Reassessing the Incidence and Risk Factors of Radiation Pneumonitis in Treatment‐Naive EGFR ‐Mutant NSCLC With Concurrent Third‐Generation

ABSTRACT

This single‐center retrospective study evaluated radiation pneumonitis (RP) in 209 treatment‐naive EGFR‐mutant non‐small cell lung cancer (NSCLC) patients receiving first‐line third‐generation EGFR tyrosine kinase inhibitors (EGFR‐TKIs) plus thoracic radiotherapy (TRT), with concurrent defined as any overlap of ≥ 1 day between EGFR‐TKI and TRT, at Shandong Cancer Hospital and Institute between January 2019 and September 2024, excluding concurrent chemotherapy and anti‐angiogenic therapy. RP was diagnosed by chest computed tomography (CT), clinical symptoms, and irradiated field concordance, while infectious pneumonia and tumor progression were excluded by laboratory tests and serial imaging. Grade ≥ 2 RP occurred in 43.54% of patients (22.01% grade 2, 21.53% grade 3; no grade 4/5 RP), with osimertinib showing the highest rates of grade ≥ 2 and grade 3 RP, followed by aumolertinib and furmonertinib. For grade ≥ 2 RP, patients receiving aumolertinib or furmonertinib had a lower observed risk than those receiving osimertinib, while ipsilateral lung V5 ≥ 35.93% and gross tumor volume (GTV) ≥ 12.62 mL were independent risk factors. For grade 3 RP, an inverse association between smoking history and RP risk was observed, whereas ipsilateral lung V30 ≥ 24.61% and GTV ≥ 14.56 mL were associated with increased risk. Median progression‐free survival (PFS) was 26.70 months, with no significant difference among the three TKIs. In this cohort, first‐line third‐generation EGFR‐TKI plus TRT was associated with frequent but generally manageable RP. TKI type, ipsilateral lung V5/V30, and GTV were key predictors of RP, although the dosimetric thresholds and drug‐specific differences identified in this cohort require external validation.