Initial Feasibility and Acute Toxicity Outcomes from a Phase II trial of FDG-PET response-based de-escalated definitive chemoradiotherapy for p16+ oropharynx cancer, a Planned Interim Analysis.

PURPOSE: 18 F-Fluorodeoxyglucose-positron emission tomography (FDG-PET) parameters are prognostic of oncologic outcomes in human papillomavirus-associated oropharyngeal squamous cell carcinoma (OPSCC). We utilized FDG-PET imaging biomarkers to select patients for de-escalated chemoradiotherapy (CRT) hypothesizing that acute toxicity will be improved with de-escalation.

METHODS: This is a planned interim initial feasibility and acute toxicity report from a phase II prospective, non-randomized study which enrolled patients with stage I-II p16+ OPSCC. All patients started definitive CRT to 70 Gy in 35 fractions, and those that met de-escalation criteria on mid-treatment FDG-PET at fraction 10 completed treatment at 54 Gy in 27 fractions. We report the acute toxicity and patient reported outcomes on 59 patients with a minimum follow-up of 3 months.

RESULTS: There were no statistically significant differences between baseline patient characteristics in the standard and de-escalated cohorts. There were 28/59 (47.5%) patients who met FDG-PET de-escalation criteria and collectively received 20-30% less dose to critical organs at risk known to affect toxicity. At 3 months post-treatment, patients who received de-escalated CRT lost significantly less weight (median 5.8% vs 13.0%, p<0.001), had significantly less change from baseline in Penetration-Aspiration Scale score (median 0 vs 1, p=0.018), and had significantly fewer aspiration events on repeat swallow study (8.0% vs 33.3%, p=0.037) as compared to patients receiving standard CRT.

CONCLUSION: Approximately half of early-stage p16+ OPSCC patients are selected for de-escalation of definitive CRT using mid-treatment FDG-PET biomarkers, which resulted in significantly improved rates of observed acute toxicity. Further follow up is ongoing and will be required to determine if this de-escalation approach preserves the favorable oncologic outcomes for p16+ OPSCC patients before adoption.