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. 2025 Oct 13.
doi: 10.1002/hed.70064. Online ahead of print.

When Should Elective Neck Dissection Be Considered for Early-Stage Oral Cavity Tumors? Insights From a Multicenter Study of 1109 Patients and Development of a Multiparametric Predictive Model

Luca Calabrese  1 , Monir Abousiam  1 , Marta Tagliabue  2 , Marco Ferrari  3 , Rita De Berardinis  2 , Gerardo Petruzzi  4 , Francesco Mazzola  4 , Alberto Grammatica  5 , Davide Mattavelli  5 , Remo Accorona  6 , Alberto Vito Marcuzzo  7 , Pierre Guarino  8 , Francesco Mattioli  9 , Alessia Rubini  9 , Matteo Fermi  10 , Andrea Sacchetto  11 , Elisa Laura  12 , Riccardo Nocini  13 , Fabiola Incandela  14 , Pietro De Luca  15 , Andrea Iandelli  16 , Filippo Marchi  16 , Mario Turri Zanoni  17 , Leone Giordano  18 , Andrea Galli  18 , Simone Mauramati  19 , Virginia Corazzi  20 , Chiara Bianchini  20 , Mario Ciniglio Appiani  21 , Matteo Garotta  21 , Maria Silvia Lazio  22 , Domenico Michele Modica  23 , Salvatore Poma  23 , Martina Renna  24 , Annalisa Tosi  25 , Melania Franco  26 , Davide Di Santo  27 , Giulia Togo  28 , Paola Stritoni  29 , Cecilia Albi  1 , Ilaria Girolami  30 , Enrico Fazio  1 , Fabrizio Russo  31 , Daniele Spada  32 , Angela Gasparini  33 , Virginia Dallari  34 , Sara Bassani  13 , Bianca Maria Festa  35   36 , Dario Gregori  37 , Carlotta Borghini  37 , Gloria Brigiari  37 , Francesca Angioletti  37 , Alessandra Sordi  5 , Milena Fior  4 , Alessandra Ruaro  3 , Valero Arietti  13 , Giulia Gobbo  13 , Francesco Uderzo  7 , Rossana Bussani  38 , Maurizio Pinamonti  38 , Giuseppe Maruccio  10 , Guglielmo Ronzani  39 , Elisa Castelluccio  40 , Pasquale d'Alessio  41 , Daria Salsi  22 , Roberto Di Carlo  24 , Stefano Pelucchi  20 , Giuseppe Bertolini  32 , Massimo Ducci  26 , Alberto Dragonetti  6 , Mario Galfano  23 , Franco Ionna  28 , Doriano Politi  29 , Roberto Saetti  11 , Vincenzo Saita  31 , Antonio Sarno  21 , Giandomenico Maggiore  42 , Angelo Camaioni  43 , Luca De Campora  43 , Luca Sacchetto  13 , Paolo Castelnuovo  17 , Marco Radici  15 , Claudio Donadio Caporale  8 , Domenico Cuda  22 , Alberto Deganello  14 , Andy Bertolin  12 , Marco Benazzo  19 , Giorgio Peretti  16 , Mario Bussi  18 , Daniele Marchioni  9 , Livio Presutti  10 , Giancarlo Tirelli  7 , Mohssen Ansarin  2 , Cesare Piazza  5 , Piero Nicolai  3 , Raul Pellini  4 , Gabriele Molteni  10 , Luca Gazzini  1
Affiliations

When Should Elective Neck Dissection Be Considered for Early-Stage Oral Cavity Tumors? Insights From a Multicenter Study of 1109 Patients and Development of a Multiparametric Predictive Model

Luca Calabrese et al. Head Neck. .

Abstract

Background: Nodal metastases significantly affect prognosis in oral cavity squamous cell carcinoma (OCSCC). In early-stage OCSCC (cT1-T2 cN0), management of the clinically negative neck (cN0) remains controversial. Depth of invasion (DOI) is a key determinant for END, but other histopathological parameters, such as grading, perineural invasion (PNI), lymphovascular invasion (LVI), and worst pattern of invasion (WPOI), are emerging prognostic factors.

Methods: This multicenter retrospective study analyzed 1109 patients with cT1-T2 cN0 OCSCC treated at 30 Italian hospitals since 2017. Data on histopathological parameters, tumor characteristics, and patient outcomes were collected via the REDCap platform. Simple and multivariable logistic regression models were developed to assess predictors of occult nodal metastases.

Results: A total of 585 patients were clinically classified as cT1 tumors (53%), 503 as cT2 (45%), and cTis (1.9%). Of the 1109 patients, 193 (28%) had occult nodal metastases, with DOI, LVI, PNI, WPOI, and grading emerging as significant predictors. A predictive model integrating these variables demonstrated superior accuracy compared to a DOI-only model (AUROC comparison, p < 0.01).

Conclusion: This study highlights the importance of incorporating multiple histopathological parameters into risk models for occult nodal metastases, overcoming the fixed DOI as a cutoff. The proposed predictive model offers a more precise method for guiding END in early-stage OCSCC, allowing individualized risk estimation.

Keywords: clinically negative neck; neck dissection; occult metastasis; oral cavity.

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