Squamous cell carcinoma of the oropharynx, UICC TNM (8th ed.) stage cT1–2N+ or cT3–4cN0–3 M0, treated with curative intent RT (TD 66–70 Gy, bilateral neck irradiation) with or without concurrent chemotherapy | Newly diagnosed malignant tumor anywhere in the body within the last two years |
Two years or more after treatment with no evidence of locoregional recurrence or systemic metastasis | Active smoker |
Nonsmoker or former smoker (quit smoking ≥ 2 years ago) | Use of xerogenic medications (e.g., tricyclic antidepressants, antipsychotics, decongestants, bronchodilators, antihypertensive agents such as beta blockers and diuretics, antihistamines, hypnotic sedatives, opioids, and muscle relaxants) |
Mean radiation dose > 26 Gy to each of the parotid glands and > 35 Gy to each of the submandibular glands | Other salivary gland disorders (e.g., Sjoegren's syndrome, scleroderma, sialolithiasis, etc.) |
Grade 2 or 3 xerostomia as assessed by the CTCAE v5.0 scale | Patients receiving anticoagulant therapy that cannot be discontinued during the procedure |
Clinically decreased salivation and hyposalivation (unstimulated total salivary flow of 0.05–0.20 ml/min) | Pregnancy or planned pregnancy within the next two years |
Age between 18–75 years | Breastfeeding |
Both sexes | Active, uncontrolled infection |
Signed “Informed Consent Form” to participate in the study | Other medical (including psychiatric) conditions that, in the opinion of the investigators, preclude safe administration of the planned therapy and completion of follow-up visits |
Known substance abuse or alcoholism |
Patient screening with clinical and objective evaluation of xerostomia |
X | |||||
Complete blood count, biochemistry | X | X | X | |||
Coagulation profile | X | |||||
Measurement of unstimulated and stimulated salivary flow rate | X | X | X | |||
Determination of salivary composition | X | X | X | |||
Magnetic resonance imaging | X | X | X | |||
US elastography | X | X | X | |||
Scintigraphy with [99mTc]Tc-HMPAO labeled MSCs | X | |||||
Scintigraphy with ( |
X | X | ||||
Core needle biopsy of the gland |
X | X | ||||
Visual Analog Scale questionnaire | X | X | X | |||
Xerostomia Questionnaire | X | X | X | |||
EORTC QLQ-H&N35 | X | X | X | |||
Toxicity assessment, CTCAE v.5 | X | X | X | X | X |
Evaluation of the safety of administration of allogeneic MSCs | Adverse event assessment (CTCAE v.5 criteria): pain at application site, mouth sensation, infection | From the start of therapy to the last follow-up (days 1, 5, 28, and 120) |
Efficacy of the procedure | Measurement of unstimulated/stimulated salivary flow and saliva composition | During recruitment, day 28 and 120 post-procedure |
Assessment of subjective degree of xerostomia (questionnaires) | During recruitment, days 28 and 120 after the procedure | |
Immediately after the procedure (day 0) | ||
Scintigraphic evaluation of grafting, retention, and migration of allogeneic MSCs | During recruitment, on days 28 and 120 after the procedure | |
Assessment of patients’ quality of life | ||
Radiological changes of the salivary tissue | Magnetic resonance imaging (MRI): volume, signal, and diffusivity changes | During recruitment, on days 28 and 120 after procedure |
Ultrasonography (US): consistency (firmness) | ||
Functional changes of the salivary tissue | Scintigraphy with ([99mTc]TcO4− (pertechnetate): uptake of radioisotope in parenchyma, ejection fraction | During recruitment, on days 28 and 120 after procedure |
Morphological changes of the salivary tissue | Core needle biopsy specimens: composition, inflammatory infiltrate, metaplasia, reactive changes | During recruitment, on day 120 after the procedure |