Page 13 - Effects of radiotherapy and hyperbaric oxygen therapy on oral microcirculation Renee Helmers

General introduction and outline of the thesis
RADIOTHERAPY SIDE EFFECTS IN HEAD AND NECK 1
In the Netherlands head and neck (HN) cancer has an incidence of 17 per 100,000 persons with an increasing 10-year survival rate over the last decades [the Netherlands Comprehensive Cancer Organization]. With this increasing survival rate long-term side effects of cancer treatment become more relevant as they negatively influence quality of life (QoL). Radiotherapy (RT) plays an important part in the treatment of HN malignancies and is known for inducing late side effects that develop over several months to years after treatment. Although RT regimen are aimed at protecting healthy tissue as much as possible, healthy peritumoral tissue will inevitably be affected to some extent.
Acute irradiation injury develops during the course of treatment and predominantly affects tissues with rapid cell division such as the oral mucosa, which can result in oral mucositis. Subsequent to the acute injury phase of oral mucositis, fibrin leaks into surrounding tissues driven by the release of vasoactive cytokines. Progression into the late injury state results in blockage of vascular lumen which induces tissue hypoperfusion and regional hypoxia.43 It is not entirely clear if late tissue injury is caused by direct damage to mesenchymal cells, or indirectly through vascular injury or a combination of both.43 In the 80’s Marx proposed the 3 H’s theory in which late irradiation damage in tissue is expressed in a hypovascular, hypocellular and hypoxic tissue state.23,24 More recent an alternative theory was proposed by Delanian et al. in which radiation-induced fibrosis caused fibroatrophy in soft tissue and bone by aberrant fibroblast activity and extracellular matrix disruption.9 This thesis will mainly focus on microvascular alterations associated with RT.
Late radiation tissue injury (LRTI) in the HN region usually manifests from 3-6 months after start of RT and can result in damage to salivary glands, dentition, periodontium, oral mucosa, muscles, nerves, cartilage and bone.7,38,43 The progress of radiation induced tissue deterioration can ultimately result in necrosis of soft tissue, cartilage and bone (osteoradionecrosis (ORN)). The definition of ORN is described as “exposed and necrotic bone associated with ulcerated or necrotic surrounding soft tissue which persists for greater than 3 months in an area that had been previously irradiated (not caused by tumor recurrence)”.32 ORN in HN cancer patients has a reported incidence of 2-22%27,29,39 and is a feared late complication as it could lead to mutilation and severe impairment of function. Due to the compromised health state
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