Radiogenomic Predictors of Adverse Effects following Charged Particle Therapy

Radiogenomics is the study of genomic factors that are associated with response to radiation therapy. In recent years, progress has been made toward identifying genetic risk factors linked with late radiation-induced adverse effects. These advances have been underpinned by the establishment of an international Radiogenomics Consortium with collaborative studies that expand cohort sizes to increase statistical power and efforts to improve methodologic approaches for radiogenomic research. Published studies have predominantly reported the results of research involving patients treated with photons using external beam radiation therapy. These studies demonstrate our ability to pool international cohorts to identify common single nucleotide polymorphisms associated with risk for developing normal tissue toxicities. Progress has also been achieved toward the discovery of genetic variants associated with radiation therapy-related subsequent malignancies. With the increasing use of charged particle therapy (CPT), there is a need to establish cohorts for patients treated with these advanced technology forms of radiation therapy and to create biorepositories with linked clinical data. While some genetic variants are likely to impact toxicity and second malignancy risks for both photons and charged particles, it is plausible that others may be specific to the radiation modality due to differences in their biological effects, including the complexity of DNA damage produced. In recognition that the formation of patient cohorts treated with CPT for radiogenomic studies is a high priority, efforts are underway to establish collaborations involving institutions treating cancer patients with protons and/or carbon ions as well as consortia, including the Proton Collaborative Group, the Particle Therapy Cooperative Group, and the Pediatric Proton Consortium Registry. These important radiogenomic CPT initiatives need to be expanded internationally to build on experience gained from the Radiogenomics Consortium and epidemiologists investigating normal tissue toxicities and second cancer risk.