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机器学习模型在脊髓神经胶质瘤患者个体化生存预测中的开发和内部验证。

Development and internal validation of machine learning models for personalized survival predictions in spinal cord glioma patients.

机构信息

Department of Neurosurgery, Mount Sinai Health System, 1468 Madison Ave, New York, NY, USA.

Department of Neurosurgery, Mount Sinai Health System, 1468 Madison Ave, New York, NY, USA.

出版信息

Spine J. 2024 Jun;24(6):1065-1076. doi: 10.1016/j.spinee.2024.02.002. Epub 2024 Feb 15.


DOI:10.1016/j.spinee.2024.02.002
PMID:38365005
Abstract

BACKGROUND CONTEXT: Numerous factors have been associated with the survival outcomes in patients with spinal cord gliomas (SCG). Recognizing these specific determinants is crucial, yet it is also vital to establish a reliable and precise prognostic model for estimating individual survival outcomes. OBJECTIVE: The objectives of this study are twofold: first, to create an array of interpretable machine learning (ML) models developed for predicting survival outcomes among SCG patients; and second, to integrate these models into an easily navigable online calculator to showcase their prospective clinical applicability. STUDY DESIGN: This was a retrospective, population-based cohort study aiming to predict the outcomes of interest, which were binary categorical variables, in SCG patients with ML models. PATIENT SAMPLE: The National Cancer Database (NCDB) was utilized to identify adults aged 18 years or older who were diagnosed with histologically confirmed SCGs between 2010 and 2019. OUTCOME MEASURES: The outcomes of interest were survival outcomes at three specific time points postdiagnosis: 1, 3, and 5 years. These outcomes were formed by combining the "Vital Status" and "Last Contact or Death (Months from Diagnosis)" variables. Model performance was evaluated visually and numerically. The visual evaluation utilized receiver operating characteristic (ROC) curves, precision-recall curves (PRCs), and calibration curves. The numerical evaluation involved metrics such as sensitivity, specificity, accuracy, area under the PRC (AUPRC), area under the ROC curve (AUROC), and Brier Score. METHODS: We employed five ML algorithms-TabPFN, CatBoost, XGBoost, LightGBM, and Random Forest-along with the Optuna library for hyperparameter optimization. The models that yielded the highest AUROC values were chosen for integration into the online calculator. To enhance the explicability of our models, we utilized SHapley Additive exPlanations (SHAP) for assessing the relative significance of predictor variables and incorporated partial dependence plots (PDPs) to delineate the influence of singular variables on the predictions made by the top performing models. RESULTS: For the 1-year survival analysis, 4,913 patients [5.6% with 1-year mortality]; for the 3-year survival analysis, 4,027 patients (11.5% with 3-year mortality]; and for the 5-year survival analysis, 2,854 patients (20.4% with 5-year mortality) were included. The top models achieved AUROCs of 0.938 for 1-year mortality (TabPFN), 0.907 for 3-year mortality (LightGBM), and 0.902 for 5-year mortality (Random Forest). Global SHAP analyses across survival outcomes at different time points identified histology, tumor grade, age, surgery, radiotherapy, and tumor size as the most significant predictor variables for the top-performing models. CONCLUSIONS: This study demonstrates ML techniques can develop highly accurate prognostic models for SCG patients with excellent discriminatory ability. The interactive online calculator provides a tool for assessment by physicians (https://huggingface.co/spaces/MSHS-Neurosurgery-Research/NCDB-SCG). Local interpretability informs prediction influences for a given individual. External validation across diverse datasets could further substantiate potential utility and generalizability. This robust, interpretable methodology aligns with the goals of precision medicine, establishing a foundation for continued research leveraging ML's predictive power to enhance patient counseling.

摘要

背景情境:许多因素与脊髓神经胶质瘤(SCG)患者的生存结果相关。认识到这些特定的决定因素至关重要,但建立一个可靠和精确的预后模型来估计个体的生存结果也同样重要。

目的:本研究的目的有两个:第一,创建一系列可解释的机器学习(ML)模型,用于预测 SCG 患者的生存结果;第二,将这些模型集成到一个易于浏览的在线计算器中,以展示其潜在的临床适用性。

研究设计:这是一项回顾性、基于人群的队列研究,旨在使用 ML 模型预测 SCG 患者的感兴趣结局,这些结局是二元分类变量。

患者样本:国家癌症数据库(NCDB)被用于确定 2010 年至 2019 年间诊断为组织学证实的 SCG 的 18 岁及以上成年人。

结局测量:感兴趣的结局是在诊断后三个特定时间点的生存结局:1 年、3 年和 5 年。这些结局是通过组合“生存状态”和“最后联系或死亡(从诊断起的月数)”变量形成的。模型性能通过视觉和数值进行评估。视觉评估使用了接收器操作特征(ROC)曲线、精度-召回曲线(PRC)和校准曲线。数值评估涉及敏感性、特异性、准确性、PRC 下面积(AUPRC)、ROC 曲线下面积(AUROC)和 Brier 评分等指标。

方法:我们使用了五种 ML 算法-TabPFN、CatBoost、XGBoost、LightGBM 和 Random Forest-以及 Optuna 库进行超参数优化。选择具有最高 AUROC 值的模型用于集成到在线计算器中。为了增强我们模型的可解释性,我们使用 SHapley Additive exPlanations(SHAP)来评估预测变量的相对重要性,并结合部分依赖图(PDP)来描绘单个变量对表现最佳模型的预测的影响。

结果:对于 1 年生存率分析,纳入了 4913 例患者[5.6%的患者在 1 年内死亡];对于 3 年生存率分析,纳入了 4027 例患者(11.5%的患者在 3 年内死亡);对于 5 年生存率分析,纳入了 2854 例患者(20.4%的患者在 5 年内死亡)。顶级模型在 1 年死亡率方面的 AUROC 为 0.938(TabPFN),在 3 年死亡率方面为 0.907(LightGBM),在 5 年死亡率方面为 0.902(Random Forest)。跨不同时间点的生存结局的全局 SHAP 分析确定了组织学、肿瘤分级、年龄、手术、放疗和肿瘤大小是表现最佳模型的最重要预测变量。

结论:本研究表明,ML 技术可以为 SCG 患者开发高度准确的预后模型,具有出色的区分能力。交互式在线计算器为医生提供了一个评估工具(https://huggingface.co/spaces/MSHS-Neurosurgery-Research/NCDB-SCG)。局部可解释性为给定个体的预测影响提供了信息。在不同数据集之间进行外部验证可以进一步证实其潜在的效用和通用性。这种强大的、可解释的方法符合精准医学的目标,为利用 ML 的预测能力来增强患者咨询的持续研究奠定了基础。

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[2]
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[3]
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