HYHOPE: A phase I study of de-intensified hypofractionated radiation therapy for human papillomavirus-associated oropharynx cancer.

Abstract

Background: Various de-escalation strategies for human papillomavirus-associated oropharynx cancers are under investigation. We have incorporated hypofractionated radiotherapy (RT) in a phase I study to assess the tolerability of dose and volume de-intensified RT completed in 3 weeks with weekly cisplatin.

Methods: Patients with favorable oropharynx cancer, defined as T1-3, N0-2, p16 positive, and ≤10 pack-years, were enrolled using a rolling 6 design with 46.5 Gy in 15 fractions as level 0 and 52 Gy in 20 fractions as level -1. The elective neck was restricted to the involved plus adjacent nodal levels. The primary endpoint was the maximum tolerated dose/fractionation (MTD) of hypofractionated RT. Additional patients were enrolled at the MTD on the dose expansion cohort. All patients received three weekly doses of cisplatin (40 mg/m²).

Results: Six patients were treated on level 0 with no dose limiting toxicity, and thus 46.5 Gy in 15 fractions was deemed the MTD. On the dose expansion cohort, 18 additional patients were enrolled for a total of 24 patients. Acute grade 3 toxicity occurred in 7 (29%) patients including oral mucositis, dysphagia, and weight loss. One patient experienced an acute grade 4 toxicity of lymphopenia, which resolved with time. Late toxicity consisted of one grade 2 xerostomia and one grade 2 dysphagia, with no late grade 3+ toxicity. Mean (standard deviation) MD Anderson Dysphagia Inventory composite score at baseline, 3 and 12 months were 86.5 (13.7), 85.5 (11.3), and 89.4 (9.4), respectively. With a median follow-up of 26.6 months, the 2-year cumulative incidence of locoregional recurrence was 13.8% (95% confidence interval 3.2-32%).

Conclusion(s): De-intensified hypofractionated RT with weekly cisplatin completed in 3 weeks is well-tolerated with excellent toxicity profile and patient-reported swallow function warranting further investigation to assess efficacy.