Prospective assessment of dosimetric/physiologic-based models for predicting radiation pneumonitis

Purpose: Clinical and 3D dosimetric parameters are associated with symptomatic radiation pneumonitis rates in retrospective studies. Such parameters include: mean lung dose (MLD), radiation (RT) dose to perfused lung (via SPECT), and pre-RT lung function. Based on prior publications, we defined pre-RT criteria hypothesized to be predictive for later development of pneumonitis. We herein prospectively test the predictive abilities of these dosimetric/functional parameters on 2 cohorts of patients from Duke and The Netherlands Cancer Institute (NKI). Methods and Materials: For the Duke cohort, 55 eligible patients treated between 1999 and 2005 on a prospective IRB-approved study to monitor RT-induced lung injury were analyzed. A similar group of patients treated at the NKI between 1996 and 2002 were identified. Patients believed to be at high and low risk for pneumonitis were defined based on: ( 1 ) MLD; ( 2 ) OpRP (sum of predicted perfusion reduction based on regional dose-response curve); and ( 3 ) pre-RT DLCO. All doses reflected tissue density heterogeneity. The rates of grade ≥2 pneumonitis in the "presumed" high and low risk groups were compared using Fisher's exact test. Results: In the Duke group, pneumonitis rates in patients prospectively deemed to be at "high" vs. "low" risk are 7 of 20 and 9 of 35, respectively; p = 0.33 one-tailed Fisher's. Similarly, comparable rates for the NKI group are 4 of 21 and 6 of 44, respectively, p = 0.41 one-tailed Fisher's. Conclusion: The prospective model appears unable to accurately segregate patients into high vs. low risk groups. However, considered retrospectively, these data are consistent with prior studies suggesting that dosimetric ( e.g. , MLD) and functional ( e.g. , PFTs or SPECT) parameters are predictive for RT-induced pneumonitis. Additional work is needed to better identify, and prospectively assess, predictors of RT-induced lung injury.