Top

Published in:

Open Access 01-12-2023 | Radiotherapy | Research

Trehalose versus carboxymethylcellulose oral spray for relieving radiation-induced xerostomia in head and neck cancer patients: a randomized controlled trial

Authors: Pornpan Piboonratanakit, Joao N. Ferreira, Kulpriya Pravinvongvuthi, Khwanchanok Maison, Ganokon Urkasemsin, Thirayu Boonroung, Anussara Prayongrat, Chawalit Lertbutsayanukul, Jeerus Sucharitakul, Anjalee Vacharaksa

Published in: BMC Oral Health | Issue 1/2023

Abstract

Background

The aim of this study was to investigate the effect of trehalose oral spray to relieve radiation-induced xerostomia on a randomized controlled trial (RCT).

Methods

Prior to RCT, the effect of trehalose (5–20%) on the epithelial growth of fetal mouse salivary gland (SG) explants was evaluated to confirm if 10% trehalose exerted the best epithelial outcomes. Participants who completed radiotherapy for head and neck cancer (HNC) treatment were enrolled in a double-blind RCT, according to inclusion and exclusion criteria as per the CONSORT statement. The experimental group (n = 35) received 10% trehalose spray, while the control group (n = 35) received carboxymethylcellulose (CMC) spray to apply intra-orally 4 times/day for 14 days. Salivary pH and unstimulated salivary flow rate were recorded pre- and post-interventions. The Xerostomia-related Quality of Life scale (XeQoLs) was filled, and scores assessed post-interventions.

Results

In the SG explant model, pro-acinar epithelial growth and mitosis was supported by 10% topical trehalose. As for RCT outcomes, salivary pH and unstimulated salivary flow rate were significantly improved after use of 10% trehalose spray when compared to CMC (p < 0.05). Participants reported an improvement of XeQoLs dimension scores after using trehalose or CMC oral sprays in terms of physical, pain/discomfort, and psychological dimensions (p < 0.05), but not social (p > 0.05). When comparing between CMC and trehalose sprays, XeQoLs total scores were not statistically different (p > 0.05).

Conclusions

The 10% trehalose spray improved salivary pH, unstimulated salivary flow rate, and the quality-of-life dimensions linked with physical, pain/discomfort, and psychological signs. The clinical efficacy of 10% trehalose spray was equivalent with CMC-based saliva substitutes for relieving radiation-induced xerostomia; therefore, trehalose may be suggested in alternative to CMC-based oral spray.(Thai Clinical Trials Registry; https://www.thaiclinicaltrials.org/ TCTR20190817004).

Available only for authorised users

De Felice F, Polimeni A, Valentini V, et al. Radiotherapy controversies and prospective in head and neck cancer: a literature-based critical review. Neoplasia. 2018;20:227–32. https://doi.org/10.1016/j.neo.2018.01.002.CrossRefPubMedPubMedCentral

Lastrucci L, Bertocci S, Bini V, et al. Xerostomia Quality of Life Scale (XeQoLS) questionnaire: validation of italian version in head and neck cancer patients. Radiol Med. 2018;123:44–7. https://doi.org/10.1007/s11547-017-0798-7.CrossRefPubMed

Dirix P, Nuyts S, Van den Bogaert W. Radiation-induced xerostomia in patients with head and neck cancer: a literature review. Cancer. 2006;107:2525–34. https://doi.org/10.1002/cncr.22302.CrossRefPubMed

Shiboski CH, Hodgson TA, Ship JA, Schiødt M. (2007) Management of salivary hypofunction during and after radiotherapy. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 103 Suppl: S66.e1-19. doi: https://doi.org/10.1016/j.tripleo.2006.11.013.

Porter SR, Scully C, Hegarty AM. An update of the etiology and management of xerostomia. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2004;97:28–46. https://doi.org/10.1016/j.tripleo.2003.07.010.CrossRefPubMed

Guchelaar HJ, Vermes A, Meerwaldt JH. Radiation-induced xerostomia: pathophysiology, clinical course and supportive treatment. Support Care Cancer. 1997;5:281–8. https://doi.org/10.1007/s005200050075.CrossRefPubMed

Deasy JO, Moiseenko V, Marks L, Chao KS, Nam J, Eisbruch A. Radiotherapy dose-volume effects on salivary gland function. Int J Radiat Oncol Biol Phys. 2010;76:58–S63. https://doi.org/10.1016/j.ijrobp.2009.06.090.CrossRef

Lin CY, Ju SS, Chia JS, Chang CH, Chang CW, Chen MH. Effects of radiotherapy on salivary gland function in patients with head and neck cancers. J Dent Sci. 2015;10:253–62.CrossRef

Dodds M, Roland S, Edgar M, Thornhill M. Saliva. A review of its role in maintaining oral health and preventing dental disease. BDJ Team. 2015;2:15123.CrossRef

10.

Plemons JM, Al-Hashimi I, Marek CL. Managing xerostomia and salivary gland hypofunction: executive summary of a report from the american Dental Association Council on Scientific Affairs. J Am Dent Assoc. 2014;145:867–73. https://doi.org/10.14219/jada.2014.44.CrossRefPubMed

11.

Silvestre-Donat FJ, Miralles-Jorda L, Martınez-Mihi V. Protocol for the clinical management of dry mouth. Med Oral. 2004;9:273–9.PubMed

12.

Ota Y, Morito A, Fujisawa K, et al. Evaluation of a moisturising micro-gel spray for prevention of cell dryness in oral mucosal cells: an in vitro study and evaluation in a clinical setting. Eur J Cancer Care. 2012;21:728–34. https://doi.org/10.1111/j.1365-2354.2012.01349.x.CrossRef

13.

Davies AN. The management of xerostomia: a review. Eur J Cancer Care. 1997;6:209–14. https://doi.org/10.1046/j.1365-2354.1997.00036.x.CrossRef

14.

Murakami M, Nishi Y, Fujishima K, et al. Impact of types of moisturizers and humidity on the residual weight and viscosity of liquid and gel oral moisturizers. J Prosthodont. 2016;25:570–5. https://doi.org/10.1111/jopr.12341.CrossRefPubMed

15.

Mardani H, Ghannadi A, Rashnavadi B, Kamali R. The effect of ginger herbal spray on reducing xerostomia in patients with type II diabetes. Avicenna J Phytomed. 2017;7:308–16.PubMedPubMedCentral

16.

Hahnel S, Behr M, Handel G, Burgers R. Saliva substitutes for the treatment of radiation-induced xerostomia-a review. Support Care Cancer. 2009;17:1331–43. https://doi.org/10.1007/s00520-009-0671-x.CrossRefPubMed

17.

Mori Y, Yano F, Shimohata N, Suzuki S, Chung UI, Takato T. Trehalose inhibits oral dryness by protecting the cell membrane. Int J Oral Maxillofac Surg. 2010;39:916–21. https://doi.org/10.1016/j.ijom.2010.04.047.CrossRefPubMed

18.

Elbein AD, Pan YT, Pastuszak I, Carroll D. New insights on trehalose: a multifunctional molecule. Glycobiology. 2003;13:17R–27R. https://doi.org/10.1093/glycob/cwg047.CrossRefPubMed

19.

Guo N, Puhlev I, Brown DR, Mansbridge J, Levine F. Trehalose expression confers desiccation tolerance on human cells. Nat Biotechnol. 2000;18:168–71. https://doi.org/10.1038/72616.CrossRefPubMed

20.

Matsuo T. Trehalose protects corneal epithelial cells from death by drying. Br J Ophthalmol. 2001;85:610–2. https://doi.org/10.1136/bjo.85.5.610.CrossRefPubMedPubMedCentral

21.

Tanaka M, Machida Y, Nukina N. A novel therapeutic strategy for polyglutamine diseases by stabilizing aggregation-prone proteins with small molecules. J Mol Med (Berl). 2005;83:343–52. https://doi.org/10.1007/s00109-004-0632-2.CrossRefPubMed

22.

Mancini RJ, Lee J, Maynard HD. Trehalose glycopolymers for stabilization of protein conjugates to environmental stressors. J Am Chem Soc. 2012;134:8474–9. https://doi.org/10.1021/ja2120234.CrossRefPubMed

23.

Luyckx J, Baudouin C. Trehalose: an intriguing disaccharide with potential for medical application in ophthalmology. Clin Ophthalmol. 2011;5:577–81. https://doi.org/10.2147/OPTH.S18827.CrossRefPubMedPubMedCentral

24.

Mateo Orobia AJ, Casas Pascual P, Cristóbal Bescós J, et al. Effects of 3% trehalose as an adjuvant treatment after LASIK. Clin Ophthalmol. 2017;11:347–53. https://doi.org/10.2147/OPTH.S125203.CrossRefPubMedPubMedCentral

25.

Neta T, Takada K, Hirasawa M. (2000) Low-cariogenicity of trehalose as a substrate. J Dent 2000 28:571–576. doi: https://doi.org/10.1016/s0300-5712(00)00038-5.

26.

Gómez-Moreno G, Cabrera‐Ayala M, Aguilar‐Salvatierra A, et al. Evaluation of the efficacy of a topical sialogogue spray containing malic acid 1% in elderly people with xerostomia: a double‐blind, randomized clinical trial. Gerodontology. 2014;31:274–80. https://doi.org/10.1111/ger.12034.CrossRefPubMed

27.

Sulistiyani E, Brimson JM, Chansaenroj A, et al. Epigallocatechin-3-gallate protects pro-acinar epithelia against salivary gland radiation injury. Int J Mol Sci. 2021;22:3162. https://doi.org/10.3390/ijms22063162.CrossRefPubMedPubMedCentral

28.

Boonroung T, Narongdej T, Vadcharavivad S. A comparative study of carboxymethylcellulose and enzyme-containing saliva substitute on quality of life in head and neck cancer patients with self-reported postradiation-xerostomia. Thai Pharm Health Sci J. 2011;6:17–24.

29.

Henson BS, Inglehart MR, Eisbruch A, Ship JA. Preserved salivary output and xerostomia-related quality of life in head and neck cancer patients receiving parotid-sparing radiotherapy. Oral Oncol. 2001;37:84–93. https://doi.org/10.1016/s1368-8375(00)00063-4.CrossRefPubMed

30.

Meirovitz A, Murdoch-Kinch CA, Schipper M, Pan C, Eisbruch A. Grading xerostomia by physicians or by patients after intensity-modulated radiotherapy of head-and-neck cancer. Int J Radiat Oncol Biol Phys. 2006;66:445–53. https://doi.org/10.1016/j.ijrobp.2006.05.002.CrossRefPubMed

31.

Oh DJ, Lee JY, Kim YK, Kho HS. Effects of carboxymethylcellulose (CMC)-based artificial saliva in patients with xerostomia. Int J Oral Maxillofac Surg. 2008;37:1027–31. https://doi.org/10.1016/j.ijom.2008.06.006.CrossRefPubMed

32.

Doan S, Bremond-Gignac D, Chiambaretta F. Comparison of the effect of a hyaluronate-trehalose solution to hyaluronate alone on ocular surface Disease Index in patients with moderate to severe dry eye disease. Curr Med Res Opin. 2018;34:1373–6. https://doi.org/10.1080/03007995.2018.1434496.CrossRefPubMed

33.

Hey J, Setz J, Gerlach R, et al. Parotid gland-recovery after radiotherapy in the head and neck region–36 months follow-up of a prospective clinical study. Radiat Oncol. 2011;6:125. https://doi.org/10.1186/1748-717X-6-125.CrossRefPubMedPubMedCentral

34.

Blanco AI, Chao KS, El Naqa I, et al. Dose-volume modeling of salivary function in patients with head-and-neck cancer receiving radiotherapy. Int J Radiat Oncol Biol Phys. 2005;62:1055–69. https://doi.org/10.1016/j.ijrobp.2004.12.076.CrossRefPubMed

35.

Chao KS, Deasy JO, Markman J, et al. A prospective study of salivary function sparing in patients with head-and-neck cancers receiving intensity-modulated or three-dimensional radiation therapy: initial results. Int J Radiat Oncol Biol Phys. 2001;49:907–16. https://doi.org/10.1016/s0360-3016(00)01441-3.CrossRefPubMed

36.

Likhterov I, Ru M, Ganz C, et al. Objective and subjective hyposalivation after treatment for head and neck cancer: long-term outcomes. Laryngoscope. 2018;128:2732–9. https://doi.org/10.1002/lary.27224.CrossRefPubMedPubMedCentral

37.

Jensen SB, Pedersen AML, Vissink A, et al. A systematic review of salivary gland hypofunction and xerostomia induced by cancer therapies: prevalence, severity and impact on quality of life. Support Care Cancer. 2010;18:1039–60. https://doi.org/10.1007/s00520-010-0827-8.CrossRefPubMed

38.

Vistoso MA, Polonsky G, Shiboski C, et al. Salivary gland dysfunction secondary to Cancer Treatment. Front Oral Health. 2022;3:907778. https://doi.org/10.3389/froh.2022.907778.CrossRef

39.

Meyer-Lueckel H, Tschoppe P, Kielbassa AM. Linseed based saliva substitutes and their effect on mineral dissolution of predemineralized bovine dentin in vitro. J Dent. 2006;34:751–6. https://doi.org/10.1016/j.jdent.2006.01.006.CrossRefPubMed

40.

Tschoppe P, Meyer-Lueckel H, Kielbassa AM. Effect of carboxymethylcellulose-based saliva substitutes on predemineralised dentin evaluated by microradiography. Arch Oral Biol. 2008;53:250–6. https://doi.org/10.1016/j.archoralbio.2007.10.001.CrossRefPubMed

41.

Meyer-Lückel H, Kielbassa AM. Influence of calcium phosphates added to mucin-based saliva substitutes on bovine dentin. Quintessence Int. 2006;37:537–44.PubMed

42.

Portmann M-O, Birch G. Sweet taste and solution properties of α,α-trehalose. J Sci Food Agri. 1995;69:275–81.CrossRef

43.

Vissink A, Waterman HA, s-Gravenmade EJ, Panders AK, Vermey A. Rheological properties of saliva substitutes containing mucin, carboxymethylcellulose or polyethylenoxide. J Oral Pathol. 1984;13:22–8. https://doi.org/10.1111/j.1600-0714.1984.tb01397.x.CrossRefPubMed

Title: Trehalose versus carboxymethylcellulose oral spray for relieving radiation-induced xerostomia in head and neck cancer patients: a randomized controlled trial
Authors: Pornpan Piboonratanakit
Joao N. Ferreira
Kulpriya Pravinvongvuthi
Khwanchanok Maison
Ganokon Urkasemsin
Thirayu Boonroung
Anussara Prayongrat
Chawalit Lertbutsayanukul
Jeerus Sucharitakul
Anjalee Vacharaksa
Publication date: 01-12-2023
Publisher: BioMed Central
Keyword: Radiotherapy
Published in: BMC Oral Health / Issue 1/2023
Electronic ISSN: 1472-6831
DOI: https://doi.org/10.1186/s12903-023-02966-4

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Trehalose versus carboxymethylcellulose oral spray for relieving radiation-induced xerostomia in head and neck cancer patients: a randomized controlled trial

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 1/2023

Effect of platelet concentrates for pain and symptom management in oral lichen planus: an evidence-based systematic review

Interrelationship between dental clinicians and laboratory technicians: a qualitative study

Development and accuracy validation of a fat fraction imaging biomarker for sialadenitis in the parotid gland

Correction to: Conservative management of mandibular fractures in pediatric patients during the growing phase with splint fiber and ligature arch wire

Salivary macrophage chemokines as potential biomarkers of gingivitis

Efficiency of occlusal splint therapy on orofacial muscle pain reduction: a systematic review