Magnitude of benefit for adjuvant radiotherapy following minimally invasive surgery in intermediate to high risk HPV-positive oropharyngeal squamous cell carcinoma

Objective: To determine the outcomes and toxicities of minimally-invasive surgery with adjuvant intensity-modulated radiotherapy +/− chemotherapy (AT) compared to definitive surgical therapy (ST) in a contemporary cohort of HPV-positive oropharyngeal squamous cell carcinoma (OPSCC). Methods: From 2005 to 2013, a consecutive cohort of 190 HPV-positive OPSCC patients was retrospectively reviewed from multi-institutional databases maintained by the Departments of Otorhinolaryngology and Radiation Oncology. A total of 116 AT patients and 42 ST patients with intermediate or high risk pathologic features were included in the final analysis. All patients received minimally invasive surgery. Time to recurrence and time to death from the onset of surgery were evaluated. Toxicity data collected included dysphagia or xerostomia requiring feeding tube placement >6 months, or mandibular osteonecrosis requiring surgery or hyperbaric oxygen. Results: All AT patients received IMRT to a median dose of 60 Gy. Chemotherapy delivered to 67.2% of AT patients. AT group included more high-risk patients given higher nodal classification (p = 0.005) and extracapsular extension (p = 0.0005). AT improved disease-free survival (HR 2.77, CI 1.22–6.28; p = 0.02) and local-regional control (HR 14.83, CI 3.240–67.839; p = 0.001). Disease-free survival with AT and tumor extracapsular extension was improved when compared to ST (HR of 4.34, CI 1.540–12.213; p = 0.006). Dysphagia or mandibular osteonecrosis toxicity after AT vs. ST of 19.0% vs. 2.4%. Conclusions: AT improved local-regional control and disease-free survival but was associated with greater toxicity. The recurrence benefit was most pronounced in tumors with extracapsular extension.