Development and validation of a novel TNM staging N‐classification of oral cavity squamous cell carcinoma

Author:

de Almeida John R.12ORCID,Su Jie Susie3,Kolarski Mirko Manojlovic14,Truong Tra5,Weinreb Ilan5,Perez‐Ordonez Bayardo5,Smith Stephen M.5,Hosni Ali6,Patel Snehal7ORCID,Valero Cristina7ORCID,Xu Bin8ORCID,Ghossein Ronald8,Katabi Nora8,Clark Jonathan910,Low Tsu‐Hui (Hubert)910,Gupta Ruta1011,Graboyes Evan M.12ORCID,Davies Joel1213,Richardson Mary14,Pasham Vishu14,Jester Rachel14,Goldstein David P.1,Huang Shao Hui16,Xu Wei3,O’Sullivan Brian1615

Affiliation:

1. Department of Otolaryngology‐Head and Neck Surgery Princess Margaret Cancer Centre/University Health Network University of Toronto Toronto Ontario Canada

2. Institute of Health Policy, Management, and Evaluation University of Toronto Toronto Ontario Canada

3. Department of Biostatistics Princess Margaret Cancer Centre Toronto Ontario Canada

4. Department of Otolaryngology‐Head and Neck Surgery Health Sciences North Sudbury Ontario Canada

5. Department of Pathology University Health Network Toronto Ontario Canada

6. Department of Radiation Oncology Princess Margaret Cancer Center Toronto Ontario Canada

7. Head and Neck Service Department of Surgery Memorial Sloan Kettering Cancer Center New York New York USA

8. Department of Pathology and Laboratory Medicine Memorial Sloan Kettering Cancer Center New York New York USA

9. Department of Head and Neck Surgery Chris O’Brien Lifehouse Sydney New South Wales Australia

10. Sydney Medical School Faculty of Medicine and Health Sciences the University of Sydney Sydney New South Wales Australia

11. Department of Tissue Pathology and Diagnostic Oncology Royal Prince Alfred Hospital NSW Health Pathology Sydney New South Wales Australia

12. Department of Otolaryngology‐Head and Neck Surgery Medical University of South Carolina Charleston South Carolina USA

13. Department of Otolaryngology‐Head and Neck Surgery Sinai Health Systems Toronto Ontario Canada

14. Department of Pathology Medical University of South Carolina Charleston South Carolina USA

15. Department of Radiation Oncology Centre Hospitalier de L’University de Montreal Montreal Quebec Canada

Abstract

AbstractBackgroundFor 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).MethodsResected 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.ResultsA 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.ConclusionA 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.

Publisher

Wiley

Subject

Cancer Research,Oncology

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