Risk Factors for Osteoradionecrosis of the Jaw in the Era of Modern Head and Neck Radiotherapy

Abstract

Radiotherapy is an essential component of curative treatment for head and neck cancer, either as a neoadjuvant or adjuvant treatment to surgery or as a definitive treatment with or without chemotherapy, depending on the stage of the disease and general health.However, aggressive RT or chemoradiotherapy can result in radiation-induced severe late toxicities, including the severely debilitating osteoradionecrosis of the jaws (ORNJ), which may affect a relatively small but significant proportion of this patient population.ORNJ is characterized by necrosis of bone tissue and failure to heal for at least three months.In the majority of cases, ORNJ progresses gradually, worsening and becoming more painful, which results in infection and pathological fracture.In the absence of a proven curative treatment other than aggressive surgeries, the prevalence of ORNJ could theoretically be decreased by implementing a wellorganized multidisciplinary oral care program and reducing the ORNJ-related risk factors.These risk factors include the patient, the tumor, pre-radiotherapy mandibular surgery, tooth extractions, implant placement, radiation modality, and radiation dosimetryrelated factors.Therefore, the present paper provides a literature review and update on the established and frequently disputed risk factors underlying ORNJ and their radiobiological bases.ORNJ is a severe late toxicity of RT and CCRT (Figure 1), with a prevalence rate ranging from 0.4 to 56% [5].This wide range in prevalence can be attributed to a variety of factors, including the presence or absence of concurrent chemotherapy use, mandibular resection, pre-or post-treatment tooth extractions, implant placement, periodontitis, chronic infections, RT modality and technique, total and per fraction RT doses, use of dose constraints for the jaw, mean or Vx (volume receiving a specified dose or more) dose of the jaw, and likely many more.Newer, more sophisticated RT techniques, such as three-dimensional conformal RT (3D-CRT), intensity-modulated RT (IMRT), and intensity-modulated proton therapy (IMPT), have reduced the risk of ORNJ due to their improved tissue sparing properties, thanks to advancements in computer-aided technology.However, depending on the tumor and involved nodal

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