Optimization of radiotherapy to reduce xerostomia is difficult, because many gland locations cannot be seen with current imaging modalities and biological dose-effect are currently insufficiently understood. PSMA PET is a new diagnostic instrument which can visualize the presence of vital acinar cells in salivary gland locations throughout the head and neck, with a sensitive and quantitative signal. A reduction of PSMA accumulation in salivary glands is thought to correlate with loss of vital acinar cells. The PET images can be correlated with radiotherapy dose distributions in gland-based or voxel-based evaluations. This makes PSMA PET a suitable instrument to derive the radiobiological dose-effect relations that are required to develop better and gland-specific dose constraints for radiotherapy. The results of this study can contribute to lower toxicity and better quality of life in patients treated with high-dose radiotherapy in the head and neck.

Primary objective of this prospective observational study is to determine the gland-based dose-effect relation between conventionally fractionated radiotherapy (RT) and long-term loss of acinar cells, per salivary gland type. The study population consists of a maximum of 20 patients with HNSCC referred for high-dose (CC)RT. There is no therapeutic intervention. Diagnostic intervention is PSMA PET/CT.

Inclusion Criteria:

• HNSCC of the head-neck area, cTx-4 N0-3 M0
• Accepted for EBRT in a conventionally fractionated schedule of 6-7 weeks.

Exclusion Criteria:

• Age <18y
• Pregnancy or lactation
• Participation in conflicting studies, e.g. with non-standard treatment and/or imaging
• Inability to provide informed consent

Patients with proven mucosal squamous cell carcinoma in the head-neck area who are referred for high dose EBRT based on current clinical criteria. AVL currently treats multiple new patients per week, and with an inclusion rate of 50% this observational study can complete inclusion well within one year. The study will close after 6 months of follow-up of the last included patient, for an expected total study duration of 1.5 years.