Changes in the epidemiology of head and neck cancers have resulted in an increased number of younger and healthier patients being treated with definitive external beam radiotherapy (EBRT). The long term sequelae of irradiation in a patient population with good clinical outcomes and extended life expectancy are becoming increasingly relevant in the management of treatment-associated morbidity and mortality. Osteoradionecrosis (ORN) of the mandible is a devastating complication of irradiation with an estimated rate of up to 16% across head and neck histologies. Altered bone vascularity and opportunistic infections within the oral cavity contribute to the development of ORN leading to an inexorable process of bone destruction which lacks the normal sequence of healing events. Early-stage ORN is often managed using antibiotics, local wound care and hyperbaric oxygen (HBO). Advanced ORN requires surgical resection and reconstruction with healthy non-irradiated tissue. Successful management of this disease process requires an improved ability to identify patients at risk for ORN, monitor the effectiveness of conservative management and improve pre-operative planning to insure clear margins at time of resection. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is a clinically available quantitative imaging method that is increasingly employed to assess microvascular function in the study of solid tumors of the head and neck. At our institution, DCE-MRI is integrated into a multi-modality clinical algorithm aimed at improving the diagnosis, staging and oncologic surveillance of head and neck tumors. DCE-MRI can detect altered bone vascularity associated with bone healing, necrosis and metastatic involvement, with excellent spatial resolution. We hypothesize that DCE-MRI can be used to detect alterations in bone vascularity following irradiation to monitor ORN clinical progression and response to treatment. To test this hypothesis, we will evaluate the potential of DCE-MRI to identify patients at risk for mandibular ORN, monitor response to conservative management, and identify the extent of advanced mandibular ORN to assist in surgical planning. Successful completion of this proposal has the potential to revolutionize the diagnosis and management of mandibular ORN. For the first time, clinicians will be able to identify patients at risk for ORN and manage post-irradiation care appropriately. The effectiveness of currently employed conservative measures could be tested using an objective measure and improved pre-operative planning could reduce the rate of surgical failure due to residual compromised bone.
The proposed clinical research will use dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) to assess the natural history of osteoradionecrosis (ORN) and treatment for this devastating complication related to irradiation of head and neck cancers. The work is relevant to public health because this approach will provide a reliable and validated measure of clinical outcomes for ORN. This work is particularly relevant to the part of the NIH's mission that pertains to developing and applying fundamental knowledge that will help to reduce the burdens of human illness.
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