Evaluating the impact of the degree of extranodal extension on outcomes in locally advanced oral cavity cancer.
Authors: Yalamanchali Anirudh , Griffith Christopher , Reddy Chandana A. , Koyfman Shlomo A. , Woody Neil McIver , Campbell Shauna , Silver Natalie L. , Scharpf Joseph , Lorenz Robert R , Prendes Brandon , Ku Jamie , Lamarre Eric , Geiger Jessica Lyn 
Published: June 2022

e18058

Background: The presence of extranodal extension (ENE) in oral cavity cancer is associated with a higher risk of distant metastasis and worse overall survival (OS). Trials show that patients with locally advanced head and neck cancer and ENE benefit from concurrent chemoradiation over radiation therapy alone.We explored whether degree of ENE impacts survival outcomes in individuals with oral cavity cancer. Methods: From an IRB-approved database of 303 pts with locally advanced oral cavity cancer treated with surgical resection between 2001-2020, patients with pathologic ENE who received adjuvant treatment were included. Patient demographics, tumor staging, treatment information, disease recurrence, and survival were collected. Surgical slides were reviewed to confirm the extent of ENE. All staging was updated to AJCC 8th edition. Cox proportional hazards regression was used to relate patient, tumor, or treatment characteristics with either disease-free survival (DFS, composite of disease recurrence and death) or OS, from the time of radiation therapy completion. ENE was analyzed as both a dichotomous variable (major if > 2 mm, minor if ≤2 mm) and as a continuous variable in the subset of patients for whom exact ENE extent could be confirmed. Results: A total of 113 patients were identified who underwent surgery and adjuvant therapy for advanced oral cavity cancer with ENE, with 35 having major ENE and 78 having minor ENE. Forty-one patients had T1-T2 disease while 72 had T3-T4 disease. Additionally, 24 had N2a disease and 89 had N3b disease. Of these, 78 received concurrent chemoradiation while 35 received radiation therapy alone. Ninety-nine patients had pathologic slides available for review to determine exact ENE extent. Median ENE distance was 1 mm (IQR 1-2, range 0.1-10). With a median follow up time of 22.3 months, there were 48 recurrences and 67 deaths. Median DFS was 21.3 months (95%CI 11.1-33.2) and median OS was 29.9 months (95%CI 20.6-66.6). Between major vs minor ENE, there was no statistically significant difference in DFS (HR 1.18, 95%CI 0.72-1.92, p = 0.51) or OS (HR 1.17, 95%CI 0.70-1.96, p = 0.55). Furthermore, there was no statistically significant association between ENE as a continuous variable and DFS (HR 0.97 per mm, 95%CI 0.87-1.4, p = 0.96) or OS (HR 0.96 per mm, 95%CI 0.83-1.11, p = 0.58). The benefit of concurrent chemotherapy on OS was not seen (HR 0.74, 95%CI 0.44-1.22, p = 0.24), though those patients on average had more advanced nodal disease (85% N3b vs 66%). Conclusions: No significant relationship was seen between extent of ENE and DFS or OS in individuals with locally advanced oral cavity cancer. This analysis was limited by the small number of patients, that most patients had ≤2 mm of ENE, and the presence of confounding risk factors such as nodal stage and receipt of chemotherapy. Overall, the effect of the degree of ENE on outcomes in advanced oral cavity cancer remains unclear.