Date(s) - 03/31/2014
Radiation therapy (RT) induced symptomatic pneumonitis is a significant problem for patients with tumors of the thorax; predicting RT-induced pulmonary toxicity remains elusive. The purpose of this study was to quantify changes in lung ventilation following RT.
Subjects from a prospective IRB approved clinical trial were analyzed. 6-10 MV x-ray treatments were prescribed for doses between 61.2 to 70 Gy in 2 Gy fractions. Pulmonary function was derived for each voxel of the lung from 4DCT scans using deformable image registration techniques. The Jacobian determinant of the deformation map yielded the spatial distribution of ventilation for each subject. Patient specific changes in ventilation maps from 4DCT scans acquired prior to and 3 months post-RT were defined as pulmonary function change (PFC) by (i) deformation of post-RT ventilation maps into the pre-RT map coordinate system, and (ii) computing the ratio of ventilation measured post-RT to pre-RT. PFC was correlated with radiation dose at the voxel level to establish a dose-response curve (DRC); average PFC in all voxels grouped in 5 Gy dose bins was evaluated using linear regression. PFC was correlated with initial pulmonary function grouped in 5% expansion bins. DRC’s were determined for regions of lung with minimal lung function (≤ 5% tissue expansion) compared to those with higher function (≥ 10% expansion). Our measure of PFC at the voxel level was compared to clinically observed pulmonary toxicity determined by diffusion lung capacity for carbon monoxide (DLCO).
Subjects showed a clear relationship between regions irradiated and a decline in pulmonary function. In univariate analysis a strong correlation was found (r2=0.92) between calculated radiation dose to a voxel and the PFC observed 3 months post-RT. PFC correlated strongly with the initial pulmonary function of the lung tissue (r2=0.97); dose differences in those tissues were negligible (< 1 Gy mean dose). The DRC for regions of lung with minimal lung function had a linear regression line with far less slope (-0.0003, r2=0.57) than regions with higher lung function (slope=-0.0011, r2=0.95). The increased radiosensitivity of high functioning lung was significantly different from regions with minimal lung function (p=0.039). The measured percent reduction in DLCO had a modest correlation with the amount of lung demonstrating a > 5% reduction in PFC at 3 months post-RT (r2 = 0.52).
Regions of increasing pre-RT lung function show greater fractional reduction in function post-RT. Our data reveals the increased sensitivity of high functioning lung, providing direct support for the hypothesis that improved oxygenation via ventilation increases the radiosensitivity of lung tissue.