Immune checkpoint inhibitors-related thyroid dysfunction: influencing factor analysis, prediction model development, and management strategy proposal.

IF 4.6 2区 医学 Q2 IMMUNOLOGY
Xinya Li, Zaiwei Song, Yixuan Chen, Jingjing Wu, Dan Jiang, Zhen Zhang, Zeyuan Wang, Rongsheng Zhao
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Abstract

Background: With the extensive utilization of immune checkpoint inhibitors (ICIs) across various cancers, ICIs-related thyroid dysfunction (ICI-TD) has become a growing concern in clinical practice. This study aimed to devise an individualized management strategy for ICI-TD to enhance the early identification and proactive management in cancer patients.

Methods: We designed and conducted a three-phase study. Initially, we analyzed the influencing factors through a systematic review and meta-analysis, which adhered to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. Moreover, the study protocol was registered with PROSPERO (CRD42019131133). Subsequently, prediction models for ICI-TD were developed utilizing 11 algorithms based on the real-world cohort data from July 20, 2018 (the approval date of the first ICIs, Pembrolizumab in China), to October 31, 2022. Considering discrimination, calibration, and clinical utility, we selected the model with the best performance for web calculator development. Finally, individualized management strategies for ICI-TD were proposed by combining evidence-based analysis with practical considerations.

Results: The systematic review encompassed 21 observational studies involving 4,145 patients, revealing associations between ICI-TD and factors such as female gender, age, receipt of Pembrolizumab (versus other ICIs), and baseline levels of thyroid-stimulating hormone, free thyroxine, and antithyroid antibodies. In the prediction model development phase, 621 participants were enrolled, with 36 patients developing ICI-TD. The model based on the LightGBM algorithm demonstrated superior performance, leading to the development of a web calculator. Based on these findings and existing guidelines, individualized monitoring and treatment pathways for pharmacists were devised.

Conclusion: This study offers comprehensive insights into managing ICI-TD, potentially enhancing tailored cancer immunotherapy management.

免疫检查点抑制剂相关甲状腺功能障碍:影响因素分析、预测模型开发和管理策略建议。
背景:随着免疫检查点抑制剂(ICIs)在各种癌症中的广泛应用,ICIs相关甲状腺功能障碍(ICI-TD)已成为临床实践中日益关注的问题。本研究旨在为ICI-TD制定个体化管理策略,以加强对癌症患者的早期识别和积极管理:我们设计并开展了一项三阶段研究。首先,我们根据系统综述和荟萃分析(PRISMA)指南,通过系统综述和荟萃分析分析了影响因素。此外,研究方案已在 PROSPERO 注册(CRD42019131133)。随后,根据从2018年7月20日(中国首个ICIs--彭博利珠单抗的批准日期)到2022年10月31日的真实世界队列数据,利用11种算法开发了ICI-TD的预测模型。考虑到辨别力、校准和临床实用性,我们选择了性能最佳的模型用于网络计算器的开发。最后,结合循证分析和实际情况,提出了ICI-TD的个体化管理策略:系统综述包括21项观察性研究,涉及4145名患者,揭示了ICI-TD与女性性别、年龄、接受Pembrolizumab治疗(与其他ICI相比)以及促甲状腺激素、游离甲状腺素和抗甲状腺抗体基线水平等因素之间的关联。在预测模型开发阶段,共招募了 621 名参与者,其中 36 名患者出现了 ICI-TD。基于 LightGBM 算法的模型表现出卓越的性能,因此开发了网络计算器。根据这些研究结果和现有指南,为药剂师设计了个性化的监测和治疗路径:本研究为 ICI-TD 的管理提供了全面的见解,有可能加强量身定制的癌症免疫疗法管理。
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来源期刊
CiteScore
10.50
自引率
1.70%
发文量
207
审稿时长
1 months
期刊介绍: Cancer Immunology, Immunotherapy has the basic aim of keeping readers informed of the latest research results in the fields of oncology and immunology. As knowledge expands, the scope of the journal has broadened to include more of the progress being made in the areas of biology concerned with biological response modifiers. This helps keep readers up to date on the latest advances in our understanding of tumor-host interactions. The journal publishes short editorials including "position papers," general reviews, original articles, and short communications, providing a forum for the most current experimental and clinical advances in tumor immunology.
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