Fig. 2: Dynamics of cfDNA release in radiotherapy.

The release of tumour and normal tissue cfDNA occurs earlier than the onset of clinically apparent radiation toxicity, giving a window of opportunity for adapting radiation dose if excessive normal tissue-derived cfDNA is detected early in treatment (solid compared to dashed green line), measured as ΔcfDNA TOX. Without adaptation, the higher level of acute clinical radiation toxicity (end of week 4, solid blue line) may not be repaired, leading to subsequent life-changing permanent late radiation damage (solid blue line) by month 24. Assessment of tumour cfDNA release (dashed red line) can ensure that any reduction in normal tissue dose does not adversely impact tumour control or could possibly safely escalate the dose to tumour. Monitoring cfDNA release from tumour and normal tissue creates the ability to personalise dosage early in treatment and would redefine precision radiotherapy.