Christian Grønhøj1, David H Jensen2, Peter Vester-Glowinski3, Siri Beier Jensen4, Allan Bardow5, Roberto S Oliveri6, Lea Munthe Fog6, Lena Specht7, Carsten Thomsen8, Sune Darkner9, Michael Jensen9, Vera Müller10, Katalin Kiss10, Tina Agander10, Elo Andersen11, Anne Fischer-Nielsen6, Christian von Buchwald2. 1. Department of Otorhinolaryngology-Head and Neck Surgery and Audiology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark. Electronic address: christian.groenhoej@regionh.dk. 2. Department of Otorhinolaryngology-Head and Neck Surgery and Audiology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark. 3. Department of Plastic Surgery, Breast Surgery and Burns Treatment, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark. 4. Department of Dentistry and Oral Health, Faculty of Health, Aarhus University, Aarhus, Denmark; Section of Oral Medicine, Department of Odontology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. 5. Section of Oral Medicine, Department of Odontology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. 6. Cell Therapy Facility, The Blood Bank, Department of Clinical Immunology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark. 7. Department of Oncology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark. 8. Department of Radiology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark. 9. Department of Computer Science, University of Copenhagen, Copenhagen, Denmark. 10. Department of Pathology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark. 11. Department of Oncology, Herlev Hospital, University of Copenhagen, Copenhagen, Denmark.
Abstract
BACKGROUND: Salivary gland hypofunction and xerostomia are major complications to head and neck radiotherapy. This trial assessed the safety and efficacy of adipose tissue-derived mesenchymal stem cell (ASC) therapy for radiation-induced xerostomia. PATIENT AND METHODS: This randomized, placebo-controlled phase 1/2 trial included 30 patients, randomized in a 1:1 ratio to receive ultrasound-guided transplantation of ASCs or placebo to the submandibular glands. Patients had previously received radiotherapy for a T1-2, N0-2A, human papillomavirus-positive, oropharyngeal squamous cell carcinoma. The primary outcome was the change in unstimulated whole salivary flow rate, measured before and after the intervention. All assessments were performed one month prior (baseline) and one and four months following ASC or placebo administration. RESULTS: No adverse events were detected. Unstimulated whole salivary flow rates significantly increased in the ASC-arm at one (33%; P = .048) and four months (50%; P = .003), but not in the placebo-arm (P = .6 and P = .8), compared to baseline. The ASC-arm symptom scores significantly decreased on the xerostomia and VAS questionnaires, in the domains of thirst (-22%, P = .035) and difficulties in eating solid foods (-2%, P = .008) after four months compared to baseline. The ASC-arm showed significantly improved salivary gland functions of inorganic element secretion and absorption, at baseline and four months, compared to the placebo-arm. Core-needle biopsies showed increases in serous gland tissue and decreases in adipose and connective tissues in the ASC-arm compared to the placebo-arm (P = .04 and P = .02, respectively). MRIs showed no significant differences between groups in gland size or intensity (P < .05). CONCLUSIONS: ASC therapy for radiation-induced hypofunction and xerostomia was safe and significantly improved salivary gland functions and patient-reported outcomes. These results should encourage further exploratory and confirmatory trials.
RCT Entities:
BACKGROUND:Salivary gland hypofunction and xerostomia are major complications to head and neck radiotherapy. This trial assessed the safety and efficacy of adipose tissue-derived mesenchymal stem cell (ASC) therapy for radiation-induced xerostomia. PATIENT AND METHODS: This randomized, placebo-controlled phase 1/2 trial included 30 patients, randomized in a 1:1 ratio to receive ultrasound-guided transplantation of ASCs or placebo to the submandibular glands. Patients had previously received radiotherapy for a T1-2, N0-2A, human papillomavirus-positive, oropharyngeal squamous cell carcinoma. The primary outcome was the change in unstimulated whole salivary flow rate, measured before and after the intervention. All assessments were performed one month prior (baseline) and one and four months following ASC or placebo administration. RESULTS: No adverse events were detected. Unstimulated whole salivary flow rates significantly increased in the ASC-arm at one (33%; P = .048) and four months (50%; P = .003), but not in the placebo-arm (P = .6 and P = .8), compared to baseline. The ASC-arm symptom scores significantly decreased on the xerostomia and VAS questionnaires, in the domains of thirst (-22%, P = .035) and difficulties in eating solid foods (-2%, P = .008) after four months compared to baseline. The ASC-arm showed significantly improved salivary gland functions of inorganic element secretion and absorption, at baseline and four months, compared to the placebo-arm. Core-needle biopsies showed increases in serous gland tissue and decreases in adipose and connective tissues in the ASC-arm compared to the placebo-arm (P = .04 and P = .02, respectively). MRIs showed no significant differences between groups in gland size or intensity (P < .05). CONCLUSIONS: ASC therapy for radiation-induced hypofunction and xerostomia was safe and significantly improved salivary gland functions and patient-reported outcomes. These results should encourage further exploratory and confirmatory trials.
Authors: Alexander Rühle; Ramon Lopez Perez; Bingwen Zou; Anca-Ligia Grosu; Peter E Huber; Nils H Nicolay Journal: Stem Cell Rev Rep Date: 2019-06 Impact factor: 5.739
Authors: Grace C Blitzer; Nicole M Rogus-Pulia; Ryan J Mattison; Tomy Varghese; Olga Ganz; Richard Chappell; Jacques Galipeau; Kimberly A McDowell; Ross O Meyers; Tiffany A Glazer; Randall J Kimple Journal: Cytotherapy Date: 2022-02-16 Impact factor: 5.414
Authors: Per Marcus Jansson; Charlotte Duch Lynggaard; Amanda Fenger Carlander; Siri Beier Jensen; Bjarke Follin; Cecilie Hoeeg; Birgitte Saima Kousholt; Rasmus Tolstrup Larsen; Christian Grønhøj; Kathrine Kronberg Jakobsen; Susie Rimborg; Anne Fischer-Nielsen; Julia M L Menon; Christian von Buchwald Journal: Syst Rev Date: 2022-04-18
Authors: Mark Jakob; Mario Hambrecht; Jennifer L Spiegel; Julia Kitz; Martin Canis; Ralf Dressel; Katrin Streckfuss-Bömeke Journal: Cells Date: 2020-12-28 Impact factor: 6.600