放射诱导的淋巴细胞减少症 (RIL) 会恶化生存率并降低免疫检查点抑制剂在肺癌联合治疗中的益处。鉴于各种研究中关于 RIL 预测因素的数据不一致，我们的目标是系统地阐明这些预测因素，并为临床医生制定实用指南。我们在四个三级癌症中心进行了观察性队列研究。患有非小细胞肺癌和小细胞肺癌且淋巴细胞减少程度不大于 1 且接受至少 15 次独立放疗 (RT) 的患者符合资格。使用各种预测变量选择方法和统计模型（线性回归器、弹性网络、贝叶斯回归器、Huber回归、基于k近邻的回归、高斯过程回归器、决策树回归器、随机回归器）对结构和临床因素的剂量体积参数进行综合分析。森林回归器、极限梯度提升、自动机器学习）并进行排序以预测淋巴细胞计数最低点 (alc_nadir)。238 名患者（I 期-3.4%、II-17.6%、III-75.2%、IV-3.8%）对接受中位剂量 60 Gy 的 RT 的患者进行了分析。中位 alc_nadir 为 0.68K/mm3。在 600 个模型中评估了 60 个功能集（RMSE 0.27-0.41K/mm3）。最重要的特征是基线淋巴细胞计数 (alc_1)、平均肺剂量、肺 v05、肺 v10、心脏 v05 和免疫细胞有效剂量 (edic)。在alc_1 ≤ 2.005K/mm3 的患者中，lung_v05p > 51.8% 的中位alc_nadir 预测为0.54K/mm3，lung_v05p ≤ 51.8% 的中位alc_nadir 预测为0.76K/mm3。在 alc_1 > 2.005K/mm3 的患者中，淋巴细胞减少症很少见。早期淋巴细胞计数较低的患者中，RIL 最严重，主要由心脏和肺部的低 RT 剂量引发。版权所有 © 2024 Kuncman、Pajdziński、Smółka、Bilski、Socha、斯坦多、佩辛斯卡-皮奥伦、科拉布、耶雷切克-福萨和菲尤斯。

Radiation induced lymphopenia (RIL) deteriorate survival and diminishes the benefit of immune checkpoint inhibitors in combined treatment of lung cancer. Given the inconsistent data across various studies on the predictors of RIL, we aim to methodically elucidate these predictors and formulate a practical guide for clinicians.We conducted observational cohort study in four tertiary cancer centers. Patients with non-small cell lung cancer and small cell lung cancer, without lymphopenia grade >1, who underwent standalone radiotherapy (RT) in minimum 15 fractions were eligible. Dose-volume parameters of structures and clinical factors were comprehensively analyzed using various predictors selection methods and statistical models (Linear Regressors, Elastic Net, Bayesian Regressors, Huber Regression, regression based on k-nearest neighbors, Gaussian Process Regressor, Decision Tree Regressor, Random Forest Regressor, eXtreme Gradient Boosting, Automated Machine Learning) and were ranked to predict lymphocytes count nadir (alc_nadir).Two hundred thirty eight patients (stage I-3.4%, II-17.6%, III-75.2%, IV-3.8%) who underwent RT to median dose of 60 Gy were analyzed. Median alc_nadir was 0.68K/mm3. The 60 feature sets were evaluated in 600 models (RMSE 0.27-0.41K/mm³). The most important features were baseline lymphocyte count (alc_1), mean lung_dose, lung v05, lung v10, heart v05 and effective dose to immune cells (edic). In patients with alc_1 ≤ 2.005K/mm3, median alc_nadir predictions were 0.54K/mm3 for lung_v05p > 51.8% and 0.76K/mm3 for lung_v05p ≤ 51.8%. Lymphopenia was rare in patients with alc_1 > 2.005K/mm3.RIL was most severe in patients with low early lymphocyte counts, primarily triggered by low RT doses in the heart and lungs.Copyright © 2024 Kuncman, Pajdziński, Smółka, Bilski, Socha, Stando, Peszyńska-Piorun, Korab, Jereczek-Fossa and Fijuth.