A prospective study of the feasibility of FDG-PET/CT imaging to quantify radiation-induced lung inflammation in locally advanced non-small cell lung cancer patients receiving proton or photon radiotherapy.

PURPOSE: This prospective study assessed the feasibility of 18F-2-fluoro-2-deoxy-D-glucose (FDG) positron emission tomography/computed tomography (PET/CT) to quantify radiation-induced lung inflammation in patients with locally advanced non-small cell lung cancer (NSCLC) who received radiotherapy (RT), and compared the differences in inflammation in the ipsilateral and contralateral lungs following proton and photon RT. METHODS: Thirty-nine consecutive patients with NSCLC underwent FDG-PET/CT imaging before and after RT on a prospective study. A novel quantitative approach utilized regions of interest placed around the anatomical boundaries of the lung parenchyma and provided lung mean standardized uptake value (SUVmean), global lung glycolysis (GLG), global lung parenchymal glycolysis (GLPG) and total lung volume (LV). To quantify primary tumor metabolic response to RT, an adaptive contrast-oriented thresholding algorithm was applied to measure metabolically active tumor volume (MTV), tumor uncorrected SUVmean, tumor partial volume corrected SUVmean (tumor-PVC-SUVmean), and total lesion glycolysis (TLG). Parameters of FDG-PET/CT scans before and after RT were compared using two-tailed paired t-tests. RESULTS: All tumor parameters after either proton or photon RT decreased significantly (p < 0.001). Among the 21 patients treated exclusively with proton RT, no significant increase in PVC-SUVmean or PVC-GLPG was observed in ipsilateral lungs after the PVC parameters of primary tumor were subtracted (p = 0.114 and p = 0.453, respectively). Also, there were no significant increases in SUVmean or GLG of contralateral lungs of patients who received proton RT (p = 0.841, p = 0.241, respectively). In contrast, among the nine patients who received photon RT, there was a statistically significant increase in PVC-GLPG of ipsilateral lung (p < 0.001) and in GLG of contralateral (p = 0.036) lung. In the subset of nine patients who received a combined proton and photon RT, there was a statistically significant increase in PVC-GLPG of ipsilateral lung (p < 0.001). CONCLUSION: Our data suggest less induction of inflammatory response in both the ipsilateral and contralateral lungs of patients treated with proton compared to photon or combined proton-photon RT.

Implementation of FDG-PET/CT imaging methodology for quantification of inflammatory response in patients with locally advanced non-small cell lung cancer: results from the ACRIN 6668/RTOG 0235 trial.

We measured changes in 18F-fluorodeoxyglucose (FDG) uptake on positron emission tomography/computed tomography (PET/CT) images in the lung parenchyma to quantify the degree of lung inflammation in patients with locally advanced non-small cell lung cancer (NSCLC) who received radiotherapy (RT). The goal of this study was to demonstrate successful implementation of this imaging methodology on NSCLC patients and to report quantitative statistics between pre-RT and post-RT. Seventy-one patients with NSCLC underwent FDG-PET/CT imaging before and after RT in a prospective study (ACRIN 6668/RTOG 0235). Comparisons between pre-RT and post-RT PET/CT were conducted for partial volume corrected (PVC)-mean standardized uptake value (SUVmean), PVC-global lung parenchymal glycolysis (GLPG), and lung volume for both ipsilateral and contralateral lungs using the nonparametric Wilcoxon signed-rank test. Regression modeling was conducted to associate clinical characteristics with post-RT PET/CT parameters. There was a significant increase in average SUVmean and GLPG of the ipsilateral lung (relative change 40% and 20%) between pre-RT and post-RT PET/CT scans (P<0.0001 and P=0.004). Absolute increases in PVC-SUVmean and PVC-GLPG were more pronounced (ΔPVC-SUVmean 0.32 versus ΔSUVmean 0.28; ΔPVC-GLPG 463.34 cc versus ΔGLPG 352.90 cc) and highly significant (P<0.0001). In contrast, the contralateral lung demonstrated no significant difference between pre-RT to post-RT in either GLPG (P=0.12) or SUVmean (P=0.18). The only clinical feature significantly associated with post-RT PET/CT parameters was clinical staging. Our study demonstrated inflammatory response in the ipsilateral lung of NSCLC patients treated with photon RT, suggesting that PET/CT parameters may serve as biomarkers for radiation pneumonitis (RP).

Dynamics of fluorine-18-fluorodeoxyglucose uptake in the liver and its correlation with hepatic fat content and BMI.

PURPOSE: The aim of this study was to explore the rate of elimination of fluorine-18-fluorodeoxyglucose (F-FDG) from the liver and assess the impact of hepatic fat and obesity on F-FDG clearance in early and delayed PET scans. We hypothesized that an increase in liver fat may cause a decline in hepatic F-FDG elimination with potential consequences as measured by dual time-point F-FDG PET/CT imaging. PATIENTS AND METHODS: A total of 32 patients from the Cardiovascular Molecular Calcification Assessed by F-NaF PET/CT (CAMONA) clinical trial (17 males, 15 females; mean age: 47.2 years, range: 23-69 years, mean BMI: 27.2 kg/m) were enrolled and underwent F-FDG PET/CT 90 and 180 min after tracer injection. Global mean standardized uptake value (SUVmean) (i.e. the average of SUVmean in segmented liver slices) and average maximum standardized uptake value (SUVmax) (i.e. the average of the SUVmax values recorded in same slices) were calculated for semiquantification of liver F-FDG uptake at both time-points. Percentage difference in global SUVmean and average SUVmax were also calculated to yield respective retention indices (RImean and RImax). Changes in global SUVmean, average SUVmax, RImean, and RImax from 90 to 180 min were correlated with BMI and liver fat content as measured by CT Hounsfield units. RESULTS: There was a 12.2±3.5 percent reduction in global liver SUVmean and a 4.1±5.8 percent reduction in average SUVmax at 180 min scan as compared with the 90 min time-point. RImean and RImax were inversely correlated with liver fat content and positively correlated with BMI. CONCLUSION: We observed a time-dependent decrease in global hepatic SUVmean and average SUVmax, which was affected by the amount of liver fat. Patients with higher BMI and hepatic fat content tended to retain F-FDG.