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

Abstract

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.

A new CT-based method to quantify radiation-induced lung damage in patients

“…1c). Since the range of mean density changes measured in the present study was comparable with a study using similar radiotherapy techniques [12], our results suggest that the DS method is more sensitive in detecting radiation damage from CT scans than the Dmean method. DS corresponds better to physician-rated score and symptoms We next investigated whether the DS method corresponds better than the Dmean method to physician-rated pneumonitis.…”

“…Besides direct measurements of biological changes, several studies therefore utilized quantitative analysis of CT-scans as a surrogate for histopathological changes after chest radiotherapy [12][13][14]. However to explain a broad range of radiation-induced histopathological changes only (regional) mean density changes of the lung were quantified.…”

Lung Texture in Serial Thoracic Computed Tomography Scans: Correlation of Radiomics-based Features With Radiation Therapy Dose and Radiation Pneumonitis Development

“…Phernambucq et al (35) found no relationship between CT scan density changes and increasing dose or RP status, although the authors attributed this result in part to the small sample size (7 patients with RP). To our knowledge, the present study is the first to demonstrate that texture changes following thoracic RT are associated with patient RP status.…”

Prediction of lung density changes after radiotherapy by cone beam computed tomography response markers and pre-treatment factors for non-small cell lung cancer patients

“…The continuous nature of this end-point makes it ideal for radiobiological response modelling. However, the radiological changes may be sub-clinical, and although RP has been shown to correlate with the development of radiologic consolidation on CT [4], a firm association between clinically scored RP and CT density changes has yet to be established for lung cancer patients [5,14]. Low-responsive patients are therefore not necessarily free from symptomatic RP and vice versa.…”