The “JaW PrinT” Study: Jaw reconstruction With Printed or ... · presentation than early stage...

JaWPrinTProtocolv1.8_22.12.2017 1

The“JaWPrinT”Study:

JawreconstructionWithPrintedorflexedTitaniumandfreetissuetransfer.

AcollaborationbetweenAbertaweBroMorgannwgUniversityHealthBoard,UniversityofSouthWalesandRenishawPLC.


Table of Contents Table of Contents ..................................................................................................... 2

List of Abbreviations ................................................................................................. 3

1.0 Study Team ...................................................................................................... 31.1DetailsofResearchTeam.............................................................................................................................32.0 Literature Review and Study Rationale............................................................ 42.1 Introduction/context...............................................................................................................................42.2 Computeraided3Dplanningandcrudecustomisationofmandibularreconstructionosseosynthesisplates............................................................................................................62.3 3Dprintinginmandibularreconstruction......................................................................................62.4 Summary...........................................................................................................................................................73.0 Study aims and objectives ............................................................................... 73.1 Primaryoutcome..........................................................................................................................................73.2 Secondaryoutcomes...................................................................................................................................74.0 Study design..................................................................................................... 84.1 Inclusioncriteria........................................................................................................................................124.2 Exclusioncriteria.......................................................................................................................................124.3 Recruitment..................................................................................................................................................124.4 Randomization............................................................................................................................................124.5 Studyprocedures.......................................................................................................................................134.5.1 BaselineAssessment..........................................................................................................................134.5.2 Perioperative/inpatientdatacollection..................................................................................134.5.3 6weeksfollowup................................................................................................................................144.5.3 6monthsfollowup.............................................................................................................................144.5.4 1yearfollowup...................................................................................................................................14

5.0 Risk management .......................................................................................... 15

6.0 Statistical analysis .......................................................................................... 16

7.0 Data management and quality control .......................................................... 16

8.0 Ethical considerations .................................................................................... 16

9.0 Funding .......................................................................................................... 17

10.0 Study timeline .............................................................................................. 17

11.0 References ................................................................................................... 18

12.0 Appendices .................................................................................................. 20AppendixA................................................................................................................................................................20AppendixB................................................................................................................................................................23


List of Abbreviations ABMUHB AbertaweBroMorgannwgHealthBoardCAD-CAM Computeraideddesign–ComputeraidedmanufactureCMF Cranio-maxillo-facial(surgery)CBCT Cone-beamcomputertomography(dental)CT Computertomography(medical)H&N Head&Neck(surgery)HRQOL HealthrelatedqualityoflifeORN Osteoradionecrosis(ofthemandible)PI PrincipalinvestigatorPSI Patient-specificimplantSLM Selectivelasermelting3D Three-dimensional

1.0 Study Team MrAlexanderGoodson Postgraduate(PhD)student

investigatorProfessorMarkWilliams ChiefInvestigator&PhDDirectorof

StudiesMrMadhavKittur PrincipalInvestigatorforABMU

HealthBoardMrPeterEvans Co-investigator,ABMUHealthBoard

1.1 Details of Research Team Name: ProfessorMarkWilliamsRole: ChiefInvestigatorAddress: FacultyofLifeSciencesandEducation UniversityofSouthWales CemeteryRoad

GlyntaffCF374BD

Telephone: 01443654578Email: [email protected]


Name: MrAlexanderGoodsonRole: PhDStudentInvestigatorAddress: FacultyofLifeSciencesandEducation UniversityofSouthWales GlyntafCampus Pontypridd,CF371DL Telephone: 01443654578Email: [email protected]: MrMadhavKitturRole: PrincipalInvestigatorforABMUHealthBoardAddress: MorristonHospital HeolMaesEglwys

MorristonSwanseaSA66NL

Telephone: 01792703162Email: [email protected]: MrPeterEvansRole: Co-investigatorAddress: MorristonHospital HeolMaesEglwys

MorristonSwanseaSA66NL

Telephone: 01792703162Email: [email protected]

2.0 Literature Review and Study Rationale

2.1 Introduction / context Headandneck(H&N)cancerincludescancersoriginatingfromvarious(andoftenoverlapping)sub-sitesintheheadandneckregion(includingtheoralcavity,pharynx,larynx,noseandparanasalsinuses).H&NcanceristheeighthmostcommoncancerintheUK(2014).IntheUK(mainland)itisfourtimescommonerinmenthanwomen,andgeographicallyEuropeanage-standardised(AS)incidenceratesarehigherinmalesinWalesthanEngland(withrateshighestinScotlandoverallforbothsexes).H&Ncancerincidencehasincreasedinbothsexessincethe1990swithagreaterpercentageincreaseamongstfemales,closingthegenderdifferenceinincidenceovertime.(Cancer_Research_UK)

Forheadandneckcanceringeneral,latestagediseaseisacommonerpresentationthanearlystagedisease(62%arestageIII/IVatpresentation


versus38%atstageI/II).(NICR,2016)Consequently,majorresectivesurgery,aimingforcure(withimmediatereconstructionforoptimalfunctionaloutcome)iscommonplace.Inthecaseoforalcancerspecifically,advancedtumoursfrequentlyinvolvethemandible(lowerjawbone),requiringresection/removalofpartofthemandibletoavariableextent,dependingonthenatureofthetumour(with/withoutpostoperativeradiotherapy,dependinguponpatientandtumour-specificfactors).

Radiotherapyiscommonlyusedinheadandneckcancerinisolation(asanalterativetosurgery),mostcommonlyforlaryngealandtonguebasetumoursasithelpstopreservenaturalspeechandswallowing.Howeverforadvancedsquamouscellcarcinomas(SCCs),combinedtreatmentmodalities(surgeryandradiotherapy/chemotherapyandradiotherapy)offerthehighestchanceofcure.(Nutting,2016)Forpatientsinwhomradiotherapyisused,thereisanadditionallifelongriskofdevelopingosteoradionecrosis(ORN)ofthemandibleasaside-effect.Osteoradionecrosisisineffect,“hypovascularityandnecrosisofbonefollowedbytrauma-inducedorspontaneousmucosalbreakdown,leadingtoanon-healingwound.”(Butterworthetal.,2016)Inthelatterstagesofthediseaseprocess,ORNcanresultinpathologicalfractureofthemandibleand/oranorocutaneousfistula,requiringfreetissuetransfertorepairthedefect.(LyonsandBrennan,2014)Consequently,inthecontextofmanagingheadandneckcancer,mandibularreconstructionwithtitaniumplatesandfreetissuetransferiscommonlyperformed;notonlyforimmediatereconstructionaftersurgicalresectionofadvancedtumours,butalsofortreatmentoflate-stageORN.Furthermore,similartechniquescanbeusedforextensiveandprogressive(buthistologicallybenign)jawtumours.

Choiceofreconstructivetechniqueformandibulardefectsdependsontheamountofbonetoberesected.(Brownetal.,2016)However,inlargerdefects,itisfeltbymanysurgeonsthatthegoldstandardformandibularreconstructionisafibulafreeflap(autologousvascularizedboneandsofttissue,transplantedfromthelegandanastomosedtoanarteriovenoussupplyintheneck)supportedwithinanosseosynthesisplatetofacilitateprimarybonyunion/healing.(Kokosisetal.,2016)Otherchoicesofbonyfree-flapscanbeusedsuchasthedeepcircumflexiliacartery(DCIA)flap,favouredoverthefibulafreeflapbysomeauthors.(Chenetal.,2014)Mostosseosynthesisplatesusedforthispurposearecomposedoftitanium,becauseofitsintrinsicbiocompatibilityandhighstrength-to-weightratio.(Parthasarathy,2014).Traditionally,titaniumwasflexedormouldedintraoperativelybyeye(duringsurgery)toreconstructmandibulardefects,withoutthemodernbenefitsofpreoperative3Dcomputer-aidedplanning.Theprocessofflexingarigidosseosynthesisplateformandibularreconstructioninherentlycontributestotheoveralldurationofthesurgery,isdependentupontheexperienceandskillofthesurgeonandcarriestheriskofhumanerrorindimensionalaccuracyofthereconstruction,simplybecauseitisdone‘byhandandbyeye’.Furthermore,manuallydeformingtitaniumimplantsinthismannercreatesintrinsicstresseswithintheimplantedmaterial,potentiallyweakeningtheoverallreconstructioninthelongtermwhilstsubjectedtocyclicalloadingforcesfrommastication/chewingforexample.(Parketal.,2016)


2.2 Computer aided 3D planning and customisation of mandibular reconstruction osseosynthesis plates Threedimensional(3D)planningandvirtualsurgeryhasevolvedinrecentyearsanditispostulatedthatitimprovesefficiency,accuracy,creativityandreproducibilityinCMFsurgeryinparticular.(Steinbacher,2015)Rapidprototypingisaprocessbywhichastereolithigraphicresinmodelcanbeproducedfollowingcollectionofdatafrom3Dimagingsuchascomputertomography(CT)scanning.Theprocessofvirtualsurgery(followinganalysisof3Dimagingdata)providesthemeanstorapid-prototypeastereolithigraphicresinmodel/moulduponwhichatitaniumimplantcanbeflexed,pressedormouldedpreoperatively(andmostimportantly,checkedagainstthestereolithigraphicmodel)forsubsequentintraoperativeuse.ThistechniquehasbecomecommonplaceinUKmaxillofacialcentres.Whencomparedtotraditionalintraoperativeshapingtechniques,itimprovesaccuracyandefficiencyinmandibularreconstruction(notablyeliminatingthetimetakenduringsurgerytobendtheplatebyeyethatwouldotherwiseberequiredusingthetraditionalapproach,yetallowingasmuchtimeasneededbythetechnicianpreoperativelytoachievethebest‘handmade’resultpossible).(Giletal.,2015)Nevertheless,thistypeof‘customisation’stillremainsopentoconsiderableinaccuracies/humanerrorsofthetechnicianinflexingtheplatebyhand.Furthermoretheriskofintroducingmechanicalweaknessesbyflexingtheplateremains.Besidesproducingpatient-specificimplants(PSIs),3Dplanningandvirtualsurgeryfacilitatestheproductionofintraoperativesurgicalcuttinganddrillingguides/’stents’,whichimproveaccuracyofbonecuts(osteotomies)inmandibularreconstructionwithfibulafreeflapsandaidspreciseplacementofosseointegrateddentalimplants(Wangetal.,2016,Allum,2008).

2.3 3D printing in mandibular reconstruction Itisclearthattodate,3DCAD-CAMhasimprovedtheaccuracyofmandibularreconstructionsinhead&neckoncologysurgery.Withtheadventof“3Dprinting”(morespecificallyselectivelasermelting;SLM),ithasbeenproposedbyoneauthorgroupthatlasersinteredmandibularreconstructionplatesreducethedurationofsurgeryandfrequencyofcomplications,aswellasproducingamoreaccuratereconstructionduetotheeliminationofhumanerrorinthefinalstagesoffabrication(incontrasttothe“pre-flexingtoarapid-prototypedstereolithigraphicmodel”approach).TheauthorssuggestthatfurtherrandomizedstudieswouldbeusefultodeterminewhetherCAD-CAMmandibularreconstructioniseconomicallysustainableinmaxillofacialoncologysurgery(Tarsitanoetal.,2016).CurrentlyateaminHongKongareprospectivelyevaluatingclinicaloutcomesandcomplicationsoflasersinteredmandibularreconstructionplatesinaproposedseriesof48patients(Su,2017).However,todatetherearenorandomizedtrialscomparingclinicaland


economicoutcomesin3D-printedmandibularreconstructionplatesandcuttingguidesversusmanuallypre-flexedplatetechniques.

2.4 Summary Insummary,3Dprinting(SLM)oftitaniumprovidesanopportunitytonegatetheimpactofhumanerrorincustomisationofmandibularreconstructionosseosynthesisplatesandalignmentofosteotomies,potentiallyimprovinguponthepredictabilityandprecisionofmandibularreconstructioninhead&neckcancerpatients.However,withalackofhigh-levelevidencetodate,thereisnoclearconsensusonwhethertheSLMapproachprovidesabettertreatmentsolutionwhencomparedtoothermoreestablished,butpotentiallymorecrudetechniquesofplatecustomization(pre-flexingtoarapidprototypedmodel).Consequentlyasituationofclinicalequipoiseexistsandinthiscontext,warrantsawell-designedobservationalstudytoevaluateanydifferencesbetweenthetwotreatmentapproaches.

3.0 Study aims and objectives

3.1 Primary outcome Primarily,thestudyaimstoevaluate:

1. Predictabilityandresultantdimensionalaccuracyofmandibularreconstructionsperformedusing:

o Fibularfree-flapreconstructionofthemandiblewithacustomizedpre-flexedmandibularreconstructionplateandcuttingguides(TreatmentpathwayA)

ORo Fibularfree-flapreconstructionofthemandiblewithacustomized

SLMmandibularreconstructionplateandcuttingguides(TreatmentpathwayB)

3.2 Secondary outcomes Secondarily,thestudyaimstocomparetreatmentpathwaysAandBfor:

2. Thedurationofsurgery(inparticularindividualcomponentsofthesurgerysuchasflapwarmischaemiatime,durationofosteotomiesandplatefixationprocedures.


3. Theoperators’perceptionsoftheoverallintraoperativeusability,confidencewiththetechniqueandimmediatesatisfactionofthesurgicalresult.

4. Theneedtomakeminoradjustmentstoeithertheplate,osteotomyorscrewholesinordertofittheplateduringsurgery.

5. Incidenceofpostoperativecomplications(asrecordedduringinpatientstayaswellasat6weeks,6monthsand1yearoutpatientfollowupvisits),forexample:

a. Localisedinfectionb. Plateextrusion/exposurec. Lengthofhospitalstay(includingdurationofintensivecare/high-

dependency/wardrequirements)d. Mal/non/delayed-unionofthebonycomponentsofthe

mandibularreconstruction(fromobjectiveanalysisofclinicallyroutinepostoperativeCTscanimaging)

e. Platefractures/failures6. Medium-term(upto1year)functionaloutcomes,forexample:

a. Feasibilityofdentalimplantrehabilitation(specificallyinthetechnicalcontextofclinicaland/orradiologicalperspectiveofbonequalityandanatomyaswellasintheholisticcontextofthepatient’ssuitabilityoverall,inordertodeterminetheimportanceofreconstructedbonyanatomyinthedecisionprocessesandplanningofdentalrehabilitation)

b. Objectiveevaluationofchangesindentalocclusion(withtheaidofdentalmodelanalysis).

c. Objectiveassessmentofchangesinfacialaesthetics(facialsymmetrybaseduponbaselineandpostoperative3Dphotography(stereophotogrammetry).

7. Patient-perceivedqualityoflife:a. usingavalidatedqualityoflifeassessmenttools:

i. UniversityofWashingtonQualityofLifeQuestionnairev4ii. Short-formDerrifordappearancescale(DAS24)iii. Liverpooloralrehabilitationquestionnaire

b. bytimetoreturntowork/socialstatusat1year(whereapplicable)

8. Economicimplications(witheconomicanalysistakingtheaboveclinicalandsocialoutcomesintoaccount).

4.0 Study design JaWPrinTisa‘real-world’prospectiveobservationalpilotstudy,evaluatingtheclinicaleffectiveness,usabilityandeconomicsoftwoapproachestomandibularreconstructionsurgery(figure1).Patientparticipantswillberecruitedprospectivelyoveraminimumperiodof18months(withobservationofatleast10participantsineachtreatmentpathway).Thefiguresarebaseduponthehistoricalclinicalpracticeoftheresearchsite,withbothtechniquesinequaluse;


choicedependingonresources,surgicaltrainingrequirementsandsurgeon’sclinicalpreference.Asapurelyobservationalstudy,treatmentchoicewillbemadeinthenormalclinicalmannerandwillinnowaybeinfluencedbythestudyitself.Participantswillbefollowedupattheirroutineoutpatientclinics(6weeks,6monthsand1yearpostoperatively)withprospectiveoutcomesdatacollection(figure1).


PI to prospectively identify potential study participants from weekly maxillofacial and H&N surgery clinics

• Participants to be recruited over a minimum period of 18 months; minimum of 10 patients in each

treatment pathway. • On clinic, potential participants will be asked by the PI if they are interested in taking part in the study. • The PI, after meeting the potential participant, will confirm their eligibility. • Eligible participants meeting inclusion and exclusion criteria will be sent an invitation letter with a

participant information sheet and a consent form (emphasizing the option to either decline or accept the offer of study participation).

Preoperative baseline data collection (CRF01 form). • Medical history and screening of comorbidities (including comorbidity score & performance status), smoking and alcohol status. • Evaluate for history of any previous radiotherapy treatment (date started and completed, regime details). • Physical assessment (BMI, oral hygeine status). • Detailed social history • University of Washington QoL Questionnaire v4. • Short-form Derriford appearance scale (DAS24). • Liverpool oral rehabilitation questionnaire. • 3D Photograph (Stereophotogrammetry) of the head and neck • Baseline clinical blood tests (FBC, U&E, Clotting screen)

Do not enter study

Treatment allocated in normal clinical manner by surgeon to either pathway A (surgery with pre-flexed plate) or pathway B (surgery

with SLM plate).

Participant blinded to treatment allocation at this stage

Pathway A (Customized pre-

flexed plate) n ≥10

Pathway B (Customized SLM

plate) n ≥10

Perioperative / inpatient data collection (CRF02 form). • Prior to commencing surgery, bite registration to be obtained (using viscoelastic silicone impression putty) • At surgery, record of:

o Times at which mandibular osteotomies are first started (cutting guides first placed onto mandible) and completed o Time of knife-to-skin for flap harvest o Time of flap detachment o Time of completing fixation of the plate (with flap) in its final resting position (i.e. when completion of fixation to the residual mandible) o Time of completing arterial anastomosis

• Record of need for any intraoperative adjustment to the plate, osteotomies and/or planned drill hole positions. • Surgeon rating of usability, confidence of use, satisfaction with reconstructive procedure. • Scrub nurse rating of usability, confidence of use, satisfaction with reconstructive procedure. • Record of days-stayed on ITU / HDU and/or Ward, date of discharge. • Record of all complications as inpatient (peri & post operative).

Consent • At the next routine clinical appointment, the potential patient participant’s decision will be noted. • Should the patient wish to participate, the PI will obtain their written informed consent accordingly.


6 weeks follow up (CRF03 form). • Physicalassessment(BMI,oralhygeinestatus).• UniversityofWashingtonQoLquestionnaire.• Short-formDerrifordappearancescale(DAS24).• Liverpooloralrehabilitationquestionnaire.• Reportoncomplications.• 3D Photograph (Stereophotogrammetry) of the head and neck. • Detailedsocialhistory(e.g.currentoccupation/employment)

6 months follow up (CRF04 form). • Data recorded as per CRF03 form. • Postoperative CT mandible scan (evaluation of actual vs. planned dimensions, quantitative evaluation of bony cortical union at osteotomy sites)

1 year follow up (CRF05 form). • Data recorded as per CRF03 form. • Dental assessment (including routine cone beam CT scan) and restorative dentist rating of technical and practical feasibility of prosthetic rehabilitation

options

End of study Patients informed of treatment type received.

Figure1.TheJaWPrinTstudydesign


4.1 Inclusion criteria

• Ageover18years• Abletoprovideinformedconsent• Aplannedfibularfree-flapreconstructionofthemandible• PlannedpostoperativesurveillanceCTscan6monthsfollowingsurgery

4.2 Exclusion criteria

• Clinicallyunfitorinappropriate(baseduponprognosis/lifeexpectancy)forreconstructionusingfreetissuetransfertechniques

• Patientswithplannedsurgicaldefectsinvolvingreconstructionofthecondyle:i.e.BrownclassIc,IIcorIVc.(Clinicaluseofprintedplatesforcondylarreconstructionswouldineffectbe‘off-licence’andnon-standardtreatmentwhichisbeyondtheremitofanobservationalresearchstudy).

• Flapfailurewithinthestudyfollow-upperiod,asthiswouldrequireearlyremovaloftheflapandthereforeprecludecollectionoffollow-upoutcomedata.However,anyflapfailures(andassociatedclinicalcomplications/events)willberecordedandreported.

4.3 Recruitment ParticipantswillberecruitedprospectivelyastheypresentasnewpatientcasestotheABMUMaxillofacialandHead&Neckcancermultidisciplinaryteam(MDT)clinics.Onceapotentialpatientparticipanthasbeengivenhis/herdiagnosisanditisconfirmedbytheprincipalinvestigator(PI)thathe/shemeetstheinclusioncriteria,clinicstaffwillprovidethepotentialparticipantwithaninvitationletterintroducingthestudyaswellasapatientinformationsheetandconsentform(explainingtheavailableoptionsofparticipatingorrefrainingfromthestudy).Patientswillbeallowedupto24hourstodecidewhetherornottoparticipateastoavoidanyimpact/delayontheschedulingoftheirclinicaltreatment.ThePIwillobtainwritteninformedconsentfromwillingparticipants.

4.4 Treatment pathway allocation Uponrecruitment,provisionofinformedconsentandcollectionofbaselinedata,asperstandardclinicalpractice,thepatientparticipant’sCTscandataisusedtoproduceavirtualsurgicalplanforthemandibularresectionandfibularfree-flapreconstruction.Oncetheclinicallyoptimalreconstructivesurgicalplanisestablishedbythesurgeonandtechnician,thechoiceofsurgicalapproachwillbemadeintheroutineclinicalmannerbythesurgeon:PathwayA(pre-flexedcustomizedmandibularreconstructionplateandcuttingguides)ortopathwayB(SLMcustomizedmandibularreconstructionplateandcuttingguides).Both


treatmentpathwaysarealreadypartofroutine/standardclinicalpracticeatABMUHB.Theexpected/plannedpatientnumbersforthisstudyarebaseduponthehistoricalworkloadoftheOralandMaxillofacialSurgerydepartmentatAbertaweBroMorgannwgUniversityHealthBoard(ABMUHB)of10-20casesannually.Arecruitmentperiodof18monthswithfollow-upfor1yearfitswithinthetimeconstraintsofthepostgraduatestudentinvestigator’sPhDtimeline.

4.5 Study procedures

4.5.1 Baseline Assessment Thiswillbeperformedusinga“baselinecasereportform”(CRF01),whichwillincludepastmedicalhistory(withattentiontoanyhistoryofpreviousradiotherapytotheheadandneckregion);a‘systemsreview’toscreenforundisclosedcomorbiditiesaswellassmokingandalcoholstatus.Thepatientparticipant’scomorbidityandperformancestatusscoreswillalsoberecorded.Thequalitative/subjectiveassessmentoforalhygienestatus(good/fair/poor)byaconsultantoralandmaxillofacialsurgeonwillalsoberecorded.Collectedfromroutineclinicalpreoperativetests,BMIandserumalbuminconcentrationwillberecordedasanindicatorofnutritionalstatus,alongwithafullbloodcount,ureaandelectrolytesandclottingscreen.BaselinequalityoflifeassessmentwillbeperformedusingtheUniversityofWashingtonQoLQuestionnairev4(Rogersetal.,2002)(AppendixA).Abaselineassessmentoftheparticipant’sperceivedappearanceandoralfunctionwillbeevaluatedusingtheshort-formDerrifordappearancescale(DAS24)(Carretal.,2005)whichissuitedasaresearchofappearanceinH&Ncancers(DjanandPenington,2013),andtheLiverpooloralrehabilitationquestionnaire(Pace-Balzanetal.,2006)(AppendixB)respectively.Presurgicalfacialaestheticswillalsobeevaluatedbymeansofassessingfacialsymmetrywithstereophotogrammetry(clinical3Dphotographyinthemedicalillustrationdepartment)oftheheadandneckregion.

4.5.2 Perioperative/inpatient data collection Duringtheinpatientphaseoftheparticipant’smedicaltreatment,alldatawillberecordedonthe“inpatientcasereportform”(CRF02).Toevaluatethepresurgicaldentalocclusion(ifoccludingteethpresent),abiteregistrationwillbetakenwhilstthepatientparticipantisanaesthetised.Thesewillbeobtainedusingaviscoelasticsiliconeimpressionmaterial.Atsurgery,overalltimefromknifetoskin,totransferringthepatientparticipantofftheoperatingtablewillberecorded.Furthermorethetimingsofspecificlandmarksofreconstructivecomponentsofsurgerywillberecorded:

• Timesatwhichmandibularosteotomiesarefirststarted(whenmandibularcuttingguidesfirsttouchesmandible)andcompleted(whenmandibularcuttingguidesremoved)


• Timeofknife-to-skinforflapharvest• Timeofflapdetachment• Timeofcompletingfixationoftheplateinitsfinalrestingposition(i.e.

whencompletionoffixationtotheresidualmandible)• Timeofcompletingarterialanastomosis

Toevaluatetheimpactofcuttingguidesonthefitofthebonyflap,thesurgeonwillbeaskedtorecordthenumberofsubsequentadjustmentsneededtothemandibular/fibularosteotomies,drillholesand/ortheplateitself.Tofurtherevaluatetheefficiencyofeithersurgicaltechnique(andanypotential‘learningcurve’effect),thesurgeonandscrubnursewillbeaskedtoprovidea5-pointLikertscaleratingforthefollowingcriteriaattheendoftheoperation:

• Easeofuse• Confidenceinperformingthetechnique• Immediatesatisfactionwithreconstructivecomponentofsurgery

Intheimmediatepostoperative(inpatient)phaseofrecovery,datesofstayintheintensivecareunit(ITU),highdependencyunit(HDU)and/ortheinpatientwardwillberecorded,alongwithafinaldischargedate.Duringthisperiod,anypostoperativecomplicationsaretoberecordedif/astheyoccur.

4.5.3 6 weeks follow up Thiswillincludereportingofanycomplicationssincedischargefromhospital,aswellasrepetitionofsomedatacollectedinthebaselineassessment,usingthe“6weekscasereportform”(CRF03).Specificdatatobecollectedincludes:

• Physicalassessment(BMI,oralhygeinestatus,reportonwoundhealing).• UniversityofWashingtonQoLquestionnaire.• Short-formDerrifordappearancescale(DAS24).• Liverpooloralrehabilitationquestionnaire.• Reportoncomplications.• Stereophotogrammetry(3Dphotography)oftheheadandneck.

4.5.3 6 months follow up The“6monthscasereportform”(CRF04)willbeusedtocollectidenticaldatatothatcollectedat6weeksfollow-up.Thisfollowuppointisselectedasinthecaseofcancersurgery,itisastandardfollow-uppointforassessmentofsignsofearlydiseaserecurrence.Forthisreason,routinemedicalCTscanningtoevaluatefordiseaserecurrenceisperformed.A3DrenderofDICOMdatafromthisclinicalscancanbeusedtodimensionallyandvolumetricallycomparetheactualbonyreconstructionwiththepreoperativeplan,evaluatingoverallaccuracyandprecisionofthereconstructivetechniqueused.Furthermore,CTassessmentofbonyunionwillbeperformedusingaquantitativenumericalratingscore,adaptedfromAkashietal.(Akashietal.,2015)

4.5.4 1 year follow up


The“1yearcarereportform”(CRF05)willbeusedtocollectidenticaldatatothatcollectedat6weeksfollow-up.Furthermore,insomecasesroutineclinicalandradiographic(conebeamCT)dentalassessmentisperformed1yearpostoperativelywithaviewtofurtherdentalrehabilitation(withdentalimplantsinsomepatients).Fromthisdentalassessment,wewouldaimtoevaluatetheclinician’sopinion(usinga5pointLikertscale)ofthepatientparticipant’soverallsuitabilityfordentalrehabilitation(ifnotalreadyinplace)withavarietyofpossibleprostheticsolutions:

• Simpledentures• Bridge• (Multiple)singletoothimplants• Implantretainedbridge• Implantretaineddentures

Dentalradiology(conebeamCT)ifusedaspartofthisroutinedentalassessmentwillalsobeanalysedtofurtherevaluateanybony(dimensional/volumetric/healing)changesthatoccurovertime.Post-surgicaldentalocclusionwouldclinicallyroutinelybeevaluatedwithabiteregistration.Thiscanbecomparedtothepre-surgicalbiteregistrationtoevaluatetheimpactofthereconstructivesurgeryondentalocclusion.

5.0 Risk management Allclinicaltesting(physical,serologicalandradiological)performedwithinthisstudyiswithintheremitofstandardclinicalcareandthereforethestudyitselfwillnotputtheparticipantatadditionalriskofmedicalcomplicationsorside-effects.Forqualitativedatacollection,validatedscoringtoolswillbeusedwhereverpossible.Bothtreatmentpathways(A&B)observedinthisstudyconstituteroutinesurgicalpractice,withbothtechniquesroutinelyusedatABMUHB.Botharegold-standardtreatmentwithsubtledifferencesintechnique;neitherisexperimentalinanyway.Consequentlyanyclinicalcomplicationscanbedealtwithinthenormalclinicalmanner,regardlessofthestudy.Itwillbemadecleartoparticipantsfromthestartoftheirinvolvementthattheyarefreetowithdrawfromthestudyatanytime,withoutanyreasonandwithoutanyimpactupontheirstandardofcare.Participantswillbegiventhecontactdetailsforthestudyteam,withtheirprimarylinkbeingtheircentre’sPIwhowillsuperviseboththeirclinicalcareanddatacollectionthroughoutthestudyperiod.Shouldclinicalneedrequiredeviationfromthestudyprotocolandsubsequentexclusionastoavoidconfoundingeffectsonstudyresults,thiswillbedisclosedandreportedintheresults.Whereitisfeltthatanydatacollectedwasunaffectedbythisprocess,itwillbeusedwhereverfeasible.


6.0 Statistical analysis Datawillbecollatedandanalyzedusingastatisticalsoftwarepackage.Descriptivestatisticswillbeusedforbaselinemeasures,categoricalstatisticsforquestionnaireoutcomedata,andrelationshipswillbeevaluatedusingtestsofcorrelationandcomparison,alongwithregressionalanalysis.

7.0 Data management and quality control DatawillbecollatedandstoredincompliancewiththeDataProtectionAct1998andtheABMUHBdataprotectionpolicy.Alldatausedbeyondtheparticipant’simmediateclinicalenvironmentwillbeanonymizedaccordingly.Thestudyteamwillmeetthroughoutthestudywithquarterlymeetingstodiscussandauditparticipantrecruitment,datacollectionandanyissueswiththestudyprotocolthatmayarise.AllclinicalrecordswillremainwithinABMUHBandstoredwithinthepatient’sclinicalrecordsinthenormalmanner.CaseReportForms(CRFs)willbekeptinthePI’sofficeinalockedcabinet.Tomaintainanonymityfromtheearlieststage,recruitedparticipantswillbeassignedanumericidentitycode(insteadofidentifiableinformationsuchasageordateofbirth)fromthebeginning.Onceanonymised,patientdatawillbestoredelectronicallyonapassword-protectedlaptopcomputerandbacked-uponanexternalharddriveonadailybasis.Asanonymisedrawdata,CRFswillbephysicallystoredfor15yearsbeyondtheterminationofthestudybythePI(asthedatacustodian).ThisstrategyisbasedupontherecommendationsoftheABMUHBresearchanddevelopmentdepartment(wherelocalpolicyadvisesadatastorageperiodof5to15yearsfollowingterminationofthestudy)andtheUKPolicyFrameworkforhealthandsocialcareresearch(Health_Research_Authority,2017).Identifiabledatathatrequiresstorageforclinicalreasonsalone,willonlybestoredintheusualNHSclinicalmanneraccordingtoNHSWalespolicy(The_National_Assembly_For_Wales,2000).

8.0 Ethical considerations Alltreatmentsprovidedtostudyparticipantsarenormal,routineclinicalpracticeatABMUHB.ApartfromHRQOLquestionnairesandgaininginformedwrittenconsentfortheresearchstudy,allinvestigations/testsinthisstudyareroutineclinicalpracticeatABMUHBforpatientsundergoingjawreconstructionsurgery.Withregardstosomespecifictests:


• Clinical3Dphotography(stereophotogrammetry)isroutinelyavailableandcommonlyusedforABMUHBpatientsundergoingfacialreconstructivesurgery,althoughnotroutinelyinallcases.Inthisstudy,stereophotogrammetry(3Dphotos)willbeobtainedatbaseline(preoperatively),aswellas6weeks,6monthsand1yearpostoperatively.ThishasbeendiscussedwiththeMedicalIllustrationdepartmentatMorristonHospital.

• Dentalbiteregistrationsareroutinelyperformedafterjawreconstructionsurgeryinordertoplanthepatientforrehabilitationwithdentalprostheses.Insome,dentalimpressionsandbiteregistrationsareobtainedpriortothesurgeryaswellbutnotinallcases.Inthisstudy,weplantoobtaindentalimpressions(immediatelybeforesurgerywhilstundergeneralanaesthesia)aswellasseveralmonthslater(asperroutinepractice).Thestudyteamfeltthatcollectingthepreoperativedentalimpressionsatthebeginningoftheparticipant’ssurgeryprovidesanopportunistic,efficient,safeandcontrolledsettinginwhichtodothis.

Theaboveitemsareexplainedfully(inlayterms)inthepatientinformationsheet.

9.0 Funding ThisstudyisfundedexternallythroughKESS,inpartnershipwithRenishawplcandtheUniversityofSouthWalesandincludesthecostofconsumables/equipmentandotherincidentalcostsrelatingtothestudyitself.Knowledge Economy Skills Scholarships (KESS) is a pan-Wales higher level skillsinitiative ledbyBangorUniversityonbehalf of theHE sector inWales. It ispartfunded by the Welsh Government’s European Social Fund (ESF) convergenceprogrammeforWestWalesandtheValleys.

10.0 Study timeline ThestudytimelineisillustratedinthefollowingGanttchart(figure2).


11.0 References AKASHI,M.,HASHIKAWA,K.,KAKEI,Y.,SAKAKIBARA,A.,HASEGAWA,T.,

MINAMIKAWA,T.&KOMORI,T.2015.Sequentialevaluationforboneunionoftransferredfibulaflapsinreconstructedmandibles:panoramicX-rayversuscomputedtomography.IntJOralMaxillofacSurg,44,942-947.

ALLUM,S.2008.Immediatelyloadedfull-archprovisionalimplantrestorationsusingCAD/CAMandguidedplacement:maxillaryandmandibularcasereports..BrDentJ.,204,377-381.

BROWN,J.,BARRY,C.,HO,M.&SHAW,R.2016.Anewclassificationformandibulardefectsafteroncologicalresection.LancetOncol,17,e23-30.

BUTTERWORTH,C.,MCCAUL,L.&BARCLAY,C.2016.Restorativedentistryandoralrehabilitation:United

KingdomNationalMultidisciplinaryGuidelines.JLO,130,41-44.CANCER_RESEARCH_UKOralcancerincidencestatistics.CARR,T.,MOSS,T.&HARRIS,D.2005.TheDAS24:AshortformoftheDerriford

AppearanceScale(DAS59)tomeasureindividualresponsestolivingwithproblemsofappearance.BritishJournalofHealthPsychology,10,285-298.

CHEN,S.,CHEN,H.,HORNG,S.,TAI,H.,HSIEH,J.,YEONG,E.,CHENG,N.,HSIEH,T.,CHIEN,H.&TANG,Y.2014.Reconstructionforosteoradionecrosisofthemandible:superiorityoffreeiliacboneflaptofibulaflapinpostoperativeinfectionandhealing.AnnPlastSurg,73,18-26.

DJAN,R.&PENINGTON,A.2013.Asystematicreviewofquestionnairestomeasuretheimpactofappearanceonqualityoflifeforheadandneckcancerpatients.JPlastReconstrAesthetSurg,66,647-659.

GIL,R.,ROIG,A.,ARRANZOBISPO,C.,MORLA,A.,MARTIPAGES,C.&LLOPISPEREZ,J.2015.Surgicalplanningandmicrovascularreconstructionofthemandiblewithafibularflapusingcomputer-aideddesignandrapidprototypemodelling,andprecontouredtitaniumreconstructionplates:aprostpectivestudy..BrJOralMaxillofacSurg,53,49-53.

Quarter 1st 2nd 3rd 4th(1yr)

5th 6th 7th 8th(2yrs)

9th 10th EndofStudy

Participantsrecruited

- Unblindingof

studyparticipants

- Disseminationofdata

- Peer-reviewed

publication- Presentation

Participantscompletestudy

Landmarkevents

Studyteammeet

Studyteammeet

Studyteammeet

Studyteammeet

StudyteammeetFirstparticipantcompletesstudy

Studyteammeet

Studyteammeet

Studyteammeet

Studyteammeet

StudyteammeetLastparticipantcompletesstudy

Figure2.Ganttchartillustratingthestudytimeline


HEALTH_RESEARCH_AUTHORITY2017.UKPolicyFrameworkforhealthandsocialcareresearchv3.3.

KOKOSIS,G.,SCHMITZ,R.,POWERS,D.&ERDMANN,D.2016.MandibularReconstructionUsingtheFreeVascularizedFibulaGraft:AnOverviewofDifferentModifications.ArchPlastSurg,43,3-9.

LYONS,A.&BRENNAN,P.2014.Osteoradionecrosisanewclassification.BrJOralMaxillofacSurg,52,e64-e65.

NICR2016.NorthernIrelandCancerRegistry,QueensUniversityBelfast,Incidencebystage2010-2014.

NUTTING,C.2016.Radiotherapyinheadandneckcancermanagement:UnitedKingdomNationalMultidisciplinaryGuidelines.JLO,130,66-67.

PACE-BALZAN,A.,CAWOOD,J.,HOWELL,R.,BUTTERWORTH,C.,LOWE,D.&ROGERS,S.2006.ThefurtherdevelopmentandvalidationoftheLiverpoolOralRehabilitationQuestionnaire:Across-sectionalsurveyofpatientsattendingfororalrehabilitationandgeneraldentalpractice.IntJOralMaxillofacSurg,35,72-78.

PARK,S.,LEE,D.,LEE,J.,KIM,Y.,KIM,L.&NOH,G.2016.Stabilityofthepermanentlybentplatesusedinmandibularreconstructivesurgery.201638thAnnualInternationalConferenceoftheIEEEEngineeringinMedicineandBiologySociety(EMBC).Orlando,FL.

PARTHASARATHY,J.2014.3Dmodeling,cusomimplantsanditsfutureperspectivesincraniofacialsurgery.AnnalsofMaxillofacialSurgery,4,9-18.

ROGERS,S.,GWANNE,S.,LOWE,D.,HUMPRHIS,G.,YUEH,B.&WEYMULLER,E.2002.TheadditionofmoodandanxietydomainstotheUniversityofWashingtonQualityofLifeScale.Head&Neck,24,521-529.

STEINBACHER,D.2015.Three-DimensionalAnalysisandSurgicalPlanninginCraniomaxillofacialSurgery.JOralMaxillofacSurg,73,S40-S56.

SU,Y.2017.Three-DimensionalPrintingofPatient-SpecificTitaniumPlatesinJawSurgery:APilotStudy[Online].https://clinicaltrials.gov/ct2/show/NCT03057223:U.S.NationalInstitutesofHealth.[Accessed2/4/172017].

TARSITANO,A.,BATTAGLIA,S.,CRIMI,S.,CIOCCA,L.,SCOTTI,R.&MARCHETTI,C.2016.Isacomputer-assisteddesignandcomputer-assistedmanufacturingmethodformandibularreconstructioneconomicallyviable?JCraniomaxillofacSurg,44,795-799.

THE_NATIONAL_ASSEMBLY_FOR_WALES2000.Fortherecord-ManagingRecordsinNHSTrustsandHealthAuthorities.WelshHealthCircular.

WANG,Y.,ZHANG,S.,FAN,S.,ZHANG,D.,HUANG,Z.,CHEN,W.,YE,J.&LI,J.2016.Mandibularreconstructionwiththevascularisedfibulaflap:comparisonofvirtualplanningsurgeryandconventionalsurgery..intJOralMaxillofacSurg,45,1400-1405.


12.0 Appendices

Appendix A


Appendix B

The “JaW PrinT” Study: Jaw reconstruction With Printed or ... · presentation than early stage...

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