Mandible Osteoradionecrosis and Asymmetry in Pediatric Patients Treated with Proton Therapy for Head and Neck Malignancies

Abstract

<h3>Purpose/Objective(s)</h3> Osteoradionecrosis (ORN) is a serious and long-lasting complication of radiation therapy that is especially prevalent in the mandible with the treatment of head and neck malignancies. Relatively little is known about factors associated with pediatric ORN, especially with proton therapy. Additionally, little is known about the effect of proton therapy on asymmetric mandible growth. In this study, we aim to determine factors associated with ORN and asymmetric growth in the mandible in pediatric patients treated with proton therapy. <h3>Materials/Methods</h3> Using an IRB-approved prospective single-institution database of pediatric patients treated for head and neck malignancies at our institution between 12/2006 and 2/2020, we gathered demographic, disease, and treatment characteristics using their electronic medical records. We obtained radiation treatment fields and dosimetric information from the radiation treatment plans of the patients. Univariate and multivariate regression analyses were performed to determine factors associated with development of ORN and mandible asymmetry. <h3>Results</h3> Our cohort consisted of 117 pediatric patients with median age 7 years (range, 0.5-20 years). Median follow-up was 59.1 months (range, 6.2-160.9 months). 53.8% of patients were female and 47.9% were Caucasian. All primary malignancies were in the head and neck. Rhabdomyosarcoma was the most common malignancy, accounting for 43.6% of cases. Prescribed radiation doses ranged from 21.6GyRBE to 73GyRBE (median 50.4GyRBE) with dose/fraction ranging from 1.68GyRBE to 2.2GyRBE (median 1.8 GyRBE). 23 patients had hemimandible Dmax >60GyRBE. 2 patients had development of ORN 10.9 months and 62.1 months after completion of radiation. Hemimandible Dmax for the affected portion of the mandible were 68.3GyRBE and 65.0GyRBE with mean doses of 62.6GyRBE and 12.0GyRBE. 5 patients developed asymmetric mandible growth with asymmetry first noted 15.4-58.2 months after completion of radiation (median 34.2 months). For these patients, hemimandible Dmax range was 53.2GyRBE-67.3GyRBE with mean hemimandible dose range of 7.3GyRBE-52.0GyRBE. On univariate analysis, mean hemimandible dose was significantly associated with development of mandible asymmetry (p=0.02). However, on multivariate analysis, no demographic, disease, radiation, or dosimetric parameters were significantly associated with ORN or mandible asymmetry. <h3>Conclusion</h3> Our results suggest that osteoradionecrosis and mandibular asymmetry is uncommon in pediatric patients receiving proton therapy for head and neck malignancies, occurring in 1.7% and 4.3% of patients respectively. We found mean hemimandible dose to be a predictor of mandible asymmetry on univariate analysis, but no predictors of ORN or asymmetry on multivariate analysis, likely attributable to the low incidence of both. Longer follow-up is needed as mandibular asymmetry may continue to occur until the treated child is fully grown.