Session Item

Osteoradionecrosis (ORN) of the mandible is a severe late effect of radiotherapy for head and neck tumors. It is most often observed in premolar and molar regions, which suggest not all mandibular regions are equally prone for development of ORN. Therefore, we investigated the interaction between the ORN location, the dose to that location and the location of teeth extractions in a group of 324 oropharyngeal squamous cell carcinoma patients treated with (chemo)radiotherapy.

For patients with ORN after radiotherapy, the ORN volume was delineated on the planning CT. All dose distributions were converted to 2 Gy equivalent dose based on α/β=3 Gy, accumulated, and deformed non-rigidly to a reference patient using ADMIRE 3.7.7 (Elekta AB, Stockholm, Sweden). The reference patient contained delineations of 16 mandible subregions corresponding to the 16 dental elements. Multi-variable logistic regressions were performed per mandible subregion to relate the presence of ORN in a subregion to its mean dose, whether the dental element in the subregion was extracted and whether its neighbor elements (i.e. other dental elements on the same side of the mandible) were extracted. Likelihood ratio tests were performed to compare models, with p≤0.05 considered statistically significant. In the first regression all dental elements from all patients were combined. Next, separate regression analyses were performed per subregion (left and right combined). 

Patients could be registered accurately to the reference patient. The 95 percentile of the distance between the mandible delineations was on average 3.50 mm (range 1.51-8.12 mm). 27 Patients developed ORN (8%). In the combined analysis the mean dose to the mandible subregion, pre-radiotherapy teeth extraction in the mandible subregion, and pre-radiotherapy teeth extractions of neighboring dental elements were all associated with an increased risk of ORN (Figure 1). The odds ratios were 1.073 per unit increase in Gy (95% confidence interval (CI): (1.059,1.088)), 1.79 (95% CI: (1.023,3.11)), and 2.24 (95% CI: (1.39,3.54)), respectively. In the analysis per mandible subregion (Table 1) the dose was associated with an increased risk of ORN in the second premolar, first molar, second molar, and third molar. Extractions were associated with an increased risk of ORN only in the second premolar (p-value = 0.03) and in the second molar (p-value = 0.004). Due to limited statistical power, extraction of neighboring dental elements was not taken into account in the regressions per subregion.

Large intra-mandible differences in radio-sensitivity for ORN were observed. Dose effect relations were established for different regions of the mandible corresponding to dental elements. Extraction of the dental element of interest or its neighbors increased the local sensitivity of the mandible for ORN. These findings strongly support, and can guide studies to selectively spare sensitive regions of the mandible to decrease the risk of ORN.