Risk of Osteoradionecrosis in Reconstructed vs.Native Mandibles in Oral Cavity Cancer Following Intensity-Modulated Radiotherapy

Abstract

<h3>Purpose/Objective(s)</h3> Osteoradionecrosis (ORN) is a serious complication of radiation therapy characterized by non-healing exposed bone, and occurs in 5-35% of head and neck cancers treated with intensity-modulated radiotherapy (IMRT). High radiation dose, oral cavity subsite, and mandibular surgery are known risk factors for ORN development. However, whether mandibles reconstructed with fibular flaps carry an elevated risk of ORN compared to native mandibles in patients with IMRT-treated oral cavity squamous cell carcinoma (OCSCC) is unknown. <h3>Materials/Methods</h3> An IRB-approved database of head and neck cancer patients treated at a tertiary care center was queried for patients with OCSCC treated with surgery and post-operative IMRT. Patients were included if they underwent free flap surgery, received IMRT ≥45 Gy in ≥20 fractions, and completed treatment at least two years prior to analysis to provide adequate follow-up time. ORN was graded according to Schwartz and Kagan classification: grade 1, superficial involvement of mandible; grade 2, exposed cortical bone and underlying medullary bone necrosis; grade 3, full diffuse involvement. Competing risk regression, with death as a competing event, was used to assess risk factors for the development of ORN. <h3>Results</h3> A total of 151 patients met inclusion criteria with median follow-up time of 32.6 months (range 0.2-190.6). Patient demographics included 60.3% male, 88.7% Caucasian, and median age 62.4 years (range 28.1-93.2). Of the 151 patients, 27.8% were current smokers and 45.7% were former smokers. Oral cavity subsites were grouped as lateralized tumors in 32.5% of patients (11.9% buccal mucosa, 8.6% retromolar trigone, 6.0% alveolar ridge, 4.0% gingiva, and 2.0% hard palate) and midline tumors in 67.6% of patients (21.2% floor of mouth, 46.4% mobile (oral) tongue). Reconstruction with soft-tissue free flap was performed in 74.8% of patients, and 25.2% of patients underwent fibular flap for mandibular reconstruction. Median radiation dose was 60 Gy in 30 fractions. ORN occurred in 13.9% of patients (n=21; 11 grade 1, 3 grade 2, 7 grade 3) and 42.4% of patients died without ORN. For patients who developed ORN, the median time to ORN was 23.9 months (range 2.4-71.2). On univariate analysis, no individual factors were associated with development of ORN; the 1-year (5.4%, 95%CI 2.5-9.8%) and 2-year (7.5%, 95%CI 3.9-12.5%) rates of ORN were low. <h3>Conclusion</h3> Fibular flap mandibular reconstruction was not associated with increased risk of developing mandibular ORN compared to native mandibles in patients with oral cavity cancer following IMRT. The risk of ORN in patients treated with IMRT after mandible reconstruction is low, and fibular flaps can be safely performed with no excess concern for this mandibular ORN. Larger prospective studies are needed to definitively assess risk factors for development of ORN in this patient population.