Dysthyroidism during immune checkpoint inhibitors is associated with improved overall survival in adult cancers: data mining of 1385 electronic patient records.
Dysthyroidism during immune checkpoint inhibitors is associated with improved overall survival in adult cancers: data mining of 1385 electronic patient records.
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DOI：
10.1136/jitc-2023-006786
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发表时间：
2023-08
影响因子：
10.9
通讯作者：
中科院分区：
文献类型：
--
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甲状腺功能障碍（DT）是免疫检查点抑制剂（ICI）的常见毒性，先前的工作表明甲状腺功能障碍（DT）可能与ICI疗效相关。在这项回顾性研究中使用了新一代数据挖掘解决方案ConSoRe，从Institut Paoli-Calmettes（马赛，法国）接受ICI治疗的成年癌症患者的电子病历中提取数据。验证每个DT，仅保留ICI诱导的DT。生存分析采用Kaplan-Meier法（log-rank test）和考克斯模型。为了解释不朽时间偏倚，进行了条件性地标分析（2个月和6个月），以及随时间变化的考克斯模型。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与总生存期（OS）改善相关（HR 0.46，（95% CI 0.33至0.65），p<0.001），DT组中位OS为35.3个月，非DT组（NDT）为15.4个月。使用6个月里程碑分析，DT的生存影响一致，DT组的中位OS为36.7个月（95% CI 29.4至未报告），NDT组为25.5个月（95% CI 22.8至27.8）。在多变量分析中，DT与OS改善独立相关（HR 0.49，95% CI 0.35 - 0.69，p=0.001）。在时变考克斯模型中调整后，该相关性仍然显著（调整后HR 0.64，95% CI 0.45 - 0.90，p=0.010）。此外，与单纯DT患者相比，DT和其他免疫相关不良事件患者的OS增加，中位OS分别为38.8个月和21.4个月。数据挖掘确定了大量ICI诱导DT的患者，这与OS改善相关，说明了不朽时间偏倚。
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.
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影响因子：
4
作者：
Bellera CA;MacGrogan G;Debled M;de Lara CT;Brouste V;Mathoulin-Pélissier S
通讯作者：
Mathoulin-Pélissier S
影响因子：
4.2
作者：
Labrosse, Julie;Lam, Thanh;Hamy, Anne-Sophie
通讯作者：
Hamy, Anne-Sophie
DOI：
10.1038/s41571-022-00600-w
发表时间：
2022-04
期刊：
Nature reviews. Clinical oncology
影响因子：
--
作者：
Johnson DB;Nebhan CA;Moslehi JJ;Balko JM
通讯作者：
Balko JM
影响因子：
168.9
作者：
Felip, Enriqueta;Altorki, Nasser;Wakelee, Heather
通讯作者：
Wakelee, Heather
影响因子：
168.9
作者：
Cortes, Javier;Cescon, David W.;Schmid, Peter
通讯作者：
Schmid, Peter