Rapid Recurrence in Head and Neck Cancer: an Underappreciated Problem with Poor Outcome

Abstract

Rapid recurrence, defined as tumor recurrence after primary surgery and prior to initiating postoperative radiation therapy (PORT), is an underappreciated problem in head and neck cancer (HNC). The purpose of our study is to determine risk factors and treatment outcomes of rapid recurrence. CT simulation images of HNC patients treated with primary surgery and PORT between 2009 and 2017 were retrospectively reviewed by a neuroradiologist blinded to patient outcome but provided with pre-operative imaging and surgical pathology report. The primary site, ipsilateral neck, and contralateral neck at the time of simulation were separately evaluated and those images interpreted as either suspected or definite recurrence were categorized as rapid recurrence. Multivariable analysis (MVA) was conducted to identify risk factors for rapid recurrence as well as predictors of local, regional, and distant recurrence and overall survival (OS). Patients appreciated to have rapid recurrence at the time of CT simulation by the treating radiation oncologist were treated with dose escalated radiation. A total of 195 HNC patients were included; oral cavity and squamous cell carcinoma were the most common subsite (58%) and histology (85%), respectively. Patients were primarily white (87%) and male (61%), with median age of 63 (range 25-90). 62% of patients were AJCC 7th edition pathologic stage IV, 23% had extranodal extension (ENE), 24% had lymphovascular invasion, 45% had perineural invasion (PNI), and the mean pathologic tumor size was 2.8 cm. Rapid recurrence occurred in 40 patients (21%) with a median time from operation to CT simulation of 37 (range 12 – 91) days. On MVA, ENE was the only predictor of rapid recurrence (p= .02). Positive surgical margin occurred in 20 patients (10%) but was not associated with rapid recurrence (p= 1.0). On univariate analysis, rapid recurrence at either the primary site or ipsilateral neck was associated with local, regional, distant recurrence and OS while recurrence in contralateral neck was associated with regional recurrence and OS. Rapid recurrence was associated with local, regional, and distant recurrence on MVA (p < .001 for all). Local recurrence was associated with tumor size (p = .05) while regional recurrence was associated with tumor size, ENE and PNI (p <0.05 for all). 2 year OS in patients retrospectively appreciated to have rapid recurrence treated with 60 Gy (n= 23) and >60 Gy (n= 17) were 25% and 60%, respectively (p= .12). While rapid recurrence, ENE, PNI and tumor size were all associated with poor overall survival on MVA, rapid recurrence was the strongest predictor (HR 5.3, 95% CI 2.9- 9.7) followed by ENE (HR 2.6, 95% CI 1.3-5.3). Rapid recurrence at time of CT simulation occurs at an underappreciated rate and is associated with poor survival outcomes. Patients with ENE are at highest risk and may benefit from diagnostic imaging evaluations immediately prior to PORT. Dose escalated salvage therapy may be beneficial.