Beyond safety: rethinking concomitant radiotherapy and trastuzumab deruxtecan in metastatic breast cancer - from feasibility to precision practice.

Visani et al. [1]. Provide the largest real-world evidence that concomitant trastuzumab deruxtecan (T-DXd) and radiotherapy (RT) does not significantly increase acute severe adverse events (AEs) in metastatic breast cancer. Yet "concomitant" is not a biological concept: radiosensitisation depends on RT intent, anatomical site, fractionation and tumour biology, not merely a temporal window. This Viewpoint argues that the field must move beyond binary safety questions to stratified decision-making, distinguishes the distinct radionecrosis risk profiles of T-DM1 and T-DXd payloads, expand the decision framework to conventional and moderately hypofractionated radiotherapy beyond stereotactic techniques, and identify three high-priority research gaps: thoracic irradiation, HER2-low metastatic breast cancer, and cardiac vulnerability during combined therapy.