关键词: 胸部肿瘤, Toll样受体4, NF-κB, 营养评价, 预测, 放射性肺损伤

Abstract:

Objective To explore the predictive value of controlling nutritional status （CONUT） score combined with serum Toll-like receptor-4 （TLR-4） and nuclear factor-κB （NF-κB） for radiation-induced lung injury in patients with thoracic malignancies undergoing radiotherapy. Methods A total of 86 patients with thoracic malignancies （esophageal cancer， non-small cell lung cancer） undergoing radiotherapy for 6-7 weeks in People's Hospital of Hunan Province between June 2023 and June 2024 were selected as the research objects. Before radiotherapy， after 3 weeks of radiotherapy and at the end of radiotherapy， detection of serum TLR-4 and NF-κB， and evaluation of CONUT score were performed. At 1 month after radiotherapy， patients were divided into injury group and non-injury group according to presence or absence of radiation-induced lung injury， and differences in all indicators before and after radiotherapy were compared between the two groups. The correlation between CONUT score and serum TLR-4， NF-κB levels was evaluated by Pearson correlation analysis， and predictive value of each indicator for radiation-induced lung injury in different periods was evaluated by logistic regression and receiver operator characteristic （ROC） curve analysis. Results In the 86 patients at 1 month after radiotherapy， there were 21 cases with radiation-induced lung injury （injury group） and 65 cases without injury （non-injury group）. The proportions of smoking history （χ²=5.18， P=0.023）， combined chemotherapy （χ²=4.57， P=0.033） and radiotherapy dose ≥60 Gy （χ²=4.59， P=0.032） in injury group were higher than those in non-injury group. Before radiotherapy， there were no statistically significant differences in CONUT score [（2.65±0.83） points vs. （2.21±0.96） points] and levels of serum TLR-4 [（36.54±4.26） ng/L vs. （37.12±4.93） ng/L] and NF-κB [（14.19±2.69） ng/L vs. （14.26±1.36） ng/L] between injury group and non-injury group （t=1.88， P=0.063； t=0.48， P=0.630； t=0.16， P=0.875）. After 3 weeks of radiotherapy， CONUT score [（3.98±1.24） points vs. （3.25±1.02） points] and levels of serum TLR-4 [（49.26±5.17） ng/L vs. （42.86±5.12） ng/L] and NF-κB [（17.59±3.25） ng/L vs. （15.14±2.29） ng/L] were higher in injury group than non-injury group （t=2.70， P=0.008； t=4.97， P<0.001； t=3.83， P<0.001）. At the end of radiotherapy， CONUT score [（5.27±1.47） points vs. （3.51±1.09） points] and levels of serum TLR-4 [（53.57±6.95） ng/L vs. （44.16±4.19） ng/L] and NF-κB [（19.66±2.16） ng/L vs. （17.34±1.18） ng/L] were higher in injury group than non-injury group （t=5.89， P<0.001； t=7.52， P<0.001； t=6.28， P<0.001）， and all the three indicators of the two groups of patients at 3 weeks after radiotherapy and at the end of radiotherapy were all higher than those before radiotherapy （all P<0.05）. Pearson correlation analysis showed that CONUT score was positively correlated with the levels of serum TLR-4 and NF-κB at 3 weeks after radiotherapy and at the end of radiotherapy （r=0.53， P<0.001， r=0.44， P<0.001； r=0.57， P<0.001， r=0.47， P<0.001）. After correcting for confounding factors， logistic regression analysis showed that CONUT score at 3 weeks after radiotherapy （OR=5.73， 95%CI： 2.09-15.76， P=0.001） and at the end of radiotherapy （OR=6.40， 95%CI： 2.33-17.59， P<0.001）， along with the levels of serum TLR-4 （OR=6.51， 95%CI： 2.37-17.91， P<0.001； OR=7.07， 95%CI： 2.57-19.44， P<0.001） and NF-κB （OR=5.75， 95%CI： 2.09-15.81， P=0.001； OR=6.33， 95%CI： 2.30-17.42， P<0.001） were all independent factors for predicting radiation-induced lung injury in patients with thoracic malignancies undergoing radiotherapy. ROC curve analysis demonstrated that CONUT score at 3 weeks after radiotherapy （AUC=0.69） and at the end of radiotherapy （AUC=0.86）， along with serum levels of TLR-4 （AUC=0.77 and 0.89， respectively） and NF-κB （AUC=0.69 and 0.73， respectively）， both individually and in combination （AUC=0.90 and 0.97， respectively）， exhibited predictive value for radiation-induced lung injury in patients with thoracic malignancies undergoing radiotherapy. Furthermore， the AUC values of combined indicators at 3 weeks after radiotherapy and at the end of radiotherapy were higher than those of individual indicator alone. The AUC values of combined indicators at the end of radiotherapy exceeded those obtained at 3 weeks after radiotherapy （all P<0.05）. Conclusions The CONUT score at 3 weeks after radiotherapy and at the end of radiotherapy， as well as the levels of serum TLR-4 and NF-κB， all have predictive value for radiation-induced lung injury in patients with thoracic malignancies undergoing radiotherapy， and the predictive efficacy of combined detection with the above indicators at the end of radiotherapy is higher.

Key words: Thoracic neoplasms, Toll-like receptor 4, NF-kappa B, Nutrition assessment, Forecasting, Radiation-induced lung injury