Plasma Levels of IL-8 and TGF-β1 Predict Radiation-Induced Lung Toxicity in Non-Small Cell Lung Cancer: A Validation Study.
Plasma Levels of IL-8 and TGF-β1 Predict Radiation-Induced Lung Toxicity in Non-Small Cell Lung Cancer: A Validation Study.
复制标题
DOI：
10.1016/j.ijrobp.2017.03.011
复制
发表时间：
2017-07-01
期刊：
影响因子：
--
通讯作者：
Kong FS
中科院分区：
文献类型：
--
作者：
Wang S;Campbell J;Stenmark MH;Zhao J;Stanton P;Matuszak MM;Ten Haken RK;Kong FS
我们之前报道过，平均肺剂量（MLD）和炎症细胞因子（IL-8和TGF-β1）的组合可能为58名非小细胞肺癌（NSCLC）患者的辐射诱导肺毒性（RILT）预测提供更准确的模型。本研究旨在通过新患者验证之前的研究结果，并探索具有更多细胞因子的新模型。前瞻性研究中纳入了 142 名接受明确放射治疗 (RT) 的 I-III 期 NSCLC 患者。 65 名新患者用于验证之前的发现，所有 142 名患者用于探索新模型。在 RT 之前、RT 期间 2 周和 4 周（RT 前、2 周、4 周）时，在血浆样本中测量了 30 种炎症细胞因子。 ≥2 级 RILT 定义为 2 级及以上放射性肺炎或症状性肺纤维化，这是主要终点。采用Logistic回归评估RILT的危险因素。受试者工作特征 (ROC) 曲线的曲线下面积 (AUC) 用于模型评估。 65 名患者中有 16 名 (24.6%) 出现 RILT2。较低的前 IL-8 和较高的 TGF-β1 2w/pre 比率与较高的 RILT2 风险相关。结合 MLD、前 IL-8 和 TGF-β1 2w/pre 比率，AUC 增加至 0.73，而单独使用 MLD 预测 RILT 时，AUC 为 0.61。在所有 142 名患者中，29 名患者 (20.4%) 出现 ≥2 级 RILT。在测量的 30 种细胞因子中，只有 IL-8 和 TGF-β1 与 RILT2 风险显着相关。 MLD、前IL-8水平和TGF-β1 2w/pre比率被纳入最终的预测模型中。联合使用 MLD、前 IL-8 和 TGF-β1 2w/pre 比例时，AUC 增加至 0.76，而单独使用 MLD 时，AUC 为 0.62。我们验证了平均肺剂量、前 IL-8 水平和 TGF-β1 2w/pre 比率的组合提供了比单独 MLD 更准确的模型来预测 RILT2 风险。
We previously reported that combination of mean lung dose (MLD), and inflammatory cytokines (IL-8 and TGF-β1) may provide a more accurate model for radiation-induced lung toxicity (RILT) prediction in 58 patients with non-small cell lung cancer (NSCLC). This study is to validate the previous findings with new patients and explore new models with more cytokines. 142 patients with stage I–III NSCLC treated with definitive radiation therapy (RT) from prospective studies were included. Sixty-five new patients were used to validate previous findings, and all 142 patients to explore new models. Thirty inflammatory cytokines were measured in plasma samples before RT, 2 weeks and 4 weeks during RT (pre, 2w, 4w). Grade ≥2 RILT defined as grade 2 and higher radiation pneumonitis or symptomatic pulmonary fibrosis was the primary endpoint. Logistic regression was performed to evaluate the risk factors of RILT. The area under the curve (AUC) for the Receiver Operating Characteristic (ROC) curves was used for model assessment. Sixteen of 65 patients (24.6%) developed RILT2. Lower pre IL-8 and higher TGF-β1 2w/pre ratio were associated with higher risk of RILT2. The AUC increased to 0.73 by combining MLD, pre IL-8 and TGF-β1 2w/pre ratio compared with 0.61 by MLD alone to predict RILT. In all 142 patients, 29 patients (20.4%) developed grade ≥2 RILT. Among the 30 cytokines measured, only IL-8 and TGF-β1 were significantly associated with the risk of RILT2. MLD, pre IL-8 level and TGF-β1 2w/pre ratio were included in the final predictive model. The AUC increased to 0.76 by combining MLD, pre IL-8 and TGF-β1 2w/pre ratio compared with 0.62 by MLD alone. We validated that a combination of mean lung dose, pre IL-8 level and TGF-β1 2w/pre ratio provided a more accurate model to predict the risk of RILT2 compared to MLD alone.