Dosimetric Effects and Estimated Osteoradionecrosis Development in Oropharynx Cancer Patients Treated With Intensity Modulated Radiotherapy With the Adoption of Dose Volume Histogram Based Mandibular Constraints.

PURPOSE/OBJECTIVE(S) Dose constraint recommendations to limit mandible (MN) osteoradionecrosis (ORN) are largely unchanged since the advent of head and neck intensity modulated radiotherapy (IMRT). Updated MN dose volume histogram (DVH) constraints have been proposed but not validated in a prospective dataset. We hypothesize that after adopting more stringent MN constraints at our institution, we lowered the estimated ORN rate without compromising target coverage / organ at risk (OAR) avoidance. MATERIALS/METHODS This is a single institution retrospective study of a prospective database of non-metastatic oropharynx cancer (OPC) patients ≥ 18 years treated with standard fractionation adjuvant or definitive IMRT from 01 / 2014 - 08 / 2020. In 09 / 2017, MN dose constraint was changed from 0.1 cm3 < 70 Gy - historical constraints (HC) - to V44 < 42%, V58 < 25%, 0.5cc < 70 Gy - modified constraints (MC). No other target / OAR criteria were altered. ORN was defined as having exposed MN bone for ≥ 3 months without recurrence. Impact on ORN rate and resulting dosimetric changes in MN and other OARs (parotid and submandibular glands, oral cavity, pharyngeal constrictors) between HC and MC groups were evaluated. Continuous variables were compared via the Wilcoxon test, discrete variables via Fisher's exact test. Due to shorter follow-up (FU), regression modeling was used to estimate ORN cases in MC group. RESULTS There were 174 patients total, 71 in MC group. The mean prescription dose was 67.7 Gy and 68.5 Gy in HC and MC groups, respectively. More of the HC group (37%) had clinical T3 - T4 tumors compared to MC group (25%). More patients in the MC group met both the V44 < 42% (62 v 87%, P < 0.01) and the V58 < 25% constraints (73 v 92%, P < 0.01). Percent of patients meeting neither, one, or both MN constraints in the HC group was 23%, 13%, and 63%, versus 8%, 4%, and 87% in the MC group, respectively (P < 0.01). Mandible V44 and V58 were significantly associated with ORN (P < 0.01 and P = 0.03, respectively) across entire patient cohort. In HC group, mean MN V44 was significantly associated with ORN (62% in ORN cases vs 38%, P = 0.01) while mean MN V58 was approaching significance (P < 0.06). There were too few ORN cases in the MC group for similar analysis. Mean dose to OARs was not increased in MC group. There were 7 cases (76%) of ORN in the HC group at median FU 39 months (range: 2 - 78 months) and 2 cases (33%) of ORN in the MC group at median FU 11 months (range: 2 - 39 months). To account for shorter FU in MC group, logistic regression of ORN based on V44 in HC patients resulted in a model to predict ORN cases in MC group. This model estimates a total of 3.2 ORN cases (55%) in MC group (95% CI: 0.00 - 6.4). CONCLUSION We confirm MN V44 and V58 are predictive of ORN development. The goals of MN V44 < 42% and V58 < 25% were achievable in 87% of cases without sacrificing target coverage or other OAR constraints. Regression modeling estimates fewer ORN cases in MC group.