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肿瘤靶向治疗和免疫治疗药物引起的皮肤药物不良反应危险因素分析及预测模型的建立

Risk Factors Analysis of Cutaneous Adverse Drug Reactions Caused by Targeted Therapy and Immunotherapy Drugs for Oncology and Establishment of a Prediction Model.

作者信息

Zhang Zimin, Zhu Mingyang, Jiang Weiwei

机构信息

Department of Pharmacy, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.

College of Pharmacy, Chongqing Medical University, Chongqing, China.

出版信息

Clin Transl Sci. 2025 Jan;18(1):e70118. doi: 10.1111/cts.70118.

Abstract

Targeted therapy and immunotherapy drugs for oncology have greater efficacy and tolerability than cytotoxic chemotherapeutic drugs. However, the cutaneous adverse drug reactions associated with these newer therapies are more common and remain poorly predicted. An effective prediction model is urgently needed and essential. This retrospective study included 1052 patients, divided into train set, test set, and external validation set. As a data-driven study, a total of 76 variables were collected. Univariate logistic analysis, least absolute shrinkage and selection operator regression, and stepwise logistic regression were utilized for feature screening. Finally, nine machine-learning models were constructed and compared, and grid search was performed to adjust the parameters. Model performance was evaluated using calibration curve and the area under the receiver operating characteristic curve (AUROC). Nine risk factors were eventually identified: age, treatment modality, cancer types, history of allergies, age-corrected Charlson comorbidity index, percentage of eosinophils, absolute number of monocytes, Eastern Cooperative Oncology Group Performance Status, and C-reactive protein. Among the models, the logistic model performed best, demonstrating strong performance in test set (AUROC = 0.734) and external validation set (AUROC = 0.817). This study identified nine significant risk factors and developed a nomogram prediction model. These findings have important implications for optimizing therapeutic efficacy and maintaining the quality of life of patients from the perspective of managing cutaneous adverse drug reactions. Trial Registration: ChiCTR2400088422.

摘要

肿瘤学的靶向治疗和免疫治疗药物比细胞毒性化疗药物具有更高的疗效和耐受性。然而,与这些新疗法相关的皮肤药物不良反应更为常见,且仍难以预测。迫切需要一个有效的预测模型且该模型至关重要。这项回顾性研究纳入了1052名患者,分为训练集、测试集和外部验证集。作为一项数据驱动的研究,共收集了76个变量。采用单因素逻辑回归、最小绝对收缩和选择算子回归以及逐步逻辑回归进行特征筛选。最后,构建并比较了9种机器学习模型,并进行网格搜索以调整参数。使用校准曲线和受试者工作特征曲线下面积(AUROC)评估模型性能。最终确定了9个风险因素:年龄、治疗方式、癌症类型、过敏史、年龄校正的查尔森合并症指数、嗜酸性粒细胞百分比、单核细胞绝对计数、东部肿瘤协作组体能状态和C反应蛋白。在这些模型中,逻辑模型表现最佳,在测试集(AUROC = 0.734)和外部验证集(AUROC = 0.817)中表现出强大性能。本研究确定了9个显著风险因素并开发了列线图预测模型。这些发现对于从管理皮肤药物不良反应的角度优化治疗效果和维持患者生活质量具有重要意义。试验注册号:ChiCTR2400088422。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f079/11702459/7bea84b4daaa/CTS-18-e70118-g001.jpg

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