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预测恶性肿瘤 PD-1 抑制剂治疗中近期严重免疫相关不良事件的预测模型的预测价值。

Predictive value of near-term prediction models for severe immune-related adverse events in malignant tumor PD-1 inhibitor therapy.

机构信息

Department of Respiratory, Pengzhou People's Hospital, Chengdu, Sichuan, China.

Department of Statistics, University of Auckland, Auckland.

出版信息

Hum Vaccin Immunother. 2024 Dec 31;20(1):2398309. doi: 10.1080/21645515.2024.2398309. Epub 2024 Sep 13.

Abstract

Immune-related adverse events (irAEs) impact outcomes, with most research focusing on early prediction (baseline data), rather than near-term prediction (one cycle before the occurrence of irAEs and the current cycle). We aimed to explore the near-term predictive value of neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), absolute eosinophil count (AEC) for severe irAEs induced by PD-1 inhibitors. Data were collected from tumor patients treated with PD-1 inhibitors. NLR, PLR, and AEC data were obtained from both the previous and the current cycles of irAEs occurrence. A predictive model was developed using elastic net logistic regression Cutoff values were determined using Youden's Index. The predicted results were compared with actual data using Bayesian survival analysis. A total of 138 patients were included, of whom 47 experienced grade 1-2 irAEs and 18 experienced grade 3-5 irAEs. The predictive model identified optimal α and λ through 10-fold cross-validation. The Shapiro-Wilk test, Kruskal-Wallis test and logistic regression showed that only current cycle data were meaningful. The NLR was statistically significant in predicting irAEs in the previous cycle. Both NLR and AEC were significant predictors of irAEs in the current cycle. The model achieved an area under the ROC curve (AUC) of 0.783, with a sensitivity of 77.8% and a specificity of 80.8%. A probability ≥ 0.1345 predicted severe irAEs. The model comprising NLR, AEC, and sex may predict the irAEs classification in the current cycle, offering a near-term predictive advantage over baseline models and potentially extending the duration of immunotherapy for patients.

摘要

免疫相关不良事件(irAEs)影响治疗结局,大多数研究都集中在早期预测(基线数据)上,而不是近期预测(irAEs 发生前一个周期和当前周期)。我们旨在探讨中性粒细胞/淋巴细胞比值(NLR)、血小板/淋巴细胞比值(PLR)、绝对嗜酸性粒细胞计数(AEC)对 PD-1 抑制剂引起的严重 irAEs 的近期预测价值。数据来自接受 PD-1 抑制剂治疗的肿瘤患者。在 irAEs 发生的前一周期和当前周期中获得 NLR、PLR 和 AEC 数据。使用弹性网络逻辑回归建立预测模型,使用约登指数确定截断值。使用贝叶斯生存分析比较预测结果与实际数据。共纳入 138 例患者,其中 47 例发生 1-2 级 irAEs,18 例发生 3-5 级 irAEs。Shapiro-Wilk 检验、Kruskal-Wallis 检验和逻辑回归显示,只有当前周期的数据有意义。NLR 在预测前一周期 irAEs 方面具有统计学意义。NLR 和 AEC 都是当前周期 irAEs 的显著预测因子。该模型的 ROC 曲线下面积(AUC)为 0.783,灵敏度为 77.8%,特异性为 80.8%。概率≥0.1345 预测严重 irAEs。包含 NLR、AEC 和性别在内的模型可能预测当前周期的 irAEs 分类,与基线模型相比具有近期预测优势,并可能延长患者免疫治疗的持续时间。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c63/11404634/f052c00dd712/KHVI_A_2398309_F0001_OC.jpg

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