First Edition

European Oral Care in Cancer Group Oral Care Guidance and Support

Contents

1.0 • Introduction

2.0 • Assessment

3.0 • Care of the Oral Cavity

4.0 • Prevention of Oral Complications

5.0 • Treatment of Oral Complications

6.0 • Conclusion

7.0 • References

8.0 • Appendices

ContributorsProject Chair B. Quinn (UK)Task Group S. Botti (IT), M. Kurstjens (NL), A. Margulies (CH), L. Orlando (IT), C Potting (NL), D. Riesenbeck (DE), A. Sabbatini (IT), M. Tanay (UK), M. Thomson (UK), S. Vokurka (CZ), A. Vasconcelos (P)Supported by P. Feyer (DE), A. Mank (NL), D. Kiprian (PL), M. Mravak Stipetic (HR)

Expert reviewers Expert reviewer N. Blijlevens (NL)

EOCC Guidance has been endorsed by

Vorstand

Vorsitzende: Beirat: Prof. Dr. med. P. Feyer Prof. Dr. med. H. H. Bartsch Dr. med. M. Horneber Prof. Dr. med. O. Rick PD Dr. Sportwiss. F. Baumann Prof. Dr. med. K. Jordan Dr. med. T. Behlendorf Dr. med. J. Körber Prof. Dr. med. G. Egerer Prof. Dr. med. H. Link PD Dr. med. R. Caspari Dr. rer. nat. P. Ortner

Dr. med. W. Hoffmann Assoziierte Beiratsmitglieder: Dr. med. T. Dauelsberg (DGHO) Prof. Dr. med. I. J. Diel (DOG)

Prof. Dr. med. H. Strik

ASORS in der DKG e.V. – Kuno-Fischer-Straße 8 – 14057 Berlin Barry Quinn Assistant Director of Nursing/ Senior Lecturer Chelsea & Westminster NHS Foundation Trust Dear Mr. Quinn, We support the recommendation of the EOCC in behalf of the German Supportive Care Group Kind regards from Germany Steffi Weiss (Secretary ASORS) on behalf of Prof. Dr. med. P. Feyer Prof. Dr. med. O. Rick

Vorsitzende der Arbeitsgemeinschaft Supportive Maßnahmen in der Onkologie, Rehabilitation u. Sozialmedizin (ASORS) der Deutschen Krebsgesellschaft (DKG) www.asors.de

ASORS Arbeitsgemeinschaft Supportive Maßnahmen in der Onkologie, Rehabilitation und Sozialmedizin Prof. Dr. med. P. Feyer Prof. Dr. med. O. Rick E-mail: petra.feyer@vivantes.de oliver.rick@klinik-reinhardshoehe.de

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1.0 Introduction

TheEuropeanOralCareinCancerGroup(EOCC)isamulti-professionalgroupoforalcareexpertsworkingincancersettingsfromacrossEuropewhohavecometogetherwiththeaimofimprovingoralcareinclinicalpractice.HavingbeingengagedindeliveringlecturesandworkshopsacrossEuropeonthesubjectandasmembersofanumberofnationalandinternationalclinicalgroups,thegroupwaskeentousetheirknowledgetofurthersupportmulti-professionalcolleagues.Mindfulofthemanydevelopmentsincancercareaimedatimprovingsurvivalandqualityoflife,thecorrectandconsistentapproachtomanagingoralcareproblemsstillremainsachallengeinmanyclinicalsettingsacrossEurope.Thereismuchevidencetoshowthatmanyclinicalsettingsratherthantakingaproactiveapproachtothisaspectofcarestillsimplyreacttooralcomplicationsoncetheyoccurwithasometimesinconsistentandanecdotalapproach.

Usingtheexistingguidelinesandguidancefromtheirowncountries(Appendix:1)andinternationalorganisations,thecurrentevidenceandtheirownclinicalexpertisethegroupdevelopedthisguidancetosupportclinicalpracticeinthepreventionandtreatmentoforalproblemssecondarytomalignantdiseaseandtreatmentsincludingsystemictreatments,radiationandsupportivetherapies(Table:1).

Table: 1 Oral complications of cancer treatments include -

1.1 Purpose of the Guidance Cancerandthetreatmentrequireddirectlyimpactonthepatientwithcancerinamultitudeofwayswhichmayincludechangestotheoralcavityaffectingtheirwell-being,potentiallycausingsevereacuteandlongtermphysical,psychologicalandsocialproblems(Quinnetal2015).

Oralproblemsanddamagemaybetemporaryorpermanentresultinginasignificanthealthburdenfortheindividualwhilemakingsubstantialdemandsonlimitedhealthcareresources.However,oralcomplicationsarenotalwaysinevitableandmuchcanbedonetoreduceorminimisetheseverityofsymptomsbytakingamoreproactiveapproachtothisaspectofcare.CriticallyexaminingcurrentevidenceandclinicalpracticeacrossEurope,EOCCestimatethatthehealthburdenontheindividualandthedemandsonhealthcareresourcescanbegreatlyreducedbythecorrectassessment,preventativemeasures,careandtreatmentoforalproblems.Thisguidancewillassistteamsinbothplanningandimplementingoralcaretherebypreventingorreducingtheseverityofthissideeffectofdiseaseandtreatment.

Workingasamulti-disciplinaryteamwiththepatientatthecentreofcareandtreatmentplan,theearlydetectionofpotentialandactualproblemsandtreatmentcanhelptoreduceoralproblems,preventinterruptionstocancertreatmentplansandmaximisepatientsafetyandcomfort(NationalCancerInstitute2013).Eachofthesefactorsneedstobecriticallyconsideredwhileapplyingtheprinciplessetoutinthisguidance.

Oralmucositis Xerostomia

Oralinfections OralGraftversusHostDisease

Ulceration Trismus

Tastechanges Halitosis

Bleeding Drylips

Pain Dentaldecay

Ostenecrosis Oralfibrosis

Leading to difficulties in eating, sleeping, talking and a reduction in quality of life

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2.0Assessment

1.2 Oral mucositis (OM) Oneofthemajorchallengesinthecancersettingistheneedtocorrectlyandconsistentlyaddressthedamagecausedbyoralmucositis(OM).Mucositisisageneraltermthatdescribestheinflammatoryresponseofmucosalepithelialcellstothecytotoxiceffectsofchemotherapyandradiotherapy.Mucositiscanaffectallmucousmembrane-coveredsurfacesfromthemouthtotheintestinalmucosa.OMhasbeendefinedbyRubensteinetal(2004),Al-Dasoogiet(2013)andothersastheinflammationofthemucosalmembrane,characterisedbyulceration,whichmayresultinpain,dysphagiaandimpairmentoftheabilitytotalk.ThemucosalinjurycausedbyOMprovidesanopportunityforinfectiontoflourish,andinparticularputtingtheseverelyimmunocompromisedpatientatriskofsepsisandsepticaemia.

OralmucositisoccursasafrequentsideeffectofanticancertreatmentbecausethecellshaveahighturnoverrateandtherebyaresusceptibletodamagefromanyinfluencecausingDNA-damageleadingtocelldeathandreducedreproduction(Al-Dasoogietal2013).Thereductionofnewcellsplusanincreaseincellulardamageresultinabreakdownofthemucosalbarrier,givingwaytomanydifferentsymptomsandrisksasshowninFig:1.

Figure: 1

TheincidenceofOMinthecancersettingismuchhigherthanpreviouslythoughtandcanbeexpectedtooccurinatleast50%ofpatientsundergoingsomechemotherapytotreatasolidtumour,althoughsomestudiesandreports(Eladetal2014)indicatethattheincidenceislikelytobemuchhigher.Asmanyas98%ofpatientsundergoinghaematopoieticstemcelltransplantation(HSCT)arethoughttobeaffectedbyOMandoraldamage(Bhattetal2010,Filickoetal2003).LiandTrovato(2012)estimatethatasmanyas97%ofallpatientsreceivingradiotherapy(withorwithoutchemotherapy)forheadandneckcancerswillsufferfromsomedegreeofOM.Withtheincreasinguseoftargeteddrugtherapiesandapproaches,problemsintheoralcavitywillincreaseandbecomeevenmoreofachallenge(Quinnetal2015).

Alltreatmentstrategiesaimedatimprovingmouthcarearedependentonfourkeyprinciples:accurateassessmentoftheoralcavity;individualizedplanofcare,initiatingtimelypreventativemeasuresandcorrecttreatment,(Quinnetal2008).Theassessmentprocessshouldbeginpriortotreatmentbyidentifyingpatientrisksandtreatmentsmostlikelytocauseoraldamage(Tables:2&3).Table: 2 Risk of oral mucositis• 5%-15%duringstandarddosechemotherapy• 50%duringmyelosuppressivechemotherapy• 50%duringhead-neckradiotherapy• 68%autologousstemcelltransplantation• 98%myeloablativeallogeneicstemcelltransplantation• 97%duringhead-neckRT/CT

(Bellmetal,2000,Bhattetal2010,Eltingetal2003,Filickoetal2003,Kostleratal2001,Li&Trovato2012,Rose-Pedatal2002,Sonisetal2004,Trottietal2003,Vagliainoetal2011)

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Table:3Someofthesystemictreatmentsthatmaycauseoraldamage

(Barasch,&Peterson2003,Boers-Doetsatal2011)

2.1 The oral assessmentEachpatientalsoneedstobeassessedinrelationtootherriskfactorsthatmayputthemathigherriskoforalcomplicationsduringtreatmentincluding:

• Pre-existingdentalproblems• Olderpatientsandfemales(athigher

riskoforaldamage)• Historyofalcoholand/ortobaccouse• Poornutritionandhydration• Supportivefeeding(Nasogastric,PEG,

RIG)• Supportivetherapies(opiates,diuretics,

sedatives,oxygentherapy-maycausedryness)

Patients,particularlythosewhoareabouttocommencehaematopoieticstemcelltransplantation(HSCT)andheadandneckradiationtreatments,shouldundergocomprehensiveoralanddentalassessmentbyaspecialist(Eladetal2015).Thisistoestablishgeneraloralhealthstatusandidentifyandmanageexistingand/orpotentialsourceofinfection,traumaorinjury.Somepatientswillneedregularperiodontalfollow-upthroughoutandaftertreatment.Dependingonpatients’oralhealth,theymayneedregularoralhygienistvisitsbefore,duringandaftertreatment(Quinnetal2015).

Theoralcavityshouldbeassessedbytrainedhealthcareprofessionalsusingarecognizedgradingsystem.Theexpert

grouprecommendsusingarecognizedoralassessmenttool(Appendix:2)toensureaccuratemonitoringandrecordkeeping.Thetoolchosenwilldependontheclinicalsituationbutshouldcontainbothobjectiveandsubjectiveelements.Theassessmentshouldincludechangestotheoralmucosa,thepresenceorabsenceofpainandthepatient’snutritionalstatus(Quinnetal2008).

Assessmentsshouldbecompletedatregularintervalstomonitorinterventionsthiswillvaryonwhetherthepatientisbeingcaredforintheoutpatientsettingwherethemajorityofpatientswillbecaredfororonaninpatientwardduetothenatureoftreatmentorcomplications.Theassessmentshouldalsofocusonthepersonalimpactoneachpatientandtheassessmentmustbedocumentedinthemedicalandnursingrecords.Patientsundergoingregimenswithahighriskoforalmucositisshouldhavedailyassessments.Patientsshouldbeencouragedtoassesstheirownmouthusingapatientreportedtoolandtoreportanychangestheynoticeorexperiencetotheirmedicalteamorkeyworker.Theoralcavityshouldbereviewedwheneverapatientvisitsthetreatmentcentreforanychemotherapy,targetedtherapy,radiotherapytotheheadandneckregionorfollowingheadandnecksurgery.Theassessmentisalsoafurtheropportunitytosupportandeducatethepatient(Quinnetal2008).

Targeted Agents Chemotherapy ChemotherapyAlemtuzumab Busulfan Melphalan

Cetuximab Capecitabine Methotrexate

Erlotinib Carboplatin Mitomycin

Everolimus Cisplatin Mitoxantrone

Gemtuzumab Daunorubicin Oxaliplatin

Pazopanib Docetaxel Paclitaxel

Pertuzumab Doxorubicin Pemetrexed

Sorafenib Epirubicin Pentostatin

Sunitinib Etoposide Thiotepa

Temsirolimus Fluorouracil Topotecan

Trastuzumab Idarubicin Vinblastine

Trastuzumabemtansine Irinotecan Vincristine

Temsirolimus Vinorelbine

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Strongly recommended • Oraldamageshouldbeassessedusing

astandardizedprotocol,oralcareassessmentsshoulduseinstrumentsoracombinationofsuitablescalescontainingelementscoveringphysicalchangesintheoralmucosa,functionalchangesandsubjectivechanges.

• OralassessmentsshouldcontinueaftertheendtreatmentuntilOMisfullyresolvedorthetrendtoresolutionisestablished(Fig:2).

Recommended based on expert opinion• Acomprehensivebaselinedentaland

oralassessmentshouldbemadepriortotreatment,whereoraldamageisexpected.

• Afurtherbaselineassessmentoftheoralcavityshouldbetakenasclosetotheadministrationofthefirsttreatmentdoseaspossible.

• Anyidentifieddentalproblemsshouldbetreatedbeforestartingtreatmentregimen.

• Theuseofpainscoring,inrelationtochangesintheoralcavity,shouldformpartoftheoralassessment.

• Thehealthcareprofessionalassessingpatientsshouldbespecificallytrainedintheapplicationofthescale.

• Sincethereareanumberofassessmentscalesavailable,itisrecommendedthatallmembersoftheteamwhoassesspatients’mouthsusealwaysthesamescaleastoavoidinterobserverdifferences.

InclinicalpracticethemostcommonlyusedaretheWorldHealthOrganization(WHO)gradingscalewhichcombinesbothobjectivefindingsandfunctionintoasinglescore,andNationalCancerInstituteCommonToxicityCriteria(NCICTC)whichscoresonlyfunctionalelements.Thehealthcareprofessionalassessingpatientsshouldbespecificallytrainedintheapplicationofthescale.Periodicinter-raterreliabilityshouldbeusedtomonitortheneedforstafftraining.

2.2 Frequency of oral assessment Theoptimumcareforpatientsvarieswithdifferentsettingsandrisks.Asforinpatients,everyoneatriskoforalmucositisrequiresabaselineassessment,andpatientsatriskoforalmucositisshouldgetdailyoralassessments.

Intheoutpatientsetting,againallpatientsatriskoforalmucositisrequireabaselineassessment,andpatientsatriskoforalmucositisshouldbeassessedduringeveryclinicalvisit.Itisusefultoconsiderguidingthepatienttouseaself-assessmentinstrumentathome.

Fig: 2

OralOncologyVolume46,Issue62010452–456

Inmostclinicalsettingschemotherapy-inducedmucositisusuallydevelopswithin4–7daysafterinitiationoftreatmentandpeakswithin2weeks.Radiotherapyhasamoregradualclinicalcoursesinceitismostoftenadministeredinsmallfractionsgivenoverweeks.Radiation-inducedmucositistypicallybeginsatcumulativedosesofabout15Gy(afteraround10days)andtypicallyreachesfullyseverityat30Gythatcanlastforweeksandevenmonths(LiandTrovato(2012),Sonisetal(2004))(Fig:2)

2.3Inspecting the oral cavity• Clinicaltools:goodlightsource,gloves,

tonguedepressor,drygauze.• Patientinconvenientandcomfortable

position.• Usevalidandreliableassessment

instrumentwhichiseasytointerpret.• Oralsitestobeevaluated(Fig:3)

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Leftandrightinnerinsideofthecheek

Tonguedorsal Tonguerightandleftlateral Floorofthemouth

Softpalate

2.4Examples of oral assessment tools Thechoiceoforalassessmenttoolwilldependontheclinicalsetting.Sometoolsarespecificallydesignedfortheoutpatient,inpatientandradiotherapysettings,somefocusonaspectsofcomplicationsincludingpainandothersencouragepatientstoassesstheirownoralcare.ThesearesomeofthetoolstoconsiderandtheyaretobefoundinAppendix2.

• WorldHealthOrganisationrecommendedwithapainscoringtool(WHO)(i)• NationalCancerInstitutegradingscale(NCI-CTCAE)(ii)• OralAssessmentGuide(OAG)(iii)• NumericalRatingScore(iv)• AcuteRadiationMorbidityScoringCriteriafortheevaluationofRadiotherapy

treatments(RTOG)(v)• Patient-ReportedOralMucositisExperienceQuestionnaire(vi)

LowerinnerinsideofthelipUpperinnerinsideofthelip

Fig: 3 Sites to be examined

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3.0Care of the Oral Cavity

Careoftheoralcavityiscentraltohelpingtopreventand/orreduceoralcomplicationsduringandaftertreatment.Whatcomprisestheoralcareteammayvaryforeveryhealthcaresetting.Mostoften,thisteamconsistsof:dentalprofessionals,dietician,nurse,doctorandpharmacist.Thesupportprovidedbytheteamalongwithgoodcommunicationandthepatientatthecentreofallcareplansiscentraltomaintainingpatient’soralhealth.

Oralcareandassessmentshouldbeperformedroutinely.Patientsshouldbeencouragedtoobservetheirmouthsandreportchangesearlyaschangesinthepatient’soralconditionmayrequirechangesinoralcareinterventions.

3.1Patient education Allpatientsshouldbeprovidedinstructionsandencouragedtomaintaingoodoralhygiene.Educationshouldalsoincludepotentialoralcomplicationstoenablepatientstoidentifyandreporttheseearly(Clarksonetal2011,Quinnetal2015).Allpatientsshouldreceivewritteninformation,aswellasverbalinstructionaboutoralcareaspartofthepreventionandtreatmentoforalchanges.Patienteducationshouldbecarriedoutinadvanceoftreatmentcommencingandregularlyduringtreatmentandafterthecompletionoftreatment.Educationshouldalsoincludedietaryrequirementsandadvice.

3.2Nutritional screening and choice of foods Goodnutritionisvitalinhelpingtofightinfection,maintainmucosalintegrity,enhancemucosaltissuerepairandreduceexacerbationofexistingmucositis.Patientsshouldbereferredtoadieticianforbaselinenutritionalscreeningandeducation(Eladetal2014).Issuesthatmayaffectnutritionsuchaslossofappetite,tastechangesanddysphagiashouldbeassessed.Referraltoaspeechandlanguagetherapistmaybenecessaryforpatientsundergoingheadandnecktreatmenttoassessdysphagia.

Therearecertainfoodsthatcanincreaseorescalatedamagetotheoralmucosathismayincluderough,sharpandhardfoodsandshouldbeavoided.Spicy,very

salty,andacidicfoodsmaycausemucosalirritationbutmaybepreferredortoleratedbysomepatients.

3.3BrushingDependingonoralstatus,gentlebrushingofteeth,gumsandtongueshouldbeperformedtwotofourtimesadaypreferablyaftermealsandbeforegoingtobed(Peterersonetal2015).Soft-bristledtoothbrush(manualorelectric)isrecommendedtopreventinjurytotheoralmucosa;andmustberinsedthoroughlywithwateraftereachuse.Toenhanceplaqueremoval,smallcircularbrushingmovementsarerecommended,makingsureallsurfacesarecoveredincludinghard-to-reachareas(Petersonetal2015).Ifthemouthispainfulorpatientscannotopentheirmouthsfully,softoralspongesmaybeused.However,oralspongesarenoteffectiveforplaquecontrolorpreventionofdentalcaries,andshouldnotbeconsideredasalternativeforbrushing.Brushingoftongueisnotrecommendedforpatientswhoareundergoingradiotherapytotheheadandneck.

Topreventinfections,toothbrushshouldbestoredwiththebrushheadupwardsandnotsoakedindisinfectantsolution.Toothbrushshouldbechangedregularlyeverymonthormorefrequentlyinrelationtopatient’sinfectionrisk.Theseshouldalsobemonitoredforevidenceoffungal/bacterialcolonisation.

Inordertoprotecttheenamel,non-abrasivetoothpastecontainingmildfluoride(1000-1500ppm)shouldbeused.Someheadandneckpatientsmayrequirehigherfluoridecontent(over1500ppm).Thesepatientsshouldfollowthedosefluoridecontent(oftoothpaste)asprescribedbytheoralcareteam.Ensurethatpatientscantoleratetheflavour.Forexample,somepatientsmaynotbeabletotoleratetoothpastewithmint.

3.4Interdental cleaning Dailyinterdentalcleaningwithbrushesmayreduceplaqueformationbetweenteeth(Sambunjaketal2011).However,itmustbeensuredthatpatientsareableandconfidentontheirusetopreventmucosalinjury.Theuseofinterdentalcleanersshould

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beusedwithcautionforpatientswiththrombocytopaeniaorclottingdisorders;andthosereceivingradiotherapyforheadandneckcancer.

3.5DenturesBothfullandpartialprosthesisshouldfitwell,asill-fittingdenturescausemovementthatirritatesthemucosaandbreaksintegrity.Aftereachmeal,denturesmustberinsed.Thoroughcleaningbybrushingwithsoapandwatershouldbeperformedatleasttwiceaday.Denturesshouldbecleaned,driedandstoredinaclosecontainerovernight(Duycketal2013).Duringthecourseofradiotherapyandafterwardsuntilcompletehealingoforalmucositis,patientsshouldbeadvisedtoweardenturesaslittleaspossible.

3.6MouthwashThegoalofusingmouthwashesmayinclude:oralhygiene,preventing/treatinginfection,moisteningtheoralcavityorprovidingpainrelief.Asaminimumtokeepthemouthclean,blandgarglesandrinseswithwater,normalsaline(0.9%NaCl)orsaltwaterarerecommendedatleastfourtimesaday(Lallaetal2014,Quinnetal2015).Itisvitalthatcliniciansassesstheabilityandconfidenceofpatientsusingmouthwashes,garglingshouldbeencouraged.Somepatientswillrequireassistance,itmaybenecessaryforhealthcareprofessionalstoperform/supportoralcareincludingthroughrinsingwithnormalsaline(0.9%NaCl)and/orbicarbonatesolutions(Eladetal2015),withorwithoutsuction.

3.7Dryness of lips and mouthLubricants,lipbalmorlipcreammaybeusedtomoistenthelips.Water-soluble

lubricantsshouldbeusedforpatientswhoareundergoingradiotherapyoftheheadandneck;andthosereceivingoxygentherapy(Quinnetal2008).Patientsshouldmaintainadequatehydrationanddrinkwaterfrequentlytokeepthemouthmoist.Severalfactorscouldcontributetodrynesssuchasoxygentherapyandsupportivecaremedications(e.g.antidepressants,antihistamines,phenytoin,steroidinhalersandopioids);patientswhoareolderorterminallyillaremorepronetodrynessofthelipsandmouth.• Tokeeptheoralmucosamoist,regular

sippingorsprayingwatermayhelp.• Useofsalinespraysandmouthwashes

mayhelp.• Salivasubstitutesmaybeused.Some

salivasubstitutesmayhaveacidicpHthatcouldaffecttheteeth,thereforeuseproductswithneutralpHorcontainsfluoride,ifindicated.Somesalivasubstitutesalsocontainanimalcomponents,thusmustbecheckedagainstpatient’spreference.

• Sugar-freegummaystimulatesalivaproduction.

• Thereisanecdotalevidencethatfreshpineapplechunksmayalsohelpstimulatesalivabutshouldbeusedwithcautionasacidcouldirritatetheoralmucosaandaffecttheteeth(Lallaetal2014).

• Steaminhalationornebulisersmayhelploosenthicksecretions.Normalsalineorsodiumbicarbonatesolutionsmaybeused.

• Suctioningmayberequiredtoassistthosewhofindgettingridoftheirsecretionsdifficult,butmustbeusedwithcautionasoralsuctioningmaycausemucosalinjury.

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4.0Prevention of Oral Complications

Inpreventingoralcomplicationsanddevelopingatreatmentplanalwaysconsidertheindividual,thedisease,thecancertreatmentandotherriskfactorsasdiscussedinsection2.1.Compliancewiththepreventionmeasuresandgoodoralhygienewillminimisetheriskofsubsequentoralcomplications,andifanythingoccurs,earlyinterventioniskeytosuccessfullyavoidfurthercomplications.Inaddition,manypatientsareatriskofmalnutritionormalnourishedatthetimeofdiagnosiswithcancer,sotheearlierinterventionsincludenutritionalscreening,thesooneryoucanpreventmalnutrition.

Alcoholandtobaccodamagestheoralmucosa.Adviceshouldbeprovidedtohelppatientsgraduallyminimiseoravoidthese,ifappropriate.

Thechoiceofpreventionregimensshouldbeguidedbyevidencebasedinterventions,workingwiththepatientandthepotentialriskoforalmucositiswhichmayincludethefollowingriskclassification(adaptedQuinnetal2015)

4.1Risk Classification• Norisk• Lowriskoforaldamageand/orOM• Moderateriskoforaldamageand/or

OM• Highriskoforaldamageand/orOM4.2.Preventative InterventionsLow risk: Patients with no prior oral problems, minimal related risk factors and planned treatment not known to cause moderate or severe oral damage. • Educateandencourageself-reporting

ofanyoralchanges• Correctpatientand/orprofessional

assessmentoforalcavityandrecordingoffindings

• Baselinedental/oralassessmentandinterventionasrequired

• Goodandregularoralhygieneincludinggarglingtoremoveanyunwanteddebris

• Plaquereduction• Usehighfluoridetoothpaste/foam/gel/

tray

• Use0.9%sodiumchloride/saltwaterrinse

• Encourageandsupportsmokingcessation

• Encouragereductionofalcohol• Earlynutritionalinterventionincluding

dieticiansupporttodetectpossiblemalnutritionbeforetherapybegins

Moderate risk: Patients with a previous history of oral problems, receving treatments known to cause moderate OM, low dose radiation to the head and neck, any pharmacological agents and/or related risk factors that may cause oral damage

Inadditiontolowriskinterventions

• Furthermonitoringforanyearlychangestotheoralcavity

• Increasesaltwater/0.9%salinerinses• Cryotherapy/suckingicechipsduring

bolusinjectionof5FUandMelphalaninfusion

Consideroralrinses(Caphosol®,Benzydamine®)

Mucosalprotectants/barrierrinseslicencedtouseasapreventativemeasure/reducepain(Mugard®,Episil®).

High Risk: Patients with previous moderate or severe oral problems, high risk agents, high dose chemotherapy and/or radiation prior to stem cell transplantation, radical radiation to the head and neck

Inadditiontolowandmoderateinterventions

• Nutritionalmonitoringandfollowup• Anti-infectiveprophylaxis(see4.2)• Palifermin(inHSCTsetting)• LowLevelLasertherapy

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5.0Treatment of Oral Complications

4.3Anti-Infective ProphylaxisWhilstgoodoralhygieneisfundamental,anti-fungalandanti-viraltreatmentsmaybeprescribedtopreventinfectionsforpatientswhoareimmunocompromisedincludingpatientswithhaematologicalcancerswhoarereceivingchemotherapy(accordingtolocalpolicies/guidance).Infectionprophylaxisforpatientswithothercancersisonlyrequiredifthepatientisknowntobeatriskofinfectionduetoknownco-morbidityfactors.

Anti-fungalprophylaxisshouldbegiventopatientsreceivinghigh-dosesteroids(theequivalentofatleast15mgprednisolone

perdayforatleastoneweek).High-riskpatients,includingthoseundergoingHSCT,shouldalsoreceiveananti-fungalagentgivenorallyorintravenously.Thechoiceofdrugwillbedependentonlocalpolicies/guidance.

Anti-viralprophylaxisshouldbegivenaccordingtolocalpolicies/guidance).Higherdosesmayberequiredforsomehaematologypatients.

Onceoralcomplicationsoccur,atreatmentregimenisneeded.Asmentionedabove,thetreatmentofOMsimilartogeneraloralcareshouldbecarriedoutbyamulti-professionalteam.Thismayincludemedicalstaff,dentists,oralhygienists,specialistnursingstaff,pharmacistsorradiographers.Goodcommunicationandeducationofthepatientiskeytoensureanytreatmentprovidedgivesmaximumrelieftopatients.Alltreatmentplansshouldbebaseduponthegradingoforaldamageandpatientreports.

5.1Mild/Moderate Mucositis/Oral Complications • Onceoraldamagedevelopspatients

shouldbesupportedtocontinueoralcare

• Frequencyoforalrinsingmaybeincreased.Theaimistokeeptheoralsurfacescleanandmoist(Eladetal2014)

• Checkfororalinfections,swabandtreatappropriately.Antifungaltreatment,localorsystemicshouldbeadministeredifrequired.(Watsonetal2011)

• Dexamethasonecontaininggelsmaybeusedforapthtouslesions

• Considermucosalprotectants(Quinnetal2015)

• Dietaryrequirementsshouldbeassessedandfoodscausingdiscomfortavoided.

• Swallowingproblems,malnutritionandweightlossshouldbemonitoredandpatientsgivensupport/advice.

Adjustmentstofoodconsistency,methodsofintake,foodfortificationandmethodsofintakeshouldbeassessed,supportandeducationofferedtopatients.Useofsupplementdrinks,PEG,RIGorNasogastricfeedingshouldbeconsidered(Quinnetal2015).

• Fluidintakeshouldbeassessedandrouteofadministrationofpainreliefcontinuallymonitored.Generalhealthproblemsshouldalsobeassessed(swallowingoftablets,decreasedbloodsugarlevelsanddecreasedbloodpressure,decreasedrenalfunctionleadingtooverdosingofsubstances)

• Patientswillneedadequatepainmedicationincludingtopicalandsystemicanalgesiasuchasparacetamol,codeine,morphinerinses,benzydaminemouthwash,trimecain,lidocain.Patientsshouldbeofferededucationonuseandpossiblesideeffectsincludingnumbnessoftheoralmucosa

5.2Severe Mucositis/Oral Complications • increasepainmedicationfollowing

patientneeds• increasenutritionalsupport• increaseoralrinsesandcare

Whenoraldamageprogressesclosermonitoringandsupportforpatientsisrequired.Animportantaspectofcareistocontrolthepaintherebyhelpingthepatienttocontinuefoodandfluidintake,communicationandsleep.

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Fortopicaltreatmenttheuseoftopicalanalgesicscanbeintensified.Thereisinsufficientevidencethatmanyproductsreducetheseverityofmucositisbutcomfortcanbeprovidedforthepatientbysomeoftheseoralcareproducts.Institutionscanofferarangeofmouthwashesselectingthemostappropriatefortheclinicalsituationandthepatientstryingoutwhichoneworksbestforthem.Generallyspoken,topicalantibacterialsubstancesarenotrecommended.Theuseoforalrinses,topicalgelsorfilmscanbeindividuallyconsidered.Anywithsufficientsafetyandpositiveexperiencescanbeused:Caphosol®,Mugard®,Oralife®,Gelclair®,Episil®arejustafewofthem.

Forsystemicpainmedication,itisusefultofollowastep-by-stepincrease,withtheaimofthepatientbecomingpainfreewithintwentyfourhours.ItcanbehelpfultomonitortheefficacyofpainmedicationwithNRSscales.InstitutionsshouldfollowastandardizedpatternofpainmedicationfollowingtheWHOrecommendationswhereapplicable.

Inseveremucositis,theuseofopiateswiththeoptimalapplicationrouteshouldbeused.Thebestrouteofapplicationdependsonmanyindividualandsettingfactorsandmaybeoral,subcutaneous,intravenousortransdermalwithpatches.Patientsmayrequireacombinationofslowreleaseandfastactingdrugs.Carefulmonitoringshouldincludepainreliefandanypotentialsideeffects,andincludingfamilymembersmayprovehelpfultoobtainawiderviewofhowwellthepatientcopesoutsidethetreatmentunit.

5.3Treatment of Specific Oral ComplicationsBleeding from OM Continuemouthgargling.InspecificclinicalsituationsincludingHSCTandheadandneckcancersTranexamicacidwhichhasbeenwidelyusedinoralsurgerymaybeworthconsidering,gargling/swishingwithtranexamicacid(500mg)asamouthwash(Watsonetal2011).

Xerostomia/HyposalivationAsthismaybeduetoorincreasedbyconcurrentmedication,areviewofthepatient’smedicationsisneededandifpossibleadjustmentsmade.Patients

shouldbeencouragedtoincreasesippingoffluids.Artificalsaliva,viscoussolutionsandgelstoprotectandmoistenthemucosashouldbeconsidered,patientsshouldbecounselledoncorrectapplication.

Inchronicradiotherapyrelatedxerostomiawherethereissomeevidenceofsomesalivaproduction,pilocarpincouldbeused.

TrismusThisisacommonsideeffectduringandposthighdoseradiotherapy.Patientsshouldbeadministeredhelpfulmandibularstretchingexercises,physiotherapy,triggerpointinjections,musclerelaxantsandanalgesics.Theteammayconsidermechanicaldevicessuchasdentalstabilizationandrelaxationappliancestohelpalleviatetheproblem.

Graft versus Host Disease (GvHD)Unlikemucositiswhichrepresentsdose-limitingtoxicityforbothchemotherapyandradiotherapy,graftversushostdisease(GvHD)isanautoimmuneandalloimmunedisorderthatoccursafterhematopoeticstemcelltransplant(HSCT)andusuallyaffectsmultipleorgansandtissues.Itcanmanifestsineitheracuteorchronicform.TheacuteGvHDispotentiallyfatalandtypicallyaffectstheskin,gastrointestinaltractandliver(Demarosietal,2005).Thechronicformischaracterizedbytheinvolvementofanumberoforgansinaveryvariablefashion.Oralcavityisinvolvedin45-83%(Maysetal2013)andmaybetheonlyaffectedsite(Triesteretal2008).Atpresent,thedistinctionbetweenthesetwoformsofGvHDisbasedonlyontheclinicalcharacteristics,sincechronicGvHDisnotsimplyandevolutionofprecedingacuteGvHD(Flowersetal2011).(Jagasiaetal.2015).AccordingtotheNIH2004consensusrecommendations(Filipovichetal2005)whicharerefinedin2014(Jagasiaetal2015)diagnosticsignoforalchronicgraftversushostdisease(cGvHD)inpatientsafterHSCTistheoccurenceoflichenplanuslikechangesonoralmucosa.CommonfeaturesseenwithbothacuteandchronicGvHDincludegingivitis,mucositis,erythemaandpain.Distinctiveclinicalsignscomprisexerostomia,theappearanceofmucoceles,mucosalatrophy,pseudomembranesandulcersbutwithoutdiagnosticsignsthese

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manifestationsalonearenotenoughtoestablishthediagnosisoforalchronicGvHD(Jagasiaetal2015).Kuten-Shorreretal(2014)suggestthatsolutionsofdexamethasoneorothersteroidsareusedasfirstlinetreatment,secondlinemayincludesolutionsofsteroidsincombinationwithotherimmunesuppressantdrugs.

5.4Post Treatment Care/Follow-upAfterstandardchemotherapy,mostoralcomplicationshealquickly,sogenerallynoadditionalfollowupisrequired.OraldamageintheHSCTsettingaswellasintheheadandneckradiotherapy/chemo-radiationsettingwillneedseveralweeks/monthstohealandpatientsneedcontinuingsupportandcareduringthisperiod.Adviceandsupportbysuitablyqualifiedhealthprofessionalshouldcontinueduringthisperiod.Supportto

managesideeffectsincludingpainandthegradualreductionofanalgesiaisextremelyimportant

Chronicsideeffectsofradiotherapyforheadandneckcancers–especiallydentaldecay,osteoradionecrosis,trismus,fibrosis,lymphedema,chronicxerostomiaandchronicpainrequirecarefulmanagement.Patientsreceivingbonemodifyingagentsareatriskofosteonecrosisofthejawrequiringthemedicalanddentalteamtoworkcloselyinminimisingrisks.Allpatientsshouldbeindividuallyassessedandappropriatecareandtreatmentgiven.FollowupcareshouldbeplannedandsupervisedespeciallyinpatientsafterradiotherapyandHSCTandthosereceivingbonemodifyingagentstoaddresslongertermandlatecomplications.

6.0Conclusion

Theprinciplespresentedinthisguidanceareintendedasasupportandinnowayshouldreplaceclinicaldecisionmakingrelatedtotheparticularpatientandclinicalsituation.Dependingontheseverityoforalcomplicationsandtheimpactonthe

patient,theteamwillneedtoreviewtheplanofcare.Althoughthisguidanceandrecommendationsfocusontheoncologyandthemalignanthaematologysettingtheprinciplesmaybeappropriatetothepalliativecareandtheterminallyillsetting.

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(ii) National Cancer Institute grading scale (NCI-CTCAE)

Grade Description

0 None

1 Painlessulcers,erythemaormildsorenessinabsenceoflesions

2 Painfulerythema,edema,orulcers,butpatientscaneat/swallow

3 Painfulerythema,edema,orulcers,requiringi.v.hydration

4 Severeulcerations,orrequiresparenteral/enteralnutritionalsupportorprophylacticintubation

5 Deathduetotoxicity

NCI-CTCv2.0,1999:http://ctep.cancer.gov/

Appendix1

Appendix2

National and International Guidance Reviews

• GITMO(Italy)(2016)• Nationalguidelinesoralmucositis(Netherlands)(2015)• Nationalguidelinesoralmucositis(Switzerland)(2016)• Polishgroupspecialistguidelines(2015)• Institutionalguidelines(Portugal)(2015)• Institutionalguidelines(France)(2016)• Institutionalguidelines(CzechRepublic)(2015)• ItalianMinistryofHealthDepartmentofPublicHealthandInnovation(2014).• UKOralMucositisinCancer(UKOMiC)Guidelines,SecondEdition(2015)• MultinationalAssociationofSupportiveCareinCancer(2014)• EuropeanSocietyMedicalOncology(2015)

(i) WHO Health Organization Toxicity Criteria Stomatitis (WHO 1979)

Grade Description

0(none) None

1(mild) Soreness,erythema

2(moderate) Erythema,ulcers;Patientscanswallowsoliddiet

3(severe) Ulcers,Extensiveerythema;Patientscannotswallowsoliddietonly

4(life-threatening) Mucositistoextentthatalimentationisnotpossible

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(iii) Oral Assessment Guide (OAG)(Eilers et al 1988)

(iv) Numerical Rating scale (NRS). (Farrar et al 2001)

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(vi) 10 Patient-Reported Oral Mucositis Experience Questionnaire (Gussgard et al 2014)

Grade Description

0(none) Nochangeoverbaseline

I(mild) Irritation,mayexperienceslightpain,notrequiringanalgesic

II(moderate) Patchymucositisthatmayproduceinflammatoryserosanguinitisdischarge;mayexperiencemoderatepainrequiringanalgesia

III(severe) Confluent,fibrinousmucositis,mayincludeseverepainrequiringnarcotic

IV(life-threatening)

Ulceration,hemorrhage,ornecrosis

RTOG:http://www.rtog.org/

(v) RTOG Scoring Criteria