{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,15]],"date-time":"2026-08-15T22:49:29Z","timestamp":1786834169639,"version":"build-2736575974"},"reference-count":27,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2025,3,28]],"date-time":"2025-03-28T00:00:00Z","timestamp":1743120000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Head &amp; Neck"],"published-print":{"date-parts":[[2025,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Extranodal extension (ENE) is an important adverse prognostic indicator for head and neck cancers. However, ENE needs further risk stratification in terms of optimum cutoff for the extent of ENE and interaction with clinicopathological risk factors.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Retrospective single\u2010center study on patients with treatment\u2010na\u00efve head and neck cancer with final histology indicating ENE.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Pathological ENE was observed in 122 patients (12.4%). With the 2\u2009mm cutoff separating Mi\u2010ENE and Ma\u2010ENE, no difference was observed in overall survival (OS) and disease\u2010free survival (DFS) for unmatched (OS: 40.9% vs. 33.6%, <jats:italic>p<\/jats:italic>\u2009=\u20090.7; DFS: 34.05% vs. 26.12%, <jats:italic>p<\/jats:italic>\u2009=\u20090.5) as well as propensity score\u2010matched cohort (OS: HR 1.08, <jats:italic>p<\/jats:italic>\u2009=\u20090.82; DFS: HR 0.95, <jats:italic>p<\/jats:italic>\u2009=\u20090.89). Receiver\u2010operator curve (ROC) analysis showed the highest area under the curve with a 4\u2009mm cutoff for the extent of ENE (AUC: 0.52). On assessing the impact of adjuvant chemoradiation (CRT) on Ma\u2010ENE and Mi\u2010ENE, only Ma\u2010ENE showed OS (HR: 0.42, 95% CI: 0.18\u20130.9) and DFS (HR: 0.33, 95% CI: 0.15\u20130.70) benefit with CRT, which was statistically significant. The revised 4\u2009mm cutoff was predictive of therapeutic benefit with adjuvant CRT (HR: 0.27, 95% CI: 0.1\u20130.73). Clinicopathological factors with statistically significant interaction with ENE in worsening OS and DFS were tumor location in tongue\/floor of mouth (OS), T3\/T4 category (OS), depth of invasion greater than 10\u2009mm (OS), \u2265\u20095 nodes with metastasis (OS), and male sex (DFS).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The standard 2\u2009mm cutoff for the extent of ENE failed to reveal sufficient hazard discrimination for OS\/DFS. Instead, the 4\u2009mm cutoff determined on ROC analysis was found to have the best predictive ability for DFS.<\/jats:p><\/jats:sec>","DOI":"10.1002\/hed.28144","type":"journal-article","created":{"date-parts":[[2025,3,30]],"date-time":"2025-03-30T14:19:40Z","timestamp":1743344380000},"page":"2270-2279","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Risk Stratification for Extranodal Extension in Head and Neck Cancers\u2014Implication for Treatment Intensification"],"prefix":"10.1002","volume":"47","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1257-8611","authenticated-orcid":false,"given":"Smriti","family":"Panda","sequence":"first","affiliation":[{"name":"Department of ENT\u2010Oncology National Cancer Institute \u2013 All India Institute of Medical Sciences (Jhajjar Campus)  Jhajjar Haryana 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