Circulating tumor DNA as an arbitrator for postmastectomy radiotherapy: bridging molecular residual disease and locoregional control.

The NSABP B-51 trial left unresolved whether postmastectomy radiotherapy benefits ypN0 patients after neoadjuvant chemotherapy. Meanwhile, the PREDICT-DNA study showed that ctDNA clearance after neoadjuvant therapy identifies patients with favorable outcomes irrespective of pathologic response. We propose integrating these datasets: ctDNA status may serve as a tiebreaker for radiotherapy decisions, particularly in patients with residual disease, offering a molecularly guided framework for de-escalation.