Differential inflammatory response dynamics in normal lung following stereotactic body radiation therapy with protons versus photons

Abstract Background and purpose To compare time-dependent changes in lung parenchyma of early-stage non-small cell lung carcinoma (NSCLC) patients after stereotactic body radiation therapy with protons (SBPT) or photons (SBRT). Materials and method We retrospectively identified NSCLC patients treated with SBPT and matched each one with a SBRT patient by patient, tumor, and treatment characteristics. Lung parenchyma on serial post-treatment chest computer tomography (CT) scans was deformably registered with the treatment plan to analyze lung density changes as function of dose, quantified by Houndsfield Unit (HU)/Gy. A thoracic radiologist also evaluated the CTs using an established grading system. Results We matched 23 SBPT/SBRT pairs, including 5 patients treated with both modalities (internally matched cohort). Normal lung response following SBPT significantly increased in the early time period (CTs acquired p  = 0.007). These differences were most pronounced in sensitive (response >6 HU/Gy) patients and in the internally matched cohort. However, there was no significant difference in the maximum observed response in the entire cohort over all time periods, median 3.4 [IQR, 1.0–5.4] HU/Gy (SBPT) versus 2.5 [1.6–5.2] HU/Gy (SBRT). Qualitative radiological evaluation was highly correlated with the quantitative analysis ( p Conclusion While there was no significant difference in maximum response after SBPT versus SBRT, dose-defined lung inflammation occurred earlier after proton irradiation. Further investigation is warranted into the mechanisms of inflammation and therapeutic consequences after proton versus photon irradiation.