Emerging technologies for detection of circulating tumour DNA (ctDNA) are expanding the possibilities for clinical impact to patients with localized, potentially curable cancer. For such patients, ctDNA analysis could aid in prognostication, prediction of treatment response, longitudinal monitoring for adaptive treatment, and evaluation of minimal residual disease. Radiation oncologists currently have few tools at their disposal for predicting or rapidly assessing treatment efficacy. By reflecting the genetic and epigenetic makeup of tumours as well as dynamic changes with treatment, ctDNA as a biomarker for radiation response could enable new personalized treatment approaches. In this review, we will discuss recent advances in ctDNA technologies and potential clinical applications of ctDNA analysis throughout the therapeutic course. Furthermore, we will consider how ctDNA analysis could someday guide radiotherapy prescriptions by revealing differences in tumour radiophenotype.
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