Department of Medical Oncology, Institut Paoli-Calmettes, Marseille, France.
Department of Endocrinology, Assistance Publique - Hôpitaux de Marseille (AP-HM), Marseille, France.
J Immunother Cancer. 2023 Aug;11(8). doi: 10.1136/jitc-2023-006786.
Dysthyroidism (DT) is a common toxicity of immune checkpoint inhibitors (ICIs) and prior work suggests that dysthyroidism (DT) might be associated with ICI efficacy.
ConSoRe, a new generation data mining solution, was used in this retrospective study, to extract data from electronic patient records of adult cancer patients treated with ICI at Institut Paoli-Calmettes (Marseille, France). Every DT was verified and only ICI-induced DT was retained. Survival analyses were performed by Kaplan-Meier method (log-rank test) and Cox model. To account for immortal time bias, a conditional landmark analysis was performed (2 months and 6 months), together with a time-varying Cox model.
Data extraction identified 1385 patients treated with ICI between 2011 and 2021. DT was associated with improved overall survival (OS) (HR 0.46, (95% CI 0.33 to 0.65), p<0.001), with a median OS of 35.3 months in DT group vs 15.4 months in non-DT group (NDT). Survival impact of DT was consistent using a 6-month landmark analysis with a median OS of 36.7 months (95% CI 29.4 to not reported) in the DT group vs 25.5 months (95% CI 22.8 to 27.8) in the NDT group. In multivariate analysis, DT was independently associated with improved OS (HR 0.49, 95% CI 0.35 to 0.69, p=0.001). After adjustment in time-varying Cox model, this association remained significant (adjusted HR 0.64, 95% CI 0.45 to 0.90, p=0.010). Moreover, patients with DT and additional immune-related adverse event had increased OS compared with patients with isolated DT, with median OS of 38.8 months vs 21.4 months, respectively.
Data mining identified a large number of patients with ICI-induced DT, which was associated with improved OS accounting for immortal time bias.
甲状腺功能紊乱（DT）是免疫检查点抑制剂（ICI）的常见毒性反应，先前的研究表明 DT 可能与 ICI 的疗效相关。
在这项回顾性研究中，我们使用了新一代数据挖掘解决方案 ConSoRe，从法国马赛的 Institut Paoli-Calmettes 接受 ICI 治疗的成年癌症患者的电子病历中提取数据。每例 DT 均经过验证，仅保留由 ICI 引起的 DT。通过 Kaplan-Meier 法（对数秩检验）和 Cox 模型进行生存分析。为了考虑到无事件时间偏倚，我们进行了条件 landmark 分析（2 个月和 6 个月），并结合了时变 Cox 模型。
数据提取确定了 2011 年至 2021 年期间接受 ICI 治疗的 1385 例患者。DT 与改善的总生存（OS）相关（HR 0.46，95%CI 0.33 至 0.65，p<0.001），DT 组的中位 OS 为 35.3 个月，而非 DT 组为 15.4 个月。使用 6 个月的 landmark 分析，DT 组的中位 OS 为 36.7 个月（95%CI 29.4 至未报告），而非 DT 组为 25.5 个月（95%CI 22.8 至 27.8），结果一致。多变量分析表明，DT 与改善的 OS 独立相关（HR 0.49，95%CI 0.35 至 0.69，p=0.001）。在时变 Cox 模型中调整后，这种关联仍然显著（调整后的 HR 0.64，95%CI 0.45 至 0.90，p=0.010）。此外，与仅发生 DT 的患者相比，发生 DT 合并其他免疫相关不良事件的患者 OS 更高，中位 OS 分别为 38.8 个月和 21.4 个月。
数据挖掘确定了大量由 ICI 引起的 DT 患者，这些患者的 OS 得到改善，且考虑了无事件时间偏倚。
