Shortened Course Adjuvant Radiotherapy Following TORS

This is a single-arm Phase II non-inferiority study of adjuvant radiation for locally-advanced HPV-Associated oropharyngeal squamous cell carcinoma. Patients with pT0-T3, N0-N1, M0 disease (per AJCC 8th Edition), detectable pre-operative and undetectable postoperative ctHPVDNA will be eligible. Patients will have undergone TORS primary site resection and neck dissection. Patients will undergo adjuvant RT +/- guideline-indicated chemotherapy. The neck and the primary site will be considered separately.

The primary objective of the study will be to determine the 2-year locoregional control (LRC) rate. Secondary objectives include measures of toxicity (as measured by CTCAE, version 5.0), patient-reported QOL (as measured by the MDASI and MDADI questionnaire), progression-free survival, metastasis-free survival, and overall survival. Differences between patients treated with IMRT and proton therapy in terms of toxicity and QOL will serve as another secondary objective.

Inclusion criteria

• Patients ≥ 18 years old
• Histologically confirmed diagnosis of squamous cell carcinoma of the oropharynx, p16-positive on immunohistochemistry or HPV-positive by In-Situ Hybridization
• Pathologic T0 (unknown primary), T1, T2, or T3 disease (per AJCC 8th Ed)
• Pathologic N0-N1 disease (per AJCC 8th Ed)
• Preoperative plasma ctHPVDNA of ≥ 50 copies/mL
• Undetectable postoperative plasma ctHPVDNA
• ECOG Performance Status 0-1

Exclusion criteria

• Prior external beam radiation therapy to the head and neck
• Presence of T4 disease
• ≥ 5 positive lymph nodes (which is pathologic N2 disease, per AJCC 8th edition)
• Presence of distant metastatic disease
• Uncontrolled inter-current illness including, but not limited to, symptomatic congestive heart failure, unstable angina pectoris, connective tissue disease or psychiatric illness/social situations that would limit compliance with study requirements.