Imaging Extranodal Extension (iENE) Predicts Higher Rates of Distant Recurrence for Human Papillomavirus-Positive Oropharyngeal Cancer.

Abstract

Pathologic extranodal extension is a known predictor of poor outcomes in head and neck cancer. However, data on imaging-identified extranodal extension (iENE) in oropharyngeal cancer (OPC) outcomes are limited. This study aimed to evaluate the prognostic value of iENE for human papillomavirus-positive (HPV+) OPC patients. This retrospective study included patients treated at a tertiary referral hospital. All eligible TNM eighth edition stage I to III HPV+ OPC patients treated with curative intent, including definitive or postoperative radiation therapy from 2009 to 2020, were included. The presence of iENE on pretreatment computed tomography or magnetic resonance imaging was assessed by 2 neuroradiologists masked to clinical characteristics. iENE grade (0, 1, 2, or 3) was based on standard definitions used in previous studies. Clinical outcomes were compared based on the presence of iENE and grade. χ² and t tests were used for the univariate analysis of categorical and continuous variables. The Cox-proportional hazards model was used to assess time-to-event outcomes while controlling for N category, smoking history, chemotherapy type, and surgery use. Of 421 patients, 134 were iENE-negative (iENE-) and 287 iENE-positive (iENE+), with 271 patients having grade 2 or 3 iENE. iENE+ patients were more likely to receive chemotherapy (96% vs 79%, respectively; p≤ .001) and less likely to have had surgery (7% vs 13%, respectively; p = .03). The iENE+ cohort had a higher number of positive lymph nodes (1.9 vs 4.8 nodes, p≤ .001) and a higher proportion of patients with low neck nodes (16% vs 1%, p≤ .001). At 3 years, the presence of iENE was associated with decreased progression-free survival (PFS) (85% vs 94%; hazard ratio (HR), 2.01; p = .007) and increased distant metastases (16% vs 7%; HR, 2.36; p = .031). Looking at individual grades, grade 3 iENE was associated with an increased risk of death or recurrence, ie, decreased PFS (HR, 3.56; p≤ .001) and increased distant recurrence (HR, 3.37; p = .007), and grade 2 iENE was associated with distant recurrence only (HR, 2.27; p = .041). Locoregional control was similar between the iENE+ and iENE- groups (HR, 1.35; p = .5). HPV+ OPC patients with ENE evident on imaging, likely driven by grade 3 iENE, have an increased risk of distant metastases and decreased PFS. Incorporating iENE into HPV+ OPC staging may help improve prognostication and refine the clinical trial design.