. 2025 Jan 10;33(2):87.

doi: 10.1007/s00520-024-09113-x.

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

Valeria Mercadante¹, Derek K Smith², Ragda Abdalla-Aslan^{3

4}, Ana Andabak-Rogulj⁵, Michael T Brennan⁶, Graziella Chagas Jaguar⁷, Haley Clark⁸, Eduardo Rodrigues Fregnani⁹, Luiz Alcino Gueiros¹⁰, Allan Hovan¹¹, Seema Kurup¹², Alexa M G A Laheij^{13

14}, Charlotte Duch Lynggaard¹⁵, Joel J Napeñas⁶, Douglas E Peterson¹⁶, Sharon Elad¹⁷, Stephanie Van Leeuwen¹⁸, Arjan Vissink¹⁹, Jonn Wu²⁰, Deborah P Saunders²¹, Siri Beier Jensen²²

Affiliations

¹ Eastman Dental Institute, University College London, London, England. v.mercadante@ucl.ac.uk.
² Vanderbilt University, Nashville, TN, USA.
³ Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.
⁴ Department of Oral and Maxillofacial Surgery, Rambam Health Care Campus, Haifa, Israel.
⁵ Department of Oral Medicine, University of Zagreb School of Dental Medicine, Zagreb, Croatia.
⁶ Department of Oral Medicine/Oral & Maxillofacial Surgery, Atrium Health Carolinas Medical Center, Charlotte, NC, USA.
⁷ Stomatology Department - A.C. Camargo Cancer Center, Sao Paulo, Brazil.
⁸ Department of Medical Physics, BC Cancer, Surrey, BC, Canada.
⁹ Centro de Oncologia Molecular, Hospital Sírio-Libanês, São Paulo, Brazil.
¹⁰ Departamento de Clínica E Odontologia Preventiva, Universidade Federal de Pernambuco, Recife, Brazil.
¹¹ Oral Oncology/Dentistry, British Columbia Cancer Agency-Vancouver Centre, Vancouver, BC, Canada.
¹² Department of Oral & Maxillofacial Diagnostic Sciences, School of Dental Medicine, UConn Health, Farmington, CT, USA.
¹³ Department of Oral Medicine, Academic Centre for Dentistry Amsterdam, University of Amsterdam and VU University, Amsterdam, The Netherlands.
¹⁴ Department of Oral and Maxillofacial Surgery, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.
¹⁵ Department of Otorhinolaryngology, Head and Neck Surgery and Audiology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
¹⁶ School of Dental Medicine and Neag Comprehensive Cancer Center, UConn Health, Farmington, CT, USA.
¹⁷ Eastman Institute for Oral Health, University of Rochester Medical Center, Rochester, NY, USA.
¹⁸ Department of Dentistry, Radboud University Medical Center, Nijmegen, The Netherlands.
¹⁹ Department of Oral & Maxillofacial Surgery, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
²⁰ British Columbia Cancer Agency, University of British Columbia, Vancouver, Canada.
²¹ North East Cancer Center, Health Sciences North, Northern Ontario School of Medicine, Sudbury, ON, Canada.
²² Department of Dentistry and Oral Health, Faculty of Health, Aarhus University, Aarhus, Denmark.

PMID: 39792256
PMCID: PMC11723892
DOI: 10.1007/s00520-024-09113-x

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

Valeria Mercadante et al. Support Care Cancer. 2025.

. 2025 Jan 10;33(2):87.

doi: 10.1007/s00520-024-09113-x.

Authors

Affiliations

¹ Eastman Dental Institute, University College London, London, England. v.mercadante@ucl.ac.uk.
² Vanderbilt University, Nashville, TN, USA.
³ Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.
⁴ Department of Oral and Maxillofacial Surgery, Rambam Health Care Campus, Haifa, Israel.
⁵ Department of Oral Medicine, University of Zagreb School of Dental Medicine, Zagreb, Croatia.
⁶ Department of Oral Medicine/Oral & Maxillofacial Surgery, Atrium Health Carolinas Medical Center, Charlotte, NC, USA.
⁷ Stomatology Department - A.C. Camargo Cancer Center, Sao Paulo, Brazil.
⁸ Department of Medical Physics, BC Cancer, Surrey, BC, Canada.
⁹ Centro de Oncologia Molecular, Hospital Sírio-Libanês, São Paulo, Brazil.
¹⁰ Departamento de Clínica E Odontologia Preventiva, Universidade Federal de Pernambuco, Recife, Brazil.
¹¹ Oral Oncology/Dentistry, British Columbia Cancer Agency-Vancouver Centre, Vancouver, BC, Canada.
¹² Department of Oral & Maxillofacial Diagnostic Sciences, School of Dental Medicine, UConn Health, Farmington, CT, USA.
¹³ Department of Oral Medicine, Academic Centre for Dentistry Amsterdam, University of Amsterdam and VU University, Amsterdam, The Netherlands.
¹⁴ Department of Oral and Maxillofacial Surgery, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.
¹⁵ Department of Otorhinolaryngology, Head and Neck Surgery and Audiology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
¹⁶ School of Dental Medicine and Neag Comprehensive Cancer Center, UConn Health, Farmington, CT, USA.
¹⁷ Eastman Institute for Oral Health, University of Rochester Medical Center, Rochester, NY, USA.
¹⁸ Department of Dentistry, Radboud University Medical Center, Nijmegen, The Netherlands.
¹⁹ Department of Oral & Maxillofacial Surgery, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
²⁰ British Columbia Cancer Agency, University of British Columbia, Vancouver, Canada.
²¹ North East Cancer Center, Health Sciences North, Northern Ontario School of Medicine, Sudbury, ON, Canada.
²² Department of Dentistry and Oral Health, Faculty of Health, Aarhus University, Aarhus, Denmark.

PMID: 39792256
PMCID: PMC11723892
DOI: 10.1007/s00520-024-09113-x

Erratum in

Correction to: A systematic review of salivary gland hypofunction and/or xerostomia induced by non‑surgical cancer therapies: prevention strategies.
Mercadante V, Smith DK, Abdalla-Aslan R, Andabak-Rogulj A, Brennan MT, Jaguar GC, Clark H, Fregnani ER, Gueiros LA, Hovan A, Kurup S, Laheij AMGA, Lynggaard CD, Napeñas JJ, Peterson DE, Elad S, Van Leeuwen S, Vissink A, Wu J, Saunders DP, Jensen SB. Mercadante V, et al. Support Care Cancer. 2025 Mar 20;33(4):305. doi: 10.1007/s00520-025-09327-7. Support Care Cancer. 2025. PMID: 40111560 Free PMC article. No abstract available.

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.

Keywords: Checkpoint inhibitors; Chemotherapy; Radiotherapy; Salivary gland hypofunction; Xerostomia.

PubMed Disclaimer

Conflict of interest statement

Declarations. Competing interests: The authors declare no competing interests.

Figures

**Fig. 1**
PRISMA (Preferred Items for Systematic Review and Meta-Analysis) flow diagram of the systematic review

See this image and copyright information in PMC

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

Affiliations

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

Authors

Affiliations

Erratum in

Abstract

Conflict of interest statement

Figures

References

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MeSH terms

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LinkOut - more resources

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Medical

Research Materials