FDG Pulmonary Uptake Changes During and Post-Radiation Therapy Compared to Pretreatment in Predicting Radiation-Induced Lung Toxicity in Non-Small Cell Lung Cancer

Abstract

We hypothesize that the 18F-fludeoxyglucose (18FDG) uptake changes during early radiation therapy reflect subclinical radiation lung injury that is predictive of post-treatment radiation induced lung toxicity (RILT). The primary aim of our study was to investigate the relationship between clinically significant RILT and pulmonary 18FDG uptake changes during and post-radiation therapy. We studied a prospectively recruited cohort of 84 NSCLC patients treated with chemoradiation therapy. All patients had 18FDG PET performed before and during RT and 49 patients also had post-RT PET images. Pulmonary 18FDG uptake were assessed using Hick's visual grading scale (0-3) by a physician blinded to clinical RILT results: Grade 0∼ no abnormality identified in normal tissues within the radiation treatment volume; Grade 1∼increased activity in the pleural reflections and soft tissues within the radiation treatment volume but no parenchymal lung changes; Grade 2 = increased parenchymal lung uptake in the radiation treatment volume of equal or lower intensity than normal soft tissues in the mediastinum or chest wall located outside the radiation field; Grade 3 = increased parenchymal lung uptake in the radiation treatment volume of greater intensity than normal soft tissues in the mediastinum or chest wall. Common Terminology Criteria for Adverse Events version 3.0 was used to score RILT and event was defined as grade 2 or higher. On during-RT PET images, 75 (89.3%), 5 (6.0%), 4 (4.7%) and 0 (0%) patients had grade 0, 1, 2, and 3 changes, respectively. At 3 months after completion of RT, 42.9% patients had visible changes: 12 (24.5%) grade 1, 3 (6.1%) grade 2, and 6 (12.2%) grade 3 on the post-RT PET images. Overall, 11 patients (13.1%) developed RILT and the median time to RILT after radiation therapy was 4.6 months (range, 2-10). Among patients developed clinical RILT, 3 patients (37.5%) grade 1-2, 4 (50%) had grade 3 FDG uptake on the post-RT PET images. In 9 patients with increased FDG uptake during-RT, 5 (55.6 %) developed RILT, and 3 of them had grade 3 and above. Among 8 RILT patients with post-RT PET images available for assessment, 7 (89%) had grade 1-3 changes on FDG uptake. There was a significant correlation between the incidence of severe RILT and FDG uptake changes on during-RT (p = 0.002) and post-RT (p < 0.001) PET images. FDG uptake is commonly increased at 3 months after RT, but infrequently increased on during-RT PET. Increase in FDG uptake in lung either during- or post-RT may be associated with increased risk of RILT. Increased uptake during-RT may identify patients at highest risk for RILT. Visual assessment of PET may identify patients at high risk for toxicity and guide individualized radiation plan to decrease RILT.