Predicting Radiation-Induced Lung Injury in Patients With Lung Cancer: Challenges and Opportunities

Radiation-induced lung injury (RILI) is one of the main dose-limiting toxicities in radiation therapy (RT) for lung cancer. Approximately 10% to 20% of patients show signs of RILI of variable severity. The reason for the wide range of RILI severity and the mechanisms underlying its development are only partially understood. A number of clinical risk factors have been identified that can aid in clinical decision making. Technological advancements in RT and the use of strict organ-at-risk dose constraints have helped to reduce RILI. Predicting patients at risk for RILI may be further improved with a combination of cytokine assessments, γH2AX-assays in leukocytes, or epigenetic markers. A complicating factor is the lack of an objective definition of RILI. Tools such as computed tomography densitometry, fluorodeoxyglucose-positron emission tomography uptake, changes in lung function measurements, and exhaled breath analysis can be implemented to better define and quantify RILI. This can aid in the search for new biomarkers, which can be accelerated by omics techniques, single-cell RNA sequencing, mass cytometry, and advances in patient-specific in vitro cell culture models. An objective quantification of RILI combined with these novel techniques can aid in the development of biomarkers to better predict patients at risk and allow personalized treatment decisions.