De-Escalation In Hpv Era: Definitive Unilateral Neck Radiation For T3 Or N2b/N3 P16+Tonsil Squamous Cell Carcinoma Using Prospectively Defined Criteria

American College of Radiology recommends unilateral neck radiation (RT) for small lateralized tonsillar cancer with low-volume nodal disease. Safety of unilateral RT for larger primaries or advanced nodal disease remains to be explored but provides an important opportunity for treatment de-escalation. We report oncologic and functional outcomes of patients with advanced-stage p16+ oropharyngeal cancer treated with unilateral RT using prospectively defined criteria. Patients (pts) with T3 or N2b/N3 (per AJCC 7th, N1/N3 per AJCC 8th) lateralized oropharyngeal tumors >1cm from midline and functional imaging confirmation of unilateral nodal disease were reviewed. An initial cohort was treated on a prospective trial; subsequent pts who met criteria were treated accordingly. Post-RT flexible endoscopic evaluation of swallowing function (FEES) was performed and swallowing outcome measured with Yale Pharyngeal Residue Severity and Penetration Aspiration Scale (PAS) ratings. Patient reported functional outcome was assessed with Functional Oral Intake Scale (FOIS). Thirty-five pts (6 T3, 33 N2b, 1 N3) received definitive unilateral RT with concurrent chemotherapy. Four pts received 60 Gy on a prospective de-escalation protocol; all others received 70 Gy. Mean doses to organs at risk were superior constrictor 52 Gy, middle constrictor 37 Gy, inferior constrictor 23 Gy, larynx 30 Gy, proximal esophagus 26 Gy, contralateral submandibular gland 18 Gy and parotid gland 11 Gy. At median follow-up of 27 months, 2-yr actuarial estimates were disease free survival 92%, local control 100%, ipsilateral neck control 94%, distant metastasis-free survival 92%, and overall survival 97%. No contralateral neck failures were observed. No failures were noted in pts treated with dose de-escalation. Median weight loss after RT was 8.1% (range, -1.3%—20.3%). One patient required temporary PEG placement due to severe weight loss. Of 15 pts who underwent FEES, exam revealed impaired volitional clearing (79% pts) up to 26 months from RT and airway penetration (14% pts) up to 22 months. No patient treated with dose de-escalation scored PAS >3 during follow up. Of 12 pts with baseline FOIS, 92% reported at least 1-point decrease in score at median of 1 month after RT. FOIS scores improved or stabilized over time. In one of the largest series of p16+ advanced-stage oropharyngeal cancer, definitive unilateral neck RT using prospectively defined criteria resulted in excellent oncologic outcomes. Objective and patient reported measures revealed mild to moderate acute swallowing dysfunction in majority of pts and low rates of severe chronic swallowing dysfunction despite meeting dose constraints for optimal swallowing function. Further treatment de-escalation with dose reduction remains important to improve function preservation using the unilateral RT approach.