Prognostic Factors of Mandibular Osteoradionecrosis Including Accurate Colocalization of Avulsions and Dosimetric Dental Mapping Software, a Case Control Study.

IntroductionOsteoradionecrosis of the mandible (ORN) remains a significant complication in the intensity modulated radiotherapy (IMRT) era. Dental dose cannot be predicted from heterogeneous IMRT dose distributions; mandibular dose metrics cannot guide dentist avulsion decisions in high risk ORN situations. Using a mapping tool to report dental root dose, avulsions and ORN sites, we reexamined ORN risk factors in a case-control study.MethodsFrom 2008 to 2019, 897 consecutive patients with oral cavity/oropharynx (OC/OR) or unknown primary cancer (CUP) and undergoing IMRT were analyzed to identify ORN cases. These were matched (1 ORN/2 controls) retrospectively for tumor, surgery, tobacco in a monocentric case-control study. Univariate and multivariate analyses integrated ORN factors and accurate dental dose data (grouped into 4 mandibular sectors). Generalizability was investigated in a simulated population database.Results171 patients were included. Median follow-up was 5.2 and 4.5 years in the ORN and control groups, respectively. Median time to ORN was 12 months. In univariate analysis, post-IMRT avulsions at the ORN site (Hazard ratio (HR) = 3.6; 95% confidence interval (CI) = 1.5-8.9; p=0.005), tumor laterality (HR =4.4; 95% CI = 1.4-14, p = 0.01), mean mandibular dose (HR = 1.1; 95% CI = 1.01-1.1; p = 0.018) and mean dose to the ORN site (HR = 1.1; 95% CI = 1.1-1.2; p < 0.001) correlated with higher ORN risk. In multivariate analysis, mean dose to the ORN site (HR = 1.1; 95% CI = 1.1-1.2; p < 0.001) and post-IMRT avulsions at the ORN site (HR = 4.6; 95% CI = 1.5-14.7; p = 0.009) were associated with ORN. For each increase in Gray in dental dose, the ORN risk increased by 12%. Simulations confirmed study observations.ConclusionDental dose and avulsions are associated with ORN with a 12% increase in risk with each additional Gray. Accurate dose information can help dentists in their decisions after IMRT.