Radiogenomics researchers are seeking genetic biomarkers that can predict which patients are most likely to suffer radiotoxicities and which can safely undergo intensified radiation oncology treatment regimens. Recent studies have identified candidate gene polymorphisms and validated the association between the candidate radiotoxicity gene variant C-509T and the development of radiation-induced breast fibrosis.
Radiation genomics is the search for gene variants associated with patients’ responses to radiation therapy. Like the separate, emerging discipline of imaging genomics — the study of medical imaging features that reveal details of gene expression in tumors or other tissues — radiation genomics is frequently referred to as radiogenomics.
If irradiation of patients’ healthy non-targeted tissue could be avoided entirely and an entire radiation dose could be precisely targeted to tumor tissue, radiotherapy would be a routinely curative treatment modality. In reality, of course, beam paths and targeting uncertainties and errors all render that impossible. But external beam radiotherapy techniques have advanced dramatically in recent years to tailor radiation fields to tumor contours and minimize off-target irradiation.
If researchers can identify and validate genomic biomarkers to predict radiosensitivity for risk stratification, radiation oncologists should be able to even more precisely tailor radiotherapy regimens to individual patients, bringing radiation oncology more fully into the “personalized medicine” era.1-4 Markers of radiotoxicity risk could identify which patients can safely undergo intensified radiotherapy regimens and which should be spared the probable adverse effects of aggressive treatment.5 Genomic biomarkers of gene expression might also serve as early indicators of radiation toxicity for more timely changes in treatment, such as fractional dose de-escalation.2,5
Progress in this field has seemed at times to move at a glacial rate. Early work focused on the possible role of DNA-repair and cell cycle checkpoint-regulating gene variants in modulating radiotoxicity risks in prostate and breast cancer treatment and to a lesser extent lung cancer radiotherapy.4 But recent years have seen important advances and validation efforts that could point the way forward toward clinical translation of radiogenomic tools.4.6-8