Protocol“The effect of dental and salivary glandradiation dose on the occurrence of post-radiotherapydentaldiseaseinpatientswithheadandneckcancer.”Dateofdocument:(Version313/04/2018)

ClinicalhypothesisTheprimaryhypothesis is that increasedmean radiationdose to the teeth and to the‘spared’ parotid gland is associated with an increase in the mean number of cariousteethandintheproportionwithperiodontaldisease2yearspost-radiotherapy.Studydesign:Prospectivecohortstudy.-Pre-radiotherapyassessmentatbaselineandpatientsrendereddentallyfit(i.e.freeofdentaldisease).-Post-radiotherapyfollow-upassessmentsat6months,12months,and24months.Selection criteria: Adult dentate patients (i.e. patients with natural teeth) diagnosedwithaprimaryorsecondarymalignanttumouroftheoralcavity,nasalcavity,sinuses,salivary glands, pharynx, or larynx* requiring radiation treatment within NorthernIreland.*InternationalClassificationofDiseases(ICD-10)codesC00.0-C14.8andC30.0-32.9.1

Exclusioncriteria:-Patientsdeemedtohavepoorprognosis,orpatientstoreceivepalliativetreatmentonly(asadvisedbytheClinicalOncologyteam).-Patientswithlessthan6teethbeforetheradiotherapystartdate.-Patientswithrecurrentheadandneckcancer,orpatientsreceivingarepeatcourseofheadandneckradiotherapy.-Patients with diseases affecting tooth development (e.g. amelogenesis ordentinogenesisimperfecta)orsalivaryglandfunction(e.g.Sjogren’sSyndrome).-Patientswithpre-existingtrismus(mouthopeninglessthan35mm).Protocolforpre-radiotherapydentalassessmentIn linewithcurrentpractice,theMultidisciplinaryHeadandNeckCancerTeam(RoyalVictoriaHospital,Belfast)willcontinuetoreferheadandneckcancerpatientsforpre-radiotherapy dental assessment to the School of Dentistry, Belfast. Referred patientswill be assessed in the existing ‘Head and Neck Clinic’ on a Wednesday morning orafternoon in the Prosthetics Department of the School of Dentistry, Belfast, as percurrentclinicalpractice.All potentially eligible patients will be informed of the research study and invited toparticipate.Willingparticipantswillbeaskedtosignawrittenconsentform.Amemberofthedirectcareteam–adentist–willcompleteallofthisprocess.Eachrecruitedpatientwillbeassessedbyatrainedandcalibrateddentist(examiner).Examinerswillundergopre-studytrainingandcalibrationtoensureconsistentclinicalmeasurements.2 Inter-examiner consistency will be calculated using the Kappastatistic.3,4Thesameexaminer(s)willalsointerpretandrecorddatafromallprescribedradiographs.Clinicalassessment-Dental caries: The presence or absence of dental caries on each tooth will bedetermined using the World Health Organization’s criteria and coding system, andICDAS, and recorded in a modified version of the Oral Health Assessment Form forAdults, 2013.2,5All surfaces of the crown and root of each tooth will be assessed by:visualisationusingamouthmirror,dentalprobe,adequatelighting,andcompressedairfroma3-in-1tip.

Presenceorabsenceofdentalcariesoneachsurfacewillberecordedasfollows(Figures1and2):

Figure1:WHOcriteriaandcodingsystem

Figure2:ICDAScoronalcariesdecisiontree-Periodontal disease: A six-point periodontal charting will be performed for allpatients.Clinicalattachment lossandprobingpocketdepthswillbemeasuredusingaWilliams Periodontal Probe and recorded for six sites on each tooth using the OralHealth Assessment Form. The ‘Centers for Disease Control and Prevention (CDC)’, inpartnership with the ‘American Academy of Periodontology (AAP)’ workgroupdefinitionofperiodontitiswillbeusedtoidentifythosewithactiveperiodontaldisease:2ormoreinterproximalsiteswithattachmentloss≥3mm,and2ormoreinterproximalsiteswithpocketdepths≥4mm(notonsametooth)oronesitewithpocketdepth≥5mm.6,7

-Stimulated salivary flow rate using paraffin pellets.8 Patients will chew anunflavoured paraffin pellet for 5 minutes whilst expectorating into a pre-weigheddisposable specimen pot. This will be undertaken in one of the private units in theProsthetics Department of the School of Dentistry, Belfast. Following collection, thespecimenpotwillbetransportedtotheInstituteofPathology,RoyalVictoriaHospital,Belfast. The mass of collected saliva will be determined using a calibrated precisionweighingbalance.Afterthecalculationofsalivaryflowrate,eachpatient’ssalivasamplewill be disposed of as clinical waste and destroyed by incineration in line with theHumanTissueAct2004.Patientswillbeaskedtorefrainfromsmoking,eatinganddrinking,andotherformsoforal stimulation (e.g. oral hygiene) 90 minutes prior to the collection of saliva. It isanticipatedthatthelengthofeachpatient’spre-radiotherapydentalassessmentwillbeat least 90 minutes (based on current clinical practice). Patients will therefore beinstructednot toengage inoral stimulation for90minutesafter theyhavesigned thewrittenconsentformatthestartoftheappointment.

-Ruler measurement of mouth opening.9 Maximum interincisal distance will bemeasuredwhentheupperandlowercentralincisorsarepresent(naturalorprosthetic).Alternatively, the alveolar ridge(s)will beused as a referencepoint formeasurementwherenonaturalorprostheticcentralincisorsarepresent.Alloftheabovedata,includingtheOralHealthAssessmentForms,willberecordedandstoredinpatients’clinicalrecords(dentalnotes).-Oral hygiene practice anddietary assessmentswillbeperformedusing theWorldHealthOrganization’sOralHealthQuestionnaireforAdults.2

-Quality of life and experience of xerostomia will be assessed using questionnairebooklets containing theEuropeanOrganization forResearchandTreatmentofCancer(EORTC) QLQC30 quality-of-life instrument, the associated head and neck specificmodule HN35, the Oral Health Impact Profile, and the modified XerostomiaQuestionnaire.10-14

-Micro-costings study. Patientswill also be asked to complete a short questionnaireenquiringof theirgrossannual income, themodeof transport theyused forattendingtheir dental appointment, and whether another person accompanied them to theirdentalappointment.Themicro-costingsstudyquestionnairewillbeattachedtotheoralhygiene/diet/qualityoflife/xerostomiaquestionnairebookletoutlinedabove.Thequestionnairebookletswillbecompletedanonymously.Uponacceptance into thestudy, a random number generator will assign each recruited patient a 6-digitanonymouscode.Eachpatientwillbeinformedofhisorheranonymouscode.Thiswillbetheonlyidentifierrecordedoncompletedquestionnairebooklets.Patientswillbeaskedtocompletethequestionnairebookletinoneofthedentalunitsinthemain clinic of the School of Dentistry, Belfast. The questionnaire bookletswill begivento,andcollectedby,thedentistperformingtheclinicalassessments.TheywillbestoredsecurelyinalockedcupboardinalockedroomintheSchoolofDentistry,Belfast.A password-protected spreadsheetwill be createdwith a list of patients’ anonymouscodesandtheircorrespondingDentalHealthandH&Cnumbers.Thiswillbestoredonapassword-protectedBelfastHealthandSocialCareTrustcomputer.RadiographsThe decision to prescribe, take, and interpret dental radiographs for the purposes ofdiagnosis and treatment-planning should bemade on a case-by-case basis and followcurrentclinicalpractice.Thereshouldbeclearjustificationforthemedicalexposureofpatients in line with the Ionising Radiation (Medical Exposure) (Amendment)Regulations(NorthernIreland)2010.15Thefollowingcriteria,adaptedfromtheFGDP’sSelection Criteria for Dental Radiography16, is intended to guide the decision-makingprocess:Dentalpantomogram(DPT)–mandatoryIOPAs–symptomaticteeth,clinicalsigns(sinus,swelling),carieswithsuspectedpulpalinvolvement, toothwear with suspected pulpal involvement, previous root canaltreatment (RCT), crowned teeth, heavily restored teeth with restoration in closeproximitytopulp,clinicalattachmentloss>6mm,furcationdisease.

Bitewings–lackofclarityregardingthepresenceofinterproximalcariesonDPT.Radiographic evidence of secondary caries or caries into dentinewill be recorded oneachpatient’sOralHealthAssessmentForm.OtherspecialinvestigationsElectricpulptest–carieswithsuspectedpulpalinvolvement,toothwearwithsuspectedpulpalinvolvement,heavilyrestoredteethwithrestorationincloseproximitytopulp.PreventionandtreatmentplanningAllpatientswillreceivestandardisedoralhygieneanddietaryadvice:Dietadvice

• Sugaryandacidicfood/drinktobeconsumedatmealtimesonly• Rinsemouthwith0.05%fluoridemouthwashaftereachsugarattack• Adviceontheuseofsugar-freemedications

Oralhygieneinstructions

• Poweredormanualmediumtoothbrushtobeused(Basstechnique)• 5,000ppmDuraphatfluoridetoothpastetobeusedtwicedaily• 0.05% fluoridemouthwash to be used at least once daily (different time from

brushing)• Flossand/orinterdentalbrushes(asappropriate)tobeuseddaily• Corsodyl(chlorhexidinegluconate)0.2%mouthwashtobeusedtwicedailyfor1

weekpriortoradiotherapy

Denturehygieneinstruction

• Don’tweardenturesduringthecourseofradiotherapyifpossible• Rinsedenturesaftereverymealincoldrunningwater• Cleandentures at least oncedailywith a toothbrushand5,000ppmDuraphat

fluoridetoothpaste• SteepinMiltons(1in80dilution)overnightifthedentureismadeofplasticonly• Alternatively,steepinCorsodyl(chlorhexidinegluconate)0.2%overnightifthe

denturehasmetalcomponentsAdental treatmentplanwillbe formulated foreachpatient toensureadequatedentalfitnesspriortoradiotherapy.ConsultantsinRestorativeDentistry,willoverseepatients’treatment plans. Dental treatment required pre-radiotherapy (e.g. restorations andextractions)willbeco-ordinatedbytheSchoolofDentistryinlinewithcurrentpractice,including the possibility of routine treatment within the primary care setting (i.e.completedbythepatient’sgeneraldentalpractitioner).Tofacilitatethemicro-costingsstudy,allpatientswillbeaskedtoretaindetailsofanytreatment costs that they incurred from their general dental practice. Patientswill beaskedtoprovidethiscostinformationatfollow-upappointments(forexample,withtheproduction of invoices). Information on the cost of dental treatment incurredwill berecorded on each patient’s anonymised questionnaire booklet completed at thesubsequentfollow-upappointment.

Treatmentplanningcomponents:Mayincludeanycombinationofthefollowing:1.ExtractionsThe following table is intended to guide the decision-making process for pre-radiotherapy dental extractions in line with current practice.17-21 The decision toundertake extractions should be taken after careful consideration of individual toothprognosis, tooth abutment potential, and the patient’s medical history (see also‘SPECIALCASES’below).

Molars Premolars AnteriorsApicaldisease YES YESwhenboth

marginalridgeslost

YESifpost-crown

Furcationdisease YES YES N/AGradeIImobileorworse YES YES YES

Lossof>50%marginalboneloss YES YES YESCrownwithsecondarycaries YES YESifpost-crown YESifpost-

crownCrownwithsubgingivalmargins YES YES NO

Cariesortoothwearwithsuspectedpulpalinvolvement

YES YESwhenbothmarginalridges

lost

NO

PreviousRCT/non-vitaltooth YES YESwhenbothmarginalridges

lost

NO

Caries/toothmargin>1mmsubgingival YES YES YESRootcaries>1surface YES YES YES

Rootperforation/resorption/fracture/retainedinstrument

YES YES YES

Periodontalpocket>5mm YES YES YESSPECIALCASESDentalphobicpatients–mayconsideradditionalextractionofanytoothwithcaries.Impacted/uneruptedteeth–extractwhenincommunicationwithoralcavity,carious,orotherpathologysuspected(e.g.cystformation,resorptionofadjacentteeth).Retainedroots/apices–leavewhennopathologyandencasedentirelywithinbone.Patientsdeemed tohavepoorprognosisor to receivepalliative treatmentonly–maylimitnumberofextractionsonthisbasis.Dental neglect (toothbrushing <1x per day, intake of >5 sugar attacks per day, cariesaffecting >75% of remaining teeth) – may consider additional extraction of teeth orcompletedentalclearance.

Patientswithoral cancer – additional teeth in closeproximity to tumourmay requireremovalaspartoftheoncologysurgicalapproach.Patients taking bisphosphonate medications – need to liaise with Oral Surgery orMaxillofacialTeam.2.Dentalrestorations(“fillings”)Permanentrestorationsshouldbeundertakenwherepossible.Minimum=Rendertoothcaries-free(includingcrownremovalwhereappropriate)andadequatetemporization(e.g.withglassionomerrestoration).Minimum when a tooth has been diagnosed with pulpal/apical pathology = 1ststageRCTandadequatetemporization(e.g.withglassionomerrestoration).3.Non-surgicalperiodontaltreatmentNon-surgical periodontal treatment to remove supra and subgingival calculus andplaque.ProtocolforpostradiotherapydentalassessmentsParticipants will be followed-up at 6 months, 12 months, and 24 months post-radiotherapy.PatientswillundergodentalassessmentonaWednesdaymorningorafternoon in theProstheticsDepartmentoftheSchoolofDentistry,Belfast.Thefollowingmeasurementswillbe collected (using the samemethodsandexaminersoutlinedabove): chartingofdental caries, 6-point clinical attachment loss and probing pocket depth charting,stimulatedsalivaryflowrate,mouthopening,oralhygienepractice,dietaryassessment,qualityoflife,patientreportedxerostomia,micro-costingsstudy.N.B. – For each patient, all efforts must be made to ensure that saliva collection isundertakenatasimilartimeofdayforeachofthefourdentalassessmentappointments(i.e. the pre-radiotherapy assessment appointment and the three post-radiotherapyassessment appointments). This is due to the diurnal variation in saliva production.Patientswillbeaskedtorefrainfromsmoking,eatinganddrinking,andotherformsoforalstimulation(e.g.oralhygiene)90minutesprior to thecollectionofsalivaatpost-radiotherapy assessment appointments. These instructions will be explained andprovided inwriting,andattachedwiththepost-radiotherapyassessmentappointmentletterasaremindertopatients.RadiographsThe decision to prescribe, take, and interpret dental radiographs for the purposes ofdiagnosis and treatment-planning should bemade on a case-by-case basis and followcurrentclinicalpractice.Thereshouldbeclearjustificationforthemedicalexposureofpatients in line with the Ionising Radiation (Medical Exposure) (Amendment)Regulations(NorthernIreland)2010.15Thefollowingcriteria,adaptedfromtheFGDP’sSelection Criteria for Dental Radiography16, is intended to guide the decision-makingprocess:DPT – suspected bony pathology (e.g. osteoradionecrosis, cyst), gross caries orperiodontaldiseaseassessment,wisdomtoothassessment.

IOPAs-symptomaticteeth,clinicalsigns(sinus,swelling),carieswithsuspectedpulpalinvolvement, toothwear with suspected pulpal involvement, previous RCT, crownedteeth, heavily restored teeth with restoration in close proximity to pulp, clinicalattachmentloss>6mm,furcationdisease.Bitewings–wherevisualizationofapproximalsurfacesofposteriorteethimpeded.Radiographic evidence of secondary caries or caries into dentinewill be recorded oneachpatient’sOralHealthAssessmentFormasabove.OtherspecialinvestigationsElectricpulptest–carieswithsuspectedpulpalinvolvement,toothwearwithsuspectedpulpalinvolvement,heavilyrestoredteethwithrestorationincloseproximitytopulp.Patients’ general dental practitioners will also be asked to immediately inform theresearchteamiftheycarryoutanydentaltreatmentduringthecourseofthestudy.Preventionandtreatmentplanningpost-radiotherapyAt each visit, patients will receive standardised oral hygiene and dietary advice (asabove). Consultantswill oversee treatment plans for the restoration of dental health.Requiredtreatmentwillbeco-ordinatedbytheSchoolofDentistryinlinewithcurrentpractice,includingthepossibilityofroutinetreatmentwithinprimarycare.ExtractionsThe decision to undertake extractions should be taken after careful consideration ofindividual toothprognosis, toothabutmentpotential, thepatient’smedicalhistoryandother cancer related factors e.g. radiotherapy dose to mandible/maxilla. It isrecommended that extractions be limited to teeth that are deemed unrestorable (seeboxbelow).17-21AlldentalextractionsshouldbeundertakeninahospitaldentalsettingandfollowingliaisonwithanOralSurgeryorMaxillofacialSurgeryteam.

ClinicaldatatransferandstorageOralHealthAssessmentformswillbestoredineachpatient’sclinicalnotesastheyformanintegralpartofeachpatient’soverallclinicalassessment.Relevantanonymiseddatarelating to dental caries, periodontal disease, saliva flow, andmouth opening will betransferred to a password-protected data spreadsheet on an encrypted password-protected Centre for Public Health, Queen’s University computer. Informationwill berecordedalongsideeachpatient’sanonymouscode.Pleasenotetheregisterofpatients’Dental Health and H&C numbers and anonymous codes will be stored on a separatepassword-protectedspreadsheetonaBelfastHealthandSocialCareTrustcomputer.

UNRESTORABLETEETH:Subgingivalcaries/toothmargin>1mmPeriodontalpocket>5mmatoneormoresitesnon-responsivetonon-surgicalperiodontaltreatmentGradeIImobileorworseApicalpathologynotresponsivetoorthograderootcanaltherapyRootfracture/perforation/resorption

RadiationdoseandtumourlocationdeterminationPatientswillreceiveradiotherapyasprescribedbytheirConsultantClinicalOncologist.The Clinical Oncologistwill also plan individual tissue exposures in linewith currentpractice.Therewillbenoalterationorexperimentationwithradiotherapydoseortheradiotherapytreatmentplanforthepurposesofconductingthisresearchstudy.Using additional research software (Non-Clinical Eclipse System by Varian MedicalSystemsUKLtd),radiationdoseexposurestotheteethand ‘spared’parotidglandwillbecalculatedaftertheteethandparotidglandshavebeencontouredoneachpatient’sradiotherapyplanningCTscan.TheClinicalOncologistwillcontourtheparotidglandsinlinewith current practice. A dentistwill contour the teeth on patient-anonymised CTscans. Tumour locationwill be determined from the initial referral letter sent by theHeadandNeckCancerMultidisciplinaryTeam.The dentist will be blinded to patient details when contouring teeth on CT scans. A‘uniqueidentifier’willbegeneratedforeachpatient’sCTscan.Amemberoftheclinicalradiotherapy team (not involved in the study) will securely store a list of patients’‘unique identifiers’ and H&C numbers on a Belfast Health and Social Care Trustcomputer.Thedentistwilltheninputradiationdosedata(dosestotheteethandtothe‘spared’ parotid gland) alongside each patient’s ‘unique identifier’ onto a separatepassword-protectedspreadsheetstoredonanencryptedpassword-protectedCentreforPublicHealth,Queen’sUniversityBelfastcomputer.SamplesizeSamplesizecalculationswereconductedbaseduponanindependentsamplest-testandcorrelationcoefficient.Assumingthestandarddeviationofthenumberofcariousteethinpost-radiotherapyheadandneckcancerpatients is4.0(basedupontheresultsofa10-year School of Dentistry audit conducted by the applicant fellow) and comparingpatientsreceivingover20Graytothe‘spared’parotidglandwiththosereceivingunder20Gray(basedupona80%/20%distributionseenintheCancerCentreradiationdoseaudit),wewouldrequireatotalsampleof150patientswithavailabledatatohaveover80%powertodetectadifferenceof3.0 inthemeannumberofcariousteethbetweenthe under 20 Gy and over 20 Gy groups as statistically significant at the 5% level.Furthermore a sample size of 150 patients would allow 80% power to detect, assignificantatthe5%level,acorrelationcoefficientof0.22fortheassociationbetweenradiation dose to the ‘spared’ parotid gland (Gy) and the number of carious teeth.Assuming30%dropoutwewouldthereforeneedtorecruit215patients.StatisticalanalysisPrimaryoutcomemeasurestobeanalysedinclude:(1)thenumberofcariousteethand(2)thepresenceofperiodontaldisease.(1)Initialcomparisonsbetweentheradiationdosetothe‘spared’parotidglandandthenumber of carious teeth will be performed using independent t-tests (categorisingradiationdoseas<20Gyand>20Gy)andANOVA(categorisingradiationdoseas<20Gy,20-30Gy, 30-40Gy, and >40Gy) as appropriate. Adjusted analysis will be performedusing multiple linear regression, with the number of carious teeth as the outcomevariable, radiation dose to the ‘spared’ parotid gland as an explanatory variable

(categorised as above) along with potential confounding variables: dental radiationdose, oral hygiene practice, diet, and mouth opening. Without categorising radiationdose,aseparateanalysiswillbeconductedusinglinearregressionwiththenumberofcarious teethas theoutcomevariableandradiationdose to the ‘spared’parotidgland(Gy)astheexplanatoryvariabletogivetheincreaseinthenumberofcariousteethper10 unit increase in Gray. If the number of carious teeth is not normally distributedtransformationswillbeusedpriortoanalysisorequivalentnon-parametrictechniqueswillbeused.(2)Initialcomparisonsoftheassociationbetweenradiationdosetothe‘spared’parotidgland(categorisedasabove)andthepresenceofperiodontaldisease(Yes/No)willbeperformed using chi-square tests. Adjusted analysis will be performed using logisticregressionwithpresenceofperiodontaldiseaseastheoutcomevariable,radiationdosetothe‘spared’parotidglandastheexplanatoryvariableanddentalradiationdose,oralhygiene practice, diet, smoking, medical history, and mouth opening as potentialconfounders.Similaranalyseswillbeundertakentodeterminetheeffectsofdentalradiationdoseandtumourlocationonthenumberofcariousteethandthepresenceofperiodontaldiseaseinpost-radiotherapyheadandneckcancerpatients.Secondaryoutcomestobeanalysedinclude:qualityof life,salivaryflowrate,diet,oralhygienepractice,mouthopening,xerostomia(allchangefrombaseline);toothloss,anddenture wear. Dichotomous outcomes will be analysed using chi-square tests andlogisticregressionasabove.Continuousoutcomeswillbeanalysedasabove,apartfromvariables with baseline measurements, for which ANCOVA will be used to compareoutcome measurements adjusting for baseline.22 Adjusted analyses will use multiplelinear regression models as above but with baseline measurements as an additionalexplanatoryvariable.Micro-costingsanalysisAmicro-costingsanalysiswillbeundertakentoevaluatepatientandhealthcarecostsinrelationtothediagnosisandtreatmentofpre-andpost-radiotherapydentaldisease.-Patientcoststobeevaluatedinclude:totalcostoftraveltodentalappointments,totaltimeoffworktoattendfordentaltreatment,totalcostofdentaltreatmentincurredpreand post-radiotherapy (general or private practice), total out-of-pocket expenses (e.g.pain-reliefmedications).Patientswillalsobeaskedtostatetheirgrossannualincomeinordertobeabletoquantifytheirindividualeconomicburdenofdentaldisease.23-Healthcarecoststobeevaluatedinclude:(1) clinical and administration hospital costs for pre- and post-radiotherapy dentalassessments and treatment via the National Schedule of Reference Costs for NHSTrusts.24(2) remuneration of primary care dental practitioners via the Statement of DentalRemunerationmadeavailablebytheBusinessServicesOrganisation.25Costsavingsduetoimprovedtreatmentplanningofpatientswillalsobehypothesised.Distressprotocol

Ifanyparticipantshowsemotionaldistressoranxietyduringoneofthestudyvisits,theexaminerwill follow the protocol outlined below to ensure the safety of the researchparticipant.Theassessmentappointmentwillbestopped.Distressedparticipantswillbeinvitedtotake a break in the private side clinic of the Prosthetics Department in the School ofDentistry, Belfast, and, if appropriate, to discuss their concerns or worries with theexaminer, a family member, or friend. A senior clinician (one of the RestorativeDentistryConsultants)mayalsobe invited into the side room.Theparticipantwillbesupported to recommence the assessment if they decide to do so. Alternatively, theassessment may be rearranged. Any participant has the right to withdraw from thestudy at any time and those who do not wish to continue will be provided with thecontact details of the research team and relevant support agencies (e.g. their GP orMacmillanCancerSupport).Inallinstances,participantswillbeencouragedtocontacttheironcologist,theirdentist,ortheirGPiftheyhaveanyfurtherworriesorconcernsabouttheirparticipationinthestudy.Whereappropriate,aresolutionwillbe found.Thismay involvesimplyreassuringthepatientorofferingremedyingtreatmentwhereappropriate.Remedyingtreatmentmayinclude(inlinewithcurrentclinicalpractice):-Managementofdrymouth (e.g. through theuseof salivasubstitutes, constant sipsofwater).-Managementoftoothache(e.g.throughrootcanaltreatment,dentalextraction).-Managementoflimitedmouthopening(e.g.throughtheuseofaTherabitedevice,jawexercises).-Management of osteoradionecrosis (e.g. oral surgery/maxillofacial surgery referral,pharmacologicalmeasures).CalibrationofexaminersTwoqualifieddentistswillactasexaminersforthestudy.Theywillundertakeallofthepre- and post-radiotherapy dental assessments. The examiners are already employedwithin the School of Dentistry, Belfast, Belfast Health and Social Care Trust. Bothdentists will undergo calibration prior to the commencement of the study(approximately3monthsbeforehand).2The calibration session will re-educate examiners on the processes involved in theclinical assessment of head and neck radiotherapy patients. This will be led byConsultantsinRestorativeDentistry.ThecalibrationsessionwillbeundertakenoutsideofBelfastHealthandSocialCareTrustnormalworkinghoursandwillbeaccreditedasa‘Continual Professional Development’ study session for both examiners. Topics to becovered include: dental caries assessment, periodontal assessment, measurement ofstimulated salivary flow rate, ruler measurement of mouth opening, prescribing ofdental radiographs, pre- and post-radiotherapy dental extractions, and instructingpatientsonoralhygiene,denturehygiene,anddiet.Inter-examiner consistency regarding the assessment of dental caries and theassessment of periodontal disease indices will be determined via a series of clinicalphotographs,radiographs,andartificialphantom-headsintheClinicalTeachingLab,2ndfloor,SchoolofDentistry,Belfast.Agreementbetweenexaminerswillbedeterminedbythe calculation of the kappa statistic. The target level of agreement will be 0.81-1.00

(almost perfect agreement). Where there are major discrepancies, inter-examinerdifferenceswillbereviewedandresolvedbygroupdiscussion.Both examiners are currently involved in the pre- and post-radiotherapy dentalassessmentofheadandneckcancerpatients in theProstheticsDepartment,SchoolofDentistry,Belfast,aspartoftheircurrentjobrole.Theyalreadyundertakedentalcariesandperiodontaldiseaseindicesassessments,aswellastherulermeasurementofmouthopeningandthedeterminationofsalivaryflowrates,onaday-daybasis.SpreadsheetsSeparatepassword-protectedspreadsheetswillbecreatedonanencryptedpassword-protectedQueen’sUniversitycomputer/laptopasfollows:1.Fourclinicaldataspreadsheetscontainingpatients’anonymouscodesalongsidedatafromtheirclinicalassessment(caries,periodontalassessment,stimulatedsalivaryflow,mouth opening, questionnaire results). This data will be input by one of the dentalexaminerswithintheprivatesideclinic intheProstheticsDepartmentoftheSchoolofDentistry,Belfast, aftereachclinical sessionhasended.Therewillbeonespreadsheetforeachofthefourdentalassessmentappointments.2. A radiotherapy dose spreadsheet containing patients’ ‘unique identifiers’ alongsidetheirradiotherapydosedata(dosetoteeth,dosetosparedparotidgland,locationofthetumour).Thiswillbeinputbythedentalexaminertaskedwithcontouringteethoneachpatient’sradiotherapyplanningCTscan.The following informationwill retainedsecurelywithin theTrust(viaaBelfastHealthandSocialCareTrustcomputer)andwithpassword-protectedaccess:1.Alistofpatients’H&CandDentalHealthnumbersalongsidetheiranonymouscodes.Tobestoredbytheapplicantfellow.2. A list of patients’ H&C numbers alongside their CT scan ‘unique identifiers’. To bestoredbyamemberoftheclinicalradiotherapyteamonaBelfastHealthandSocialCareTrustcomputer.References1.WorldHealthOrganization.InternationalClassificationofDiseases(ICD).ICD-10Version:2016.[Internet].2016[cited2016Jun2].Availablefrom:http://www.who.int/classifications/icd/en/2.WorldHealthOrganization.Oralhealthsurveys:basicmethods-5thedition.[Internet].2013[cited2016Jun2].Availablefrom:http://www.who.int/oral_health/publications/9789241548649/en/3.BulmanJ,OsbornJ.Measuringdiagnosticconsistency.BrDentJ.1989May20;166(10):377-81.4.LandisJ,KochG.Themeasurementofobserveragreementforcategoricaldata.Biometrics.1977Mar;33(1):159-74.5.IsmailA,SohnW,TellezM,AmayaA,SenA,HassonHetal.TheInternationalCariesDetectionandAssessmentSystem(ICDAS):anintegratedsystemformeasuringdentalcaries.CommunityDentOralEpidemiol.2007Jun;35:170-8.6.EkeP,PageR,WeiL,Thornton-EvansG,GencoR.Updateofthecasedefinitionsforpopulation-basedsurveillanceofperiodontitis.JPeriodontol.2012Dec;83(12):1449-54.

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