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Bayesian Monte Carlo Simulation Based on Systematic Review for Personalized Risk Stratification of Contralateral Lymph Node Metastasis in Oral Squamous Cell Carcinoma

  • Karthik N Rao
  • , M P Sreeram
  • , Prajwal Dange
  • , Andres Coca Pelaz
  • , Cesare Piazza
  • , Remco de Bree
  • , Fernando Lopez
  • , Orlando Guntinas-Lichius
  • , Luiz Paulo Kowalski
  • , Kevin T Robbins
  • , Primož Strojan
  • , Carlos Suárez
  • , Akihiro Homma
  • , Robert Takes
  • , Juan Pablo Rodrigo
  • , Marc Hamoir
  • , Avraham Eisbruch
  • , Francisco Civantos
  • , Anna Luíza Damaceno Araújo
  • , Alessandra Rinaldo
  • Małgorzata Wierzbicka, Alfio Ferlito

Research output: Contribution to journalReview articlepeer-review

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Abstract

Background: Contralateral lymph node metastasis (CLNM) in oral squamous cell carcinoma (OSCC) represents a major clinical challenge, in patients with a clinically contralateral node-negative neck. Individualized risk stratification is crucial to guide decisions on elective contralateral neck dissection. This study aimed to synthesize existing evidence and apply Bayesian Monte Carlo Simulation (MCS) to estimate CLNM probability across various clinic-pathological scenarios. Methods: A systematic search of PubMed, PubMed Central, and Embase (2000-2024) identified 26 eligible studies. Effect sizes for seven key risk factors-midline-crossing tumours, extranodal extension (ENE), ≥2 ipsilateral lymph nodes, depth of invasion (DOI) >10 mm, perineural invasion and lymphovascular invasion (PNI-LVI), poor differentiation, and floor of mouth subsite-were computed and incorporated into a Bayesian logistic model. Using the No-U-Turn Sampler (NUTS) in RStan, 100,000 virtual patient profiles were simulated to generate posterior probabilities of CLNM. Results: The baseline CLNM risk for lateralized tumours without additional risk factors was 4.2%. Single risk factors increased probability substantially: midline-crossing tumours (31.7%), ENE (27.4%), and ≥2 ipsilateral nodes (24.9%). Combinations of risk factors amplified the risk non-linearly: the presence of a midline-crossing tumour, ENE, and ≥2 ipsilateral nodes yielded a 76.8% CLNM probability, and the presence of all seven risk factors increased it to 93.7%. Risk tiers were classified from minimal (<20%) to very high (>50%) to guide clinical decision-making. Conclusions: This MCS-based model reveals that CLNM risk increases multiplicatively with the presence of various high-risk features. The simulation supports bilateral neck management in high-risk patients and observation in low-risk cases. Prospective validation is needed to integrate this model into routine clinical practice and to guide patient-specific surgical planning.

Original languageEnglish
Pages (from-to)1-25
Number of pages25
JournalDiagnostics
Volume15
Issue number21
DOIs
Publication statusPublished - 1 Nov 2025

Keywords

  • Bayesian modelling
  • Monte Carlo simulation
  • contralateral lymph node metastasis
  • oral squamous cell carcinoma
  • risk stratification

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