Do not try this at home: patterns and outcomes of radiation dose de-escalation in p16-positive oropharyngeal carcinoma

Introduction Radiation dose de-escalation for human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC) has been actively investigated to reduce long-term toxicity. Following the recent failure of randomized non-inferiority trials, the real-world adoption and outcomes of de-escalated radiation remain unclear. We evaluated contemporary patterns of dose de-escalation and associated overall survival (OS) in a national cohort. Methods The National Cancer Database was queried for patients diagnosed from 2018–2022 with p16-positive OPSCC meeting NRG-HN005 eligibility criteria (cT1–2N1 or cT3N0–1) treated with definitive external beam radiation therapy without primary surgery. Dose-de-escalated radiation therapy (DDRT) was defined as 50.0–65.9 Gy; standard-dose radiation therapy (SDRT) as ≥66.0 Gy. Multivariable logistic regression identified predictors of DDRT. OS was estimated using Kaplan–Meier methods with log-rank testing and 2-month landmark analysis. Results Among 14,869 patients, 1,119 (7.5%) received DDRT. DDRT was more frequently delivered at academic centers (50.3% vs 40.0%, p Conclusion Radiation dose de-escalation remains infrequent in contemporary U.S. practice but is more commonly delivered at academic centers. In this population-based analysis, de-escalation was associated with inferior overall survival, aligning with recent randomized evidence. Reduced-dose radiation should remain investigational pending biomarker-guided selection strategies.