Department of Pharmacy, Peking University Third Hospital, Beijing, 100191, China.
Institute for Drug Evaluation, Peking University Health Science Center, Beijing, 100191, China.
Cancer Immunol Immunother. 2024 Nov 2;74(1):2. doi: 10.1007/s00262-024-03816-0.
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.
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.
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.
This study offers comprehensive insights into managing ICI-TD, potentially enhancing tailored cancer immunotherapy management.
随着免疫检查点抑制剂（ICIs）在各种癌症中的广泛应用，ICI 相关甲状腺功能障碍（ICI-TD）已成为临床实践中的一个日益关注的问题。本研究旨在制定 ICI-TD 的个体化管理策略，以增强癌症患者的早期识别和主动管理。
我们设计并进行了三阶段研究。首先，我们通过系统评价和荟萃分析分析了影响因素，该分析符合系统评价和荟萃分析的首选报告项目（PRISMA）指南。此外，该研究方案已在 PROSPERO（CRD42019131133）上注册。随后，我们利用 11 种算法基于 2018 年 7 月 20 日（中国首个 ICIs，Pembrolizumab 获批日期）至 2022 年 10 月 31 日的真实世界队列数据开发了 ICI-TD 的预测模型。考虑到区分度、校准度和临床实用性，我们选择了性能最佳的模型用于网络计算器的开发。最后，我们结合循证分析和实际考虑，提出了 ICI-TD 的个体化管理策略。
系统评价共纳入了 21 项观察性研究，涉及 4145 名患者，结果显示 ICI-TD 与女性性别、年龄、使用 Pembrolizumab（与其他 ICIs 相比）以及基线促甲状腺激素、游离甲状腺素和抗甲状腺抗体水平等因素相关。在预测模型开发阶段，纳入了 621 名参与者，其中 36 名患者发生了 ICI-TD。基于 LightGBM 算法的模型表现出优越的性能，进而开发了一个网络计算器。基于这些发现和现有指南，我们为药师制定了个体化监测和治疗方案。
本研究全面探讨了 ICI-TD 的管理，可能会增强癌症免疫治疗的个体化管理。
