{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T01:05:21Z","timestamp":1788829521130,"version":"build-2803163510"},"reference-count":25,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T00:00:00Z","timestamp":1785456000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T00:00:00Z","timestamp":1785456000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Laryngoscope"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Vocal fold motility guides staging of glottic squamous cell carcinoma (SCC) but is subjective and operator dependent. Because impaired mobility reflects tumor depth of invasion (DOI) into the vocal muscle and paraglottic space, objective DOI measurement may better capture aggressiveness and functional impairment. This two\u2010stage study assessed radiologic\u2013pathologic agreement of DOI, derived pathologic DOI (pDOI) thresholds for altered motility and deep muscle infiltration, and externally validated these thresholds, aiming to support a more reproducible staging surrogate.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Surgically treated glottic SCC from Ospedale Policlinico San Martino (Genoa, Italy) formed the derivation cohort; external validation was performed at the European Institute of Oncology (Milan, Italy). Outcomes included correlation\/agreement between radiologic DOI (rDOI) and pDOI, and between pathologic depth of vocal muscle invasion (pDMI). Spearman's\n                      <jats:italic>\u03c1<\/jats:italic>\n                      , Bland\u2013Altman analysis, and Lin's concordance correlation coefficient (CCC) assessed agreement. ROC analysis (Youden index), likelihood ratios, and Fagan nomograms evaluated diagnostic performance and clinically meaningful thresholds.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      In 262 derivation cases, rDOI strongly correlated with pDOI (\n                      <jats:italic>\u03c1<\/jats:italic>\n                      \u2009=\u20090.75; CCC\u2009=\u20090.824). pDOI predicted altered vocal fold motility (AUC 0.725; cutoff 2.1\u2009mm) and accurately predicted muscle invasion (AUC 0.94; cutoff 2.2\u2009mm), whereas pDMI showed moderate prediction of motility (AUC 0.69). In 38 validation cases, correlation remained significant (\n                      <jats:italic>\u03c1<\/jats:italic>\n                      \u2009=\u20090.56; CCC\u2009=\u20090.56), and Genoa\u2010derived DOI cutoffs were reproducible (sensitivity 85%\u201394%, specificity 76%\u201383%).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>DOI provides a robust, objective surrogate of functional impairment and muscle infiltration in glottic SCC, with externally validated thresholds that may complement or replace subjective mobility assessment in future staging algorithms.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Level of Evidence<\/jats:title>\n                    <jats:p>3.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/lary.70784","type":"journal-article","created":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T03:52:08Z","timestamp":1785556328000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Depth of Invasion Predicts Vocal Fold Motility and Muscle Invasion in Glottic Carcinoma"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0957-8354","authenticated-orcid":false,"given":"Elisa","family":"Bellini","sequence":"first","affiliation":[{"name":"Unit of Otorhinolaryngology\u2010Head and Neck Surgery IRCCS Azienda Ospedaliera Metropolitana  Genoa Italy"},{"name":"Department of Surgical Sciences and Integrated Diagnostics (DISC) University of Genoa  Genoa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7699-2291","authenticated-orcid":false,"given":"Claudio","family":"Sampieri","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology and Head and Neck Cancer Unit Hospital Cl\u00ednic  Barcelona Spain"},{"name":"Head and Neck Cancer Unit Hospital Clinic  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Chu","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology and Head and Neck Surgery European Institute of Oncology (IEO), IRCCS  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6000-3006","authenticated-orcid":false,"given":"Marta","family":"Filauro","sequence":"additional","affiliation":[{"name":"Unit of Otorhinolaryngology\u2010Head and Neck Surgery IRCCS Azienda Ospedaliera Metropolitana  Genoa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monica","family":"Feltri","sequence":"additional","affiliation":[{"name":"U.O. Anatomia Patologica Ospedaliera, IRCCS Azienda Ospedaliera Metropolitana, Plesso: Ospedale Policlinico San Martino  Genova Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maurizio","family":"Boggio","sequence":"additional","affiliation":[{"name":"U.O. Anatomia Patologica Ospedaliera, IRCCS Azienda Ospedaliera Metropolitana, Plesso: Ospedale Policlinico San Martino  Genova Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Nozza","sequence":"additional","affiliation":[{"name":"U.O. Anatomia Patologica Ospedaliera, IRCCS Azienda Ospedaliera Metropolitana, Plesso: Ospedale Policlinico San Martino  Genova Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano Filippo","family":"Zorzi","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology and Head and Neck Surgery European Institute of Oncology (IEO), IRCCS  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8650-4909","authenticated-orcid":false,"given":"Francesco","family":"Bandi","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology and Head and Neck Surgery European Institute of Oncology (IEO), IRCCS  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simone","family":"Caprioli","sequence":"additional","affiliation":[{"name":"Unit of General and Interventional Radiology IRCCS Ospedale Policlinico San Martino  Genoa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edoardo","family":"Nizzi","sequence":"additional","affiliation":[{"name":"Department of Health Sciences (DISSAL), Diagnostic Imaging and Radiotherapy University of Genoa  Genoa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Ruju","sequence":"additional","affiliation":[{"name":"Division of Radiology European Institute of Oncology (IEO), IRCCS  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Petralia","sequence":"additional","affiliation":[{"name":"Division of Radiology European Institute of Oncology (IEO), IRCCS  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Cicchetti","sequence":"additional","affiliation":[{"name":"Postgraduate School in Radiodiagnostics University of Milan  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emanuele","family":"Zuccari","sequence":"additional","affiliation":[{"name":"Department of Health Sciences (DISSAL), Diagnostic Imaging and Radiotherapy University of Genoa  Genoa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ionela Aurora","family":"Bercea","sequence":"additional","affiliation":[{"name":"Clinic of Radiology and Medical Imaging Fundeni Clinical Institute  Bucharest Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Cittadini","sequence":"additional","affiliation":[{"name":"Unit of General and Interventional Radiology IRCCS Ospedale Policlinico San Martino  Genoa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Ravanelli","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Specialties, Radiological Sciences, and Public Health University of Brescia  Brescia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2391-9357","authenticated-orcid":false,"given":"Cesare","family":"Piazza","sequence":"additional","affiliation":[{"name":"Unit of Otorhinolaryngology \u2013 Head and Neck Surgery ASST Spedali Civili of Brescia  Brescia Italy"},{"name":"Department of Surgical and Medical Specialties, Radiological Sciences, and Public Health (DSMC) University of Brescia, School of Medicine  Brescia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8384-5388","authenticated-orcid":false,"given":"Mohssen","family":"Ansarin","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology and Head and Neck Surgery European Institute of Oncology (IEO), IRCCS  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Snehal","family":"Patel","sequence":"additional","affiliation":[{"name":"Department of Surgery Memorial Sloan Kettering Cancer Center  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giorgio","family":"Peretti","sequence":"additional","affiliation":[{"name":"Unit of Otorhinolaryngology\u2010Head and Neck Surgery IRCCS Azienda Ospedaliera Metropolitana  Genoa Italy"},{"name":"Department of Surgical Sciences and Integrated Diagnostics (DISC) University of Genoa  Genoa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Filippo","family":"Marchi","sequence":"additional","affiliation":[{"name":"Unit of Otorhinolaryngology\u2010Head and Neck Surgery IRCCS Azienda Ospedaliera Metropolitana  Genoa Italy"},{"name":"Department of Surgical Sciences and Integrated Diagnostics (DISC) University of Genoa  Genoa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,31]]},"reference":[{"key":"e_1_2_10_2_1","volume-title":"AJCC Cancer Staging Manual","author":"Amin M. B.","year":"2017"},{"key":"e_1_2_10_3_1","unstructured":"National Comprehensive Cancer Network \u201cHead and Neck Cancers (Version 2.2025) \u201d Accessed January 17 2025 https:\/\/www.nccn.org\/professionals\/physician_gls\/pdf\/head\u2010and\u2010neck.pdf."},{"issue":"5","key":"e_1_2_10_4_1","doi-asserted-by":"crossref","first-page":"e264","DOI":"10.1016\/S1470-2045(25)00020-8","article-title":"International Consensus on Laryngeal Preservation Strategies in Laryngeal and Hypopharyngeal Cancer","volume":"26","author":"Ferrari M.","year":"2025","journal-title":"Lancet Oncology"},{"key":"e_1_2_10_5_1","volume-title":"Cancer Staging Manual","author":"American Joint Committee on Cancer","year":"1977"},{"issue":"12","key":"e_1_2_10_6_1","doi-asserted-by":"crossref","first-page":"1138","DOI":"10.1001\/jamaoto.2014.1548","article-title":"Primary Tumor Staging for Oral Cancer and a Proposed Modification Incorporating Depth of Invasion: An International Multicenter Retrospective Study","volume":"140","author":"International Consortium for Outcome Research (ICOR) in Head and Neck Cancer","year":"2014","journal-title":"JAMA Otolaryngology. Head & Neck Surgery"},{"key":"e_1_2_10_7_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.oraloncology.2025.107264","article-title":"Refining Prognostic Subcategories in Intermediate\u2010Advanced Glottic Cancer: A Multicentric Study on 637 Patients Treated by Transoral Laser Microsurgery","volume":"164","author":"Marchi F.","year":"2025","journal-title":"Oral Oncology"},{"issue":"2","key":"e_1_2_10_8_1","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1097\/MOO.0000000000000036","article-title":"Magnetic Resonance for Laryngeal Cancer","volume":"22","author":"Maroldi R.","year":"2014","journal-title":"Current Opinion in Otolaryngology & Head and Neck Surgery"},{"issue":"2","key":"e_1_2_10_9_1","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1148\/radiol.2492072183","article-title":"Neoplastic Invasion of Laryngeal Cartilage: Reassessment of Criteria for Diagnosis at MR Imaging","volume":"249","author":"Becker M.","year":"2008","journal-title":"Radiology"},{"issue":"9596","key":"e_1_2_10_10_1","doi-asserted-by":"crossref","first-page":"1453","DOI":"10.1016\/S0140-6736(07)61602-X","article-title":"The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) Statement: Guidelines for Reporting Observational Studies","volume":"370","author":"Von Elm E.","year":"2007","journal-title":"Lancet"},{"key":"e_1_2_10_11_1","volume-title":"Winter 2025","author":"Bishop R. C.","year":"2025"},{"issue":"4","key":"e_1_2_10_12_1","doi-asserted-by":"crossref","DOI":"10.3390\/cancers17040712","article-title":"Outcome of T2 Glottic Cancer Treated With Radiotherapy Alone or Concurrent Chemo\u2010Radiotherapy","volume":"17","author":"Peng P. Y.","year":"2025","journal-title":"Cancers"},{"issue":"3","key":"e_1_2_10_13_1","doi-asserted-by":"crossref","first-page":"455","DOI":"10.3390\/cancers17030455","article-title":"Clinical and Pathological Staging Discrepancies in Laryngeal Cancer: A Systematic Review","volume":"17","author":"Pecorari G.","year":"2025","journal-title":"Cancers"},{"issue":"1","key":"e_1_2_10_14_1","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1002\/hed.24534","article-title":"Retrospective Analysis of Factors Influencing Oncologic Outcome in 590 Patients With Early\u2010Intermediate Glottic Cancer Treated by Transoral Laser Microsurgery","volume":"39","author":"Ansarin M.","year":"2017","journal-title":"Head & Neck"},{"issue":"5","key":"e_1_2_10_15_1","doi-asserted-by":"crossref","first-page":"1199","DOI":"10.1007\/s00405-018-4890-y","article-title":"Prognostic Value of Age, Subglottic, and Anterior Commissure Involvement for Early Glottic Carcinoma Treated With CO2 Laser Transoral Microsurgery: A Retrospective, Single\u2010Center Cohort Study of 261 Patients","volume":"275","author":"Carta F.","year":"2018","journal-title":"European Archives of Oto\u2010Rhino\u2010Laryngology"},{"key":"e_1_2_10_16_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.oraloncology.2024.106744","article-title":"How Reliable Is Assessment of True Vocal Cord\u2010Arytenoid Unit Mobility in Patients Affected by Laryngeal Cancer? A Multi\u2010Institutional Study on 366 Patients From the ARYFIX Collaborative Group","volume":"152","author":"Ferrari M.","year":"2024","journal-title":"Oral Oncology"},{"issue":"2","key":"e_1_2_10_17_1","doi-asserted-by":"crossref","first-page":"449","DOI":"10.3109\/00016489109137418","article-title":"Vocal Fold Fixation in Laryngeal Carcinomas","volume":"111","author":"Hirano M.","year":"1991","journal-title":"Acta Oto\u2010Laryngologica"},{"issue":"7","key":"e_1_2_10_18_1","doi-asserted-by":"crossref","first-page":"3230","DOI":"10.1002\/lary.31369","article-title":"Depth of Invasion Assessment in Laryngeal Glottic Carcinoma: A Preoperative Imaging Approach for Prognostication","volume":"134","author":"Filauro M.","year":"2024","journal-title":"Laryngoscope"},{"issue":"5","key":"e_1_2_10_19_1","doi-asserted-by":"crossref","first-page":"764","DOI":"10.1097\/00005537-199805000-00025","article-title":"Prognostic Significance of Depth of Invasion in Cancer of the Larynx","volume":"108","author":"Yilmaz T.","year":"1998","journal-title":"Laryngoscope"},{"issue":"2","key":"e_1_2_10_20_1","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1007\/s12105-018-0925-3","article-title":"Measuring Depth of Invasion in Early Squamous Cell Carcinoma of the Oral Tongue: Positive Deep Margin, Extratumoral Perineural Invasion, and Other Challenges","volume":"13","author":"Berdugo J.","year":"2019","journal-title":"Head and Neck Pathology"},{"issue":"12","key":"e_1_2_10_21_1","doi-asserted-by":"crossref","first-page":"1138","DOI":"10.1001\/jamaoto.2014.1548","article-title":"Primary Tumor Staging for Oral Cancer and a Proposed Modification Incorporating Depth of Invasion: An International Multicentet Retrospective Study","volume":"140","author":"International Consortium for Outcome Research (ICOR) in Head and Neck Cancer","year":"2014","journal-title":"JAMA Otolaryngology. Head & Neck Surgery"},{"issue":"22","key":"e_1_2_10_22_1","doi-asserted-by":"crossref","DOI":"10.3390\/ijerph192214900","article-title":"High\u2010Frequency Intraoral Ultrasound for Preoperative Assessment of Depth of Invasion for Early Tongue Squamous Cell Carcinoma: Radiological\u2010Pathological Correlations","volume":"19","author":"Caprioli S.","year":"2022","journal-title":"International Journal of Environmental Research and Public Health"},{"issue":"1","key":"e_1_2_10_23_1","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1177\/000348940211100114","article-title":"Functional Definitions of Vocal Fold Geometry for Laryngeal Biomechanical Modeling","volume":"111","author":"Tayama N.","year":"2002","journal-title":"Annals of Otology, Rhinology, and Laryngology"},{"issue":"2","key":"e_1_2_10_24_1","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1177\/0145561319840568","article-title":"Sexual Dimorphism in Laryngeal Volumetric Measurements Using Magnetic Resonance Imaging","volume":"99","author":"Hamdan A. L.","year":"2020","journal-title":"Ear, Nose, & Throat Journal"},{"issue":"3","key":"e_1_2_10_25_1","doi-asserted-by":"crossref","first-page":"315","DOI":"10.7162\/S1809-977720130003000012","article-title":"Diffusion of Aniline Blue Injected Into the Thyroarytenoid Muscle as a Proxy for Botulinum Toxin Injection: An Experimental Study in Cadaver Larynges","volume":"17","author":"Alonso V. M.","year":"2013","journal-title":"International Archives of Otorhinolaryngology"},{"issue":"4","key":"e_1_2_10_26_1","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1007\/s004050050228","article-title":"Endoscopic Cordectomy. A Proposal for a Classification by the Working Committee, European Laryngological Society","volume":"257","author":"Remacle M.","year":"2000","journal-title":"European Archives of Oto\u2010Rhino\u2010Laryngology"}],"container-title":["The Laryngoscope"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/lary.70784","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/lary.70784","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/lary.70784","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T03:52:14Z","timestamp":1785556334000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/lary.70784"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,31]]},"references-count":25,"alternative-id":["10.1002\/lary.70784"],"URL":"https:\/\/doi.org\/10.1002\/lary.70784","archive":["Portico"],"relation":{},"ISSN":["0023-852X","1531-4995"],"issn-type":[{"value":"0023-852X","type":"print"},{"value":"1531-4995","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,31]]},"assertion":[{"value":"2026-03-20","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-13","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-31","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"lary.70784"}}