The Host Tissue Repair Vulnerability Index (HTRVI): A Composite Biomarker for Predicting Osteoradionecrosis in Locally Advanced Nasopharyngeal Carcinoma.
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).
This retrospective cohort included 261 LA-NPC patients treated with definitive concurrent chemoradiotherapy between 2010 and 2021. HTRVI was calculated as (CRP × platelet × neutrophil)/(albumin × lymphocyte × 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.
During a median follow-up of 63.8 months, 24 patients (9.2%) developed ORNJ. HTRVI showed superior discrimination (AUC, 0.864; 95% CI, 0.769-0.932) 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, 1.10-20.99; p = 0.037). RCS analysis showed a significant continuous association between HTRVI and ORNJ risk (Poverall < 0.001) without nonlinearity (Pnonlinear = 0.736). Internal validation showed minimal optimism (bootstrap-corrected AUC, 0.993).
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-ORNJ 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.
This retrospective cohort included 261 LA-NPC patients treated with definitive concurrent chemoradiotherapy between 2010 and 2021. HTRVI was calculated as (CRP × platelet × neutrophil)/(albumin × lymphocyte × 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.
During a median follow-up of 63.8 months, 24 patients (9.2%) developed ORNJ. HTRVI showed superior discrimination (AUC, 0.864; 95% CI, 0.769-0.932) 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, 1.10-20.99; p = 0.037). RCS analysis showed a significant continuous association between HTRVI and ORNJ risk (Poverall < 0.001) without nonlinearity (Pnonlinear = 0.736). Internal validation showed minimal optimism (bootstrap-corrected AUC, 0.993).
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-ORNJ 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.