11 General introduction 1 Side-effects of the treatment Surgical resection can be mutilating and result in altered oral anatomy, tooth loss, reduction in maximum mouth opening (MMO), and soft tissue and bone defects. These side-effects can have an impact on patients’ outer appearance, social interaction and oral functions, such as mastication, deglutition, and phonetics [14-17]. For example, treatment of malignant diseases of the tongue and/or floor of mouth can significantly worsen tongue function, masticatory performance, bite force, and dental status [17-20]. Treatment of malignant diseases of the maxilla and midface, can lead to leakage through the nose, impaired speech intelligibility due to loss of air, and impaired masticatory performance [21, 22]. RT also causes damage to normal tissues located within the radiation field, e.g. skin, soft tissues of the neck, salivary glands, oral mucosa, bones, dentition, chewing and swallowing muscles, and the temporomandibular joint. The clinical consequences of RT can be divided in acute and late (lifelong) side effects. Acute side effects include mucositis, hyposalivation, loss of taste, dermatitis, pain, hair loss, and dysphagia. Late side effects include soft tissue fibrosis, xerostomia, osteoradionecrosis (ORN), radiation caries, and trismus [23]. Hyposalivation leads to a deterioration of the lubrication of the oral cavity. This can cause radiation caries, an increase in periodontal problems, dysphagia, speech problems and problems wearing dentures. These side effects impact QoL and may persist forever [16, 24-26]. The most feared side effect is ORN [27]. ORN is defined as ‘irradiated bone that becomes devitalized and is exposed through the overlying skin or mucosa, without tumor recurrence, and does not heal within 3 months’ [28]. Although the risk of ORN has decreased to nearly 5% today [27, 29] due to careful patient selection, improved pre- and post-treatment dental care and individualized RT dose calculation algorithms, the impact of ORN on oral function and QoL remains catastrophic [30-33]. CRT or bioradiotherapy (BRT) can cause severe toxicity both during treatment (acute symptoms) and in the longer term. In addition to the acute symptoms of RT itself, dysphagia, oral pain, taste (dysgeusia or hypogeusia) and smell (dysosmia or hyposmia) disturbances, nausea, and vomiting are more common when chemotherapy or biotherapy is added to RT. These symptoms interfere
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