A deintensified 60-Gy radiotherapy regimen was associated with low long-term locoregional recurrence among selected patients with human papillomavirus–associated oropharyngeal carcinoma, according to a cohort study published in JAMA Otolaryngology–Head & Neck Surgery.
The study included 240 patients treated between 2014 and 2022 across multiple sites within a single academic hospital system. Eligible patients had untreated p16-positive oropharyngeal carcinoma (OPC) or unknown primary disease, T0 to T3, N0 to N2c, M0 disease by American Joint Committee on Cancer seventh edition criteria, favorable smoking histories, and no prior head and neck cancers. Current smokers were excluded.
Patients received intensity-modulated radiotherapy to 60 Gy in 30 fractions over 6 weeks, with elective regions receiving 50 to 54 Gy. Concurrent weekly cisplatin was the preferred systemic therapy, most commonly at 30 mg/m² weekly. Patients with lower-risk disease — T0 to T2 and N0 to N1 — were generally recommended radiotherapy alone.
At 5 years, the locoregional recurrence rate was 3.4%, progression-free survival was 86.5%, and overall survival was 92.4%. Distant recurrence occurred in 7.3% of patients at 5 years.
Median time to progression was 1.9 years, and 46.2% of recurrences occurred more than 2 years following treatment — a pattern the authors suggest may warrant prolonged surveillance in human papillomavirus (HPV)-associated OPC.
Among 33 patients with lower-risk disease treated with radiotherapy alone, 5-year progression-free survival was 93.8%, with no locoregional recurrences observed at a median follow-up of 7.3 years.
On multivariate analysis, nodal stage was the only factor independently associated with progression-free survival events, with N2b–N2c disease carrying more than twice the risk of progression compared with N0–N2a disease.
The investigators also explored treatment deintensification among former heavier smokers using p53 wild-type status as a biologic selection strategy in the third-generation protocol. Although locoregional control appeared similar across smoking subgroups, patients with heavier smoking histories showed a numerically higher distant recurrence rate.
The findings add to ongoing debate regarding radiotherapy deintensification in HPV-associated OPC. In discussing their results, the researchers contrasted them with interim findings from the randomized phase 2/3 NRG-HN005 trial, in which 60-Gy treatment arms showed higher locoregional event rates and lower progression-free survival than standard 70-Gy chemoradiotherapy, leading the trial to stop before phase 3 expansion.
The researchers suggested that differences in cisplatin dosing, fractionation schedules, patient selection, and duration of follow-up could potentially contribute to discrepancies between studies, although they emphasized that such explanations remain speculative pending full NRG-HN005 publication.
The study was limited by its single-arm design, lack of a standard-dose comparator group, and treatment delivery within a specialized academic system, which may limit generalizability to broader cooperative-group practice settings. Long-term toxicity and quality-of-life outcomes also were not fully evaluated in this report.
"Modest dose deintensification of 60-Gy radiotherapy in patients with HPV-associated OPC showed high rates of locoregional control," wrote lead study author Ryan T. Morse, MD, of the University of Kansas Medical Center, and colleagues.
The researchers emphasized that the findings do not change the current standard of care but may help support ongoing deintensification studies and discussions with carefully selected patients seeking less-intensive treatment approaches with appropriate informed consent.
Disclosures: Several researchers reported consulting fees, grants, travel support, patents, royalties, or other industry relationships. The study was partly supported by the National Cancer Institute.
