Prospective study of proton beam therapy for non-small cell lung cancer patients with idiopathic pulmonary fibrosis.

Abstract

Patients with idiopathic pulmonary fibrosis (IPF) are vulnerable to severe pulmonary toxicity after thoracic radiotherapy. We prospectively evaluated pulmonary toxicity and clinical outcomes after definitive proton beam therapy (PBT) for non-small cell lung cancer (NSCLC) with IPF. From June 2020 to August 2023, 55 patients were enrolled and 41 were finally analyzed. The primary endpoint was grade ≥ 3 pulmonary toxicity (G3 + ). Secondary endpoints included pulmonary function changes, overall survival (OS), and quality of life. The most common prescribed dose was 64 GyE in 8 fractions (41.5%) with a median biologically effective dose (α/β = 10) of 115.2 GyE (interquartile range, 80.5-115.2). The median baseline predicted forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1) and diffusing capacity of the lung for carbon monoxide (DLCO) were 72.0%, 80.0% and 45.0%, respectively. Gender-Age-Physiology stages I/II/III were 17.1%/70.7%/12.2%. Clinical stages I/II/III were 56.0%/22.0%/22.0%. During a median follow-up of 21.6 months, G3 + developed in 7 (17.1%) patients, including ≥ grade 4 events in 4 patients (9.8%). G3 + were observed in 3 of 32 patients (9.4%) with clinical stage I-II disease, compared to 4 of 9 patients (44.4%) with stage III disease (p = 0.010). One-year OS and locoregional control were 67.6% and 93.2%, respectively. Overall FVC, FEV1, and DLCO showed statistically significant declines over time after PBT. Definitive PBT for patients with NSCLC and IPF showed acceptable outcomes in early-stage disease; however, severe pulmonary toxicity remained substantial in stage III disease, supporting careful patient selection.