Predicting severe radiation pneumonitis in patients with locally- advanced non-small cell lung cancer after thoracic radiotherapy: Development and internal validation of a nomogram based on the clinical, hematological and dose–volume histogram parameters

Purpose Severe radiation pneumonitis (grade≥3 RP) remains an important dose-limiting toxicity after thoracic radiotherapy (RT). This study aimed to investigate risk factors for severe RP in patients with locally-advanced non-small cell lung cancer (NSCLC) after thoracic RT, develop a prediction model to identify high-risk groups and investigate impact of severe RP on overall survival (OS). Methods We retrospectively collected clinical, hematological and dosimetric factors from 351 stage-Ⅲ NSCLC patients after thoracic RT between 2018 and 2022. The primary endpoint was development of severe RP. The secondary endpoint was OS. Logistic regression and least absolute shrinkage and selection operator (LASSO) regression analysis were used to identify risk factors of severe RP. Nomogram was generated based on multivariate regression coefficients. Area under the ROC curve (AUC), calibration curve, and decision curve analysis (DCA) were conducted to validate the model. After a long-term follow-up, OS of patients with RP vs. non-RP and mild RP vs. severe RP groups was analyzed by Kaplan‒Meier method. Results ILD (p<0.001), percentage of contralateral lung volume receiving≥5Gy (contraV ₅ ) (P=0.013), percentage of ipsilateral lung volume receiving≥20Gy (ipsiV ₂₀ )(P=0.039), pre-RT derived neutrophil lymphocyte ratio (dNLR) (P=0.015) and post-RT systemic inflammation response index (SIRI) (p=0.001) were showed to be independent predictors of severe RP and were included in the nomogram. ROC curves revealed the AUC of the nomogram was 0.782. Calibration curves showed favorable consistency, and DCA showed satisfactory positive net benefits of the model. Median follow-up time was 19.8 months (1.4-52.9 months), and cases who developed severe RP showed shorter OS than those developed mild RP (P=0.027). Conclusion We identified that ILD, contraV ₅ (>11%), ipsiV ₂₀ (>45%), pre-RT dNLR (>1.9) and post-RT SIRI (>3.4) could predict severe RP among patients with locally-advanced NSCLC receiving thoracic RT. Combining these indicators, a nomogram was first built and validated, showing its potential value in clinical practice.