Parotid gland function after radiotherapy

Abstract

Radiotherapy is a common treatment for head and neck cancer patients. Unfortunately, it produces serious acute and long-term side effects to the oral cavity. One severe complication is the loss of salivary gland function, which can persists for many years. Saliva has multiple functions relating to speech, taste perception, mastication, and swallowing and bolus formation. Cleansing and dental and mucosal protection are also important functions. In this thesis, a detailed report is given on the effects of radiotherapy on changes in the parotid gland function. Different methods of measuring gland function are described. Moreover, a preventive measure to limit the gland toxicity was investigated in rodents. The radiation field and, in particular, the volume of the parotid gland tissue exposed to radiation is of notable importance with regard to the development of gland damage and hypofunction. Therefore, it is important to achieve detailed information about the size and position of the parotid gland. Great differences in size and position of the parotid glands between the patients were seen. In order to exactly define the localisation of the glands, it is essential to use CT-based simulation of radiation fields. The radiation tolerance of the parotid glands as a function of dose and volume irradiated was accurately described. The best parameter for evaluation of the parotid gland function appeared to be the flow measurement using the Lashley cups. However, if direct flow measurements are not feasible, 99mTc-pertechnetate scintigraphy might be a good alternative. Flow reduction depended on the mean parotid gland dose. For a post treatment parotid flow ratio a 25%, the TD50 (the dose to the whole organ leading to a complication probability of 50%) was found to be 31, 35 and 39 Gy at 6 weeks, 6 months and 1 year after radiotherapy respectively. The consequences of parotid gland injury are still difficult to manage. Prophylactic treatment with sialogogues like the muscarinic receptor agonist pilocarpine has been shown to have radioprotective potential. The effects of preirradiation treatment of pilocarpine on rat parotid gland function were investigated in relation to radiation dose. Pilocarpine induced compensation, which at least underlies the radioprotective effect of the drug. This effect seemed to be dependent on the amount of damage induced. Therefore, the type of fractionation scheme and the volume of the gland that lies within the radiation portal will be crucial for the effectiveness of a prophylactic pilocarpine treatment. With the more detailed knowledge on the dose/volume effects of radiation on parotid function, we can try to focus on sparing the parotid gland function. The prevention of radiation-induced loss of parotid gland function will depend on both optimal sparing radiation therapy techniques and on pharmacological agents, which can selectively interfere with the radiation-induced effects. These preventing strategies will need a joint effort of radiation-oncologists, clinical physicists and radiobiologists.