Predicting radiation-induced lung injury in lung cancer patients – challenges and opportunities

Radiation-induced lung injury (RILI) is one of the main dose-limiting toxicities in radiotherapy (RT) for lung cancer. Approximately 10-20% of patients show signs of RILI with 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 and can aid in clinical decision making. Technological advancements in radiotherapy and the use of strict organ-at-risk dose constraints have helped to reduce RILI. Predicting who is at risk for RILI can possibly 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 CT-densitometry, FDG-PET uptake, changes in lung function measurements or the use of 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 and mass cytometry, as well as 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 future biomarkers to better predict which patients are at risk and allow personalized treatment decisions.