Developing more sensitive genomic approaches to detect radioresponse in precision radiation oncology: From tissue DNA analysis to circulating tumor DNA.

Despite the common application and considerable efforts to achieve precision radiotherapy (RT) in several types of cancer, RT has not yet entered the era of precision medicine; the ability to predict radiosensitivity and treatment responses in tumors and normal tissues is lacking. Therefore, development of genome-based methods for individual prognosis in radiation oncology is urgently required. Traditional DNA sequencing requires tissue samples collected during invasive operations; therefore, repeated tests are nearly impossible. Intra- and inter-tumoral heterogeneity may undermine the predictive power of a single assay from tumor samples. In contrast, analysis of circulating tumor DNA (ctDNA) allows for non-invasive and near real-time sampling of tumors. By investigating the genetic composition of tumors and monitoring dynamic changes during treatment, ctDNA analysis may potentially be clinically valuable in prediction of treatment responses prior to RT, surveillance of responses during RT, and evaluation of residual disease following RT. As a biomarker for RT response, ctDNA profiling may guide personalized treatments. In this review, we will discuss approaches of tissue DNA sequencing and ctDNA detection and summarize their clinical applications in both traditional RT and in combination with immunotherapy.