Quantification of radiation-induced lung damage with CT scans: The possible benefit for radiogenomics

Background. Radiation-induced lung damage (RILD) is an important problem. Although physical parameters such as the mean lung dose are used in clinical practice, they are not suited for individualised radiotherapy. Objective, quantitative measurements of RILD on a continuous instead of on an ordinal, semi-quantitative, semi-subjective scale, are needed. Methods. Hounsfield unit (HU) changes before versus three months post-radiotherapy were correlated per voxel with the radiotherapy dose in 95 lung cancer patients. Deformable registration was used to register pre- and post-CT scans and the density increase was quantified for various dose bins. The dose-response curve for increased HU was quantified using the slope of a linear regression (HU/Gy). The end-point for the toxicity analysis was dyspnoea >= grade 2. Results. Radiation dose was linearly correlated with the change in HU (mean R-2 = 0.74 +/- 0.28). No differences in HU/Gy between groups treated with stereotactic radiotherapy, conventional radiotherapy alone, sequential or concurrent chemoradiotherapy were observed. In the whole patient group, 33/95 (34.7%) had dyspnoea >= G2. Of the 48 patients with a HU/Gy below the median, 16 (33.3%) developed dyspnoea >= G2, while in the 47 patients with a HU/Gy above the median, 17 (36.1%) had dyspnoea >= G2 (not significant). Individual patients showed a nearly 21-fold difference in radiosensitivity, with HU/Gy ranging from 0 to 10 HU/Gy. Conclusions. HU changes identify objectively the whole range of individual radiosensitivity on a continuous, quantitative scale. CT density changes may allow more robust and accurate radiogenomics studies.