Abstract
Osteoradionecrosis (ORN) is one of the most feared side effects of radiotherapy following cancers of the upper aero-digestive tract and leading to severe functional defects in patients. Today, our lack of knowledge about the physiopathology restricts the development of new treatments. In this study, we refined the ORN rat model and quantitatively studied the progression of the disease. We tested the impact of radiation doses from 20 to 40 Gy, delivered with incident 4MV X-ray beams on the left mandible of the inbred Lewis Rat. We used micro-computed tomography (µCT) to obtain in vivo images for longitudinal bone imaging and ex vivo images after animal perfusion with barium sulphate contrast agent for vessel imaging. We compared quantification methods by analyzing 3D images and 2D measurements to determine the most appropriate and precise method according to the degree of damage. We defined 25 Gy as the minimum irradiation dose combined with the median molar extraction necessary to develop non-regenerative bone necrosis. µCT image analyses were correlated with clinical and histological analyses. This refined model and accurate methods for bone and vessel quantification will improve our knowledge of the progression of ORN pathology and allow us to test the efficacy of new regenerative medicine procedures.
Highlights
Osteoradionecrosis (ORN) is one of the most feared side effects of radiotherapy following cancers of the upper aero-digestive tract and leading to severe functional defects in patients
A retrospective study has demonstrated that new radiotherapy techniques, such as IntensityModulated RadioTherapy (IMRT) or Volumetric Modulated Arc Therapy (VMAT), do not further reduce the incidence of mandibular ORN1
ORN is a progressive disease leading to bone necrosis in an irradiated field unrelated to tumor recurrence and that fails to heal over 3 to 6 months
Summary
Osteoradionecrosis (ORN) is one of the most feared side effects of radiotherapy following cancers of the upper aero-digestive tract and leading to severe functional defects in patients. ΜCT image analyses were correlated with clinical and histological analyses This refined model and accurate methods for bone and vessel quantification will improve our knowledge of the progression of ORN pathology and allow us to test the efficacy of new regenerative medicine procedures. Treatment is based on surgical resection of the tumor combined with external radiation therapy and, in certain cases, chemotherapy. These treatments induce side effects and sequelae in the orofacial sphere, considerably altering the patient’s quality of life. It is primordial to set up a pertinent animal model reproducing the human disease and allowing for the analysis of quantitative methods to test the efficacy of different combinations of treatments over time, based on different parameters
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