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2013 Tim Dijkema

Salivary gland sparing radiotherapy

Dry mouth or xerostomia is the most frequently observed side-effect of radiotherapy (RT) in the head-and-neck region and is caused by salivary gland damage. The aim of this thesis was to determine the RT dose-response relationships for the parotid and submandibular glands and to investigate the effect of their sparing on patient-reported xerostomia after RT for tumors of the oropharynx. The mean parotid gland dose can be used to estimate the risk of significant functional decline (flow reduction to <25% of baseline) at 1 year after RT. Parotid gland NTCP (normal tissue complication probability) at 1 year increases gradually with increasing mean dose, with no threshold dose present. Early after RT, mean dose based models do not fully describe the effects of radiation on the parotid glands. The submandibular glands produce most saliva in the unstimulated state between meals and at night. Decline in submandibular gland function after RT is particularly linked to complaints of dry mouth at night and the associated sleep disturbances. In contrast to the parotid glands, the submandibular glands produce mucins, which retain water and help to keep the oral mucosa in a hydrated state. These functional aspects of the submandibular glands may explain why, after RT for head-and-neck cancer, parotid gland sparing alone does not seem to improve patient-reported xerostomia in a clinically significant way. The submandibular glands can show delayed functional decline at mean doses exceeding 40 Gy, but exhibit comparable radiosensitivity (in terms of volumetric output) compared with the parotid glands at 1 year after RT. Sparing the submandibular gland with intensity-modulated radiotherapy for oropharyngeal cancer is more challenging than parotid gland sparing however. The gland ipsilateral to the tumor inevitably receives a high radiation dose. With modern RT techniques, sparing of the contralateral submandibular gland is feasible in selected patients with localized tumors not crossing the midline. Sparing is not associated with an increased risk of (locoregional) disease recurrence. Compared with parotid gland sparing alone, reducing the mean dose to the contralateral submandibular gland (<40 Gy) and to both parotid glands is associated with a reduction of severe patient-reported xerostomia from 67 to 42% at 1 year after RT.