Biomarkers associated with pulmonary exacerbations in a randomized trial of nintedanib for radiation pneumonitis

Area of Science:

• Pulmonology
• Oncology
• Biomarker Discovery

Background:

• Radiation pneumonitis (RP) is a frequent complication of thoracic radiotherapy.
• RP can lead to long-term lung fibrosis and acute exacerbations.
• Currently, no validated prognostic biomarkers exist for RP patients.

Purpose of the Study:

• To identify serum protein biomarkers associated with clinical outcomes in patients with grade 2+ RP.
• To explore the correlation of these biomarkers with pulmonary exacerbations and treatment response.

Main Methods:

• Analysis of serum chemokines, cytokines, and proteins in a randomized clinical trial of nintedanib plus steroid taper versus placebo plus steroid taper.
• Application of Weighted Gene Correlation Network Analysis (WGCNA) and Poisson models to identify biomarker associations.

Main Results:

• WGCNA identified ten analytes, including TGF-β1, MCP-1, and PDGF, correlated with pulmonary exacerbations and treatment arm.
• Increased rates of change in interleukin-5 (IL-5) and TNFSF12 were linked to increased exacerbation incidence.
• Elevated epidermal growth factor (EGF) levels correlated with a decreased exacerbation rate.

Conclusions:

• A panel of serum biomarkers associated with nintedanib treatment and acute pulmonary exacerbations in RP was identified.
• This panel shows potential as a prognostic tool for RP.
• A confirmatory study is required for validation.