ArticleFrontiers in oncology2026
Do not try this at home: patterns and outcomes of radiation dose de-escalation in p16-positive oropharyngeal carcinoma.
Article in Frontiers in oncology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
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<0.001). On multivariable analysis, academic facility type (Odds Ratio: 1.76, 95% Confidence Interval 1.31-2.43, p<0.001), more recent year of diagnosis, and geographic region were independently associated with DDRT. Three-year OS was inferior with DDRT compared with SDRT (82.1% vs 88.9%, p<0.001). Among patients receiving first-course chemotherapy, DDRT remained associated with worse OS (82.5% vs. 89.8%, p<0.001). No significant difference was observed among patients not receiving chemotherapy; however, this subgroup was small and likely underpowered to detect a meaningful difference. Landmark analysis yielded consistent findings. 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.
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