Stem cell sparing radiotherapy: the road towards clinical introduction

Many head and neck cancer patients experience permanent side-effects after radiotherapy, such as the feeling of a dry mouth (“xerostomia”). The risk of xerostomia is related to the radiation dose received by the parotid glands. However, preclinical studies showed that the stem cells are critical in the parotid gland’s response to radiation. In this thesis, we confirmed that a higher radiation dose to the stem cells increases xerostomia scores by reducing the parotid gland saliva production. Next, a clinical trial was performed to test whether stem cell sparing radiotherapy (SCS-RT) would preserve saliva production better than whole parotid gland sparing radiotherapy. The trial demonstrated that dose to the stem cells is a stronger risk factor for xerostomia than dose to the whole parotid gland. Subsequently, this enhanced effect of stem cell dose on the risk of xerostomia was incorporated in prediction models for xerostomia to assist SCS-RT in clinical practice. To further facilitate the clinical introduction of SCS-RT, we provided recommendations to reduce stem cell dose without compromising the cancer treatment or the prevention of other side-effects. The use of these recommendations can lower the risk of xerostomia in patients treated with photon therapy. Finally, a multicentre study established that SCS-RT can also be applied by other institutes, each with their own standard practice. Taken together, this thesis demonstrated that SCS-RT can be adopted in daily clinical practice to further reduce the risk of xerostomia in head and neck cancer survivors.