Lung Density Changes Following SBRT: Association with Lung Dose and Clinical Pneumonitis

Abstract

Radiation pneumonitis is an inflammation of the lungs that can develop following radiation therapy, the cause of which is not fully understood. The hypothesis of this study is that radiation induced lung changes are associated with radiation dose to the lung and pneumonitis. This work investigates the relationship between lung dose and the development of radiographic lung changes following stereotactic body radiotherapy (SBRT). In addition, the lung dose and radiographic changes were investigated for their ability to predict the development of clinical grade ≥2 radiation pneumonitis (RP≥2). Regions of consolidation (dense) and ground-glass opacities (hazy) were semi-automatically contoured on 262 3- and 6-month post treatment CT-scans for 145 subjects who underwent SBRT between 2008 and 2018 receiving 40-60 Gy in 3-10 fractions. 84% of the subjects received 48Gy in 4 fractions. RP≥2 was diagnosed in 9 patients (6%). The PTV volume, relative and absolute lung volumes irradiated within defined dose bins were extracted from the treatment plans. Volumes of dense and hazy radiographic changes, both absolute volumes in mL and volumes normalized by the PTV volume were assessed at 3- and 6-months. Correlations for all 3- and 6-month hazy and dense volumes with PTV volumes, relative and absolute lung volumes in defined dose bins, and treatment technique (3D conformal radiotherapy (3DCRT), static intensity modulated radiotherapy (IMRT), or volumetrically modulated arc therapy (VMAT)) were established through Spearman correlation using Bonferroni correction. Univariate logistic models, using the Firth small sample bias correction, were developed for predicting RP≥2. PTV volume and relative lung dose bins between 25 and 40 Gy were significantly correlated with the hazy and dense volumes on both the 3 and 6 month images (p=<0.0001-0.0019). There was no significant difference in the hazy or dense volumes at either 3- or 6-months by the treatment technique. Subjects developing RP≥2 on average demonstrated a 2- to 4-fold increase in the hazy and dense absolute and normalized volumes at both 3- and 6-months (n.s.). The 3-month dense (p=0.03), 6-month dense (p=0.02), 6-month dense normalized (p=0.04), and 6-month hazy volumes (p=0.03) were significantly correlated with RP≥2 in univariate logistic models (AUC 0.64-0.67). Lung V20-40Gyappears to be correlated with radiographic changes following lung SBRT. While irradiated lung volumes were not correlated with RP≥2, the amount of dense volume present at 3 and 6 months in particular appears to be related to the development of RP≥2. This observation indicates that in addition to dose, demographic and clinical factors may influence the development of RP and need to be further investigated.