The Impact of Idiopathic Pulmonary Fibrosis on the Incidence and Severity of Radiation Pneumonitis in Non-Small Cell Lung Cancer Patients Following Radiotherapy

Background/Objectives: Idiopathic pulmonary fibrosis (IPF) is known to increase the risk of severe pulmonary toxicity in non-small cell lung cancer (NSCLC) patients undergoing radiotherapy. This study aimed to evaluate the impact of comorbid IPF on the incidence and severity of radiation pneumonitis (RP) and overall survival (OS). Methods: This retrospective cohort study included NSCLC patients who received radiotherapy to the lung between 2015 and 2025. Patients were stratified into an IPF-comorbid group and a non-IPF control group. To minimize selection bias, variable-ratio (up to 1:2) propensity score matching with a caliper of 0.2 SD and survey-weighted analyses were utilized. Results: After matching, 196 patients (72 with IPF, 124 without IPF) were analyzed. The IPF-comorbid group had a significantly higher risk of any-grade RP (OR = 2.75, p = 0.001) and grade ≥2 RP (OR = 2.87, p = 0.002). In multivariable analysis, comorbid IPF was independently associated with any-grade RP (adjusted OR = 3.55, p = 0.001) and grade ≥ 2 RP (adjusted OR = 3.79, p = 0.001). With death as a competing event, the 6-month cumulative incidence of RP was 51.8% vs. 25.2%. IPF was independently associated with worse OS (adjusted HR = 2.51, p = 0.006), with a lower 3-year OS rate (44.4% vs. 68.1%). Conclusions: Comorbid IPF was independently associated with an increased risk of RP and overall mortality in NSCLC patients receiving radiotherapy. Because the cumulative incidence of RP diverged within the first months after radiotherapy, close multidisciplinary monitoring is warranted during this early period.