Abstract
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.
Highlights
The goal of radiogenomics is to identify genomic factors that are associated with the clinical variability observed in response to radiation therapy [1, 2]
The rationale for ensuring that radiogenomic research includes charged particle therapy (CPT) cohorts is that the genomic markers identified from studies of patients treated with photons may not be entirely applicable as the radiobiology could differ between the 2 modalities. It may be more than just a matter of dosimetry and sparing of normal tissue that distinguishes CPT from photon radiation therapy as the nature of the biological processes occurring in cells and tissues following photon versus
As most previous reviews of radiogenomics have focused on normal tissue toxicities [2], a critical area that has not received adequate attention for radiogenomic studies has been the identification of genomic biomarkers associated with the development of a new cancer following radiation therapy
Summary
The goal of radiogenomics is to identify genomic factors that are associated with the clinical variability observed in response to radiation therapy [1, 2]. The rationale for ensuring that radiogenomic research includes CPT cohorts is that the genomic markers identified from studies of patients treated with photons may not be entirely applicable as the radiobiology could differ between the 2 modalities That is, it may be more than just a matter of dosimetry and sparing of normal tissue that distinguishes CPT from photon radiation therapy as the nature of the biological processes occurring in cells and tissues following photon versus. Cells irradiated with protons exhibit altered migration and invasion compared with photons [31, 32] The results of these studies suggest that important biological differences occur following irradiation with charged particles compared with photons that could result in an altered range of genomic factors associated with outcomes from these different forms of radiation. It is anticipated that as additional centers with proton and carbon ion capability are completed where RGC investigators are located, that the size of patient cohorts receiving CPT will increase
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