Development and validation of a novel TNM staging N-classification of oral cavity squamous cell carcinoma Journal Article


Authors: de Almeida, J. R.; Su, J. S.; Kolarski, M. M.; Truong, T.; Weinreb, I.; Perez-Ordonez, B.; Smith, S. M.; Hosni, A.; Patel, S.; Valero, C.; Xu, B.; Ghossein, R.; Katabi, N.; Clark, J.; Low, T. H.; Gupta, R.; Graboyes, E. M.; Davies, J.; Richardson, M.; Pasham, V.; Jester, R.; Goldstein, D. P.; Huang, S. H.; Xu, W.; O’Sullivan, B.
Article Title: Development and validation of a novel TNM staging N-classification of oral cavity squamous cell carcinoma
Abstract: Background: For oral cavity squamous cell carcinoma (OSCC), extent of extranodal extension (ENE) (minor, ≤2 mm; major, >2 mm) is differentially prognostic, whereas limitations exist with the 8th edition of American Joint Committee on Cancer/International Union Against Cancer TNM N-classification (TNM-8-N). Methods: Resected OSCC patients at four centers were included and extent of ENE was recorded. Thresholds for optimal overall survival (OS) discrimination of lymph node (LN) features were established. After dividing into training and validation sets, two new N-classifications were created using 1) recursive partitioning analysis (RPA), and 2) adjusted hazard ratios (aHRs) and were ranked against TNM-8-N and two published proposals. Results: A total of 1460 patients were included (pN0: 696; pN+: 764). Of the pN+ cases, 135 (18%) had bilateral/contralateral LNs; 126 (17%) and 244 (32%) had minor and major ENE, and two (0.3%) had LN(s) >6 cm without ENE (N3a). LN number (1 and >1 vs. 0: aHRs, 1.92 [95% confidence interval (CI), 1.44–2.55] and 3.21 [95% CI, 2.44–4.22]), size (>3 vs. ≤3 cm: aHR, 1.88 [95% CI, 1.44–2.45]), and ENE extent (major vs. minor: aHR, 1.40 [95% CI, 1.05–1.87]) were associated with OS, whereas presence of contralateral LNs was not (aHR, 1.05 [95% CI, 0.81–1.36]). The aHR proposal provided optimal performance with these changes to TNM-8-N: 1) stratification of ENE extent, 2) elimination of N2c and 6-cm threshold, and 3) stratification of N2b by 3 cm threshold. Conclusion: A new N-classification improved staging performance compared to TNM-8-N, by stratifying by ENE extent, eliminating the old N2c category and the 6 cm threshold, and by stratifying multiple nodes by size. © 2023 American Cancer Society.
Keywords: adolescent; adult; controlled study; human tissue; aged; retrospective studies; major clinical study; overall survival; histopathology; squamous cell carcinoma; carcinoma, squamous cell; cancer staging; lymph node metastasis; staging; lymph nodes; neoplasm staging; tumor volume; cohort analysis; pathology; validation study; retrospective study; head and neck neoplasms; lymph node; hazard ratio; cancer classification; adjuvant radiotherapy; mouth neoplasms; head and neck tumor; chemoradiotherapy; oral cancer; head and neck squamous cell carcinoma; mouth squamous cell carcinoma; mouth tumor; cancer prognosis; extranodal extension; humans; prognosis; human; male; female; article; squamous cell carcinoma of head and neck; n classification; extent of extranodal extension; number of nodes
Journal Title: Cancer
Volume: 130
Issue: 3
ISSN: 0008-543X
Publisher: Wiley Blackwell  
Date Published: 2024-02-01
Start Page: 410
End Page: 420
Language: English
DOI: 10.1002/cncr.35020
PUBMED: 37751180
PROVIDER: scopus
DOI/URL:
Notes: The MSK Cancer Center Support Grant (P30 CA008748) is acknowledged in the PDF -- Source: Scopus
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MSK Authors
  1. Ronald A Ghossein
    483 Ghossein
  2. Snehal G Patel
    412 Patel
  3. Nora Katabi
    304 Katabi
  4. Bin   Xu
    227 Xu