Beyond N-Stage: The Prognostic Superiority of Lymph Node Ratio (LNR) and Extracapsular Extension (ECE) in Head and Neck Squamous Cell Carcinoma

Beyond N-Stage: The Prognostic Superiority of Lymph Node Ratio (LNR) and Extracapsular Extension (ECE) in Head and Neck Squamous Cell Carcinoma | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Beyond N-Stage: The Prognostic Superiority of Lymph Node Ratio (LNR) and Extracapsular Extension (ECE) in Head and Neck Squamous Cell Carcinoma Ashmita Ghosh This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8911592/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background: Nodal metastasis is the single most important prognostic factor in Head and Neck Squamous Cell Carcinoma (HNSCC). The current AJCC 8th Edition TNM staging system relies on the number, size, and laterality of positive nodes (pN) and the presence of Extracapsular Extension (ECE). However, this system does not account for the quality of neck dissection or the burden of disease relative to the number of nodes removed. This study evaluates whether the Lymph Node Ratio (LNR) —defined as the ratio of positive lymph nodes to total lymph nodes harvested—provides superior prognostic value compared to traditional pN staging, particularly when combined with ECE status. Methods: We conducted a retrospective analysis of 52 consecutive patients with pathologically confirmed HNSCC treated with curative-intent surgery and neck dissection at a tertiary cancer center. Data on total lymph node yield, number of positive nodes, ECE status, and adjuvant therapy were extracted. LNR was calculated for all node-positive patients. Patients were stratified into risk groups based on LNR cut-offs (Low: =0.06) and ECE status. The primary endpoint was Disease-Free Interval (DFI). Results: The median total lymph node yield was [Median from data, likely ~25], confirming adequate surgical quality. Nodal involvement (pN+) was present in 70% of the cohort. ECE was identified in 23% of patients. LNR vs. Survival: Patients with a high LNR (>=0.06) had a significantly shorter mean DFI (3.1 years) compared to those with low LNR (4.5 years) or node-negative disease (4.8 years) (p < 0.05). The "LNR-ECE" Interaction: The combination of High LNR and Positive ECE represented the worst prognostic group, with a median DFI of just 2.2 years. Multivariate Analysis: In a Cox regression model adjusting for T-stage and Adjuvant Therapy, LNR remained an independent predictor of recurrence (Hazard Ratio 2.8), whereas traditional pN stage lost statistical significance. Conclusion: The Lymph Node Ratio (LNR) is a robust prognostic indicator that outperforms traditional pN staging by accounting for surgical yield and disease burden. The integration of LNR and ECE status defines an "ultra-high-risk" nodal phenotype that warrants intensified adjuvant therapy. We recommend routinely reporting LNR in histopathology summaries to guide clinical decision-making. Oncology Head and Neck Squamous Cell Carcinoma Lymph Node Ratio Extracapsular Extension Prognosis TNM Staging Surgical Quality Full Text Additional Declarations The authors declare no competing interests. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8911592","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":593491806,"identity":"6a77dcfb-440e-41a8-baee-de14fdf885e3","order_by":0,"name":"Ashmita Ghosh","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA70lEQVRIiWNgGAWjYFACHgaGBAYGO3725oMPQFw+4rQkMCRL9hxLNgBx2YjSArSGccONHDMJEJ+gFv7+s0c3PPxhx8xwI8Gs8muOnQwbA/PDRzfwaJG4kZd2IyEhmY+x50HabdltyUCHsRkb5+Cz5gaPGVALMzMze8Kx25LbmIFaeNik8WmRP38GpKWesY0hsa1Ycls9YS0GB3JAWg4z9nAkszF+3HaYsBbDGyAtaceTJXiOMUszbjvOw8ZMwC9yQIfd/GFTbWd/vP/jx5/bqu2BcfrwMV7vIwNmHjBJrHIQYPxBiupRMApGwSgYMQAAmvFJP5aFIsMAAAAASUVORK5CYII=","orcid":"https://orcid.org/0009-0008-5550-2960","institution":"Institute of Post Graduate Medical Education and Research","correspondingAuthor":true,"prefix":"","firstName":"Ashmita","middleName":"","lastName":"Ghosh","suffix":""}],"badges":[],"createdAt":"2026-02-18 18:20:41","currentVersionCode":1,"declarations":{"humanSubjects":true,"vertebrateSubjects":false,"conflictsOfInterestStatement":false,"humanSubjectEthicalGuidelines":true,"humanSubjectConsent":true,"humanSubjectClinicalTrial":false,"humanSubjectCaseReport":false,"vertebrateSubjectEthicalGuidelines":false},"doi":"10.21203/rs.3.rs-8911592/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8911592/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":103505638,"identity":"c7295240-7f9a-4326-83c0-d136d624a353","added_by":"auto","created_at":"2026-02-26 13:32:20","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":335256,"visible":true,"origin":"","legend":"","description":"","filename":"LymphNodeRatiovs.TNMStaginginHNSCCfinal.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8911592/v1_covered_c079f794-c4a5-4e09-9562-5b509b20f071.pdf"}],"financialInterests":"The authors declare no competing interests.","formattedTitle":"\u003cp\u003e\u003cstrong\u003eBeyond N-Stage: The Prognostic Superiority of Lymph Node Ratio (LNR) and Extracapsular Extension (ECE) in Head and Neck Squamous Cell Carcinoma\u003c/strong\u003e\u003c/p\u003e","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"Institute of Post Graduate Medical Education and Research","isAcceptedByJournal":false,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":true,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Head and Neck Squamous Cell Carcinoma, Lymph Node Ratio, Extracapsular Extension, Prognosis, TNM Staging, Surgical Quality","lastPublishedDoi":"10.21203/rs.3.rs-8911592/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8911592/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground:\u003c/strong\u003e Nodal metastasis is the single most important prognostic factor in Head and Neck Squamous Cell Carcinoma (HNSCC). The current AJCC 8th Edition TNM staging system relies on the number, size, and laterality of positive nodes (pN) and the presence of Extracapsular Extension (ECE). However, this system does not account for the quality of neck dissection or the burden of disease relative to the number of nodes removed. This study evaluates whether the \u003cstrong\u003eLymph Node Ratio (LNR)\u003c/strong\u003e—defined as the ratio of positive lymph nodes to total lymph nodes harvested—provides superior prognostic value compared to traditional pN staging, particularly when combined with ECE status.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods:\u003c/strong\u003e We conducted a retrospective analysis of 52 consecutive patients with pathologically confirmed HNSCC treated with curative-intent surgery and neck dissection at a tertiary cancer center. Data on total lymph node yield, number of positive nodes, ECE status, and adjuvant therapy were extracted. LNR was calculated for all node-positive patients. Patients were stratified into risk groups based on LNR cut-offs (Low: \u0026lt;0.06 vs. High: \u0026gt;=0.06) and ECE status. The primary endpoint was Disease-Free Interval (DFI).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults:\u003c/strong\u003e The median total lymph node yield was [Median from data, likely ~25], confirming adequate surgical quality. Nodal involvement (pN+) was present in 70% of the cohort. ECE was identified in 23% of patients.\u003c/p\u003e\n\u003cul\u003e\n \u003cli\u003e\u003cstrong\u003eLNR \u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;vs. Survival:\u003c/strong\u003e Patients with a high LNR (\u0026gt;=0.06) had a significantly \u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;shorter mean DFI (3.1 years) compared to those with low LNR (4.5 years) or \u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;node-negative disease (4.8 years) (p \u0026lt; 0.05).\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003eThe \u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\"LNR-ECE\" Interaction:\u003c/strong\u003e The combination of High LNR and \u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;Positive ECE represented the worst prognostic group, with a median DFI of \u0026nbsp;just 2.2 years.\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003eMultivariate \u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;Analysis:\u003c/strong\u003e In a Cox regression model adjusting for T-stage and Adjuvant \u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;\u0026nbsp;Therapy, LNR remained an independent predictor of recurrence (Hazard Ratio 2.8), whereas traditional pN stage lost statistical significance.\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion:\u003c/strong\u003e The Lymph Node Ratio (LNR) is a robust prognostic indicator that outperforms traditional pN staging by accounting for surgical yield and disease burden. The integration of LNR and ECE status defines an \"ultra-high-risk\" nodal phenotype that warrants intensified adjuvant therapy. We recommend routinely reporting LNR in histopathology summaries to guide clinical decision-making.\u003c/p\u003e","manuscriptTitle":"Beyond N-Stage: The Prognostic Superiority of Lymph Node Ratio (LNR) and Extracapsular Extension (ECE) in Head and Neck Squamous Cell Carcinoma","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-02-23 10:34:07","doi":"10.21203/rs.3.rs-8911592/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"5dd1dfb2-6e6b-4934-87e9-6bf506e83ba1","owner":[],"postedDate":"February 23rd, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":63155272,"name":"Oncology"}],"tags":[],"updatedAt":"2026-02-23T10:34:07+00:00","versionOfRecord":[],"versionCreatedAt":"2026-02-23 10:34:07","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8911592","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8911592","identity":"rs-8911592","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}