Time and dose-related changes in radiological lung density after concurrent chemoradiotherapy for lung cancer

Radiation pneumonitis is an important cause of morbidity after concurrent thoracic chemoradiotherapy (CCRT). However, asymptomatic changes in lung density on computed tomography (CT)-scans occur more commonly, and correspond to regions of inflammatory changes. Characterization of dose- and time-related changes in radiological lung density (RLD) may facilitate improved radiation planning, and allow for a more objective measure for assessing damage. We studied changes in RLD following CCRT with cisplatin-etoposide, using deformable registration to co-register follow-up scans. All CT-scans performed for up to 24 months post-treatment were evaluated in 25 patients treated with CCRT for stage III non-small-cell lung cancer. A total of 104 scans (median of 3 per patient) were co-registered with planning scans using a deformable registration tool (VelocityAI, Atlanta, USA). Last follow-up scan was at median 9.4 months (range 3.4-22.6 months). Seven patients developed clinical radiation pneumonitis. RLD changes (in Hounsfield units) were measured in regions receiving 3-66Gy. Linear mixed models were used to study dose-density changes over time. No significant changes in RLD were observed in the first 3 months post-treatment. Increases in RLD were observed at 3-6 months (p<0.0001) and 6-12 months (p=0.006), but stabilized at 1 year. Increases were most evident in regions receiving >30Gy, with only minor density changes at lower dose levels. Planning target volume size was significantly associated with RLD changes (p=0.03). Limiting lung doses to ≤30Gy during CCRT may limit sub-clinical damage, and the time-course of RLD changes may allow for early quantification of pulmonary damage when evaluating novel treatment strategies.