息

Front Oncol. 2022 Oct 10;12:988287. doi: 10.3389/fonc.2022.988287. eCollection 2022.

Abstract

PURPOSE

This study aimed to develop and validate a specific risk-stratification nomogram model for the prediction of venous thromboembolism(VTE) in hospitalized patients with lung cancer using readily obtainable demographic, clinical and therapeutic characteristics, thus guiding the individualized decision-making on thromboprophylaxis on the basis of VTE risk levels.

METHODS

We performed a retrospective case-control study among newly diagnosed lung cancer patients hospitalized between January 2016 and December 2021. Included in the cohort were 234 patients who developed PTE and 936 non-VTE patients. The patients were randomly divided into the derivation group (70%, 165 VTE patients and 654 non-VTE patients) and the validation group (30%, 69 VTE patients and 282 non-VTE patients). Cut off values were established using a Youden´s Index. Univariate and multivariate regression analyses were used to determine independent risk factors associated with VTE. Variance Inflation Factor(VIF) was used for collinearity diagnosis of the covariates in the model. The model was validated by the consistency index (C-index), receiver operating characteristic curves(ROC) and the calibration plot with the Hosmer-Lemeshow goodness-of-fit test. The clinical utility of the model was assessed through decision curve analysis(DCA). Further, the comparison of nomogram model with current models(Khorana, Caprini, Padua and COMPASS-CAT) was performed by comparing ROC curves using the DeLong's test.

RESULTS

The predictive nomogram modle comprised eleven variables: overweight(24-28) defined by body mass index (BMI): [odds ratio (OR): 1.90, 95% confidence interval (CI): 1.19-3.07], adenocarcinoma(OR:3.00, 95% CI: 1.88-4.87), stageIII-IV(OR:2.75, 95%CI: 1.58-4.96), Central venous catheters(CVCs) (OR:4.64, 95%CI: 2.86-7.62), D-dimer levels≥2.06mg/L(OR:5.58, 95%CI:3.54-8.94), PT levels≥11.45sec(OR:2.15, 95% CI:1.32-3.54), Fbg levels≥3.33 g/L(OR:1.76, 95%CI:1.12-2.78), TG levels≥1.37mmol/L (OR:1.88, 95%CI:1.19-2.99), ROS1 rearrangement(OR:2.87, 95%CI:1.74-4.75), chemotherapy history(OR:1.66, 95%CI:1.01-2.70) and radiotherapy history(OR:1.96, 95%CI:1.17-3.29). Collinearity analysis with demonstrated no collinearity among the variables. The resulting model showed good predictive performance in the derivation group (AUC 0.865, 95% CI: 0.832-0.897) and in the validation group(AUC 0.904,95%CI:0.869-0.939). The calibration curve and DCA showed that the risk-stratification nomogram had good consistency and clinical utility. Futher, the area under the ROC curve for the specific VTE risk-stratification nomogram model (0.904; 95% CI:0.869-0.939) was significantly higher than those of the KRS, Caprini, Padua and COMPASS-CAT models(Z=12.087, 11.851, 9.442, 5.340, all <0.001, respectively).

CONCLUSION

A high-performance nomogram model incorporated available clinical parameters, genetic and therapeutic factors was established, which can accurately predict the risk of VTE in hospitalized patients with lung cancer and to guide individualized decision-making on thromboprophylaxis. Notably, the novel nomogram model was significantly more effective than the existing well-accepted models in routine clinical practice in stratifying the risk of VTE in those patients. Future community-based prospective studies and studies from multiple clinical centers are required for external validation.

摘要

目的

本研究旨在开发并验证一种特定的风险分层列线图模型,用于预测肺癌住院患者发生静脉血栓栓塞症(VTE)的风险,该模型使用易于获取的人口统计学、临床和治疗特征,从而根据VTE风险水平指导血栓预防的个体化决策。

方法

我们对2016年1月至2021年12月期间住院的新诊断肺癌患者进行了一项回顾性病例对照研究。队列中包括234例发生肺栓塞(PTE)的患者和936例非VTE患者。患者被随机分为推导组(70%,165例VTE患者和654例非VTE患者)和验证组(30%,69例VTE患者和282例非VTE患者)。使用约登指数确定截断值。采用单因素和多因素回归分析来确定与VTE相关的独立危险因素。方差膨胀因子(VIF)用于模型中协变量的共线性诊断。该模型通过一致性指数(C指数)、受试者工作特征曲线(ROC)以及采用Hosmer-Lemeshow拟合优度检验的校准图进行验证。通过决策曲线分析(DCA)评估模型的临床实用性。此外,通过使用DeLong检验比较ROC曲线,将列线图模型与当前模型(Khorana、Caprini、Padua和COMPASS-CAT)进行比较。

结果

预测列线图模型包含11个变量:由体重指数(BMI)定义的超重(24 - 28):[比值比(OR):1.90,95%置信区间(CI):1.19 - 3.07],腺癌(OR:3.00,95%CI:1.88 - 4.87),Ⅲ - Ⅳ期(OR:2.75,95%CI:1.58 - 4.96),中心静脉导管(CVCs)(OR:4.64,95%CI:2.86 - 7.62),D - 二聚体水平≥2.06mg/L(OR:5.58,95%CI:3.54 - 8.94),凝血酶原时间(PT)水平≥11.45秒(OR:2.15,95%CI:1.32 - 3.54),纤维蛋白原(Fbg)水平≥3.33g/L(OR:1.76,95%CI:1.12 - 2.78),甘油三酯(TG)水平≥1.37mmol/L(OR:1.88,95%CI:1.19 - 2.99),ROS1重排(OR:2.87,95%CI:1.74 - 4.75),化疗史(OR:1.66,95%CI:1.01 - 2.70)和放疗史(OR:1.96,95%CI:1.17 - 3.29)。共线性分析表明变量之间不存在共线性。所得模型在推导组(AUC 0.865,95%CI:0.832 - 0.897)和验证组(AUC 0.904,95%CI:0.869 - 0.939)中均表现出良好的预测性能。校准曲线和DCA表明风险分层列线图具有良好的一致性和临床实用性。此外,特定VTE风险分层列线图模型(0.904;95%CI:从0.869至0.939)的ROC曲线下面积显著高于KRS、Caprini、Padua和COMPASS - CAT模型(Z分别为12.087、11.851、9.442、5.340,均<0.001)。

结论

建立了一个纳入可用临床参数、基因和治疗因素的高性能列线图模型,该模型可以准确预测肺癌住院患者发生VTE的风险,并指导血栓预防的个体化决策。值得注意的是,在对这些患者的VTE风险进行分层时,新的列线图模型在常规临床实践中比现有的公认模型显著更有效。未来需要基于社区的前瞻性研究和来自多个临床中心的研究进行外部验证。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9af3/9589115/f2acca6ed98e/fonc-12-988287-g001.jpg

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