{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T09:08:24Z","timestamp":1785143304910,"version":"3.55.0"},"reference-count":40,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T00:00:00Z","timestamp":1784851200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Med. Sci.","Medical Sciences"],"abstract":"<jats:p>Background: Osteoradionecrosis of the jaw (ORNJ) remains a major late complication of head and neck radiotherapy, and risk assessment relies mainly on clinical and dosimetric factors. We constructed the Host Tissue Repair Vulnerability Index (HTRVI), a composite biomarker integrating inflammatory, immune-nutritional, and oxygenation-related parameters, to estimate biological susceptibility to ORNJ in locally advanced nasopharyngeal carcinoma (LA-NPC). Methods: This retrospective cohort included 261 LA-NPC patients treated with definitive concurrent chemoradiotherapy between 2010 and 2021. HTRVI was calculated as (CRP \u00d7 platelet \u00d7 neutrophil)\/(albumin \u00d7 lymphocyte \u00d7 hemoglobin). HTRVI was compared with hemoglobin (Hb) and the Global Immune-Nutrition-Inflammation Index (GINI) using receiver operating characteristic analysis. Multivariable logistic regression, restricted cubic spline analysis (RCS), and bootstrap resampling assessed independent association, continuous risk relationship, and internal validation. Results: During a median follow-up of 63.8 months, 24 patients (9.2%) developed ORNJ. HTRVI showed superior discrimination (AUC, 0.864; 95% CI, 0.769\u20130.932) compared with Hb (AUC, 0.785; p = 0.001) and GINI (AUC, 0.759; p = 0.045). HTRVI remained independently associated with ORNJ after adjustment for mandibular mean dose and post-CCRT tooth extraction burden (OR per standard deviation increase, 4.81; 95% CI, 1.10\u201320.99; p = 0.037). RCS analysis showed a significant continuous association between HTRVI and ORNJ risk (Poverall &lt; 0.001) without nonlinearity (Pnonlinear = 0.736). Internal validation showed minimal optimism (bootstrap-corrected AUC, 0.993). Conclusions: HTRVI was independently associated with ORNJ and provided additional predictive information beyond established clinical and dosimetric factors in this single-center cohort. The continuous HTRVI\u2013ORNJ association supports a biological continuum model of host tissue repair vulnerability. However, HTRVI should currently be regarded as an investigational biomarker requiring independent external and prospective validation before clinical implementation.<\/jats:p>","DOI":"10.3390\/medsci14040427","type":"journal-article","created":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T08:15:56Z","timestamp":1785140156000},"page":"427","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Host Tissue Repair Vulnerability Index (HTRVI): A Composite Biomarker for Predicting Osteoradionecrosis in Locally Advanced Nasopharyngeal Carcinoma"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8251-6913","authenticated-orcid":false,"given":"Efsun","family":"Somay","sequence":"first","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, Ba\u015fkent University, Ankara 06579, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8120-7123","authenticated-orcid":false,"given":"Erkan","family":"Topkan","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Faculty of Medicine, Ba\u015fkent University, Adana 01120, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0225-2477","authenticated-orcid":false,"given":"Sibel","family":"Bascil","sequence":"additional","affiliation":[{"name":"Department of Periodontology, Faculty of Dentistry, Ba\u015fkent University, Ankara 06579, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8087-3140","authenticated-orcid":false,"given":"Ugur","family":"Selek","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, School of Medicine, Ko\u00e7 University, Istanbul 33405, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1016\/0278-2391(83)90294-X","article-title":"Osteoradionecrosis: A new concept of its pathophysiology","volume":"41","author":"Marx","year":"1983","journal-title":"J. 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