Adjuvant chemoradiotherapy for oral cavity SCC with minor and major extranodal extension Journal Article


Authors: Manojlovic-Kolarski, M.; Su, S.; Weinreb, I.; Calvisi, R.; Perez-Ordonez, B.; Smith, S.; Patel, S.; Valero, C.; Xu, B.; Ghossein, R.; Katabi, N.; Clark, J.; Low, T. H. H.; Gupta, R.; Graboyes, E.; Davies, J.; Richardson, M.; Goldstein, D.; Huang, S. H.; O'Sullivan, B.; Xu, W.; Hansen, A.; de Almeida, J. R.
Article Title: Adjuvant chemoradiotherapy for oral cavity SCC with minor and major extranodal extension
Abstract: Importance: Extranodal extension (ENE) in oral cavity squamous cell carcinoma (OSCC) is a poor prognostic feature and an indication for adjuvant chemoradiotherapy. ENE is stratified into minor (≤2 mm) or major (>2 mm) extent. The role of adjuvant chemoradiotherapy, particularly for the minor ENE subgroup, is unclear. Objective: To determine the impact of adjuvant chemoradiotherapy on oncological outcomes depending on the extent of ENE. Design, Setting, and Participants: This retrospective, multicenter cohort study was conducted across 4 high-volume head and neck surgery centers in Australia, the US, and Canada. The study included patients with surgically resected OSCC with pathologic positive nodal disease treated between 2005 and 2018. Statistical analysis took place between 2022 and 2025; final follow-up was in 2022. Exposures: Extent of ENE was restaged on archived tissue. Adjuvant radiotherapy or chemoradiotherapy was recommended per standard guidelines. Outcomes: Univariable and multivariable analysis were used to assess the effect of chemotherapy for the entire group and for propensity score-matched cohorts on locoregional control (LRC), disease-free survival (DFS), and overall survival (OS) stratified by minor vs major ENE. Results: A total of 755 patients (mean [SD] age, 61.7 [12.9] years; 36% female) were included in the study: 126 (17%) with minor ENE and 243 (32%) with major ENE. A total of 50 (39.7%) patients with minor ENE and 116 (47.8%) with major ENE received adjuvant chemotherapy. On multivariable analysis, chemotherapy was not associated with improved LRC (hazard ratio [HR], 1.07 [95% CI, 0.49-2.32]), DFS (HR, 0.96 [95% CI, 0.56-1.66]), or OS (HR, 0.97 [95% CI, 0.55-1.73]) in patients with minor ENE. However, in patients with major ENE, chemotherapy improved DFS (HR, 0.58 [95% CI, 0.41-0.81]) and OS (HR, 0.61 [95% CI, 0.38-0.98]). In propensity score-matched cohorts, chemotherapy did not improve LRC (71% vs 75%; difference, 4% [95% CI, -18% to 26%]), DFS (56% vs 56%; difference, 0% [95% CI, -25% to 25%]), or OS (57% vs 57%; difference, 0% [95% CI, -25% to 25%]) for patients with minor ENE, but improved DFS (33% vs 11%; difference, 22% [95% CI, 5%-38%]) and OS (41% vs 15%; difference, 26% [95% CI, 8%-44%]) but not LRC (61% vs 62%; difference, 1% [95% CI, -17% to 21%]) in patients with major ENE. Conclusions: This multicenter cohort study found that in patients with OSCC, adjuvant chemotherapy is beneficial in patients with major ENE, but may not be beneficial in patients with minor ENE. © 2025 American Medical Association. All rights reserved.
Journal Title: JAMA Otolaryngology - Head and Neck Surgery
Volume: 151
Issue: 8
ISSN: 2168-6181
Publisher: American Medical Association  
Publication status: Published
Date Published: 2025-08-01
Online Publication Date: 2025-06-18
Start Page: 785
End Page: 794
Language: English
DOI: 10.1001/jamaoto.2025.1721
PROVIDER: scopus
PMCID: PMC12177724
PUBMED: 40531540
DOI/URL:
Notes: Article -- MSK Cancer Center Support Grant (P30 CA008748) acknowledged in PDF -- Source: Scopus
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MSK Authors
  1. Ronald A Ghossein
    491 Ghossein
  2. Snehal G Patel
    417 Patel
  3. Nora Katabi
    309 Katabi
  4. Bin   Xu
    235 Xu