314 - HYHOPE: A Phase I Study of De-Intensified Hypofractionated Radiation Therapy for Human Papillomavirus-Associated Oropharynx Cancer

D. H. Moon¹, V. Avkshtol², R. Hughes², and D. J. Sher¹; ¹Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, TX, ²University of Texas Southwestern Medical Center, Dallas, TX

Purpose/Objective(s): There are several strategies under investigation to de-escalate therapy for favorable human papillomavirus-associated oropharynx squamous cell carcinoma (F-OPSCC). Hypofractionated radiotherapy (HFRT) has the potential to decrease the treatment burden, chemotherapy exposure, and cost. We conducted a phase I study to assess the tolerability of de-intensified HFRT completed in 3 weeks with weekly cisplatin. Materials/

Methods: Patients with F-OPSCC, defined as T1-3 (=6 cm) N0-2 (except T1-2N0), p16 positive disease, and =10 pack-years, were enrolled with a rolling 6 design followed by a dose expansion cohort from 2021-2023. Biologically effective dose accounting for repopulation approximately equivalent to 60 Gy in 30 fractions were chosen with level 0 consisting of 46.5 Gy in 15 fractions (3.1 Gy/fraction) and level -1 consisting of 52 Gy in 20 fractions (2.6 Gy/fraction). The elective neck was restricted to involved plus adjacent nodal levels and received 40.5 Gy on level 0. The primary endpoint was maximum tolerated dose/fractionation of HFRT. Dose limiting toxicity (DLT) was defined as persistent grade 3 mucositis at 3 months post-treatment or any grade 4 toxicity. All patients received 3 weekly doses of cisplatin (40 mg/m²).
Results: A total of 24 patients were enrolled with 6 on level 0 and 18 on the dose expansion cohort. Fourteen and 10 patients had stage I and II disease, respectively. The median overall treatment time was 18 days (interquartile range [IQR] 18-21). No patient experienced a DLT on level 0, and thus 46.5 Gy in 15 fractions was chosen for the expansion cohort. Acute grade 3 toxicity occurred in 7 (29%) patients including oral mucositis, dysphagia, and weight loss (Table). One patient experienced an acute grade 4 toxicity (lymphopenia). 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 (MDADI) composite score at baseline, 3 and 12 months were 85.1 (14.1), 86.1 (11.3), and 89.8 (7.4), respectively. With a median follow-up of 18.1 months (IQR 6.7-23.5), the cumulative incidences of locoregional recurrence were 4.2% and 8.5% at 12 and 18 months, respectively. One patient had an in-field regional recurrence, treated with salvage neck dissection with no subsequent evidence of disease. One patient had a locoregional recurrence followed by distant metastases, currently on systemic therapy.
Conclusion: De-intensified hypofractionated RT with weekly cisplatin completed in 3 weeks is well-tolerated with excellent toxicity profile and patient-reported swallow function in patients with F-OPSCC. This treatment paradigm warrants further investigation to assess efficacy.

Abstract 314 – Table 1: Cumulative acute toxicity

	Grade 2	Grade 3
Odynophagia/sore throat	18 (75%)	0
Oral mucositis	14 (58%)	5 (21%)
Weight loss	13 (54%)	2 (8%)
Dysphagia	11 (45%)	2 (8%)
Dysgeusia	9 (38%)	0
Xerostomia	7 (29%)	0