PredictingandManagingOralandDentalComplicationsofSurgicalandNon-Surgical

TreatmentforHeadandNeckCancer

AClinicalGuideline

November2016

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CONTENTS

KeytoevidenceStatementsandGradesofrecommendation 3

1. Introduction 4

2. Theimpactofheadandneckcancertreatmentonoralhealth 6

3. Oralanddentalmanagementpriortotreatment 9

4. Oralanddentalmanagementduringtreatment 14

5. Oralanddentalmanagementfollowingtreatment 18

6. Developmentoftheguideline 23

7. References 25

8. FurtherReading 29

9. KeyQuestions 33

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KEYTOEVIDENCESTATEMENTSANDGRADESOFRECOMMENDATIONS

LEVELSOFEVIDENCE

1++ Highqualitymeta-analyses,systematicreviewsofrandomisedcontrolledtrials(RCTs),orRCTSwithaverylowriskofbias

1+ Wellconductedmeta-analyses,systematicreviewsofRCTS,orRCTswithalowriskofbias

1 Meta-analyses,systematicreviewsofRCTsorRCTswithahighriskofbias

2++ HighqualitysystematicreviewsofcasecontrolorcohortstudiesHighqualitycasecontrolorcohortstudieswithaverylowriskofconfoundingorbiasandahighprobabilitythattherelationshipiscausal

2+ Wellconductedcasecontrolorcohortstudieswithalowriskofconfoundingorbiasandamoderateprobabilitythattherelationshipiscausal

2- Casecontrolorcohortstudieswithahighriskofconfoundingorbiasandasignificantriskthattherelationshipisnotcausal

3 Non-analyticstudies,egcasereports,caseseries

4 Expertopinion

GRADESOFRECOMMENDATION

Note:thegradeofrecommendationrelatestothestrengthoftheevidenceonwhichtherecommendationisbased.Itdoesnotreflecttheclinicalimportanceoftherecommendation.

A Atleastonemeta-analysis,systematicreviewofRCTs,orRCTratedas1++anddirectlyapplicabletothetargetpopulation;or

Abodyofevidenceconsistingprincipallyofstudiesratedas1+,directlyapplicabletothetargetpopulationanddemonstratingoverallconsistencyofresults

B Abodyofevidenceincludingstudiesratedas2++,directlyapplicabletothetargetpopulationanddemonstratingoverallconsistencyofresults;or

Extrapolatedevidencefromstudiesratedas1++or1-

C Abodyofevidenceincludingstudiesratedas2+,directlyapplicabletothetargetpopulationanddemonstratingoverallconsistencyofresults;or

Extrapolatedevidencefromstudiesratedas2++

D Evidencelevel3or4;or

Extrapolatedevidencefromstudiesratedas2+

GOODPRACTICEPOINTS

✓ Recommendedbestpracticebasedontheclinicalexperienceoftheguidelinedevelopmentgroup

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1 Introduction

1.1 THENEEDFORAGUIDELINE

Approximately9200patientswithnewcancersoftheheadandneckareregisteredintheUKeachyear.Theincidenceofthisdiseasehastendedtoincreasewithageand in the UK, 85% of cases occur in people over the age of 50. There is nowevidencethatthe incidenceofheadandneckcancers is increasingamongyoungpeopleofbothsexes.ThismaybeinassociationwithHumanPapillomaVirus(HPV)induced cancers. Head and neck cancer tends to be a disease associated withdeprivation and the risk of developing the disease is four times greater inmenlivinginthemostdeprivedareas.

Approximately90%ofpatientspresentingwithheadandneckcancerhavedentaldisease and the treatment of head and neck cancer produces significantoral/dentalsideeffects.

Morepeopleareretainingteethintooldage.TheAdultDentalHealthSurvey2009publishedin2011lookedatthedentalhealthoftheUKapartfromScotland1.Thisshowed that 94% of the combined populations of England,Wales andNorthernIrelandwere dentate (that is had at least one natural tooth). The proportion ofadultsinEnglandwhowereedentuloushadfallenfrom28%in1978to6%in2009.

Consequently,theoralanddentalmanagementofheadandneckcancerpatientsiscomplexandwillbecomean increasingchallengeaspatientsretaintheir teethlonger. These issues are managed by the Consultant in Restorative Dentistry: acorememberoftheheadandneckcancermultidisciplinaryteam2.

There are UK guidelines for the management of head and neck cancers whichoutline oral rehabilitation2,3,4. Detailed guidelines for management of oralrehabilitationforheadandneckcancerpatientsarelacking.

1.2 REMITOFTHEGUIDELINES

Theguidelinesaddressissuesrelatingtooralanddentalcareatthepre-,peri-andpost-treatment stages. They examine the quality of evidence for managing oraland dental complications from an holistic, pathway-based and multidisciplinaryteam-based approach. Opportunities for minimising these complications areconsidered.

The guidelines will be of interest to all healthcare professionals working withpatients with head and neck cancers including restorative dentistry consultants,maxillofacial surgeons, ear, nose and throat surgeons, plastic surgeons, clinicaloncologists, cancernurse specialists,dental therapists,dietitiansandspeechandlanguagetherapists.

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1.3 STATEMENTOFINTENT

These guidelines are not intended to be construed or to serve as a standard ofcare.Standardsofcarearedeterminedonthebasisofallclinicaldataavailableforan individual case and are subject to change as scientific knowledge andtechnological advances and patterns of care evolve. Adherence to guidelinerecommendationswillnotensureasuccessfuloutcomeineverycase,norshouldthey be construed as including all proper methods of care or excluding otheracceptablemethods of care aimed at the same results. The ultimate judgementregardingaparticular clinicalprocedureor treatmentplanmustbemadeby theappropriate healthcare professional(s) in light of the clinical data and patientpreferences.However, it is advised that significant departures from thenationalguidelinesoranylocalguidelinesderivedfromthemshouldbefullydocumentedinthepatient’scasenotesatthetimetherelevantdecisionistaken.

1.4 REVIEWANDUPDATING

These guidelineswere issued in 2016 andwill be considered for review in threeyears.

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2. The impact of head and neck cancer treatment on oralhealth.

Theoverallaimoftreatmentforheadandneckcanceristomaximizelocoregionalcontrol and survival with minimal resulting damage to function and form.Treatmentoftheprimarytumourandneckmayinvolvesurgicalresectionwithorwithout reconstructionor radiotherapywithorwithout chemotherapy.Adjuvantradiotherapyorchemoradiotherapymayberequiredfollowingsurgicalresection.Thesetreatmentmodalitiescanresult inadverseshort-andlong-termoral,facialanddentalcomplications.Surgicaltumourresectioncanproducealterationstothenormal anatomy which adversely affect function and outward appearance.Radiotherapycausesunavoidableradiationdamagetonormaltissuessurroundingthetumour,affectingthefunctionofthesetissuesbothintheshort-term(duringand immediately after treatment) and long-term (for months and years aftertreatment or lifelong). Chemotherapy causes acutemucosal and haematologicaltoxicity, with the former being accentuated if chemotherapy is deliveredconcurrently with radiation therapy. Thus, head and neck cancer treatment canhave adverse effects on respiration, mastication, swallowing, speech, taste,salivaryglandfunction,mouthopeningandtheoutwardappearanceof theheadand neck region. The complications of treatment need to be anticipated andmanagedbythemultidisciplinaryteamwiththeinputoftherestorativedentistryconsultantwho is a coremember of the head and neck cancermultidisciplinaryteam. Older patients increasingly have a greater proportion of retained, oftenheavily restored teeth.Oral rehabilitationandmaintenance is thereforecomplexandlifelong,oftencontinuingwellbeyonddischargefromcancerfollowup.

2.1 ORALCOMPLICATIONSOFTREATMENT

2.1.1 SHORT-TERM:

• OralMucositis:Thisisinflammationandulcerationofthemucosalliningoftheoralcavity and oropharynx. This complication affects most patients havingradiotherapy or chemoradiotherapy to the head and neck. It may be severe,requiring opioid analgesia to alleviate pain and impairs quality of life. Painfulswallowing(odynophagia)causedbymucositiscanmarkedlyimpairtheintakeandenjoymentoffoodandisasignificantfactorassociatedwithdifficultieseatinganddrinking and sustaining weight. Many centres across the UK plan nutritionalmanagementwith prophylactic tube placement in anticipation of this symptom.Oralmucositismayinhibitorcompletelypreventoralhygieneanddentaldiseaseprevention measures due to inability to tolerate the physical trauma oftoothbrushingor the strong flavoursof toothpastes andmouthwashes.Onsetofmucositis is within the first twoweeks of treatment and usually resolves by sixweeksaftertreatment.

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• Infection: Chemotherapy-inducedneutropenia renders thepatient susceptible tobacterial, viral, and fungal infections. Oral candidal infections are extremelycommon following chemotherapy or radiotherapy. Antifungal drugs absorbed orpartially absorbed from the gastrointestinal tract prevent oral candidiasis inpatientsreceivingtreatmentforcancer.Theyaresignificantlybetteratpreventingoralcandidiasisthandrugsnotabsorbed5.

• Trismus:Thisisrestrictedorlimitedmouthopeningandmandibularhypomobility.This can be due to either active spasm (tonic contraction) of the muscles ofmastication (also described as reflex guarding) or it can be due to physicalrestriction of themuscles ofmastication and/or temporomandibular joint (TMJ)capsule.Inrelationtoheadandneckcancer,thisphysicalrestrictioncanbeduetothe presence of tumour, post-surgical inflammation or can be due to fibrosis ofthosetissuesasaresultofchemotherapyandradiotherapy.Followingsurgeryandchemotherapy trismus may be reversible. However, trismus that followsradiotherapycanoccurrapidlyoverthefirst9monthsaftertreatment6, tendstobeprogressiveandmaybeirreversible.MandibularhypomobilityultimatelyresultsinbothmuscleandTMJdegeneration.Ifmusclesdonotmovethroughtheirrangeofmotionatrophyisevidentwithindays.Immobilisedjointsquicklyshowsignsofdegeneration. Restrictedmouth opening causes problemswith eating, speaking,laughing,yawning,sexualintimacy,accessfororalselfcareandaccessfororalcarebyanydentalprofessional.Thiscanresult insocial isolationandhaveanadverseeffectonqualityoflife7.

• Salivaryhypofunction:This isdefinedas reducedrestingsalivary flowratebelow0.2mlperminuteorstimulatedsalivaryflowrateoflessthan0.7mlperminute.Itiscausedbyionisingradiationdamagetosalivarytissueintheradiotherapyfields.Intheacutephase,salivathickensandstringymucousiscommon.Thereisalsoaqualitativechangeinsalivawithachangeinconsistency,reducedbufferingeffect,reduced clearance and reduced pH. The oral microflora is altered to favourcariogenic bacteria. Xerostomia, the subjective feeling of a dry mouth, is aconsequence of hyposalivation. These changes lead to problems with speech,mastication,swallowingandincreasedriskofdentalcaries.

• Aguesia/Dysguesia(tasteloss/alteredtaste):thisisusuallyreversible.Itcancausereductioninappetiteduetolossofpleasureineating.

2.1.2 LONG-TERM:• Altered anatomy/impaired function and appearance: Surgical ablation and

reconstruction can cause permanent changes in facial and oral anatomy. Theremaybesignificantdifficultieswithspeech,masticationandswallowingiftherearesurgicallyproducedintra-oraldefectsoralterationstoanatomy.Examplesincludemaxillectomy,softpalatedefectoralteration,tonguedefectoralterationorlossofsignificant numbers of opposing pairs of teeth. Facial appearance may besignificantly adversely affected. Prosthetic rehabilitation is often difficult aftersurgeryandsometimes impossible,especiallywhererehabilitation isnotplannedwiththerestorativedentistryconsultantaheadofablation.

• Trismus(asabove)• Salivaryhypofunction(asabove)

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• Radiotherapy-associated dental caries: This is an indirect effect of non-surgicaltreatment (chemotherapy and radiotherapy). Radiation associated caries candevelop as a result of reduced salivary flow and altered saliva function incombination with the high protein and calorie diet. This includes sucrose andglucose dense nutrition and ‘little and often’ dietary approach frequentlynecessary and advocated, within the context of appropriate nutritionalmanagement,bydietitians.Thiseffectcanbecompoundedbyreducedtoleranceto caries prevention measures at this phase in treatment. Rapidly developing,widespread caries can result that is often circumferential around the teeth andmay affect incisal edges. Nutritional supplements are often necessary. Somenutritional supplements are particularly cariogenic due to their sucrose andglucose content, sticky texture and frequent intake. Particular care is needed atthis time if caries is tobeavoidedandclose, joint supervisionof thepatientsbydietitiansandrestorativedentistryconsultantsisessential.

• Osteoradionecrosis(ORN):Thisentityisdefinedasanareaofexposedboneofatleast three months duration in an irradiated site and not due to tumourrecurrence.Thismaycauselong-termsignificantmorbidity.

2.2 MODERNRADIOTHERAPYSCHEDULES:

Thereisacorrelationbetweenthevolumeofparotidglandirradiatedto25-30Gyandthelong-termrecoveryofsalivaryfunction8,9.Intensity Modulated Radiotherapy (IMRT) reduces the dose delivered to theparotid gland. It is complex to plan and deliver but it achieves a better balancebetween target coverage and normal tissue avoidance than conventionalradiotherapy10.Sparing the parotid glands with IMRT significantly reduces the incidence ofxerostomiainpatientswithoropharyngealandhypopharyngealtumours111++andin nasopharyngeal tumours12,131+ and leads to recovery of saliva secretion overtimeandimprovementsinassociatedqualityoflife.IMRTmaybeassociatedwithalessfrequentprevalenceoftrismusbutthisneedsfurtherstudy14.Theweightedprevalence for ORN with IMRT is 5.2% compared with 7.3% for conventionalradiotherapybutitisnotclearifthisisclinicallysignificant153.

HPV-associated oropharyngeal cancers often occur in younger, relatively healthypatients with, possibly, healthy dentition. They may, therefore, experience latecomplicationsformanyyears.Itispossiblethattreatmentforsuchcancersmaybede-escalatedwitharesultantreductioninlatecomplicationrisk.Howeverthereisnofirmevidenceforthisasyetanditremainscontroversial.

BIMRThasbeenshowntoreducelong-termxerostomiaandshouldbeofferedtoallappropriatepatients

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3. Oralanddentalmanagementpriortotreatment

3.1 AIMSOFPRE-TREATMENTMANAGEMENT

• The restorative dentistry consultant will identify those patients who need pre-treatment assessment at the multidisciplinary teammeeting. This will generallyinclude: patients requiring an assessment to consider oral rehabilitation,particularly those planned for surgical intervention that will alter oral anatomy,dentate patients requiring radiotherapy where the treatment field includes anypart of the maxilla, mandible or salivary glands, patients with specific dentalconcerns

Aims:

• To avoid unscheduled interruptions to primary treatment as a result of dentalproblems

• Toensure thepatientunderstands thenatureand implicationsof theshort-andlong-termoralcomplications.Excellentcommunicationskillsarerequiredasthisisa time of immense anxiety for patients. Patients report that having access tocombined, comprehensiveMDT services on one site is an important advantage.ExcellentcommunicationbytheRestorativeteamwiththeMDTisessential.

• To carry out appropriate dental treatment informedby assessment of individualriskofdevelopmentofposttreatmentoralcomplicationsandtakingintoaccounttheoverallprognosis.

• Toplanpost-treatmentprostheticoralrehabilitation

Treatment planning at this stage is based around assessment of the risk ofdeveloping post-treatment long-term complications: altered anatomy, trismus,hyposalivation, radiotherapy associated caries and ORN. Patients whose oralcavity, teeth, salivary glands and jaws will be affected by radiotherapy to theoropharynx, nasopharynx, maxilla, mandible and parotid glands should haveassessment and appropriate management as early as possible after the cancertreatment plan is made to allow time for any necessary dental treatment. Thisshouldrenderpatientdentallyfitbeforetreatmentandensuretheoralcavitycanbe rehabilitated and maintained after treatment. In the case of adjuvantradiotherapy,assessmentmaybepriortosurgeryandagainpriortoradiotherapy.

Potential for altered anatomy: Joint planning consultation with maxillofacialsurgeonsandrestorativedentistryconsultantsmayberequiredwherepatientsareplanned for surgery which will alter the oral cavity or cause microstomia andaccess difficulties. This is particularly true where maxillectomy procedures orprimaryimplantsarerequired.

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Trismus risk: lack of uniform criteria to define trismus in the literature makesevaluation of study outcomes difficult when assessing risk162++. Criteria varyfromlessthan20mmofmouthopeningtolessthan40mmofmouthopening.Othersgiveagradedratherthandichotomousdefinition.Aninter-incisaldistanceof35mmorlessasthecut-offpointhasbeensuggested17.Combiningthiswithasubjectivemeasurementofpatientperceptionofchange inmouthopeningsincetreatmenthasalsobeenadvocated7.Reportedprevalenceratesfortrismusareasfollows: 25.4% for patients receiving conventional radiotherapy, 5% for thosereceiving IMRT and 30.7 % for radiotherapy and chemotherapy 2++. The risk ofdevelopingtrismusasaresultofradiotherapytotheheadandneckappearstobedosedependent. Levels in excessof 60Gyaremore likely to result in trismus18.IMRTmay be associated with less frequent incidence of trismus but this needsfurtherstudy14.RiskseemstobegreaterwhentheTMJsandpterygoidmusclesareexposed to ionizing radiation19. This is most likely in tumours of parotid gland,nasopharynx, oropharynx and posterior oral cavity. There is higher risk whenpretreatmentfunctionispoorandforT3/T4tumours.Chemoradiotherapymaybeassociated with an increased prevalence of trismus. Following development,restrictionmaybe irreversible.Exercisesearly inthecourseoftreatmentmaybeofbenefit.Somepatientsmaybegeneticallypredisposedtofibrosis.TransformingGrowthFactorβ1(TGFβ1) is themajorcytokineresponsible for theregulationoffibroblast proliferation and differentiation. The development of ORN may berelated to thepresenceof theTvariantallelewithin theTGFβ1gene 20.Trismusmay be overlooked by patients and clinicians and patients may assume it is‘normal’ orwill resolve.Onsetof trismus is progressive and, if patients areonafeeding tube or liquid diet, thismay not be evident until there is an attempt toresumenormaloralintake.

Hyposalivationrisk:Seesection2.2

ORN risk: the reported incidence of ORN development following extraction ofteeth from irradiated regionsof the jaws is low.The total incidence is7%21.Theextraction of mandibular teeth within the radiation field in patients who havereceivedaradiationdosehigherthan60GyrepresentsahigherriskofORN212++.

C Pre-radiotherapy extractions may be required especially where teeth are ofdoubtfullongtermprognosisandareinanareaofmandiblewhichwillreceive>60Gy✓ Patientsdeemedatriskoftrismusshouldhaveinstructiononhomeexerciseandthisshouldcontinuefor9monthsfollowingthestartofradiotherapy.

✓ Inter-incisal distance should be monitored and sensitive anatomicalstructuresshouldbeprotectedduringradiotherapy.

✓ If patients are deemed at risk of trismus they should be warned and theprogressiveandpotentiallyirreversiblenatureexplained.

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3.2 PRE-TREATMENTASSESSMENT

Fullhistoryandclinicalexaminationshouldbecarriedout:

Thisshouldcover:Presenting concerns, relevantmedical history: including TNMstaging and cancertreatment plan,whether treatmentwill be curative or palliative and the overallprognosis for thepatient. Informationregardingnutritional intakeshouldalsobediscussedwiththedietitianinordertogaugecariesrisk.Dental history: this should include patientmotivation or anxiety and attitude totreatmentSocial history: including smoking and alcohol intake, domestic situation andcurrentandpastemploymentstatus

Extra-oral examination: This should include assessment of cervical lymph nodes,temporomandibular joints, salivary glands and measurement of mouth openingability.Intra-oral examination: soft tissues (lips, buccalmucosa, floor ofmouth, tongue,hard and soft palate, oropharynx), periodontal tissues (oral hygiene, periodontalprobingdepths, bleedingonprobing, supra- and sub-gingival calculus, recession,mobility), dentition (teeth present, caries, tooth wear, presence and quality ofrestorations,occlusion)andanyexistingfixedorremovableprostheses.Radiographic examination: Panoramic radiograph, periapicals and bitewings asappropriate.Specialinvestigations:sensitivitytesting,salivaryflowrates

3.3 PRE-TREATMENTMANAGEMENT3.3.1 PREVENTIVEMANAGEMENT

Note:currentrecommendedmethodsofcariesprevention22maynotbetolerablefor some patients during (chemo)radiotherapy due to acute toxicity. Preventionandmanagementofmucositis,trismusandxerostomiawill,therefore,contributeindirectlytocariesprevention.

Thisshouldinclude:• Instruction on maintenance of good oral hygiene; effective toothbrushing and

interdentalcleaning.• Dietary advice with regard to caries prevention in conjunction with dietitians.

Working jointly with dietitians allows optimisation of nutritional status to bebalanced with prevention of dental caries. Management of nutritionalsupplements should be discussed specificallywith regard to cariogenic potentialandfrequencyandmethodofintake.

• Daily topical fluoride application (Duraphat 5000ppm fluoride toothpaste foradultsatriskofradiationassociatedcaries)incustom-madetraysorbrush-on.

• Daily0.05%sodiumfluoridemouthrinse.• Daily use of GC ToothMousse TM containing free calcium for patients at risk of

radiationassociatedcaries

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• Salivareplacementtherapy/useoffrequentsalinerinses• Advice on active jaw exercises in conjunction with the speech and language

therapistsfromtheoutsetoftreatmenttoreduceorpreventtrismusforpatientsatriskoftrismus.

• Writteninformationregardingtheaboveshouldbegiventothepatient.

✓ The benefits of caries prevention when cariogenic substances are taken byenteral tube should be considered alongside the importance of maintainingnutritional status, avoidance of feeding tube dependency andmaintenance ofswallowingfunction✓ Wherecariespreventativemeasuresarenottoleratedthepatientshouldbereferredtothedietitianforappropriatenutritionsupportmethodsandguidancefortheintakeofcariogenicfoodanddrinks

3.3.2 IMPRESSIONSFORSTUDYMODELSDentalimpressionspriortocancertreatmentallowfortheconstructionofplastermodelsoftheupperandlowerteethandhardpalate.Theyprovidearecordofthepre-treatment tooth position and size which can be used for reference in post-surgicalprostheticrehabilitation.Theyarealsorequiredfor:

• Primaryimplantplanning• Obturatorconstruction• Customisedfluoridetrayconstruction• Where it is considered that post treatment impressions may be difficult or

impossibleduetotrismusormicrostomia

3.3.3 RESTORATIONOFTEETH• Requiredwhere restorations are failing or have the potential to traumatise soft

tissues/flap• Requiredwherethereiscaries

3.3.4 EXTRACTIONOFTEETH

• Extractionisrequiredforteethwhichareofdoubtfulprognosis,areunrestorableoratriskofdentaldiseaseinthefutureandareinanareadeemedtobeatriskofORN. This includes grossly carious teeth, retained roots, teeth with apicalpathology, mobile teeth, teeth associated with tumour, periodontally involvedteeth,non-functional teeth, teethclose toosteotomycuts, inaccessible teeth (orthosepredictedtobeinaccessibleaftertreatment)23.

• Therearenorandomisedcontrolledtrials toassesstheeffectofextractingteethpriortoradiotherapycomparedtoleavingteethinthemouthduringradiotherapytothejaws242++.Therearenorandomisedcontrolledtrialsregardingtheminimumtime recommended between dental extractions and the onset of radiotherapy.Thereislittleevidenceintheliteratureregardingpre-radiotherapyextractionsandthe prevention of ORN. There is lack of consistency in criteria for defining ORNcomparedwithdelayedhealing.Thereislackofdetailindescriptionoftheprecise

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natureand levelofsurgical intervention involved indentalextractionand lackofdetail regarding reason for extraction. Decisions are, therefore based on clinicalexperience and expert Restorative Dentistry Consultant opinion rather than onevidencebase25.✓ Extractions should be carried out as early as possible tomaximise time forhealing.✓ Whereitisknownthatadjuvantradiotherapywillbegiven,extractionsshouldtakeplaceatprimarysurgerytomaximisethetimeforhealingandminimisethenumberofsurgicaleventsforpatients.

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4. Oralanddentalmanagementduringtreatment

4.1 ORALMUCOSITISThisconditionusuallybeginsaround1-2weeksafteronsetof treatmentandcanlast around six weeks after treatment is complete. Severe pain produced bymucositis may inhibit oral hygiene measures. This means patients may stoptoothbrushinganduseoffluorideproducts.Toothbrushingandfluorideapplicationshould be resumed as soon as comfort permits. Basic oral care including dentalcare before during and after cancer treatment should improve oral comfort264.Chlorhexidinemouthwashshouldnotbeusedtopreventoralmucositisinpatientsreceivingradiationcareforheadandneckcancer.Theremaybeotherindicationsfor its use, for example where there are difficulties with mechanical plaquecontrol263.

Various preventive and management methods for oral mucositis have beenadvocated including neutral supersaturated calcium phosphate mouthrinse(Caphosol),polyvinylpyrrolidine/sodiumhyaluronategel(Gelclair),mucoadhesiveoral rinse (Mugard), soluble aspirin, benzydamine hydrochloride (Difflam)27,28 1,lowlevellasertherapy27,293andZincsupplements27,303.

A Benzydamine mouthwash (Difflam) can prevent oral mucositis in patientshavingradiotherapytotheheadandneckreceivingmoderatedoseradiotherapy(upto50Gy).Thisdose,however,wouldonlybeusedforlymphoma.

DLowlevellasertherapy(wavelengtharound632.8nm)maybeusedtopreventoral mucositis in patients undergoing radiotherapy without concomitantchemotherapyforheadandneckcancer

DZincsupplementsadministeredorallymayhelppreventoralmucositis inoralcancerpatientsreceivingradiotherapyorchemotherapy

✓ Basicoralcareincludinguseofblandrinsessuchasnormalsalineandsodiumbicarbonateanddentalprofessionalcareduringtreatmentisofbenefit

4.2 INFECTIONOral candidal infections are common and there is strong evidence that someantifungaldrugspreventoralcandidiasiscausedbycancertreatment,butnystatindoes not appear to be effective. Chlorhexidine gluconate has antifungal andantibacterialpropertiesinadditiontoantiplaqueeffects;however,itsvalueisstillunconfirmed.Itstendencytostainteethanditsalcoholcontent,whichcanirritateinflamedtissues,areotherpotentialdrawbacks

4.3 HYPOSALIVATION(XEROSTOMIA)4.3.1 PREVENTION

• Parotidsparingtechniques

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Sparing the parotid glands with IMRT significantly reduces the incidence ofxerostomiainpatientswithoropharyngealandhypopharyngealtumours111++andin nasopharyngeal tumours12,131+ and leads to recovery of saliva secretion overtimeandimprovementsinqualityoflife.

• CytoprotectionAmifostine is a hydrophilic compound whose active metabolite, WR-1065 isselectively takenupbynormal tissues. It is preferentially accumulated in certaintissuesincludingsalivaryglands.WR-1065actsasaradioprotectantbyactingasafree radical scavenger for patients receiving radiotherapy. There is, however,question regarding the potential tumour protective effect and it has significantsideeffectsincludinghypotension,nausea,vomiting,allergicreactionsandseveretoxic epidermonecrolysis (Steven-Johnson syndrome). There is no benefit shownfromtheuseofamifostine inpatientshavingconcurrentchemoradiotherapy31,322++.Thereisnoindicationforroutineuseofpilocarpineinxerostomiaprevention31.

• SurgicaltransferofthesubmandibularglandTransfer of the submandibular gland to the submental space can preserve itsfunction and has been shown to prevent development of radiation inducedxerostomia31,324. The submandibular gland, however, will always be removed atneck dissection with lymph glands at level 1b for oral cavity disease. Thistechnique,therefore,haslimitedapplicability.

• SalivaryStimulantsPilocarpine HCl, a cholinergic parasympathomimetic agent can enhance salivarysecretions in patients who have some functional salivary gland tissue preservedfollowing radiotherapy. Oral administration of pilocarpine HCl 5mg three timesdailyiseffectiveinthetreatmentofradiation-inducedxerostomiainpatientswithheadandneckcancer.Theimprovementdeclinesafterthecessationoftreatmentand therefore has to be administered lifelong31,32,332++. Adverse effects includesweating, headache and urinary frequency. The use of pilocarpine iscontraindicated in patients with a history of bronchospasm, severe COPD,congestiveheartdisease,angleclosureglaucoma,uncontrolledasthmaandgastriculcers. Pilocarpine HCl suspended in a pastille or lozenge or administered as amouthwash is also effective in improving xerostomia. Cevimiline is amuscarinicagonistwhichactsmainlyonM1andM3muscarinicreceptorsanddonothavetherespiratory and cardiac side effects of pilocarpine 31,33. Stimulation of residualfunctioncanalsobeachievedbychewingsugarlessgumorlozenges.

• Acupuncturemaybeofbenefitbutfurtherstudiesarerequired31,32.

BPilocaprineuseisrecommended,whereappropriate,followingradiotherapyinheadandneckcancerfortheimprovementofxerostomiabutthisimprovementmaybelimited.

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4.3.2 TREATMENT

• Oralmucosallubricants/Salivasubstitutes

Xerostomia symptomsmaybe relievedby sipping sugarless fluids frequentlybutthis results inpolyuria.Several salivasubstitutesareavailable includingASSalivaOrthana® (AS Pharma), Biotene Oralbalance Gel® (GSK), Saliveze® (Wyvern),Xerotin®(SpePharm)andGlandosane®(FreseniusKabi).Theyallofferlimitedreliefandareofrelativelyshortduration.Theyaremoreeffectivethanaplacebobutnospecificmucosal lubricant is recommended31 1++. BioteneOralbalanceGel® (GSK)maybethemostacceptedbypatientsbecauseofitsextendeddurationofeffect.Acidic salivary replacements suchasGlandosane® shouldnotbeusedbydentatepatientsastheycancauseerosivedamagetotheteeth.

Mucin base saliva substitutes have higher clinical acceptance thancarboxymethylcellulose-based. From limited evidence, linseed based salivasubstitutes are also effective. Product families (e.g. Biotene or BioXtra ranges)appear tobeeffective in treatmentof xerostomiabutwithnoevidenceof theirperformance compared to saliva substitutes. Gels may have bettersubstantivity341.

C Oral mucosal lubricants/saliva substitutes are recommended for short-termimprovementinxerostomiafollowingradiationtherapy.

4.4 TRISMUS

Variouspreventive/treatmentstrategieshavebeenadvocated35.Anunderstandingofthepathogenesisisessentialinordertodevelopefficacioustreatment.

4.4.1 NON-PHARMACOLOGICALTREATMENT

These include jaw exercises , TherabiteTM, DTS Dynasplint, Corkscrew devices,stackedtonguedepressorsandmicrocurrent35.

JawexercisesandtheuseofdevicessuchastheTherabiteTMduringradiotherapyand for the first 9months after completion of head and neck cancer treatmentmay limit the severity of trismus but they will not mobilize fibrosis once fullyestablished. These techniques may help surgically-induced trismus (as maycoronoidectomy).

Exercisesmay be active, wheremovement is driven bymusculature around thejointorpassivewhichoccurswhenanexternalforceisapplied.

Pain from oral mucositis may have an inhibitory effect on exercise and use ofdevices.

Theseinterventionsappeartobeeffectiveintheshorttermbutnolong-termdataisavailable162++.

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4.4.2 PHARMACOLOGICALTREATMENT

Pentoxyfylline.Onepilottrialtreatingtwentypatientsshowedamodesteffect363.

Botulinumtoxin.Thiswaseffective inpainreductionbuthasnobeneficialeffectontrismus142++.

DRegularjawexercisesshouldcontinueduringandafterradiotherapy

✓ Patientsshouldhavethesupportofadentaltherapistduringtreatment✓ Liaison between restorative dentistry consultant, speech and languagetherapistanddietitianisessential

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5. Oralanddentalmanagementfollowingtreatment

Asearlyaspossiblefollowingprimarytreatmentpatientswillbereassessedbytherestorative dentistry consultant. Information on oral intake, as assessed by thedietitian and speech and language therapist,will be gained. Regular care by thehygienist/therapist will be continued as patients who have been fed viagastrostomytubeprogresstooralintake,especiallyifnutritionalsupplementsareprescribedorally.Forpatientswhohavebeenunabletotolerateoralhygieneandcariespreventionmethods,thesewillbere-introducedasmucositissubsidesandcomfortimproves.Patientswillbeassessedregardingtheirmaxillofacialprostheticneedsandforthepresenceoftrismus,xerostomia,radiotherapyassociatedcariesandosteoradionecrosis.Dentalworkthatwasdeferredduringradiotherapyshouldbecompleted.Ifadjuvantradiotherapyisprescribedfollowingsurgery,thepatientwillbeassessedagainbytherestorativedentistryconsultantpriortoradiotherapycommencing.

5.1 ALTEREDANATOMY/IMPAIREDFUNCTIONOral rehabilitationwithprosthesesmaybe required to replacemissinghardandsoft tissueandteeth inorder to restoreappearanceand function.Thesemaybeimplant-supportedornonimplant-supportedconventionalprostheses.

5.1.1 ORALREHABILITATIONUSINGOSSEOINTEGRATEDIMPLANTS

Osseointegrated implants allow effective oral and facial rehabilitation followingcancer treatment including radiotherapy. They areused to support oral or facialprostheses. Appropriate detailed planning and patient selection are importantpriortoproceedingwithtreatment.

Primarydentalimplants37Theplacementof intra-oral andextra-oral implants at the same timeas tumourresection may be beneficial for carefully selected patients where there iscontinuity of themandible, in patientswho require the prosthetic obturation ofsignificant maxillary defects where retention of the obturator is likely to becompromised or in patients undergoing rhinectomy or orbital exenteration. Inpatientshavingsegmental resectionandreconstructionof themandible, implantsurvival and usefulness is improved by delayed placement after suitableprosthodontic planning. Where post-operative radiotherapy is certain, there isadvantage in primary placement of implants, however time for planning idealimplantpositionmaybecompromised.SecondarydentalimplantsFormanypatients,theplacementofosseointegrated implantswillbeconsideredfollowingcancertreatmentinresponsetoongoingproblemswithoralfunction.Asecondary approach allows a detailed assessment of the patient’s overallprognosis,individualriskfactors(alcohol,smoking,oralhygiene,radiotherapyetc.)aswellasanatomicalfactorssuchasthepresenceofreconstructivehardandsofttissue grafts, metal hardware, tongue function and mouth opening.

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Comprehensive prosthodontic planning should be undertaken prior to implantsurgeryandtheuseofcomputerisedplanningandsurgicalguidestenttechnologyisoftennecessary.It is possible to place implants in irradiated jaws but careful case selection isrequired.Failureratesarehigherthaninnon-irradiatedbone383andhigherinthemaxilla than in the mandible. There is a risk of implant placement causingosteoradionecrosis.Failuresarelesslikelywitharadiationdoselowerthan45Gy3.Adelayofonetotwoyearsafterirradiationforimplantplacementandafurther6monthsdelayforabutmentconnectionhasbeenadvocatedbutthisisdebatable393.Thereisnogoodqualityevidencefortheuseofhyperbaricoxygenforpatientswhorequireimplantplacementintheirradiatedjaws401.ZygomaticimplantsThese may be used to retain obturators as an alternative to free flapreconstructionorconventionalobturation.Inthenonheadandneckcancerpatientzygomaticimplantsareusuallycombinedwith at least two conventional implants in the anterior maxilla. Alternatively ifthere is insufficient or no anterior maxillary bone in the head and neck cancerpatient two or three zygomatic implants can be used in each upper quadrant.Placementisnotstraightforwardandcarriestheriskoforbitaltrauma.Placementandabutmentconnectioncanbedifficultor impossible if trismus ispresent.Theefficacyofzygomaticimplantsinaidingmaxillaryobturationisnotclear41,42,433.ImplantsinvascularizedgraftsversusnativeboneImplants can be place into vascularized grafts at primary surgery or secondarilyintoirradiatedornon-irradiatedgrafts.Theremaybeanincreasedriskofimplantfailureinfreeflapbonethathasbeenirradiated44,453✓ Implants shouldbeconsidered forallpatientshaving resection forheadandneckcancer

5.1.2 ORALREHABILITATIONUSINGCONVENTIONALPROSTHESESWheremandibularresectionandreconstructionresultsinedentulousareas,thesemay be restored prosthetically with conventional full or partial dentures as analternative to implant-retained prostheses. Joint discussion pre-operatively withthesurgeonwillhelpensuresofttissuecontoursareoptimizedtoallowprosthesisretention.Maxillary andmid face defects can be reconstructed using surgery or obturatedusingaprosthesis.Surgicalreconstructioncanbeachievedusingnonvascularisedgrafts, local flaps and regional flaps, however, restrictions exist regarding theavailability of sufficient tissue and length of vascularised pedicle. Use of suchtechniques has been largely superseded by microvascular free tissue transferwhich provides vascularised hard and soft tissue for reconstruction. Surgicalreconstructionusingfreetissuetransferisoftencarriedoutatthetimeoftumourresection and often does not involve the patient undergoing additional surgical

20

procedures which are required following reconstruction with local and regionalflaps.Ratherthanreconstructingsurgically,defectscanbeobturatedusingaremovableprosthesis.Surgicalobturatorsareprovidedforthepatientatthetimeoftumourresection, however these require modification or replacement with anintermediate obturator during healing prior to the provision of a definitiveobturator. Obturatorscaneitherbetissueand/ortooth-borneorsupportedandretainedbyosseointegrateddentaland/orzygomatic implants. Theseprosthesesarefabricatedusingarangeofdifferentmaterialsandconstructedinonepieceormultipleparts.Theanatomyofthedefectandsurroundinghardandsofttissues,statusoftheremainingdentitioninadditiontoothersystemicandpatientfactorsallinfluencethedecisionmakingprocessregardingobturatordesign.The levelofevidenceavailabletosupportsurgical reconstructionusing free flapsversusprostheticobturationofmaxillaryandmid-facedefectsislow.Maxillectomyisarelativelyuncommonoperationsopatientnumbersarelowandlargerdefectstend to be surgically reconstructed limiting the data available for prostheticobturation. Multiple confounding factors exist including the size of defect,whetherornotthepatientreceivedchemoand/orradiotherapy,whattypeoffreeflap has been used and the status of any existing natural dentition or dentalprostheses. There is also a lack of consensus regarding standardisation andreporting of the size of maxillary defects and the most appropriate outcomesmeasures.Asthesizeofmaxillarydefect increases,sodothereportedproblemsassociatedwithHealthRelatedQualityofLife(HRQOL)andfunction.Thereappearstobenodifference in HRQOL outcomes between patients who received surgicalreconstruction using microvascular free tissue transfer versus prostheticobturation if the sizeof thedefect is not controlled for46 3. If amaxillarydefectinvolvesat leasthalfofthehardpalate,ortheanteriorhardpalate includingthecaninesbilaterally,statisticallysignificantlybetterfunctionaloutcomesforspeechare identified in patients that have received surgical reconstruction using a freeflap compared to prosthetic obturation473. As the size of the maxillary defectincreases, a higher number of patients receive surgical reconstruction usingmicrovascularfreetissuetransfer/freeflapscomparedtoprostheticobturation46,47

3. There is no statistically significant difference between the time taken todiagnosea localizedrecurrenceofaT4squamouscellcarcinomaofthemaxillarygingiva/hardpalatebetweenpatientswhoreceivedsurgicalreconstructionusingafreeflapcomparedtoprostheticobturation473.Themostsignificantpredictorofobturatorfunctionisthesizeofthedefect.Statisticallybetterobturatorfunctionisassociatedwithdefectswhereresectionofthesoftpalateisonethirdorlessandresectionofthehardpalateisonequarterorless46,48Statisticallysignificanthigherobturator speech scores are achieved as the size of soft palate resectiondecreases483.Thedecisionastowhetherobturationorfreeflapreconstructionofmaxillaryandmid-facedefectsprovidesbetteroralrehabilitation iscontroversial.Patientsmayprefertohaveareconstructionwhichbringsasenseofcompletenessratherthancopewithadefect.

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✓ The decision to carry out obturation or free flap reconstruction ofmaxillaryand mid-face defects should be discussed jointly with surgeons, restorativedentistry consultants and the patient to ensure optimal oral rehabilitationoutcomesareconsideredandachieved.

5.2 XEROSTOMIA

This is often a long-term, troublesome side effect and should continue to bemanagedasdescribedinsection4.3

5.3 RADIOTHERAPY-ASSOCIATEDDENTALCARIESRisk of caries development is removedwhen patients are exclusively fed via anenteralfeedingtube.Thehigh-risktimeiswhenpatientscontinueorrecommenceoral feedandhave frequent intakeofhighcalorie, sucroseorglucosecontainingfoodsand/ororalnutritional supplements.Close liaisonwith thedietitianat thistime is key. Recommendation for nutritional intake and monitoring should beunder the guidance of the dietitian to ensure consistent information is given topatients. In the early stages of the post radiotherapy phase patients often havevery poor oral hygiene and poor tolerance for fluoride products. Cariesmanagement must be individualised and patients must be assessed at regularintervals to determine the caries risk and caries activity to provide guidance formaintenance of the dentition. Frequent visits to the dental therapist may berequired during the first few weeks. Preventive advice should continue asdescribedinsection3.3.1

5.4 TRISMUSJawexercisesshouldbecontinuedasdescribedintherecommendationsinsection4.4.1

5.5OSTEORADIONECROSIS

Prevention isbestachievedbycarefulmanagementpriortothetreatment.Onceosteoradionecrosis has developed, its management is controversial. Someadvocate the use of hyperbaric oxygen but this is not supported by randomizedcontrolled trials49. Surgicalmanagementmay sometimesbe required.Theuseoflong-termpentoxyfilline,tocopherolandclodronatemaybeofbenefit50.

5.6 LONG-TERMFOLLOWUPImplant-supportedprosthesesandcomplexconventionalprosthesesmayneedtobe kept under long-term review by the restorative dentistry consultant. For themajorityofpatientswithradiation-inducedsideeffects,dischargetothecareofaprimary care practitioner should be possible when the initial side effects havesettled,frequentintakeofcariogenicfoodanddrinkshasbeenstopped,goodoralhygieneisre-establishedandtheuseoffluorideproductsiscomfortablytolerated.Forthesepatients, theirriskofcariesdevelopmentandORNwillmeanthattheyshould have more frequent follow up than other patients in the primary care

22

setting.Recallintervalwillbedeterminedonanindividualbasisdependentonriskfactorsandthepresenceofactivedentaldisease.Patientswhocontinuelong-termon an energy-dense diet including sucrose and glucose containing foods andsupplementsshouldbemonitoredcloselyforcariesdevelopment.

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6. Developmentoftheguideline

6.1 Introduction

This guideline was developed by multidisciplinary groups of practicing cliniciansusingastandardmethodologybasedonasystematicreviewoftheevidencebasedon the methodology outlined in “SIGN 50; A Guideline Developer’s Handbook”availableatwww.sign.ac.uk

6.2 SystematicLiteratureReview

The evidence base for this guideline was synthesized in accordance with SIGNmethodology.Theguidelinedevelopmentgroup isgrateful toSIGNEvidenceandInformation Scientist, Juliet Brown, for carrying out the systematic literaturereview.

6.2 GuidelineDevelopmentGroup

DrLornaMcCaul(Chair) ConsultantinRestorativeDentistryBradford Teaching Hospitals NHS Foundation Trust,BradfordThe Royal Marsden NHS Foundation Trust, LondonHeadandNeckCancerLead:RD-UK(TheAssociationof Consultants and Specialists in RestorativeDentistry)

DrLiamAddy ConsultantinRestorativeDentistry

CardiffDentalHospitalProfessorCraigBarclay ConsultantinRestorativeDentistry

UniversityDentalHospitalofManchesterMrChrisButterworth ConsultantinRestorativeDentistry

Aintree Regional Head & Neck CancerCentre &LiverpoolDentalHospital

MrJamesCymerman SpecialistRegistrarinOralandMaxillofacialSurgeryLondonDeanery

ProfessorMichaelFenlon ConsultantinRestorativeDentistryGuysandStThomas’HospitalsNHSFoundationTrustKing’sCollegeLondon

MrCyrusKerawala ConsultantMaxillofacial/HeadandNeckSurgeonTheRoyalMarsdenNHSFoundationTrust,London

DrMatthewLocke ConsultantinRestorativeDentistryCardiffUniversitySchoolofDentistry

SirMichaelLockett PatientrepresentativeBoardmember,OracleCancerTrust

MrsKarenMatley PatientrepresentativeProfessorJamesMcCaul ConsultantMaxillofacial/HeadandNeckSurgeon

TheRoyalMarsdenNHSFoundationTrust,London

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MrPeterNixon ConsultantinRestorativeDentistry LeedsDentalInstituteProfessorChrisNutting ProfessorinClinicalOncology

TheRoyalMarsdenNHSFoundationTrust,LondonDrJamesOwens ConsultantinRestorativeDentistry

MorristonHospitalSwanseaProfessorVinidhPaleri ConsultantENTHeadandNeckSurgeon NewcastleuponTyneHospitalsNHSTrust NewcastleUniversityDrJustinRoe Joint Head of Speech and Language Therapy/Allied

HealthProfessionsResearcher–ProjectLeadTheRoyalMarsdenNHSFoundationTrust,London

DrSamRollings ConsultantinRestorativeDentistryUniversityofAberdeenDentalSchoolandHospital

MsAudreyScott MacmillanHeadandNeckClinicalNurseSpecialistMount Vernon Cancer Centre, East and NorthHertfordshireNHSTrustChair of the British Association of Head and NeckOncologyNurses

MsBellaTalwar ClinicalLeadDietitian,Head&NeckCancerServicesUniversityCollegeLondonHospitalsNHSFoundationTrust

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8. Furtherreading

1. TangJA,RiegerJM,WolfaardtJF.Areviewoffunctionaloutcomesrelatedtoprosthetictreatmentaftermaxillaryandmandibularreconstructioninpatientswithheadandneckcancer.IntJProsthodont200821(4):337-354.

2. BernhartBJ,HurynJM,etal.Hardpalateresection,microvascularreconstruction,andprostheticrestoration:a14-yearretrospectiveanalysis.HeadNeck200325(8):671-80.

3. BianchiB,FerriA,etal.Maxillaryreconstructionusinganterolateralthighflapandbonegrafts.Microsurg200929(6):430-6.

4. BrownJS,JonesDC,etal.Vascularizediliaccrestwithinternalobliquemuscleforimmediate reconstruction after maxillectomy. Brit J Oral Max Surg 2002 40(3):183-90.

5. Browne JD,Butler S, et al. Functionaloutcomesand suitabilityof the temporalismyofascial flap forpalatalandmaxillary reconstructionafteroncologic resection.Laryngoscope2011121(6):1149-59.

6. CenziRandCarinciF.Calvarialbonegraftsandtemporalismuscleflapformidfacialreconstruction after maxillary tumor resection: a long-term retrospectiveevaluationof17patients.JCraniofacSurg200617(6):1092-104.

7. Chen W-L, Ye J-T, et al. Reverse facial artery-submental artery mandibularosteomuscular flap for the reconstruction of maxillary defects following theremovalofbenigntumors.HeadNeck200931(6):725-31.

8. ChenW-I,ZhouM,etal.Maxillaryfunctionalreconstructionusingareversefacialartery-submental artery mandibular osteomuscular flap with dental implants. JOralMaxilSurg201169(11):2909-14.

9. ClarkJR,VeselyM,etal.Scapularangleosteomyogenousflapinpostmaxillectomyreconstruction:defect, reconstruction, shoulder function, andharvest technique.HeadNeck200830(1):10-20.

10. CordeiroPGChenCM.A15-yearreviewofmidfacereconstructionaftertotalandsubtotalmaxillectomy:part I.Algorithmandoutcomes.PlastReconstrSurg 2012129(1):124-36.

11. Funk GF, Laurenzo JF, et al. Free-tissue transfer reconstruction ofmidfacial andcranio-orbito-facialdefects.ArchOtolaryngol1995121(3):293-303.

12. GendenEM,WallaceD,etal. Iliac crest internalobliqueosteomusculocutaneousfree flap reconstruction of the postablative palatomaxillary defect. ArchOtolaryngol2001127(7):854-61.

13. Ilankovan V P, Ramchandani P, et al. Reconstruction of maxillary defects withserratus anteriormuscle and angle of the scapula.Brit JOralMax Surgery 201149(1):53-7.

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14. Kim JYSBuckDW2nd,et al. The temporoparietal fascial flap is analternative tofreeflapsfororbitomaxillaryreconstruction.PlastReconstrSurg2010126(3):880-8.

15. LopezR,DekeisterC,etal.Thetemporalfasciocutaneousislandflapforoncologicoralandfacialreconstruction.JOralMaxilSurg200361(10):1150-5.

16. Miles BA and Gilbert RW. Maxillary reconstruction with the scapular angleosteomyogenousfreeflap.ArchOtolaryngol2011137(11):1130-5.

17. Mucke T, Holzle F, et al.Maxillary reconstruction usingmicrovascular free flaps.OralSurgOralMedO2011111(1):51-7.

18. OrtorpA.Threetumorpatientswithtotalmaxillectomyrehabilitatedwithimplant-supported frameworks and maxillary obturators: a follow-up report. ClinicalImplantDentistry&RelatedResearch201012(4):315-23.

19. Rieger JM, Tang JAL, et al. Comparison of speech and aesthetic outcomes inpatients with maxillary reconstruction versus maxillary obturators aftermaxillectomy.JOtolaryngol201140(1):40-7.

20. Roumanas ED, Nishimura RD, et al. Clinical evaluation of implants retainingedentulousmaxillaryobturatorprostheses.JProsthetDent199777(2):184-190.

21. Sakuraba M, Kimata Y, et al. Simple maxillary reconstruction using free tissuetransfer andprostheses.PlastReconstr Surg 2003111(2): 594-8; discussion599-600.

22. TakushimaA,HariiK,etal.Reconstructionofmaxillectomydefectswithfreeflaps--comparisonof immediateanddelayedreconstruction:a retrospectiveanalysisof51cases.ScandJPlastRecons200741(1):14-21.

23. UrkenML, Bridger AG, et al. The scapular osteofasciocutaneous flap: a 12-yearexperience.ArchOtolaryngol2001127(7):862-9.

24. AbuEl-NaajI,LeiserY,etal.Polymorphouslowgradeadenocarcinoma:caseseriesandreviewofsurgicalmanagement.JOralMaxilSurg201169(7):1967-72.

25. Arigbede, AO, Dosumu OO, et al. Evaluation of speech in patients with partialsurgically acquired defects: pre and post prosthetic obturation. The Journal ofContemporaryDentalPractice20067(1):89-96.

26. BobinskasA,ChanduA,etal.Squamouscellcarcinomainvolvingthemaxilla:A15yearreview.OralOncol201147:S144-S145.

27. Browne JD and Burke AJ. Benefits of routine maxillectomy and orbitalreconstruction with the rectus abdominis free flap.Otolaryng Head Neck 1999121(3):203-9.

28. Eckardt A, Teltzrow T, et al. Nasalance in patients with maxillary defects -Reconstructionversusobturation.JCranioMaxillSurg200735(4-5):241-245.

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29. EkstrandKandHirsch J-M.Malignant tumorsof themaxilla:virtualplanningandreal-timerehabilitationwithcustom-madeR-zygomafixturesandcarbon-graphitefiber-reinforcedpolymerprosthesis.ClinicalImplantDentistry&RelatedResearch200810(1):23-9.

30. ElFattahH,ZaghloulA,etal.Pre-prostheticsurgicalalterationsinmaxillectomytoenhancetheprostheticprognosesaspartofrehabilitationoforalcancerpatient.MedicinaOral,PatologiaOralyCirugiaBucal201217(2):e262-70.

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9. KEYQUESTIONS

1.DoesIMRTreducetheriskofxerostomia?2.DoesIMRTreducetheriskofosteoradionecrosis(ORN)?2b.DoesIMRTreducetheriskoftrismus?3a.IsORNriskworsewithanyparticulartumoursiteorstaging?3b. What is the minimum time between extraction and radiotherapy to avoidORN?3c. What is the minimum time between extraction and neo-adjuvantchemotherapytoavoidORN?3d.ExtractionofwhichteethismostlikelytocauseORN4. What are the risk factors for trismus development in patients who haveradiotherapyforheadandneckcancer?5.Dointerventionssuchasjawexerciseshelpreducetrismus?6.What primarymethods of dental disease prevention are effective in patientswhohavereceivedradiotherapy?7.Obturationvsfreeflapclosureinmaxillaryandmid-facediseasewhichisbetterfororalrehabilitation?8.Doespre-treatmentdentalcarereducetheincidenceofmucositisandinfection?9.Whatisthemosteffectivetreatmentformucositis?10. What is the most effective saliva replacement for patients with radiationinducedxerostomia?10b.Doespilocarpinereduce/preventxerostmia?11.Whatfactorsaresignificantwhenplanningaheadandneckcancerpatientforimplanttreatment?12.Whichpatientswillbenefitfromtheplacementofprimaryimplants?13.Istheplacementofzygomaticimplantsofbenefittomaxillaryobturation?14.Doesthesuccessratedifferwhenimplantsareplacedintovascularizedbonegraftscomparedwithnativebone?15.DoesprophylacticHBOinirradiatedpatientsaffectimplantsurvival?16. How often should patients with radiation induced xerostomia have dentalassessment?(xerostomiafollow-up)