Dose-Registered CT assessment of radiation-induced lung injury after chemoradiotherapy for stage III NSCLC

To quantify radiation-induced lung injury (RILI) on deformably registered CT images after chemoradiotherapy (CCRT) for stage III NSCLC, and to evaluate spatial and dosimetric associations between RILI and planned dose distribution in a pre-durvalumab cohort.

This retrospective study included 58 patients with stage III NSCLC treated with CCRT using three-dimensional conformal radiotherapy (3D-CRT) prior to the era of consolidation immunotherapy. Follow-up CT images at 6 months (acute) and 12 months (late) were registered to treatment planning CT using deformable image registration (DIR). RILI was quantified by segmented volume (mL) and isodose-line overlap (%). Dosimetric parameters (V5Gy-V60Gy, mean lung dose) and symptomatic RILI (CTCAE grade ≥2) were analysed using correlation, ROC, and logistic regression methods.

Symptomatic RILI occurred in 14 patients (24.1%). RILI volume decreased by 27.7% from the acute to the late phase, with moderate-to-strong dose-volume correlations in both phases (Spearman ρ = 0.69-0.76). Symptomatic patients showed broader spatial spread into lower-dose regions (median isodose-line overlap 20% vs 40%; p < 0.001). Acute-phase RILI reaching the ≤25% isodose line (≤16.5 Gy) was an exploratory imaging marker in this cohort (AUC 0.81) that remained associated with symptomatic RILI on multivariable analysis (p < 0.01).

Dose-registered CT analysis demonstrated consistent spatial associations between planned dose and RILI, providing a hypothesis-generating dosimetric-radiographic reference dataset that requires external validation in IMRT/VMAT- and durvalumab-treated cohorts before clinical application.