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

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

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

Oral Medicine

Research output: Contribution to Journal › Review article › Academic › peer-review

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.

Original language	English
Article number	87
Pages (from-to)	1-25
Number of pages	25
Journal	Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer
Volume	33
Early online date	10 Jan 2025
DOIs	https://doi.org/10.1007/s00520-024-09113-x
Publication status	Published - Feb 2025

Bibliographical note

Publisher Copyright:
© 2025. The Author(s).

Funding

This systematic review formed the basis for the clinical practice guideline: Salivary Gland Hypofunction and/or Xerostomia Induced by Nonsurgical Cancer Therapies: ISOO/MASCC/ASCO Guideline. The authors of this systematic review and the Oral Care Study Group of the International Society of Oral Oncology (ISOO)/Multinational Association of Supportive Care in Cancer (MASCC) wish to thank the American Society of Clinical Oncology (ASCO) and the MASCC/ISOO multidisciplinary Expert Panel who evaluated the evidence and formulated the recommendations in this systematic review: Valeria Mercadante, Siri Beier Jensen, Derek K. Smith, Kari Bohlke, Jessica Bauman, Michael T. Brennan, Robert P. Coppes, Niels Jessen, Narinder K. Malhotra, Barbara Murphy, David I. Rosenthal, Arjan Vissink, Jonn Wu, Deborah P. Saunders and Douglas E. Peterson, and the ASCO Clinical Practice Guidelines Committee and the MASCC/ISOO Guideline Committee for the collaboration.

Funders	Funder number
American Society of Clinical Oncology
Multinational Association of Supportive Care in Cancer
ISOO multidisciplinary Expert Panel

Keywords

Checkpoint inhibitors
Chemotherapy
Radiotherapy
Salivary gland hypofunction
Xerostomia

Access to Document

10.1007/s00520-024-09113-x

Persistent URL (handle)

Persistent link

Cite this

Mercadante, V., Smith, D. K., Abdalla-Aslan, R., Andabak-Rogulj, A., Brennan, M. T., Jaguar, G. C., Clark, H., Fregnani, E., Gueiros, L. A., Hovan, A., Kurup, S., Laheij, A. M. G. A., Lynggaard, C. D., Napeñas, J. J., Peterson, D. E., Elad, S., Van Leeuwen, S., Vissink, A., Wu, J., ... Jensen, S. B. (2025). A systematic review of salivary gland hypofunction and/or xerostomia induced by non-surgical cancer therapies: prevention strategies. Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer, 33, 1-25. Article 87. https://doi.org/10.1007/s00520-024-09113-x

@article{620fe1ecc4a247ac82fc1b8a89b34e82,

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

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",

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

note = "Publisher Copyright: {\textcopyright} 2025. The Author(s).",

year = "2025",

month = feb,

doi = "10.1007/s00520-024-09113-x",

language = "English",

volume = "33",

pages = "1--25",

journal = "Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer",

issn = "0941-4355",

publisher = "Springer Science and Business Media Deutschland GmbH",

}

Mercadante, V, Smith, DK, Abdalla-Aslan, R, Andabak-Rogulj, A, Brennan, MT, Jaguar, GC, Clark, H, Fregnani, E, 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 2025, 'A systematic review of salivary gland hypofunction and/or xerostomia induced by non-surgical cancer therapies: prevention strategies', Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer, vol. 33, 87, pp. 1-25. https://doi.org/10.1007/s00520-024-09113-x

A systematic review of salivary gland hypofunction and/or xerostomia induced by non-surgical cancer therapies: prevention strategies. / Mercadante, Valeria; Smith, Derek K.; Abdalla-Aslan, Ragda et al.
In: Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer, Vol. 33, 87, 02.2025, p. 1-25.

Research output: Contribution to Journal › Review article › Academic › peer-review

TY - JOUR

T1 - A systematic review of salivary gland hypofunction and/or xerostomia induced by non-surgical cancer therapies

T2 - prevention strategies

AU - Mercadante, Valeria

AU - Smith, Derek K.

AU - Abdalla-Aslan, Ragda

AU - Andabak-Rogulj, Ana

AU - Brennan, Michael T.

AU - Jaguar, Graziella Chagas

AU - Clark, Haley

AU - Fregnani, Eduardo

AU - Gueiros, Luiz Alcino

AU - Hovan, Allan

AU - Kurup, Seema

AU - Laheij, Alexa M.G.A.

AU - Lynggaard, Charlotte Duch

AU - Napeñas, Joel J.

AU - Peterson, Douglas E.

AU - Elad, Sharon

AU - Van Leeuwen, Stephanie

AU - Vissink, Arjan

AU - Wu, Jonn

AU - Saunders, Deborah P.

AU - Jensen, Siri Beier

PY - 2025/2

Y1 - 2025/2

N2 - 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.

AB - 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.

KW - Checkpoint inhibitors

KW - Chemotherapy

KW - Radiotherapy

KW - Salivary gland hypofunction

KW - Xerostomia

UR - https://www.scopus.com/pages/publications/85214901539

UR - https://www.scopus.com/inward/citedby.url?scp=85214901539&partnerID=8YFLogxK

U2 - 10.1007/s00520-024-09113-x

DO - 10.1007/s00520-024-09113-x

M3 - Review article

C2 - 39792256

AN - SCOPUS:85214901539

SN - 0941-4355

VL - 33

SP - 1

EP - 25

JO - Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer

JF - Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer

M1 - 87

ER -

Mercadante V, Smith DK, Abdalla-Aslan R, Andabak-Rogulj A, Brennan MT, Jaguar GC et al. A systematic review of salivary gland hypofunction and/or xerostomia induced by non-surgical cancer therapies: prevention strategies. Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer. 2025 Feb;33:1-25. 87. Epub 2025 Jan 10. 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

Abstract

Bibliographical note

Funding

Keywords

Access to Document

Persistent URL (handle)

Other files and links

Fingerprint

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

Cite this