The Association between RT-induced Changes in Lung Tissue Density and Global Lung Function

Radiation (RT)-induced lung injury is a common side effect following thoracic RT. The study of RT-induced lung injury is complicated by the endpoints considered (e.g., radiologic vs. symptomatic vs. functional). The association between these endpoints is not entirely clear. We herein assess the association between RT-induced changes in computed tomography (CT)-defined lung tissue density and pulmonary function tests (PFTs). As part of a prospective clinical study, patients receiving incidental partial lung irradiation underwent PFTs, CT, and single photon emission computed tomography (SPECT) scans before and repeatedly after RT. Regional lung function was assessed before and serially after RT by thoracic CT and SPECT scans and global lung function by PFTs. The percent reductions in PFTs were associated with the average changes in lung density, and perfusion for the overall group using Pearson correlations. The analyses were repeated in patient subgroups based on smoking history, tumor type (lung vs. non-lung), pulmonary symptoms (≥grade 2, i.e., requiring steroids, or worse), pre-RT surgery and chemotherapy. Comparisons were also made between the CT- and SPECT-based computations. 343 patients were enrolled between 1991 and 2004. Of these, 111 patients had a total of 203 concurrent post-RT evaluations of changes in lung density and PFTs for analyses, and 81 patients had a total of 141 concurrent post-RT SPECT scans as well. The remainders of the enrolled patients were unevaluable due to radiographic evidence of progressive tumor, pleural effusions, and/or other reasons. Patients characteristics are as follows: the majority presented with lung cancer (82%), median age was 62 (range 22-87), 83% of patients had a history of smoking with an average of 40 pack-years, 59 of the lung cancer patients had central tumors, 30% and 55% of patients had pre-RT thoracic surgery and chemotherapy respectively, the median mean lung dose was 17 Gy (range 4 ∼ 36 Gy), 27 patients had symptomatic radiation pneumonitis after RT (24%). The average increases in lung density were related to the percent reductions in PFTs, albeit with modest correlation coefficients (range, 0.20 ∼ 0.37). This was true in the overall group, as well as in most of the patient subgroups considered. The analyses also indicate that the association between lung density and PFT changes is essentially equivalent to the corresponding association with SPECT-defined lung perfusion (p = 0.25, 0.25, and 0.23 for DLCO, corrected DLCO, and FEV1, respectively). There is a quantitative association between the degree of increase in lung density as defined by CT and percent reduction in PFTs. However, the correlations are weak.