Repeated Mesenchymal Stem Cell Therapy for Radiation-Induced Hyposalivation and Xerostomia in Head and Neck Cancer Survivors

Unstimulated whole salivary flow rate measured in mL/min

Stimulated whole salivary flow rate measured in mL/min

For evaluation of the participants´ perception of xerostomia, the participants will answer validated questionnaires in Danish.

For evaluation of the participants´ perception of xerostomia, the participants will answer validated questionnaires in Danish. Patients will fill out the EORTC-QLQ- H&N35 (evaluates overall implications of the xerostomia) for the following domains:

• HNDR: dry mouth
• HNSS: sticky saliva
• HNSW: swallowing

Measured by positivity of de novo drug specific antibodies (binary outcome)

Goal attainment Scale (GAS) was developed in 1968 for assessing outcomes in mental health and has since been updated[36]. Now it is used in a wide variety of settings. It is a qualitative patient reported outcome measure. GAS can be beneficial in drug trials where patients have heterogenic symptoms of the disease[37]. The patient, supported by the health professional, picks 3 personal goals to be measured throughout the study period. The goals must be related to the disease and treatment. In this study 3 goals could be: 1. Ability to sleep better at night, ability to eat more solid foods, and less mouth pain. The goals are evaluated at baseline and at each follow up, following the scoring system seen in figure 1. Statistics are calculated from T-scores.

Evaluated by serious adverse events (SAEs), Suspected Unexpected Serious Adverse Reactions (SUSARs), treatment-related adverse events, and deaths.

The 5-point transition scale is critical in the exploratory secondary objective of developing Minimal Important Differences (MIDs) for all the outcome measures applied in the trial because it provides a subjective, patient-centered anchor to assess meaningful change. The scale, which typically ranges from "much worse" to "much better," captures participants' perceptions of change in their condition over time. By linking participants' responses on this scale to corresponding changes in clinical outcome measures, the transition scale helps identify the smallest change in those measures that is considered important or beneficial by the participants themselves. This subjective assessment of change is essential for establishing MIDs, as it ensures that the derived thresholds reflect clinically relevant improvements or deteriorations from the patients' perspectives.