This viewpoint critiques and extends real-world evidence on the safety of concomitant trastuzumab deruxtecan (T-DXd) and radiotherapy (RT) in metastatic breast cancer, arguing for stratified decision-making beyond binary safety assessments across RT intent, site, fractionation, and tumor biology.
The authors contend that 'concomitant' is not a sufficient biological concept; radiosensitization risk varies by RT site, fractionation, and payload (distinguishing T-DM1 vs. T-DXd radionecrosis profiles), and three high-priority gaps remain: thoracic irradiation safety, HER2-low metastatic breast cancer, and cardiac vulnerability during combined therapy.
This is an expert viewpoint/commentary — no original patient data, no comparator arm, and no quantitative outcomes are reported. Conclusions are largely opinion-based and derive from critique of a single referenced real-world study.
Do not treat all concomitant T-DXd + RT combinations as equivalent; stratify decisions by anatomical site, fractionation schedule, and HER2 status. Treat thoracic irradiation and cardiac exposure during combined therapy as priority areas requiring extra caution until prospective data are available.
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