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Table of Contents   
SHORT COMMUNICATION  
Year : 2020  |  Volume : 31  |  Issue : 6  |  Page : 963-966
Prevention of dental caries by regular overnight application of a low-concentration fluoride gel loaded in a custom tray in patients undergoing radiotherapy for head and neck cancer: A preliminary study


1 Department of Oral Health, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
2 Department of Clinical Oral Oncology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
3 Kyushu Dental University School of Oral Health Sciences, Kitakyushu, Fukuoka, Japan
4 Oral Management Center, Nagasaki University Hospital, Nagasaki, Japan

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Date of Submission11-Feb-2020
Date of Decision09-May-2020
Date of Acceptance15-Jul-2020
Date of Web Publication22-Mar-2021
 

   Abstract 


Background:</bold> Some studies have reported topical application of 1.0%–2.0% fluoride gel in a custom tray for 4–5 minutes every day for the prevention of radiation-related dental caries. However, in Japan, the concentration of fluoride used by patients is limited to less than 0.15%. The efficacy of a low-concentration fluoride gel in a custom tray for the prevention of radiation-related dental caries has not been investigated. <bold>Methods and Material:</bold> In this preliminary study, we enrolled 13 patients with head and neck cancer who underwent radiotherapy. They wore a custom tray containing 0.145% sodium fluoride gel during sleep every night and were examined for newly developed dental caries 1 year later. <bold>Results:</bold> No new dental caries were found in the 13 patients 1 year after radiotherapy, and no adverse events were observed. <bold>Conclusions:</bold> We conclude that low-concentration fluoride gel in a custom tray during sleep could prevent radiation-related dental caries, and we plan to conduct a multi-center phase III randomized controlled trial to examine the efficacy of this method for the prevention of radiation-related dental caries.

Keywords: Dental caries, fluorine compounds, head and neck neoplasms, sodium fluoride

How to cite this article:
Soutome S, Yanamoto S, Funahara M, Kawashita Y, Yoshimatsu M, Murata M, Saito T, Umeda M. Prevention of dental caries by regular overnight application of a low-concentration fluoride gel loaded in a custom tray in patients undergoing radiotherapy for head and neck cancer: A preliminary study. Indian J Dent Res 2020;31:963-6

How to cite this URL:
Soutome S, Yanamoto S, Funahara M, Kawashita Y, Yoshimatsu M, Murata M, Saito T, Umeda M. Prevention of dental caries by regular overnight application of a low-concentration fluoride gel loaded in a custom tray in patients undergoing radiotherapy for head and neck cancer: A preliminary study. Indian J Dent Res [serial online] 2020 [cited 2021 Nov 27];31:963-6. Available from: https://www.ijdr.in/text.asp?2020/31/6/963/311646



   Introduction Top


Radiotherapy (RT) is commonly performed in patients with head and neck cancer with or without systematic therapy. It causes various adverse events such as oral mucositis, xerostomia, dysgeusia, trismus, and osteoradionecrosis (ORN) of the jaw. ORN, one of the severe late complications, is rarely cured with conservative therapy, often requires surgical treatment, and significantly reduces quality of life. In a multi-center retrospective study of 392 patients with head and neck cancer undergoing RT, we reported that the major risk factors for developing ORN were periapical periodontitis, tooth extraction after RT, and radiation-related dental caries.[1] Therefore, in order to prevent ORN, it is important that the infected tooth is extracted before the start of RT and strict dental management is performed after RT to prevent radiation-related dental caries.

Radiation-related dental caries occurs after RT and progresses rapidly, sometimes even in patients who visit dentists regularly [Figure 1].[2] The cause of radiation-related dental caries is believed to be increased susceptibility to demineralization due to xerostomia and direct damage to the dental hard tissue.[3] Dreizen et al.[4] reported that application of 1.0% sodium fluoride (NaF) gel in a custom tray for 5 minutes every day decreased the incidence of dental caries after RT. Wang et al.[5] applied 1.23% acidulated phosphate fluoride (APF) or 2% NaF gel in a custom tray for 4 minutes everyday for patients with head and neck cancer undergoing RT. The National Comprehensive Cancer Network (NCCN) Guideline recommends daily 1.1% NaF gel or stannous fluoride (SnF2) gel in a custom tray for dental caries prevention.[6] However, in Japan, the concentration of fluoride gel used by patients was limited to less than 0.09% for a long time. The limit of fluoride gel concentration was changed to 0.15% in 2017. Application of fluoride gel using a custom tray after RT for head and neck cancer has not been implemented in Japan.
Figure 1: Radiation-related dental caries. A 36-year-old woman with tongue cancer underwent postoperative chemoradiotherapy. a: Panoramic radiograph before radiotherapy (RT) b: Three years after RT Extensive caries infiltration is seen in the mandibular teeth in the zone of irradiation

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Therefore, we would like to conduct a randomized controlled study to examine whether low-concentration fluoride gel application in a custom tray can prevent radiation-related dental caries. The purpose of this study was to perform a preliminarily test of the hypothesis before the large-scale phase III trial is undertaken.


   Subjects and Methods Top


The subjects of this study were patients with head and neck cancer who were aged 20–90 years and received RT at a dose of 50 Gy or higher at Nagasaki University Hospital between January 2017 and March 2018. Patients with nine or lesser teeth, those whose oral cavity was not included in the radiation field, and those who were not followed up for a minimum of 1 year were excluded. Initially, 21 patients were registered for participation in the study. One patient refused to wear the custom tray and seven patients were not followed-up for 1 year because of recurrent or metastatic tumor; therefore, 13 patients were included in the study [Figure 2]. Age, sex, primary tumor site, total RT dose, RT method, number of teeth before RT, stimulated saliva volume, wetness of the oral mucosa, and number of dental caries immediately before, after, and 1 year after RT were recorded. Stimulated saliva was examined by the Saxon test.[7] Oral mucosal wetness was measured using a body component analyzer (Mucus®. Life Co., Ltd., Saitama, Japan) at the surface of the bilateral buccal mucosa three times each, and the average value was recorded.
Figure 2: Flow diagram showing patient enrollment

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The 13 patients underwent topical fluoride application by the custom tray method after recovering from radiation-induced oral mucositis. The custom tray was manufactured using 2 mm thick ethylene-vinyl acetate copolymer (Bioplast®, SCHEU-DENTAL GmbH, Iserlohn, Germany) of 2.0 mm thickness. The patients wore the tray during sleep every night after brushing their teeth with a toothpaste containing 1,450 ppm NaF (Check-Up rootcare®, Lion Co., Ltd., Tokyo, Japan) [Figure 3]. They were followed up every 3 months to examine the number of new dental caries. The study duration was 1 year.
Figure 3: a: Toothpaste containing 1,450 ppm NaF and a custom tray, b: Intraoral application of the custom tray

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Ethics approval and consent to participate: This study was performed in accordance with the 1964 Declaration of Helsinki. Ethical approval was obtained from the Institutional Review Boards (IRB) of Nagasaki University Hospital. The study was registered with University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR) (UMIN000025196) Registered 9 December 2016. Written informed consent was obtained in each patient.


   Results and Discussion Top


Summary statistics of the 13 patients are shown in [Table 1]. Ten patients were men and three women, with an average age of 60.9 years. The primary site of cancer was the oral cavity or the oropharynx in seven patients and other sites in six patients. Three-dimensional conformal radiotherapy was performed in four patients, while intensity modulated radiotherapy was performed in nine patients. Although the stimulated saliva decreased after RT, oral wetness did not differ between pre- and post RT. Oral wetness is evaluated simply by measuring the wetness of the surface of the oral mucosa with a device called Mucus®, whereas the measurement of stimulated saliva by the Saxon test well reflects the function of the salivary glands. Therefore, in this study, the function of salivary gland could be declined by RT.
Table 1: Patients characteristics

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Oral examination 1 year after RT revealed no new dental caries in all 13 patients. There were no adverse events caused by the custom tray or fluoride gel. Of the 21 patients, 7 patients who failed to complete a one-year follow-up all had a poor head and neck cancer prognosis. The patients died of cancer during the observation period and the observation could not be completed.

It is well known that dental caries often occurs after RT in patients with head and neck cancer.[3] This radiation-related dental caries often progresses rapidly even if patients receive regular dental management.

We previously reported that 30 of 392 patient with head and neck cancer undergoing RT developed ORN and radiation-related dental caries.[1] Rapidly progressing dental caries was the cause of ORN in nine patients. The NCCN Guideline recommends local application of 1.1% NaF gel or SNF2 gel everyday, as well as regular dental evaluation to detect dental caries.[5] Wang et al.[5] reported that 2.0% NaF gel in a custom tray prevented radiation-related dental caries in patients with head and neck cancer. In Japan, the concentration of fluoride gel that can be used by patients was limited to 0.09% for a long time. The regulation was eased in 2017, when the concentration was set at 0.15% or lower. This is because the occurrence of mottled teeth, a side effect of fluorine, has been of concern in some regions of Japan. Therefore, local application of fluoride gel in a custom tray after RT for head and neck cancer was not performed.

We hypothesized that even low concentrations of fluoride could prevent radiation-related dental caries when applied for a long time. First, we investigated the incidence of dental caries in patients with head and neck cancer who did not receive fluoride. The mean of new dental caries after RT in 31 patients with head and neck cancer was 2.68 at 1 year and 4.91 at 2 years. This increase was significantly higher than in 25 patients with oral cancer who underwent surgery but not RT, where it was 0.00 at 1 year and 0.61 at 2 years after surgery.[2] We wished to confirm our hypothesis and performed a preliminary study to examine whether radiation-related dental caries can be prevented by long-term action of low-concentration fluoride. Our results revealed no new caries after 1 year, suggesting that this method is promising as a preventive method for radiation-related caries.

This preliminary study had some limitations. First, the number of patients was too small to perform statistical analysis. Second, the long-term effects on caries prevention remain unknown because the follow-up period only lasted 1 year. Third, attaching the tray may motivate the patients to brush their teeth, and there may have been bias associated with improvement in their oral hygiene relative to that of patients in the previous study.

Based on these results, we have decided to conduct a multicenter phase III randomized clinical trial to determine whether topical administration of low-concentration fluoride gel in a custom tray can prevent radiation-related caries. In particular, it is necessary to calculate the sample size of the future trial based on the results of this preliminary study that about 33% of patients with head and neck cancer receiving RT may not be able to follow up sufficiently due to poor prognosis.


   Conclusions Top


Low-concentration fluoride gel in a custom tray during sleep could prevent radiation-related dental caries based on the results of this preliminary study. We plan to conduct a multicenter phase III randomized controlled trial to examine the efficacy of this method for the prevention of radiation-related dental caries.

Acknowledgement

We would like to thank Editage (www.editage.com) for English language editing.

Declaration of patient consent

Written informed consent to participate in the study and consent for publication was obtained by each participant.

Financial support and sponsorship

Sakiko Soutome has received research funding to Nagasaki University Hospital from Lion Co., Ltd. The other authors declare no competing interests.

Conflicts of interest

There are no conflicts of interest.



 
   References Top

1.
Kojima Y, Yanamoto S, Umeda M, Kawashita Y, Saito I, Hasegawa T, et al. Relationship between dental status and development of osteoradionecrosis of the jaw: A multicenter retrospective study. Oral Surg Oral Med Oral Pathol Oral Radiol 2017;124:139-45.  Back to cited text no. 1
    
2.
Soutome S, Funahara M, Hayashida S, Nakamura K, Umeda M. Risk factors for radiation-induced dental caries in patients with head and neck cancer. Oral Health Care 2017;2:1-4.  Back to cited text no. 2
    
3.
Walker MP, Wichman B, Cheng AL, Coster J, Williams KB. Impact of radiotherapy dose on dentition breakdown in head and neck cancer patients. Pract Radiat Oncol 2011;1:142-8.  Back to cited text no. 3
    
4.
Dreizen S, Brown LR, Daly TE, Drane JB. Prevention of xerostomia-related dental caries in irradiated cancer patients. J Dental Res 1977;56:99-104.  Back to cited text no. 4
    
5.
Wang WC, Chen YK, Lin LM. Oral care experiences with 181 nasopharyngeal carcinoma patients receiving radiotherapy in a Taiwanese hospital. Auris Nasus Larynx 2008;35:230-4.  Back to cited text no. 5
    
6.
National Comprehensive Cancer Network. NCCN Clinical Practice Guideline in Oncology (NCCN Guidelines) Head and Neck Cancers. 2019 [cited 2019 Nov 29]. Available from: https://www.nccn.org/professionals/physician_gls/default.aspx#site.  Back to cited text no. 6
    
7.
Kohler PF, Winter ME. A quantitative test for xerostomia. The Saxon test, an oral equivalent of the Schirmer test. Arthritis Rheum 1985;28:1128-32.  Back to cited text no. 7
    

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Correspondence Address:
Dr. Souichi Yanamoto
Department of Clinical Oral Oncology, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki 852-8588
Japan
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijdr.IJDR_138_20

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