Prognostic value of pre-treatment nodal appearance, volume and kinetics in High-Risk non-HPV related oropharyngeal squamous cell carcinoma

PURPOSE: We investigated the risk and prognostic value of pre-treatment nodal progression to inform the safe de-escalation of elective nodal irradiation (ENI) in high-risk oropharyngeal squamous cell carcinoma (OPSCC). METHODS: We identified patients with p16-negative, clinical T4, node-positive OPSCC treated consecutively with definitive radiotherapy between 2008 and 2021 from a prospectively maintained database. Pre-treatment diagnostic scans were compared against simulation scans to evaluate nodal disease based on pre-specified criteria, growth kinetics, and imaging-detected extranodal extension (iENE). Association of nodal factors and oncologic outcomes were assessed using regression models. RESULTS: A total of 79 patients with a median 30-day interval between diagnostic and simulation scan were identified. Nodal growth was minimal with a median absolute change of + 0.5 cc and growth rate of 0.3%/day. Nodal kinetics and duration between imaging were not prognostic for treatment response. While no patients developed de novo pathological nodal disease, 14% of patients had indeterminant nodes on diagnostic scan, with 27% of these becoming pathological at time of simulation. Total nodal volume was highly correlated with presence of iENE, and was prognostic for locoregional failure (HR = 1.02, p = 0.03), distant failure (HR = 1.02, p = 0.02), and progression-free survival (HR = 1.02, p = 0.05). All regional failures were in-field of high dose treatment volumes. CONCLUSIONS: Pre-treatment nodal disease volume, but not growth kinetics, was a prognostic factor in locally advanced OPSCC. While lack of new nodal disease and minimal growth over a 30-day pre-treatment interval supports the investigation of novel timing of ENI, particular care should be taken in patients to identify and appropriately manage indeterminate nodes at risk for progression.