A systematic review of salivary gland hypofunction and/or xerostomia induced by non-surgical cancer therapies: prevention strategies.

Allan Hovan, Jonn Wu, Stephanie Van Leeuwen, Charlotte Duch Lynggaard, Alexa M G A Laheij, Seema Kurup, Haley Clark, Valeria Mercadante, Ana Andabak-Rogulj, Derek K Smith, Graziella Chagas Jaguar, Ragda Abdalla-Aslan, Deborah P Saunders, Michael T Brennan, Arjan Vissink, Douglas E Peterson, Siri Beier Jensen, Sharon Elad, Joel J Napeñas, Luiz Alcino Gueiros, Eduardo Rodrigues Fregnani

Journal: Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer 2025;33(2):87

PMID: 39792256

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Abstract

PURPOSE

This systematic review aimed to assess the updated literature for the prevention of salivary gland hypofunction and xerostomia induced by non-surgical cancer therapies.

METHODS

Electronic databases of MEDLINE/PubMed, EMBASE, and Cochrane Library were searched for randomized controlled trials (RCT) that investigated interventions to prevent salivary gland hypofunction and/or xerostomia. Literature search began from the 2010 systematic review publications from the Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology (MASCC/ISOO) up to February 2024. Two independent reviewers extracted information regarding study design, study population, cancer treatment modality, interventions, outcome measures, methods, results, risk of bias (RoB version 2), and conclusions for each article.

RESULTS

A total of 51 publications addressing preventive interventions were included. Eight RCTs on tissue-sparing radiation modalities were included showing significant lower prevalence of xerostomia, with unclear effect on salivary gland hypofunction. Three RCTs on preventive acupuncture showed reduced prevalence of xerostomia but not of salivary gland hypofunction. Two RCTs on muscarinic agonist stimulation with bethanechol suggested a preventive effect on saliva flow rate and xerostomia in patients undergoing head and neck radiation or radioactive iodine therapy. Two studies on submandibular gland transfer showed higher salivary flow rates compared to pilocarpine and lower prevalence of xerostomia compared to no active intervention. There is insufficient evidence on the effectiveness of vitamin E, amifostine, photobiomodulation, and miscellaneous preventive interventions.

CONCLUSION

This systematic review continues to support the potential of tissue-sparing tecniques and intensity-modulated radiation therapy (IMRT) to preserve salivary gland function in patients with head and neck cancer, with limited evidence on other preventive strategies, including acupuncture and bethanecol. Preventive focus should be on optimized and new approaches developed to further reduce radiation dose to the parotid, the submandibular, and minor salivary glands. As these glands are major contributors to moistening of the oral cavity, limiting the radiation dose to the salivary glands through various modalities has demonstrated reduction in prevalence and severity of salivary gland hypofunction and xerostomia. There remains no evidence on preventive approaches for checkpoint inhibitors and other biologicals due to the lack of RCTs.

Address: Eastman Dental Institute, University College London, London, England. [email protected].; Vanderbilt University, Nashville, TN, USA.; Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.; Department of Oral and Maxillofacial Surgery, Rambam Health Care Campus, Haifa, Israel.; Department of Oral Medicine, University of Zagreb School of Dental Medicine, Zagreb, Croatia.; Department of Oral Medicine/Oral & Maxillofacial Surgery, Atrium Health Carolinas Medical Center, Charlotte, NC, USA.; Stomatology Department - A.C. Camargo Cancer Center, Sao Paulo, Brazil.; Department of Medical Physics, BC Cancer, Surrey, BC, Canada.; Centro de Oncologia Molecular, Hospital Sírio-Libanês, São Paulo, Brazil.; Departamento de Clínica E Odontologia Preventiva, Universidade Federal de Pernambuco, Recife, Brazil.; Oral Oncology/Dentistry, British Columbia Cancer Agency-Vancouver Centre, Vancouver, BC, Canada.; Department of Oral & Maxillofacial Diagnostic Sciences, School of Dental Medicine, UConn Health, Farmington, CT, USA.; Department of Oral Medicine, Academic Centre for Dentistry Amsterdam, University of Amsterdam and VU University, Amsterdam, The Netherlands.; Department of Oral and Maxillofacial Surgery, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.; Department of Otorhinolaryngology, Head and Neck Surgery and Audiology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.; School of Dental Medicine and Neag Comprehensive Cancer Center, UConn Health, Farmington, CT, USA.; Eastman Institute for Oral Health, University of Rochester Medical Center, Rochester, NY, USA.; Department of Dentistry, Radboud University Medical Center, Nijmegen, The Netherlands.; Department of Oral & Maxillofacial Surgery, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.; British Columbia Cancer Agency, University of British Columbia, Vancouver, Canada.; North East Cancer Center, Health Sciences North, Northern Ontario School of Medicine, Sudbury, ON, Canada.; Department of Dentistry and Oral Health, Faculty of Health, Aarhus University, Aarhus, Denmark.

DOI: 10.1007/s00520-024-09113-x

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https://dx.doi.org/10.1007/s00520-024-09113-x

MeSH Terms: Humans, Xerostomia, Neoplasms, Randomized Controlled Trials as Topic, Salivary Gland Diseases, Salivary Glands, Acupuncture Therapy, Muscarinic Agonists