A Phase II Trial of Alternative Volumes of Oropharyngeal Irradiation for De-intensification (AVOID): Omission of the Resected Primary Tumor Bed Following Transoral Robotic Surgery for Human Papilloma Virus Related Squamous Cell Carcinoma of the Oropharynx

Abstract Purpose This trial tested the safety and efficacy of a novel, de-intensified radiation therapy (RT) approach after initial surgical resection for patients with HPV associated OPSCC. Methods This single arm phase II prospective clinical trial enrolled 60 patients at a single institution between May 2014-September 2017 with stage pT1-pT2 N1-3 HPV-associated OPSCC treated with transoral robotic surgery (TORS) and selective neck dissection (SND). Patients had favorable features at the primary site (negative surgical margins ≥2 mm, no perineural invasion, and no lymphovascular invasion) but required adjuvant therapy based on lymph node involvement. Surgeries were all performed at a high volume head and neck cancer center with expertise in TORS. Patients received post-operative RT to at-risk areas in the involved neck (60-66 Gy), and uninvolved neck (54 Gy). The resected primary site was treated as an active avoidance structure in the treatment planning of postop RT. Concurrent chemotherapy was administered for patients with extranodal extension (ENE). Results Median follow-up of the 60 patients enrolled was 2.4 years (range 8.5-53.8 months). A single patient recurred at the primary site, for 2-year local control of 98.3%. One patient (1.7%) developed a regional neck recurrence, and two patients (3.3%) developed distant metastases. Measured two-year local recurrence free survival was 97.9% (95% CI 86.1-99.7%). Overall survival was 100% at the time of analysis. The mean radiation dose to the primary site was 36.9 Gy [Standard Deviation (SD) 10.3 Gy]. Two patients (3.3%) experienced late soft tissue necrosis in the primary site surgical bed that resolved within 2 months. Feeding tube dependence rates were 0% during RT, 3.3% temporarily during follow-up, and 0% at last follow-up. Conclusions De-intensified post-operative RT that avoids the resected primary tumor site and targets only the at-risk neck following TORS for selected patients with HPV-associated OPSCC may be safe and is worthy of further study.