Risk Stratification by Extent of Extranodal Extension and Peri-Neural Invasion in Post-Operative Oral Cavity Squamous Cell Carcinoma Undergoing Adjuvant Radio Therapy (EXTENT Study).

Nanda, Sambit Swarup; Mukherji, Ashutosh; Dokania, Shubham; Choubey, Ajay; Mondal, Pritam; Pal, Ankita; Kapoor, Akhil; Mishra, Aseem et al. · Head Neck · 2026

retrospective_cohort · Level III

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Abstract

The AJCC 8th edition recommends subclassifying extranodal extension (ENE) and perineural invasion (PNI) in oral cavity squamous cell carcinoma (OCSCC), though their prognostic relevance remains uncertain. Post-operative OCSCC patients (2019-2024) receiving adjuvant radiotherapy or chemoradiotherapy with documented ENE and/or PNI were retrospectively analyzed. ENE (microscopic [miENE] vs. macroscopic [maENE]) and PNI (intratumoral [IPNI] vs. extratumoral [EPNI]) were correlated with disease-free survival (DFS), overall survival (OS), and failure patterns using multivariate Cox models. Among 410 patients (median follow-up: 33 months), 3-year DFS and OS were 45.6% and 53.2%. ENE subtyping did not impact DFS or OS. EPNI independently predicted inferior DFS (43.3% vs. 49.5%, p = 0.019) and OS (50.2% vs. 57.9%, p = 0.02). Combined EPNI, ENE, and lymph-node ratio > 0.05 identified a very high-risk subgroup. ENE subclassification lacked prognostic significance. EPNI predicted worse outcomes and, with ENE or high lymph node ratio, defines an aggressive phenotype warranting treatment intensification.