Prospective validation of a pretreatment 18F-FDG PET/CT and mean lung dose model for early radiation pneumonitis

Abstract

Background and purpose

Early onset radiation pneumonitis (RP_Early) after concurrent chemoradiotherapy (cCRT) can lead to consolidation immunotherapy (IO) discontinuation, and poor survival in locally advanced non-small cell lung cancer (LA-NSCLC). This work assessed the external validity of a previously published RP_Early risk model.

Material and methods

The RP_Early risk model utilizes pretreatment 18F-FDG PET/CT imaging of the normal lungs and the mean lung dose (MLD). The 90th percentile of the standardized uptake value (SUV_P90) and the MLD model parameters from the previous derivation cohort (N = 160) were applied in the independent cohort (50 consecutive LA-NSCLC patients treated with cCRT and IO) where model performance was evaluated (area under the receiver-operating characteristic curve (AUC), p-values, and the Hosmer-Lemeshow test (pHL)).

Results

Seven patients (14 %) developed RP_Early. Model performance of the previously developed SUV_P90 and MLD model improved with re-fitting (AUC = 0.76 vs. 0.72; p = 0.01 vs. 0.10; pHL = 0.66 vs. 0.94). Above a clinically desirable 10 % predicted RP_Early, after refitting model coefficients in the combined derivation and validation cohorts (N = 210), the MLD was 13 ± 2.2 EQD2₃ Gy (SUV_P90 = 1.2 ± 0.3) above the RP_Early risk threshold vs. 8.5 ± 2.6 EQD2₃ Gy (0.9 ± 0.2) below the threshold. For an SUV_P90 of 1.1 and an MLD of 11 Gy EQD2₃ Gy, 25/27 patients developing RP_Early were captured.

Conclusion

The previously developed SUV_P90 and MLD-based risk model for RP_Early demonstrated a high probability to correctly predict RP_Early in the independent cohort. This now validated RP_Early risk model with derived high-risk indications could enable personalized thoracic RT planning to reduce the risk of RP_Early and of discontinuing life-prolonging IO post-cCRT.