Longitudinal Plasma Proteomics Reveals an Immuno-thrombotic Signature that Predicts Radiation Pneumonitis in Lung Cancer

Comprehensive Summary

Radiation pneumonitis is a toxicity in lung cancer therapy, which is often poorly predicted by current clinical models. The researchers identified a blood-based signature rooted in biological response to radiation that can be used for possible risk stratification. Using 267 longitudinal samples from 57 lung cancer patients, they conducted a prospective study focused on identifying protein trajectories associated with symptomatic radiation pneumonitis. The researchers identified dysregulated immuno-thrombotic axis as a central driver of radiation pneumonitis, characterized by significant enrichment in "Platelet Activation" and "Serpin" pathways. This signature was found to be a significant independent predictor and was distinct from markers of overall survival. This can be potentially utilized as a clinical tool for early risk stratification and personalized toxicity mitigation.

Outcomes and Implications

This model developed allowed for personalized risk stratification, proactive toxicity management, and provides biological insights to clinicians. The identified signature allows clinicians to identify patients at high risk for symptomatic pneumonitis prior to treatment, outperforming current clinical models and allow for early interventions when needed. In addition, it demonstrates that a dysregulated immuno-thrombotic axis drives radiation pneumonitis, opening doors for novel therapeutic targets.