Post-radiotherapy head and neck cancer patients are at increased risk of dental caries due to radiotherapy-induced salivary gland hypofunction and radiation damage to tooth structure. Dental caries causes pain and discomfort and is likely to have a detrimental impact on patients' quality of life. This systematic review appraised and synthesised best available evidence regarding the incidence and severity of post-radiotherapy dental caries in head and neck cancer patients. Six databases and two trial registries were searched from their inception to May 2019. A total of 22 papers met the inclusion criteria. The pooled percentage of patients that developed dental caries postradiotherapy was 29% (n=15 studies; 95% CI 21%, 39%; I 2 =88.0%). Excluding studies with longer than two years follow-up, the pooled percentage was 37% (n=9 studies; 95% CI 25%, 51%; I 2 =88.6%). Meta-regression analysis revealed that studies with a higher mean/median radiotherapy dose exposure had an increased incidence of dental caries (p=0.02). Furthermore, studies with a higher proportion of patients treated with chemotherapy had an increased incidence of dental caries (p=0.02) after the exclusion of an outlier. It is important to be mindful of the high degree of observed heterogeneity and the inclusion of a large number of non-randomised studies. Data regarding the number of carious teeth, the number of carious tooth surfaces, and the number of carious lesions that developed post-radiotherapy were unsuitable for meta-analysis. There is a need for well-designed studies to improve understanding about dental cariesrisk in post-radiotherapy head and neck cancer patients. Highlights This review summarised the incidence of post-radiotherapy dental caries. Pooled estimates for post-radiotherapy caries ranged from 29-37%. A narrative review of the severity of post-radiotherapy caries is also presented. Comprehensive oral care is needed for head and neck cancer patients. Keywords Head and neck neoplasms Radiotherapy Dental caries Chemotherapy Oral health Abbreviations: CI-confidence intervals CM-Ciaran Moore (reviewer) CML-Conor McLister (reviewer) DMFS-decayed, missing, or filled tooth surfaces DMFT-decayed, missing, or filled teeth DNA-deoxyribonucleic acid GMK-Gerry McKenna (reviewer) HANC-head and neck cancer IMRT-intensity modulated radiation therapy *Manuscript (without author details) Click here to view linked References ORN-osteoradionecrosis PRISMA-Preferred Reporting Items for Systematic Reviews and Meta-Analyses PROSPERO-International Prospective Register of Systematic Reviews SD-standard deviation Author Type of study Year of Publication Number of patients Follow-up (months) Caries (outcome) data Caries assessment Site of head and neck cancer Age (years) Gendermale (%)

Background The outcome of endodontic treatment is generally assessed using a range of patient and clinician-centred, non-standardised clinical and radiographic outcome measures. This makes it difficult to synthesise evidence for systematic analysis of the literature and the development of clinical guidelines. Core outcome sets (COS) represent a standardised list of outcomes that should be measured and reported in all clinical studies in a particular field. Recently, clinical researchers and guideline developers have focussed on the need for the integration of a patient-reported COS with clinician-centred measures. This study aims to develop a COS that includes both patient-reported outcomes and clinician-centred measures for various endodontic treatment modalities to be used in clinical research and practice. Methods To identify reported outcomes (including when and how they are measured), systematic reviews and their included clinical studies, which focus on the outcome of endodontic treatment and were published between 1990 and 2020 will be screened. The COSs will be defined by a consensus process involving key stakeholders using semi-structured interviews and an online Delphi methodology followed by an interactive virtual consensus meeting. A heterogeneous group of key ‘stakeholders’ including patients, general dental practitioners, endodontists, endodontic teachers, clinical researchers, students and policy-makers will be invited to participate. Patients will establish, via interactive interviews, which outcomes they value and feel should be included in a COS. In the Delphi process, other stakeholders will be asked to prioritise outcomes identified from the literature and patient interviews and will have the opportunity at the end of the first round to add outcomes that are not included, but which they consider relevant. Feedback will be provided in the second round, when participants will be asked to prioritise the list again. If consensus is reached, the remaining outcomes will be discussed at an online meeting and agreement established via defined consensus rules of outcome inclusion. If consensus is not reached after the second round, a third round will be conducted with feedback, followed by the online meeting. Following the identification of a COS, we will proceed to identify how and when these outcomes are measured. Discussion Using a rigorous methodology, the proposed consensus process aims to develop a COS for endodontic treatment that will be relevant to stakeholders. The results of the study will be shared with participants and COS users. To increase COS uptake, it will also be actively shared with clinical guideline developers, research funders and the editors of general dental and endodontology journals. Trial registration COMET 1879. 21 May 2021.

Pre-radiotherapy dental extractions in patients with head and neck cancer: a Delphi study. ObjectivesTo gain a consensus from consultants in restorative dentistry about the types of teeth that should be extracted from head and neck cancer patients (HNC) pre-radiotherapy. MaterialsLiterature-and clinician-informed questionnaires were emailed to an 'expert panel' of consultants (n=24/28; 86%) in the United Kingdom (UK) and Ireland on three consecutive occasions (Delphi rounds). The results of Round 1 were used to revise the questionnaire that was distributed in Round 2, and this procedure was repeated for Round 3. During Rounds 2 and 3, participants were asked to indicate, on a 5-point Likert scale, their level of agreement with a series of statements on the types of teeth that should be extracted pre-radiotherapy. The target level of consensus for each statement was 70%. ResultsIn Round 2, there was consensus-agreement for 69 of 102 statements (i.e. 70% of participants rated 'agree' or 'strongly agree' to the relevant statement). Consensus agreement was also achieved for 20 of 28 statements in Round 3. Therefore, a total of 89 consensus statements are presented that illuminate the decision-making process for the pre-radiotherapy extraction of molar, premolar, and anterior teeth with periodontal pocketing, furcation disease, mobility, caries, tooth-wear, apical disease, or other pathology. ConclusionThe statements represent the consensus professional views of participated consultants in restorative dentistry in the UK and Ireland regarding the types of teeth that should be extracted from HNC patients pre-radiotherapy. The results provide a platform for the development of future guidelines. Clinical SignificancePre-radiotherapy dental assessments for head and neck cancer patients are considered mandatory. This study presents different criteria that should be considered for the treatment planning of these patients in relation to pre-radiotherapy extractions, according to the collective consensus opinion of participated consultants in restorative dentistry in the UK and Ireland. Highlights This Delphi study collated 'expert' opinion regarding pre-radiotherapy dental extractions. Consensus statements outline the types of teeth that should be extracted preradiotherapy. It is envisaged that the study's results will help to inform the development of new guidelines. Keywords Head and neck neoplasms Radiotherapy Dental caries Periodontal disease Tooth extraction Oral health Abbreviations BSSPD -British Society of Prosthodontics HNC -head and neck cancer IMRT -intensity modulated radiotherapy IQR -interquartile range M -median ORN -osteoradionecrosis P -percentage agreement QoL -quality of life QUB -Queen's University Belfast S -standard deviation UK -United Kingdom X -mean

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There is a need for further research as there are insufficient numbers of good quality randomised controlled trials currently available. Authors should be encouraged to adhere to CONSORT guidelines for randomized controlled trials, and report findings in such a way that facilitates future meta-analysis.