Oral mucositis (OM) is the term for the erythematous, inflammatory, and ulcerative lesions that occur in the mucosal lining of the mouth and pharynx secondary to cytotoxic cancer therapy. Up to 90% of patients with head and neck cancer (HNC) receiving radiotherapy (RT) will develop OM. Sequelae include pain and compromised oropharyngeal functions that affect the patient's quality of life and limits the acceptable maximum dose of delivered RT, negatively affecting curability of the disease. Thus, to reduce suffering and improve cancer treatment outcome, the prevention and care of OM should be a high priority. Currently, most animal models of OM involve the induction of mucosal damage in normal rodents through RT of the head or oral structures. While these models contribute greatly to the mechanistic understanding of the development, progression and healing of OM, they have limited use for evaluating the efficacy of novel interventions. In particular, in the absence of tumor, these models do not allow investigators to determine if therapeutic agents designed to protect or repair normal mucosa also have a protective affect on neoplastic tissue, potentially reducing the efficacy of RT. In addition, while outcome assessment in rodents focuses primarily on the mucosal changes associated with OM, clinical studies in humans focus on OM-induced pain and its interference with normal function. As such, a spontaneous tumor-bearing animal model that allows for simultaneous assessment of normal and neoplastic tissues with outcome assessments that are based on those used in clinical research would be very useful in efficacy testing of novel preventive and therapeutic interventions. Companion (pet) dogs spontaneously develop HNC and are routinely treated with RT. Like people, most dogs will develop OM and can experience mucosal injury severe enough to cause discomfort, compromise oropharyngeal function, and limit the maximum dose of RT. The overwhelming similarities between human and canine RT induced OM suggest that dogs treated with RT for the spontaneous development of HNC may serve as a useful preclinical model to investigate the prevention and treatment of human OM. However, before the potential efficacy of an intervention can be evaluated, the epidemiology of OM in dogs must first be detailed with respect to the severity, time course, and risk factors for the condition. In addition, proper tools for baseline evaluation and the ongoing assessment of oral discomfort and oropharyngeal function in dogs must be developed before this model can be used to gather preclinical information that will be useful in translation to potential human clinical applications. In this project, we propose to follow longitudinally a cohort of at least 80 dogs with OM from initiation to the completion of RT and at the 1 month follow up exam. We will detail the epidemiology of OM in canine HNC (Aim 1) and validate outcome assessments that are based on those used in pain research in humans but which have been adapted for use in dogs (Aims 2 and 3). Based on our preliminary results, we hypothesize that this canine model will serve as a valuable preclinical research model for future human trials.

Public Health Relevance

The development of oral ulcerations, called oral mucositis, is the most debilitating side effect of radiation therapy for patients with cancers of the head and neck. Oral mucositis causes pain which affects the patient's quality of life and can lead to limits in the maximum dose of radiation therapy delivered, which negatively affects the curability of the disease. This project involves the validation of a canine model that will allow for testing of new interventions for the prevention and treatment of OM, which could ultimately lead to reduced patient suffering and improve cancer treatment outcome.

National Institute of Health (NIH)
National Institute of Dental & Craniofacial Research (NIDCR)
Exploratory/Developmental Grants (R21)
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Radiation Therapeutics and Biology Study Section (RTB)
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Kusiak, John W
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University of Pennsylvania
Other Clinical Sciences
Schools of Veterinary Medicine
United States
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