Effectiveness and safety of pirfenidone for radiation-induced lung injury in non-small cell lung cancer: a retrospective pilot study

Radiotherapy (RT) remains a cornerstone in the treatment of thoracic malignancies; however, approximately one-third of patients with non-small cell lung cancer (NSCLC) develop Grade ≥ 2 radiation-induced lung injury (RILI). Despite its clinical significance, no pharmacologic standard of care has been established for RILI. Pirfenidone, an antifibrotic agent with anti-inflammatory and antioxidant properties, has demonstrated potential in preclinical models of RILI. This study aimed to evaluate the clinical efficacy and safety of pirfenidone in NSCLC patients with RILI following thoracic RT. We retrospectively analyzed 33 NSCLC patients diagnosed with Grade ≥ 2 RILI who received pirfenidone (400 mg three times daily) in combination with standard-of-care treatment. The corticosteroid regimen included intravenous methylprednisolone (20-40 mg/day for 5 days), tapered and discontinued by Day 14. Radiologic response was assessed via monthly high-resolution computed tomography (HRCT), and symptoms were graded using common terminology criteria for adverse event(CTCAE) version 5.0. Dose-volume metrics (V5, V20, mean lung dose) were recorded and analyzed for correlation with RILI severity. Radiographic improvement was observed in 78.8% (26/33) of patients, with a trend toward increased response over time. No Grade ≥ 3 pirfenidone-related adverse events (AEs) were observed. One patient experienced transient Grade 3 thrombocytopenia attributed to prior chemotherapy. Univariate analysis showed no significant association between baseline characteristics and treatment response. Four patients with overlapping RILI and immune-related pneumonitis also showed clinical improvement. Our findings provide preliminary evidence supporting the clinical benefit and tolerability of pirfenidone for RILI in NSCLC patients. These results warrant further investigation in prospective controlled trials to establish its role in routine clinical practice.