A Phase II Trial of Alternative Volumes of Oropharyngeal Irradiation for Deintensification (AVOID): Omission of the Resected Primary Tumor Bed for Squamous Cell Carcinoma of the Oropharynx

Abstract

Treatment of human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC) with initial surgical resection followed by adjuvant radiotherapy yields high cure rates, but can cause long-term toxicity. This phase II trial evaluated whether omitting high dose radiation to the resected primary tumor bed while targeting only the regional neck nodes, could maintain high local control rates while reducing late sequelae. Eligible patients were those appropriate for adjuvant RT after surgical resection for p16-positive, pathologic stage III-IVa (7th edition) p16-positive OPSCC. Pathologic inclusion criteria included: T1-T2 disease, any N1-2, negative resection margins, and no perineural or lymphovascular invasion. Patients received 60-66 Gy RT over 30-33 fractions to the regional nodes of the bilateral neck, with active omission of high-dose RT to the resected primary tumor bed. Concurrent chemotherapy was given for patients with extranodal extension. The primary end point was 2-year locoregional control. Sixty patients were enrolled. Thirty-two (53%) received intensity-modulated radiation therapy (IMRT), 27 (45%) received proton therapy, and 1 (2%) received a 50:50 hybrid IMRT:proton plan. Average follow-up was 2 years, with local control of 98%, regional control of 100%, distant control of 97%, and overall survival of 100%. Median dose delivered to the avoided primary site was 37 Gy (40 Gy for IMRT, 34 Gy for proton RT, p = 0.03). There was only 1 local recurrence, occurring 9 months after completion of RT, which was successfully salvaged via surgical resection. Two (3%) patients experienced post-RT primary site tissue necrosis, both of whom experienced complete resolution with conservative management. Percutaneous endoscopic gastrostomy (PEG) tube dependence rates were: 0 patients (0%) during RT, and 1 patient (2%) at time of last follow-up. Avoidance of radiation to the resected primary tumor bed appears safe in well-selected patients with HPV-associated OPSCC. This approach resulted in a low rate of treatment-associated complications, and is worthy of further study as a strategy for deintensification.