Detecting Biomarkers of Radiation Pneumonitis in Exhaled Breath During Chemoradiotherapy for Stage III Non-small Cell Lung Cancer: Results of a Prospective Feasibility Study

Introduction To measure inflammatory biomarkers of radiation pneumonitis in the exhaled breath condensate (EBC) and serum of patients with stage III non-small cell lung cancer (NSCLC) treated with chemoradiotherapy (CRT). Methods This single-arm pilot study (NCT04040244) enrolled adults with stage III NSCLC planned for treatment with definitive CRT (60 Gy). EBC and serum samples were collected at baseline (W0) and at 2-, 6-, and 10-weeks after CRT initiation. EBC and serum concentrations of TGF-β1, IL-1α, IL-6, and IL-10, and cartilage oligomeric matrix protein (COMP) were measured in duplicate. Unadjusted mean biomarker levels were described over time. Results Samples were available for analysis from 11 out of 16 patients enrolled before the trial was closed early due to the COVID-19 public health emergency. Measurable biomarkers were present in 288 of 302 (95%) available EBC samples and 273 of 278 (98%) serum samples. Mean concentration of TGF-β1, IL-1α, IL-6, IL-10, and COMP over time is described. Mean concentration of TGF-β1 ranged from 81 to 101 pg/mL in EBC and 2819 to 5403 in serum. All biomarkers tested had numerically lower concentrations in EBC than serum, except for IL-10. Conclusion Exhaled breath-based analysis of RP-associated biomarkers is feasible, with most available samples having measurable levels of substrate across the multiple biomarkers tested. Given the limited sample size, no tests for association between EBC or serum biomarkers and the development of radiation pneumonitis or pulmonary fibrosis were possible. Larger prospective studies are warranted to determine the association between breath biomarkers and clinical outcomes. Future studies may expand upon this work by integrating clinical and dosimetric factors, using a broader range of inflammatory biomarkers, using a multi-omics approach to identify novel biomarkers, or incorporating breath volatile organic compound profiles.