Mandibular Radiation Dose Modifies the Association Between Post-Chemoradiotherapy Dental Extraction Timing and Osteoradionecrosis Risk: A Retrospective Cohort Study

Background/Objectives: This retrospective study evaluated whether the association between post-CCRT dental extraction timing and osteoradionecrosis of the jaw (ORNJ) risk is modified by mandibular radiation exposure in patients with locally advanced nasopharyngeal carcinoma (LA-NPC) treated with definitive concurrent chemoradiotherapy (CCRT). Methods: A total of 247 patients who did not undergo pre-CCRT dental extraction but underwent post-CCRT extraction were analyzed. Mandibular radiation exposure was quantified using EQD2. Associations between clinical, tumoral, dental, and dosimetric variables and ORNJ were assessed using multivariable logistic regression, including assessment of EQD2–timing interaction. ROC analyses were performed to evaluate discriminative performance and estimate exploratory thresholds. ORNJ developed in 23 patients (9.3%). Mandibular EQD2 was independently associated with ORNJ risk (OR 2.10 per 5 Gy; 95% CI 1.40–3.15; p < 0.001). A significant interaction between EQD2 and extraction timing was observed (OR 1.07; 95% CI 1.03–1.11; p = 0.023). EQD2 demonstrated excellent discrimination (AUC 0.885; cutoff 46.5 Gy), whereas extraction timing showed modest discrimination (AUC 0.691; cutoff 10 months). At <46.5 Gy, ORNJ rates remained low regardless of timing (1.0% vs. 3.9%). At ≥46.5 Gy, delayed extraction was associated with substantially higher ORNJ incidence (31.1% vs. 11.3%). Number of extracted teeth (OR 1.16; p = 0.012) and hemoglobin level (OR 0.62; p = 0.007) were also independent predictors. Conclusions: The effect of post-CCRT dental extraction timing on ORNJ risk is modified by mandibular radiation dose, supporting interpretation in conjunction with mandibular radiation exposure rather than as an isolated factor.