Characterization of dosimetric predictors for pulmonary perfusion changes before and after hypofractionated...

Breast cancer is the most common malignancy in women, and adjuvant radiotherapy is an essential component of curative treatment. Despite advances in hypofractionated whole-breast irradiation (HF-WBI), incidental lung exposure remains unavoidable and predisposes to radiation-induced pulmonary injury, including radiation pneumonitis (RP). Traditional predictors such as mean lung dose (MLD) may inadequately capture the heterogeneous intrapulmonary dose distribution typical of breast radiotherapy.

The purpose of this study was to evaluate whether heterogeneity-sensitive dosimetric metrics and functional lung imaging better predict radiation-induced perfusion changes and RP in patients undergoing HF-WBI.

In this prospective study, 48 node-negative breast cancer patients treated with conformal HF-WBI were evaluated. Pulmonary perfusion scans (PPS) were acquired pre-RT and 6-9 months post-RT. Dose-volume histogram (DVH) parameters, including MLD, uniform effective dose (D_eff), and V₅-V₄₀, were extracted from three-dimensional conformal radiotherapy (3DCRT) or forward-planned intensity-modulated RT (FIMRT) plans. D_eff was calculated using the Lyman-Kutcher-Burman (LKB) model to integrate dose heterogeneity. Associations between dosimetric metrics, perfusion changes, and RP were analyzed using correlation and ROC analysis.

PPS revealed modest but detectable post-RT perfusion declines, most pronounced in lung regions receiving higher doses. Three patients (6.3%) developed Grade 2 RP. D_eff and high-dose lung volumes (V₃₅-V₄₀) demonstrated the strongest correlations with perfusion loss and RP (AUC 0.81-0.85, p < 0.01), whereas MLD showed weaker predictive value. ROC analysis identified clinically relevant thresholds: D_eff ≤ 13.6 Gy, V₃₅ ≤ 37.5%, V₄₀ ≤ 32%, and a ≥4% decline in total perfusion, below which minimal functional impairment and RP were observed.

D_eff and high-dose volumetric constraints outperform MLD in predicting decrease in lung perfusion in HF-WBI. Quantitative PPS provides complementary functional validation, and integration of dosimetric and functional parameters may refine lung-sparing strategies in breast radiotherapy.