The impact of nodal status in major salivary gland carcinoma: A multicenter experience and proposal of a novel N-classification

Davide Lombardi; Michele Tomasoni; Alberto Paderno; Davide Mattavelli; Marco Ferrari; Simonetta Battocchio; Francesco Missale; Francesco Mazzola; Giorgio Peretti; Davide Mocellin; Daniele Borsetto; Jonathan M Fussey; Paul Nankivell; Nikoleta Skalidi; Mario Bussi; Leone Giordano; Andrea Galli; Gianluigi Arrigoni; Elena Raffetti; Paul Pracy; Vincent Vander Poorten; Piero Nicolai

doi:10.1016/j.oraloncology.2020.105076

The impact of nodal status in major salivary gland carcinoma: A multicenter experience and proposal of a novel N-classification

Oral Oncol. 2021 Jan:112:105076. doi: 10.1016/j.oraloncology.2020.105076. Epub 2020 Oct 30.

Authors

Davide Lombardi¹, Michele Tomasoni², Alberto Paderno², Davide Mattavelli², Marco Ferrari³, Simonetta Battocchio⁴, Francesco Missale⁵, Francesco Mazzola⁶, Giorgio Peretti⁷, Davide Mocellin⁶, Daniele Borsetto⁸, Jonathan M Fussey⁸, Paul Nankivell⁸, Nikoleta Skalidi⁸, Mario Bussi⁹, Leone Giordano⁹, Andrea Galli⁹, Gianluigi Arrigoni¹⁰, Elena Raffetti¹¹, Paul Pracy⁸, Vincent Vander Poorten¹², Piero Nicolai¹³

Affiliations

¹ Department of Otorhinolaryngology - Head and Neck Surgery, University of Brescia, Italy. Electronic address: davinter@libero.it.
² Department of Otorhinolaryngology - Head and Neck Surgery, University of Brescia, Italy.
³ Department of Otorhinolaryngology - Head and Neck Surgery, University of Brescia, Italy; Section of Otorhinolaryngology - Head and Neck Surgery, Department of Neurosciences, University of Padua, Padua, Italy.
⁴ Unit of Pathology, University of Brescia, Italy.
⁵ Unit of Otorhinolaryngology - Head and Neck Surgery, IRCCS Ospedale Policlinico San Martino, Genoa, Italy; Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy.
⁶ Unit of Otorhinolaryngology - Head and Neck Surgery, IRCCS Ospedale Policlinico San Martino, Genoa, Italy.
⁷ Unit of Otorhinolaryngology - Head and Neck Surgery, IRCCS Ospedale Policlinico San Martino, Genoa, Italy; Department of Surgical Sciences and Integrated Diagnostics (DISC), University of Genoa, Genoa, Italy.
⁸ Department of ENT/Head and Neck Surgery, Queen Elizabeth University Hospital Birmingham, Birmingham, United Kingdom.
⁹ Department of Otorhinolaryngology, IRCCS San Raffaele Scientific Institute, Milan, Italy.
¹⁰ Unit of Pathology, IRCCS San Raffaele Scientific Institute, Milan, Italy.
¹¹ Epidemiology and Public Health Intervention Research Group (EPHIR), Department of Global Public Health, Karolinska Institutet, Stockholm, Sweden.
¹² Otorhinolaryngology - Head and Neck Surgery and Department of Oncology, Section Head and Neck Oncology, University Hospitals Leuven, KU Leuven, Leuven, Belgium.
¹³ Section of Otorhinolaryngology - Head and Neck Surgery, Department of Neurosciences, University of Padua, Padua, Italy.

PMID: 33137587
DOI: 10.1016/j.oraloncology.2020.105076

Abstract

Objectives: Despite differences in oncological behavior, the 8th edition of AJCC TNM staging currently proposes the same N-classification for major salivary glands (MSG) carcinoma and squamous cell carcinoma of the upper aerodigestive tract. The present study aims to investigate a more reliable definition of N-categories for MSG carcinoma.

Materials and methods: A retrospective multicenter study was performed, including 307 patients treated for primary MSG carcinoma from 1995 to 2019. Outcome measures included overall survival (OS), disease specific survival, and local, regional, and distant recurrence. Survival analysis was performed using log-rank test and Cox proportional-hazards model. Overall number (ON) and largest diameter (LD) of nodal metastases, including intra-parotid metastases, were considered to develop three novel proposals of N-classification; their performance were compared with the current TNM staging using Akaike information criterion (AIC), Bayesian information criterion (BIC), and Nagelkerke pseudo-R².

Results: Intra-parotid nodes, ON and LD of nodal metastases emerged as major prognosticators for OS, while extra-nodal extension did not impact on any survival. The current N-classification did not show a satisfactory OS stratification. Three novel N-classifications were developed according to number of metastatic nodes (0 vs 1-3 vs ≥ 4) and/or their maximum diameter (<20 mm vs ≥ 20 mm). They all showed better accuracy in OS stratification, and achieved better AIC, BIC and Nagelkerke pseudo-R² indices when compared to current N-classification.

Conclusion: All the proposed N-classifications improved OS stratification and could help in defining a specific N-classification for MSG carcinoma. Their validation and assessment in an external cohort is needed.

Keywords: Extra-nodal extension; Head and neck cancer; Major salivary gland cancer; Nodal metastasis; Parotid gland; Parotid lymph-nodes; Positive lymph-node diameter; Positive lymph-node number; Submandibular gland; Tumor staging.

Publication types

Multicenter Study
Research Support, Non-U.S. Gov't

MeSH terms

Adolescent
Adult
Aged
Aged, 80 and over
Bayes Theorem
Carcinoma, Squamous Cell / classification
Carcinoma, Squamous Cell / mortality
Carcinoma, Squamous Cell / pathology*
Child
Female
Humans
Lymph Nodes / pathology*
Lymphatic Metastasis / pathology
Male
Middle Aged
Neoplasm Grading
Neoplasm Staging*
Outcome Assessment, Health Care
Parotid Neoplasms / secondary*
Proportional Hazards Models
Retrospective Studies
Salivary Gland Neoplasms / classification
Salivary Gland Neoplasms / mortality
Salivary Gland Neoplasms / pathology*
Young Adult