PDF(Pubmed)
Abstract：
The combination of thoracic radiotherapy and immune checkpoint inhibitors (ICIs) has emerged as a novel treatment approach for malignant tumors. However, it is important to consider the potential exacerbation of lung injury associated with this treatment modality. The neutrophil-to-lymphocyte ratio (NLR), an inflammatory marker, holds promise as a non-invasive indicator for assessing the toxicity of this combination therapy. To investigate this further, a study involving 80 patients who underwent thoracic radiotherapy in conjunction with ICIs was conducted. These patients were divided into two groups: The concurrent therapy group and the sequential therapy group. A logistic regression analysis was conducted to ascertain risk factors for grade ≥2 pneumonitis. Following propensity score matching, the NLR values were examined between the concurrent group and the sequential group to evaluate any disparity. A mouse model of radiation pneumonitis was established, and ICIs were administered at varying time points. The morphological evaluation of lung injury was conducted using H&E staining, while the NLR values of peripheral blood were detected through flow cytometry. Logistic regression analysis revealed that radiation dosimetric parameters (mean lung dose, total dose and V20), the inflammatory index NLR at the onset of pneumonitis, and treatment sequences (concurrent or sequential) were identified as independent predictors of grade ≥2 treatment-related pneumonitis. The results of the morphological evaluation indicated that the severity of lung tissue injury was greater in cases where programmed cell death protein 1 (PD-1) blockade was administered during thoracic radiotherapy, compared with cases where PD-1 blockade was administered 14 days after radiotherapy. Moreover, the present study demonstrated that the non-invasive indicator known as the NLR has the potential to accurately reflect the aforementioned injury.
摘要：
胸部放疗和免疫检查点抑制剂（ICIs）的组合已成为恶性肿瘤的新型治疗方法。然而,重要的是要考虑与这种治疗方式相关的肺损伤的潜在加重。中性粒细胞与淋巴细胞比率（NLR），炎症标记物,有望作为评估这种联合治疗毒性的非侵入性指标。为了进一步调查，我们进行了一项涉及80例接受胸部放疗联合ICIs的患者的研究.这些患者分为两组：同步治疗组和序贯治疗组。进行logistic回归分析以确定≥2级肺炎的危险因素。在倾向得分匹配之后，我们检查了同时组和序贯组之间的NLR值,以评估差异.建立小鼠放射性肺炎模型,和ICIs在不同的时间点给药。肺损伤的形态学评价采用H&E染色,同时通过流式细胞术检测外周血的NLR值。Logistic回归分析显示，辐射剂量学参数(平均肺剂量，总剂量和V20)，肺炎发作时的炎症指数NLR，和治疗顺序(同时或序贯)被确定为≥2级治疗相关性肺炎的独立预测因子.形态学评估结果表明，在胸部放疗期间给予程序性细胞死亡蛋白1（PD-1）阻断的情况下，肺组织损伤的严重程度更大，与放疗后14天给予PD-1阻断的病例相比。此外，本研究表明,称为NLR的非侵入性指标有可能准确反映上述损伤.
