Purpose To report a single‐institutional experience with hypofractionated radiation therapy alone for human papillomavirus (HPV)‐positive oropharyngeal cancer. Methods and materials A total of 101 consecutive patients were treated by radiation therapy alone using a regimen of 66 Gy in 30 fractions (60 patients) or 70 Gy in 33 fractions (41 patients) for newly diagnosed p16‐positive squamous cell carcinoma of the oropharynx. Sixty‐seven patients (67%) were never smokers. Results The 3‐year actuarial rates of overall survival, local‐regional control, and progression‐free survival were 94%, 93%, and 89%, respectively. Among never‐smokers, the 3‐year rates of overall survival and local–regional control were 98% and 100%, respectively. The grade 3+ acute toxicity rate was 21%, with the most commonly observed side effects related to mucositis. Conclusion Hypofractionated radiation alone resulted in excellent outcomes for patients with HPV‐positive oropharyngeal cancer. A prospective clinical trial investigating this modality in the setting of de‐escalation is currently underway.
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