A probabilistic model of bilateral lymphatic spread in head and neck cancer

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Bibliographic Details
Title: A probabilistic model of bilateral lymphatic spread in head and neck cancer
Authors: Ludwig, Roman, Pérez Haas, Yoel, Benavente, Sergi, Balermpas, Panagiotis, Unkelbach, Jan
Contributors: Institut Català de la Salut, [Ludwig R, Pérez Haas Y, Unkelbach J] Physics, University of Zurich, Zurich, Switzerland. Radiation Oncology, University Hospital Zurich, Zurich, Switzerland. [Benavente S] Servei d’Oncologia Radioteràpica, Vall d’Hebron Hospital Universitari, Barcelona, Spain. [Balermpas P] Radiation Oncology, University Hospital Zurich, Zurich, Switzerland, Vall d'Hebron Barcelona Hospital Campus, University of Zurich, Ludwig, Roman
Source: Sci Rep
Scientia
Scientia. Dipòsit d'Informació Digital del Departament de Salut
instname
Scientific Reports, Vol 15, Iss 1, Pp 1-21 (2025)
Publication Status: Preprint
Publisher Information: Springer Science and Business Media LLC, 2025.
Publication Year: 2025
Subject Terms: 1000 Multidisciplinary, TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::técnicas de investigación::métodos epidemiológicos::estadística como asunto::modelos estadísticos, Otros calificadores::Otros calificadores::Otros calificadores::/radioterapia, ENFERMEDADES::neoplasias::procesos neoplásicos::metástasis neoplásica::metástasis linfática, Science, Metàstasi limfàtica, FOS: Physical sciences, 610 Medicine & health, 10192 Physics Institute, Estadística, Coll - Càncer - Radioteràpia, 10044 Clinic for Radiation Oncology, Physics - Medical Physics, ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Models, Statistical, Article, DISEASES::Neoplasms::Neoplasms by Site::Head and Neck Neoplasms, Cap - Càncer - Radioteràpia, DISEASES::Neoplasms::Neoplastic Processes::Neoplasm Metastasis::Lymphatic Metastasis, ENFERMEDADES::neoplasias::neoplasias por localización::neoplasias de cabeza y cuello, Medicine, Medical Physics (physics.med-ph), Other subheadings::Other subheadings::Other subheadings::/radiotherapy
Description: Current guidelines for elective nodal irradiation in oropharyngeal squamous cell carcinoma (OPSCC) recommend including large portions of the contralateral lymphatic system in the clinical target volume (CTV-N), even for lateralized tumors with no clinical lymph node involvement in the contralateral neck. This study introduces a probabilistic model of bilateral lymphatic tumor progression in OPSCC to estimate personalized risks of occult disease in specific lymph node levels (LNLs) based on clinical lymph node involvement, T-stage, and tumor lateralization. Building on a previously developed hidden Markov model for ipsilateral lymphatic spread, we extend the approach to contralateral neck involvement. The model represents LNLs I, II, III, IV, V, and VII on both sides of the neck as binary hidden variables (healthy or involved), connected via arcs representing spread probabilities. These probabilities are learned using Markov chain Monte Carlo (MCMC) sampling from a dataset of 833 OPSCC patients, enabling the model to reflect the underlying lymphatic progression dynamics. The model accurately and precisely describes observed patterns of lymph node involvement with a compact set of interpretable parameters. Midline extension of the primary tumor is identified as the primary risk factor for contralateral involvement, with advanced T-stage and extensive ipsilateral involvement further increasing risk. Occult disease in contralateral LNL III is highly unlikely if upstream LNL II is clinically negative, and in contralateral LNL IV, occult disease is exceedingly rare without LNL III involvement. This model offers an interpretable, probabilistic framework to inform personalized elective CTV-N volume reduction. For lateralized tumors that do not cross the midline, it suggests the contralateral neck may safely be excluded from elective irradiation. For tumors extending across the midline but with a clinically negative contralateral neck, elective irradiation could be limited to LNL II, reducing unnecessary exposure of normal tissue while maintaining regional tumor control.
Document Type: Article
Other literature type
File Description: application/pdf; Ludwig_40415030.pdf - application/pdf
Language: English
ISSN: 2045-2322
DOI: 10.1038/s41598-025-99978-7
DOI: 10.5167/uzh-278888
DOI: 10.48550/arxiv.2501.16910
Access URL: http://arxiv.org/abs/2501.16910
http://hdl.handle.net/11351/13405
https://doaj.org/article/f6cab7b2ce094db9bd5b26dd0d5d8d0a
https://www.zora.uzh.ch/id/eprint/278888/
https://doi.org/10.5167/uzh-278888
Rights: CC BY
Accession Number: edsair.doi.dedup.....aa6a844a7933ba2fea09be6d0d714dea
Database: OpenAIRE
Description
Abstract:Current guidelines for elective nodal irradiation in oropharyngeal squamous cell carcinoma (OPSCC) recommend including large portions of the contralateral lymphatic system in the clinical target volume (CTV-N), even for lateralized tumors with no clinical lymph node involvement in the contralateral neck. This study introduces a probabilistic model of bilateral lymphatic tumor progression in OPSCC to estimate personalized risks of occult disease in specific lymph node levels (LNLs) based on clinical lymph node involvement, T-stage, and tumor lateralization. Building on a previously developed hidden Markov model for ipsilateral lymphatic spread, we extend the approach to contralateral neck involvement. The model represents LNLs I, II, III, IV, V, and VII on both sides of the neck as binary hidden variables (healthy or involved), connected via arcs representing spread probabilities. These probabilities are learned using Markov chain Monte Carlo (MCMC) sampling from a dataset of 833 OPSCC patients, enabling the model to reflect the underlying lymphatic progression dynamics. The model accurately and precisely describes observed patterns of lymph node involvement with a compact set of interpretable parameters. Midline extension of the primary tumor is identified as the primary risk factor for contralateral involvement, with advanced T-stage and extensive ipsilateral involvement further increasing risk. Occult disease in contralateral LNL III is highly unlikely if upstream LNL II is clinically negative, and in contralateral LNL IV, occult disease is exceedingly rare without LNL III involvement. This model offers an interpretable, probabilistic framework to inform personalized elective CTV-N volume reduction. For lateralized tumors that do not cross the midline, it suggests the contralateral neck may safely be excluded from elective irradiation. For tumors extending across the midline but with a clinically negative contralateral neck, elective irradiation could be limited to LNL II, reducing unnecessary exposure of normal tissue while maintaining regional tumor control.
ISSN:20452322
DOI:10.1038/s41598-025-99978-7