Pneumonitis resulting from radiation and immune checkpoint blockade illustrates characteristic clinical, radiologic and circulating biomarker features

BACKGROUND: Pneumonitis is a potential consequence of both lung-directed radiation and immune checkpoint blockade (ICB), particularly treatment with PD-1/PD-L1 inhibitors. Significant morbidity and mortality can result, and severe pneumonitis attributed to ICB precludes continued therapy. Thus, discriminating between radiation- and ICB- related pneumonitis is of importance for the increasing number of patients receiving both treatments. Furthermore, data are limited regarding the interplay between radiation- and ICB-induced lung injury, and which biomarkers might be associated with toxicity. CASE PRESENTATION: We report longitudinal clinical and radiologic data, and circulating biomarkers in a melanoma patient treated with axillary radiation followed by ICB who developed consolidation and ground glass opacities (GGO) within the radiation field suggestive of radiation-pneumonitis followed by consolidation outside of the radiation field suggestive of ICB-related pneumonitis. Of note, symptomatic radiation-pneumonitis developed despite a low radiation dose to the lung (V20 < 8%), and ICB-related pneumonitis was limited to the ipsilateral lung, suggesting additive effect of radiation and ICB in the development of lung injury. Circulating biomarker analyses demonstrated increases in CXCR2, IL1ra and IL2ra that coincided with the development of symptomatic pneumonitis. CONCLUSIONS: These data highlight the imaging findings associated with radiation and ICB-related lung toxicity, and anecdotally describe a clinical course with circulating biomarker correlates. This information can help guide clinical evaluation and future research investigations into the toxicity of combined radiation immunotherapy approaches.