Introduction

Patients undergoing chemotherapy, radiation therapy, or both for the treatment of head and neck cancers commonly experience oral side effects, including mucositis, thrush (candidiasis), xerostomia, radiation caries, trismus, tissue damage, and osteoradionecrosis. Implementing proactive management of oral problems during and after cancer treatment can decrease the severity of these side effects and enhance the patients’ oral health-related quality of life. It has been shown that poor oral hygiene is a significant risk factor for oral complications from chemotherapy and radiation therapy (JOSHI 2010).

Mucositis, a widespread side effect experienced by patients undergoing cancer treatment, can hinder proper oral health maintenance. Mucositis is an inflammatory condition that affects the submucosal connective tissues, potentially leading to symptoms in the oral cavity and throughout the digestive tract (EILERS ET AL. 2014). The severity of mucositis can vary greatly, from subtle changes in sensation to the development of painful, ulcerative, bleeding lesions, and infections (EILERS & MILLION 2011). The discomfort associated with mucositis can make maintaining oral hygiene difficult, making oral care protocols essential.

Given the importance of oral hygiene for patients undergoing chemotherapy, radiation therapy, or both, the objective of this scoping review was to collect information on evidence-based oral hygiene instructions, guidance, and tools to effectively manage oral hygiene in these patients. Additionally, the review sought to identify preventive programs and standardized protocols to promote oral hygiene in this patient population.

Material and Methods

Four electronic databases, PubMed, Embase, Cochrane Library, and Google Scholar, were searched for studies published from January 2000 to March 2020 in English and German. The eligible sources included systematic reviews, meta-analyses, clinical studies, case series, expert opinions, and Delphi consensus reports that addressed aspects such as type of toothbrush, tooth brushing technique, frequency and duration of tooth brushing, type of toothpaste, mouthwash use, and interdental cleaning methods. Pamphlets, case reports, posters, and abstract-only reports were excluded.

For the electronic searches, the following keywords and Boolean operators were used:

 ((“cancer therapy”) AND “stomatitis”)) AND ("oral health") or (("cancer therapy") AND ("stomatitis") AND (“mucositis”)) AND ("oral hygiene") or (((“cancer therapy”) AND (“mouth hygiene”)) AND (“stomatitis”)) AND (“oral care”) or ("radiation") AND ("caries") or (((“dental caries”) AND (“radiation”)) AND (“mouth hygiene”))AND ("xerostomia")

The electronic search, the removal of duplicates, the title and abstract screening, and the full text assessments were performed by a single investigator. Journals and author names were unblinded during the eligibility assessment. The level of evidence and the grade of recommendations of studies fulfilling the eligibility criteria were assessed according to the SIGN Methodology Checklist (FIFTIETH GUIDELINE DEVELOPER’S HANDBOOK, NHS SCOTTISH INTERCOLLEGIATE GUIDELINES NETWORK SIGN. REVISED EDITION NOVEMBER 2011). Figure 1 and Figure 2 provide detailed information on the levels of evidence and grades of recommendations, respectively.

Results

Of 176 articles included in the full text assessment, 53 fulfilled the eligibility criteria. One article was a meta-analysis, 10 articles were systematic reviews, 12 articles were clinical studies, and 30 articles were narrative reviews. Four of the 10 systematic reviews were updates from guidelines of the Mucositis Study Group of the Multinational Association of Supportive Cancer in Cancer /International Society for Oral Oncology (MASCC/ISOO). The 12 clinical studies comprised one cohort study, a case series, and 10 clinical treatment trials (Figure 3). The results of the assessment of the level of evidence and the grade of recommendations are reported in detail in Tables I-VI.

The findings revealed that three different guidelines exist for patients undergoing oncological treatment: for the management of oral mucositis, radiation caries (pre-, post and during cancer treatment), and xerostomia. The recommendations varied depending on the intended treatment outcome, certain advices were recommended or discouraged by the associations.

The management of oral mucositis

A meta-analysis assessed the impact of nine mouthwashes on the prevention of oral mucositis (YU ET AL. 2020). Basic oral care and clinical guidelines for oral hygiene management were evaluated in a systematic review (HONG ET AL. 2019), a cohort study (CHENG ET AL. 2001), and three clinical treatment trials (DODD ET AL. 2000; KARTIN ET AL. 2014; NIIKURA ET AL. 2020). A clinical treatment trial assessed the effectiveness of three mouthwashes (DODD ET AL. 2000). Another clinical treatment trial evaluated the effectiveness of a saline mouthwash and education program (HUANG ET AL. 2018). One clinical treatment trial investigated the effect of improved dental care to prevent oral mucositis (DJUIRC ET AL. 2006). Four of these seven clinical treatment trials had a high risk of bias owing to poor randomization, deficiencies in group allocation concealment, shortcomings in blinding, and a lack of a control group (DODD ET AL. 2000; CHENG ET AL. 2004; DJURIC ET AL. 2006; KARTIN ET AL. 2014) These findings are summarized in Table I and Table II.

Guidelines for the prevention and treatment of oral mucositis

 A  The effectiveness of different oral care solutions in preventing oral mucositis in patients undergoing chemotherapy and radiation therapy was assessed through a meta-analysis of randomized controlled trials. The results ranked the solutions based on their effectiveness, with curcumin and honey showing the greatest effectiveness, followed by benzydamine, chlorhexidine, allopurinol, sucralfate, granulocyte-macrophage colony-stimulating factor, povidone-iodine, aloe, and placebo in that order (YU ET AL. 2020).

Oral care protocol

 B/C  A randomized controlled trial (RCT) assessed the impact of professional oral care on preventing everolimus-induced mucositis in 175 patients and was rated as level 1+ (high level of evidence) with a grade B recommendation (NIIKURA ET AL. 2020). The latest update from the MASCC/ISOO association in 2019 showed that an oral care protocol including tooth brushing with a soft toothbrush, flossing, and using more than one mouthwash was effective in preventing oral mucositis. However, there was insufficient evidence to provide a universal oral care protocol recommendation for preventing oral mucositis, with a level of evidence 2+ (moderate) and a grade C recommendation (HONG ET AL. 2019). Despite this, evidence supports the use of a basic oral care protocol. Expert opinions were sought to provide guidance, as no clinical trials showed a clear superiority of one intervention over another (MCGUIRE ET AL. 2013).

Mouthwash

 A  The study by HUANG ET AL. (2018) (2018) found that the combination of a 0.9% saline mouthwash and wet dressing gauze was effective in reducing symptoms of radiation-induced mucositis and improving oral comfort. This intervention was associated with improved physical and social-emotional function.

 B  The systematic review by MASCC/ISOO concluded that the use of chlorhexidine is not recommended for the prevention of oral mucositis in patients undergoing head and neck radiation therapy, owing to reported adverse effects such as increased discomfort, taste alteration, and teeth staining. There is limited or conflicting evidence regarding the use of chlorhexidine in cancer patients, hence a recommendation could not be made (HONG ET AL. 2019).

 C  No significant differences were found in the duration of the signs and symptoms of oral mucositis between chlorhexidine gluconate, magic mouthwash (consisting of Lidocain, Benadryl and Maalox), and a salt and sodium bicarbonate solution (DODD ET AL. 2000).

 D  The MASCC/ISOO systematic review found limited data on the use of saline or sodium bicarbonate rinses in preventing oral mucositis, making it impossible to establish guidelines. Despite the paucity of data, these rinses were recognized as non-irritating and potentially helpful in maintaining oral hygiene and improving patient comfort. (HONG ET AL. 2019).

 D  Experts recommended rinsing with bland solutions 4 to 6 times daily (HARRIS ET AL. 2008; BECKER-SCHIEBE ET AL. 2012; EILERS ET AL. 2014; PETERSON ET AL. 2015; DE SANCTIS ET AL. 2016).

The management of radiation caries

Three systematic reviews established guidelines for oral care strategies, incorporating RCTs, cohort studies, and case control studies (CARVALHO ET AL. 2018; COHEN ET AL. 2016; HONG ET AL. 2018). The systematic review by COHEN ET AL. (2016) only searched the PubMed database, a major methodological limitation. A randomized controlled trial by PAPAS ET AL. (2008) compared the effects of remineralizing and conventional toothpastes on caries prevention. Tables III and IV illustrate the evaluated studies.

Guidelines for prevention and treatment of radiation caries

Mechanical cleaning

 A  A systematic review that included only randomized controlled trials with a level 1++ or 1+ evidence recommends brushing at least three times a day with an ultra-soft bristled toothbrush. In cases of open ulcerative lesions in the oral cavity or if the patient cannot tolerate a soft toothbrush or has a low neutrophil and platelet count (< 500/mm³, < 40 000/ mm³ respectively) during oncological treatment, the oral cavity should be cleaned using gauzes moistened with 0.12% chlorhexidine or oral sponges (CARVALHO ET AL. 2018).

 A  It is recommended to practice dental flossing regularly (CARVALHO ET AL. 2018).

 D   Alternative methods to clean the oral cavity included using a gloved finger (MILLER & KEARNEY 2001) or cotton Q-tip swabs (JOSHI 2010).

 D  A single tufted toothbrush or a children's toothbrush may be helpful for plaque control, as suggested by (ELIYAS ET AL. 2013 ; KUMAR ET AL. 2013).

 D  It is recommended to brush for at least 90 s (LARSON ET AL. 1998; EPSTEIN & SCHUBERT 1999; RUBENSTEIN ET AL. 2004; HARRIS ET AL. 2008; SIERACKI ET AL. 2009).

 D  It is recommended to replace the toothbrush every month (PETERSON ET AL. 2015).

 D  Floss picks may be a useful aid for oral hygiene (CHAI ET AL. 2006).

 D  Starting interdental cleaning during oncological treatment should be avoided, as it may cause gingival bleeding and damage the epithelial barrier, particularly if it has never been performed prior to therapy (PETERSON 2015).

Toothpaste

 A Two phases fluoride toothpastes (>=1100 ppm) with calcium and phosphate ions are recommended (PAPAS ET AL. 2008; CARVALHO ET AL. 2018).

 D  Expert opinions recommended using toothpastes with an increased fluoride concentration of 5000 ppm (KIELBASSA ET AL. 2006; JOSHI 2010; KUMAR ET AL. 2013; RAY-CHAUDHURI ET AL. 2013; JAWAD ET AL. 2015).

 D  For patients with ulcers and xerostomia, the preferred toothpastes are those without detergents (MOSLEMI ET AL. 2016), non-mint flavor (TURNER ET AL. 2013; ELAD ET AL. 2015) and free of sodium lauryl sulfate (ANDREWS & GRIFFITHS 2001; PILOTTE ET AL. 2011; ELIYAS ET AL. 2013; ELAD ET AL. 2016). In the absence of such toothpastes, a children's toothpaste may serve as a suitable alternative (PILOTTE ET AL. 2011; PINNA ET AL. 2015; ELAD ET AL. 2016).

 D  Bicarbonate-based toothpastes (ANDREWS ET AL. 2001) were found to be effective in lowering the acidity of the mouth's pH (JOSHI 2010).

 D  Toothpastes containing casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) have been suggested for the prevention of caries (KÖSTLER ET AL. 2001; CHAI ET AL. 2006; RANKIN ET AL. 2008; JAWAD ET AL. 2015; PALMIER ET AL. 2020). In case of incipient carious lesions, the use of these toothpastes has been shown to aid in remineralizing the teeth (JOSHI 2010).

Mouthwash

 A  It is strongly recommended to use a 0.05% fluoride mouthwash daily prior to undergoing oncological treatment and to continue using it after the treatment has been completed (CARVALHO ET AL. 2018).

 A/B  Two systematic reviews support the use of 0.12% alcohol-free chlorhexidine for individuals with difficulty controlling bacterial biofilm (CARVALHO ET AL. 2018; HONG ET AL. 2018). It is recommended to rinse the oral cavity with the solution once or twice daily for the reduction of plaque buildup and S. mutans counts (HONG ET AL. 2018).

Toothbrushing techniques

 D  The recommended toothbrushing techniques included the Bass and the modified Bass technique (RAY-CHAUDHURI ET AL. 2013; PETERSON ET AL. 2015).

Fluoride application

 A  It is essential to use fluoride daily at the start of oncological treatment in order to prevent caries in patients undergoing head and neck radiation therapy and to continue its use afterwards (CARVALHO ET AL. 2018).

 A  An intraoral fluoride-releasing system (IFRS) that contains sodium fluoride was found to be as effective as a custom-made fluoride carrier with stannous fluoride gel in preventing caries (CHAMBERS ET AL. 2006). IFRS is recommended as a viable alternative, especially for patients with low compliance.

 B  The choice of fluoride delivery system did not have a significant impact on the level of caries in post-head and neck radiation patients (HONG ET AL. 2018).

 D  The use of a custom-made carrier for 1% sodium fluoride gel application has been recommended by some experts (VISSINK ET AL. 2003; KIELBASSA ET AL. 2006; RANKIN ET AL. 2008; SCHWEYEN ET AL. 2011; COHEN ET AL. 2016; SHEIKH ET AL. 2020).

 D  It has been advised to use a brush-on technique to apply either 0.4% stannous fluoride or 1.1% sodium fluoride to the teeth (TOLJANIC & SAUNDERS 1984; KEENE & FLEMING 1987; CHAMBERS ET AL. 1995).

Management of xerostomia

A systematic review assessed topical treatments for reducing radiation-induced dry mouth (FURNESS ET AL. 2011). Two clinical treatment trials compared the efficacy of chewing gum to artificial saliva or standard care in reducing xerostomia, with both studies finding that chewing gum was more effective, though without statistically significant results  (DAVIES 2000; KAAE ET AL. 2020). These studies were rated to have a high risk of bias owing to methodological limitations. Another RCT (CHAMBERS ET AL. 2006) compared the use of intraoral fluoride-releasing systems and fluoride carriers, with no differences in caries rates between the two fluoride systems. The findings are summarized in Table V and Table VI.

Guidelines for saliva substitutes and stimulants

 A  Artificial saliva should be used to lubricate the oral mucosa in cases of xerostomia. It should be applied before meals, before sleeping, and whenever necessary to promote lubrication of the oral cavity (CARVALHO ET AL. 2018).

 A  A systematic review evaluated saliva stimulants and substitutes and found that the oxygenated glycerol triester saliva substitute spray was more effective than an electrolyte spray. Additionally, chewing gum was equally effective in increasing saliva production for individuals with xerostomia compared to saliva substitutes (FURNESS ET AL. 2011). This conclusion was confirmed by a recent randomized controlled trial (KAAE ET AL. 2020).

 D  A case series by WARDE ET AL. (2000) found that using a combination of Biotene mouthwash, toothpaste, chewing gum, and Oral-balance gel could alleviate many symptoms of xerostomia caused by radiation therapy.

 D  A mixture of baking soda, salt, and water was found to effectively alleviate symptoms of xerostomia (COHEN ET AL. 2016)

Discussion

The aim of this scoping review was to assess the recommendations for maintaining oral health in patients undergoing chemotherapy, radiation therapy, or both. A total of 53 articles were evaluated and categorized into three groups based on their treatment objective: oral mucositis management, radiation caries prevention, and xerostomia management. The recommendations varied depending on the intended treatment outcome. Chlorhexidine was not advised for preventing oral mucositis in patients receiving head and neck radiation therapy, however, it was effective in preventing caries.

Most of the articles included in this scoping review were based on expert opinions with low levels of evidence, but the review also included ten systematic reviews and one meta-analysis with high levels of evidence. This demonstrates the availability of robust evidence for oral care in these patients.

The studies included in this review are found to entail risks of bias, such as ascertainment bias, comparison bias, and performance bias, leading to a lower rating of the level of evidence and grade of recommendation according to the SIGN Guidelines. Furthermore, the use of different mucositis severity gradings, such as the WHO Oral Toxicity and Eiler's oral assessment guide, made it difficult to compare the studies. In some cases, recommendations could not be made owing to a dearth of data. The MASSC/ISOO study group was unable to provide guidelines for the use of saline or sodium bicarbonate mouthwashes in preventing oral mucositis, but suggested that their use might be beneficial for oral hygiene. A systematic review by (FURNESS ET AL. 2011) found that an oxygenated glycerol triester saliva substitute was more effective for treating xerostomia than an electrolyte spray, but there was not enough evidence to strongly recommend its use.

This scoping review incorporated a broad range of articles, including both high- and low-evidence-based sources, but was limited by the fact that the eligibility assessment was conducted by only one investigator. This scoping review was unable to establish a standardized oral care protocol. Instead, it provided recommendations that should be considered as potential management approaches based on the current evidence base. However, it is crucial to consider that that further research in the form of randomized controlled clinical trials, systematic reviews, and meta-analyses are needed to establish more robust evidence-based recommendations.

Conclusions

This scoping review analyzed guidelines for oral health management in patients undergoing oncological treatments, including the management of oral mucositis, radiation caries, and xerostomia. The following recommendations were based on high-quality evidence:

• Oral mucositis management: Oral care protocols and professional oral care are effective in alleviating symptoms of oral mucositis. Honey and curcumin were found to be helpful in the management of oral mucositis.
• Radiation caries management: Daily use of a fluoride toothpaste with >=1100 ppm, a 0.05% fluoride mouthwash, topical fluoride application, and a fluoride-releasing system are recommended for reducing the burden of radiation caries.
• Xerostomia management: Saliva stimulants and substitutes may lubricate the oral cavity, and chewing gum was found to be as effective as saliva substitutes in increasing saliva production.

Zusammenfassung

Einleitung

Ziel dieses Scoping Review war, eine klinische Leitlinie für das Management der Mundgesundheit von Patienten nach Chemo- und/ oder Radiotherapie zu erstellen.

Materialien und Methoden

Es wurde eine elektronische  Recherche in PubMed, Embase, Cochrane und Google Scholar durchgeführt. Systematische Übersichtsarbeiten, Meta-Analysen, klinische Interventionsstudien, Fallserien und Expertenmeinungen wurden ausgewertet. Das SIGN-Guideline System wurde verwendet, um den Evidenzgrad und die Empfehlungsklasse der eingeschlossenen Studien zu bewerten.

Ergebnisse

53 Studien erfüllten die Einschlusskriterien.  Die Ergebnisse zeigten das Vorhandensein von Empfehlungen für Patienten nach Radio- und/oder Chemotherapie in drei Bereichen: das Handling von oraler Mukositis, Prävention und Kontrolle von Strahlenkaries und das Management von Xerostomie. Die Mehrheit der eingeschlossenen Studien hatten jedoch ein niedriges Evidenzniveau.   

Diskussion

Dieses Review umfasst Leitlinien für medizinisches Fachpersonal, das Patienten betreut, die eine Chemo- und/oder Strahlentherapie erhalten haben. Eine einzige Standardempfehlung konnte aufgrund mangelnden hochevidenzbasierten Daten nicht erstellt werden.

Résumé

Introduction

L'objectif de cette revue de littérature exploratoire était d'établir une ligne directrice clinique pour la gestion de la santé bucco-dentaire des patients après une chimiothérapie et/ou une radiothérapie.

Matériaux et méthodes

Une recherche a été effectuée dans PubMed, Embase, Cochrane et Google Scholar. Des revues systématiques, des méta-analyses, des études d'intervention clinique, des séries de cas et des avis d'experts ont été analysés. Le système lignes directrices de SIGN a été utilisé pour évaluer le niveau de preuve et la classe de recommandation des études incluses.

Résultats

53 études ont rempli les critères de sélection. Les résultats ont indiqué l’existence de recommandations pour les patients suivant une radiothérapie et/ou une chimiothérapie: le traitement de la mucite buccale, la prévention et le contrôle des caries radiatives la traitement de la xérostomie. La majorité des études incluses étaient basées sur un niveau de preuve faible. 

Discussion

Cette revue de littérature exploratoire contient des lignes directrices pour les professionnels de la sante qui s’occupent des patients qui ayant reçu une chimiothérapie et/ou une radiothérapie. Il n'a  pas été possible d'établir une recommandation standard en raison du manque de données à haut niveau de preuve.

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