Ma DJ, et al. - Whether the historical rates for disease control could be maintained along with decreased toxicity and preserved swallow function and quality of life (QOL) following dose de-escalation from 60 to 66 Gy to 30 to 36 Gy of adjuvant radiotherapy (RT) for selected patients with human papillomavirus–associated oropharyngeal squamous cell carcinoma was investigated in MC1273, a single-arm phase II trial. The locoregional tumor control at 2 years was considered as the primary end point. Two-year progression-free survival, overall survival, toxicity, swallow function, and patient-reported QOL were all secondary end points. Low toxicity, little decrement in swallowing function or QOL, and locoregional tumor control rates comparable to historical controls were provided by aggressive RT de-escalation.