An ¹⁸F-FDG PET/CT and Mean Lung Dose Model to Predict Early Radiation Pneumonitis in Stage III Non-Small Cell Lung Cancer Patients Treated with Chemoradiation and Immunotherapy

Radiation pneumonitis (RP) that develops early (i.e., within 3 mo) (RP_Early) after completion of concurrent chemoradiation (cCRT) leads to treatment discontinuation and poorer survival for patients with stage III non-small cell lung cancer. Since no RP_Early risk model exists, we explored whether published RP models and pretreatment ¹⁸F-FDG PET/CT-derived features predict RP_Early Methods: One hundred sixty patients with stage III non-small cell lung cancer treated with cCRT and consolidative immunotherapy were analyzed for RP_Early Three published RP models that included the mean lung dose (MLD) and patient characteristics were examined. Pretreatment ¹⁸F-FDG PET/CT normal-lung SUV featured included the following: 10th percentile of SUV (SUV_P10), 90th percentile of SUV (SUV_P90), SUV_max, SUV_mean, minimum SUV, and SD. Associations between models/features and RP_Early were assessed using area under the receiver-operating characteristic curve (AUC), P values, and the Hosmer-Lemeshow test (pHL). The cohort was randomly split, with similar RP_Early rates, into a 70%/30% derivation/internal validation subset. Results: Twenty (13%) patients developed RP_Early Predictors for RP_Early were MLD alone (AUC, 0.72; P = 0.02; pHL, 0.87), SUV_P10, SUV_P90, and SUV_mean (AUC, 0.70-0.74; P = 0.003-0.006; pHL, 0.67-0.70). The combined MLD and SUV_P90 model generalized in the validation subset and was deemed the final RP_Early model (RP_Early risk = 1/[1+e^{(- x )}]; x = -6.08 + [0.17 × MLD] + [1.63 × SUV_P90]). The final model refitted in the 160 patients indicated improvement over the published MLD-alone model (AUC, 0.77 vs. 0.72; P = 0.0001 vs. 0.02; pHL, 0.65 vs. 0.87). Conclusion: Patients at risk for RP_Early can be detected with high certainty by combining the normal lung's MLD and pretreatment ¹⁸F-FDG PET/CT SUV_P90 This refined model can be used to identify patients at an elevated risk for premature immunotherapy discontinuation due to RP_Early and could allow for interventions to improve treatment outcomes.