RadiationOncology,Physics,Total BodyIrradiation(TBI)

ID: 000490

Approved:24 May 2010

Last Modified: 16 Feb 2012

Review Due:31 Aug 2012

Thisprotocoliscurrentlybeingreviewed. Target Audience: ThisprotocolisaimedatprovidinginformationonTotalBodyirradiation(TBI)forthe following:

I I I

MedicalPhysicsRegistrars RadiationOncologyRegistrars RadiationTherapists

Overview:

Thisprotocolisdesignedtoprovideanoverviewoftheclinicalindicationsfor TBI,thetheoryandpractiseofTBI,thedifferentsetupuptechniquesused,and theconsiderationsfortreatment.Itwillalsobrieflydescribetheprocessofbone marrowtransplantationandsomeofthesideeffectsexperiencedbythepatient afterreceivingacourseofTBI. LowdoseTBIisbeyondthescopeofthisprotocol.

Key References:

I I I

AAPMreport17(outdatedbutworthreading) Galvin,J.M.,Report:AAPM2001Meetings ESTRO,EULEPandEBMT,ProceedingsoftheInternationalMeetingonPhysical, BiologicalandClinicalAspectsofTotalBodyIrradiation,Radiotherapy& Oncology,Supplement18(1),1990

Additional Resources:

I I I

AustralianBoneMarrowDonorRegistry AustralianBoneMarrowTransplantFoundation CurrentOpinioninOncology,Supplement21(1),pp146,2009

ProtocolObjectives:
Bytheendofthisprotocol,youwillhave: 1. 2. 3. 4. 5. Gainedabasicknowledgeofbonemarrowtransplantation LearntthereasonswhyTBIisprescribed Understoodsomeofthesideeffectsonthepatient UnderstoodthetreatmentconsiderationsforTBI Beengivenexamplesofdifferenttreatmenttechniques

WhyisTBIused?
Totalbodyradiation(TBI)wasfirsttrialledinthe1920s.Itwasadministeredatalowdose(0.10.25Gy)severaltimesaweek totreatmalignanciesofthelymphoma.Today,TBIisstillprescribedatalowdoseforspecificdiseasessuchasnonHodgkin's Lymphoma1. Inmodernradiationtherapycentres,TBIismorecommonlyusedinpreparationforabonemarrowtransplant.

BoneMarrowTransplantation
Bonemarrowtransplantation(BMT)iswidelyusedasatreatmentforhaematologicalmalignanciessuchasleukaemia,aswell asseverecombinedimmunoandenzymedeficienciesdisordersandhaemopoieticsystemdisorderssuchasaplasticanaemia

Page 1 of 7

Radiation Oncology, Physics, Total Body Irradiation ( TBI )

2.

However,notallpatientsaresuitableforaBMT.ConsiderationsforaBMTincludethephysicalhealthofthepatient,diagnosis andthestageofthedisease3. ApatientwhoisreceivingaBMTiscalledarecipient,andthehealthybonemarrowisgivenbyadonor.Therecipientis matchedwithasuitabledonorbytissuetyping.Thisisdonebyestablishingthehumanleucocyteantigentype,whichisa whitebloodcellmarker,fromabloodsample3. Insomecases,thedonorsbonemarrowundergoesaprocesstoremoveharmfulTlymphocytes,knownasTcelldepletion. TheseTcellscausegraftversushostdisease,wherethedonorscellsrecognisetherecipientscellsasforeignandmountan immuneresponsetorejectthem. Thebestpossibledonorisanidenticaltwinhoweverthereisonlya2535%chancethatafamilymemberwillprovidea goodmatch.Atransplantthatcomesfromanotherpersonisreferredtoasanallogeneictransplant,orasyngeneictransplant ifthedonorisanidenticaltwin4. Anautologoustransplantisonewherethepatientsownstemcellsareused.Thismaybedoneifthediseaseisinremission ordoesnotinvolvethebonemarrow.Thepatientsstemcellsaretakenandstored,thenreturnedtothepatientafter chemotherapyand/orradiationtherapy4.

Clinicalindicationsfortotalbodyirradiation
TBIisusedinaradiationoncologysettingasaconditioningregime.ItistypicallyprescribedforpatientsrequiringaBMT,with theaimofincreasingthesuccessofthetransplantintherecipient5,6. Thisisachievedthroughleukaemiacellkill,eradicatingtherecipientsbonemarrowandprovidingasufficientdegreeof immunosuppressiontoavoidgraftrejectionintherecipient7, 8.Thedonorshealthybonemarrowistheninfusedintothe recipientoverseveralhours3. AsuccessfulBMTisachievedwhenthedonorsbonemarrowattachestothecavitiesintherecipientslargebonesandbegins toproducenormalbloodcells3.

Effectonthepatient
Thepatientmayexperiencesideeffectsfromthechemotherapyandradiationtherapy,suchashairloss,nausea,vomiting, hairlossanddiarrhoea.Inadditiontothis,complicationsmayarisefromtheBMT,suchasgraftversushostdisease,rejection orinfection.ThepatientmayevenrelapsefollowingaBMT3.

TBITechniques Prescription
FractionationinTBIisusedtoexploitthedifferencesinrepaircharacteristicsbetweenleukaemicandnormallungcells9.Many dosefractionationregimesarecurrentlyinuseinAustralasiaandinternationally.Bierietal(2001)conductedastudythat assessedthe5yrsurvivalrateforpatientsprescribedwith10,12and13.5Gy.Allpatientsweregivenabidailyfractionation (bd),over3days.The5yrsurvivalrateforeachofthoseprescriptionswere62,55and46%respectively. Fractionationwasfoundtoinducelesstoxicityinthepatientsnormaltissues(lung,liver,lensetc)thanaprescriptionof10Gy inasinglefraction.However,insituationswithagraftTcelldepletion,ahigherrateofgraftfailuresafterfractionatedregimes wasobserved,indicatingthatthe1012Gyfractionatedschedulescouldbecomedetrimental.Increasingthedoseto overcomethereducedefficacyofthelowerdoseschedulewouldinturnincreasetoxicity7.Ahigherdosegiveninlarger fractions,eg16Gyin8bd,mayreducetheriskofleukaemicrelapseatthecostofincreasedmorbidity6, 10 . 12Gyin6bdiscommonlyconsideredastandardregime11,whereasintheUK14.4Gyin8bdisincreasinglyprescribed6. Otherfractionationscheduleshavebeenclinicallyusedforexample,9Gyin3dailyfractionsand12Gyin4dailyfractionsfor paediatriccases12. Thedoseisnormallyprescribedtothepatientsmidlineattheumbilicusorpelvisregion.ICRU50(1993)recommendsadose accuracyof+7%to5%howevermanyRadiationOncologistsarewillingtoacceptupto10%accuracyasTBIisconsidered aspecialtechnique. Underdosageincreasestheriskofarelapsewhilstoverdosage,particularlyincriticalstructures,increasestheriskof morbidity.Theeffectofoverdosageinthelimbshasnotyetbeenstudied6.

Energy,beamspoileranddosehomogeneity

Page 2 of 7

Radiation Oncology, Physics, Total Body Irradiation ( TBI )

Photonbeamenergiesbetween4MVand18MVarecommonlyusedinTBI.Thewidthofthepatientisaconsiderationwhen selectingbeamenergyduetothetissuelateraleffect 13.Fora52cmseparationattheshouldersofalargeadult,theentrance dosecanbeupto25%higherthanmidlinedosefora6MVbeamat500cmSSD.Reducingtheseparationto30cmreducesthe dosedifferentialtoapproximately10%14.ThismaybeachievedthroughuseofanAP/PAfieldarrangement,ratherthana bilateral.Also,raisingtheenergyto15MVreducesthisdifferentialtolessthan15%. Forpatientswiththickness<35cminaparallelopposedfieldarrangementat300cmSSD,6MVisconsideredsufficientto minimisethetissuelateraleffect.Forpatientthickness>35cm,higherenergiesshouldbeconsidered13. However,increasingthebeamenergyalsoincreasestheskinsparingeffectinherentinphotonbeams,withthedepthof maximumdose(dmax)progressingfurtherintothepatient.Henceabeamspoilerisusedtoincreasetheentrancedose,so namedbecauseitspoilsthebeam. ThebeamspoileristypicallymadeofperspexandmaybemountedontheTBItreatmentcouchorstandaloneasamoveable screen.Thethicknessissuchthattheentrancedoseisraisedtowithin90%oftheprescribeddose 13. Electronsaregeneratedinthelinearaccelerator(linac)headandattypicalTBItreatmentdistances(>300cm)progressively losetheirenergy,whilstmoreelectronsaresimultaneouslygeneratedinair.Thespoilerservestoabsorborscatterelectrons generatedinthelinacheadandairittheninturnsbecomesasourceofelectronsgeneratedbythephotoninteractions. Theseelectronshaveawideangulardistributionandhavetheeffectofincreasingdoseinthebuildupregion.Thepatientis typicallypositioned1030cmawayfromthespoilerthisseparationdistanceaffectstheprofileattheentrysurface15. Thespoilerisalsousedtohomogenisethedosetothepatient.Ideally,thepatientwouldreceivetheprescribeddose uniformlyacrossthewholebody.Thisisverydifficulttoachieveclinicallyduetothevaryingwidthsofthepatientscontours 13. Therearemanydifferentmethodsusedtocompensateandcorrectforthevariationsincontourandanatomy,aswellas shieldcriticalstructures.

Criticalstructuresandtissuecompensators
Materialssuchasperspex,ricebags,sandbagsorthegelatinelikebolusareregularlyusedtohomogenisethepatients contours(figure1)andassistinshieldingcriticalstructuressuchasthelung,liverandkidneys.

(a) (b)

Figure1:Anexampleofa)bolusbagsandb)perspexblocksusedinsomedepartmentstoshieldthepatient'sheadin bilateraltreatment
Stripsoflead,cerrobendorlowmeltingpointalloyblocksmayalsobeusedtofurtherprotectcriticalstructures13.Often,the patientsownarmsandhandsareusedasshielding:inabilateraltreatment,thepatientsarmsmaybepositionedalongtheir side,providingfurtherlungshielding(figure2).

Page 3 of 7

Radiation Oncology, Physics, Total Body Irradiation ( TBI )

(a) (b)

Figure2:Patientinlateralpositionwith(a)armscrossedoverchestforgreaterlateralchestexposure,and(b)with armsbysideto'shield'lateralchest.
Whencriticalstructuressuchaslungsandliverareshielded,anelectronbeammaybeusedtoboostthedosetothose regionstoreducetheincidenceofrelapse 16.

Doserate
LatetermcomplicationsfromaBMTandTBIconditioningregimeincludeinterstitialpneumonitis,cataracts,renaldysfunction andgraftversushostdisease.Whilstradiationalonemaynotaccountforthese,manystudieshaveinvestigatedthe relationshipbetweendoserateandspecificcomplications. Doserateisasignificantconsiderationintheonsetofrenalcomplications,withdoserates<10cGy/mingenerallyconsidered protective17.However,nosignificantdifferenceinincidenceofinterstitialpneumonitisfordoseratesof8cGy/minand 19Gy/min,forpatientswith12Gylungdose,wasobserved18.Thisisincontrastwithearlierstudieswhichreportedthatdose rates<10cGy/minpreventedhigherdoseraterelatedlungtoxicities10.Typicaltreatmentdoseratesrangefrom5cGy/minto 15cGy/min,dependentonSSDandpulserepetitionrate19, 10.

SSDandpulserepetitionrate
Varioussourcetosurfacedistances(SSD)areusedintheTBIsetup.TheextendedSSDisrequiredtoprojectawideenough fieldtoencompassthepatientswholebody.Thisisoftendictatedbythesizeofthetreatmentbunker.Smallerbunkers,or fixedgantryheadssuchassomeCobalt60units,necessitateashorterSSD(<250cm).Treatmentdistancesof300cmand 400cmcommonlyused.Forapulsedradiationlinac,thepulserepetitionrateistypicallysetto100MU/minor200MU/min.

Patientandfieldpositions
TherearemanytechniquesforpatientpositioninginTBI.Commontechniquesincludestanding,crouching,lyingonsideand lyingsupine.ThepositiondependsonmanyfactorssuchastheavailabilityandsizeofadedicatedTBItreatmentcouch,the intendeddosedeliveryandthesizeofthetreatmentroomforexample,asmallbunkermayrequirethepatienttoassumea crouchingpositioninordertoirradiatetheentirebody14.

Figure3:Exampleofpatientlyingonside Figure4:Exampleofpatientlyingsupine forAPfield forbilateralfields

Unlikeconventionalexternalbeamradiotherapy,highdoseregionsinTBIcannotbeminimisedbyalteringtheangleofthe radiationbeamoraddingmorefieldstospreadoutthedose.Onemethodofaddressingthisproblemistoirradiatethrough theminimumwidthofthepatient,ieAP/PA.Theadvantageofthisfieldarrangementistherelativeeaseofshieldingcritical structures.However,thepatientisrequiredtolieontheirside,whichmaycausediscomfortgiventhelongtreatmenttimesin TBI14(figure3). Abilateralfieldarrangementiscommonlyusedforeaseofsetupandpatientcomfort.Furthermore,thepatientmaydrawtheir legsuptodecreasethewidthofthefieldrequiredfortotalbodycoverage,anadvantageinasmallertreatmentroom 14 (figure4). AcombinationofAP/PAandbilateralfieldarrangementsmayalsobeusedtheresulting4fieldtechniqueprovidesthe advantagesofshieldinganddosehomogeneity,attheexpenseofpatientdiscomfortandincreasedsetuptime. Reproducibilityofthesepositionsmustalsobeconsidered.

ImagingandMonitoringUnitcalculation

Page 4 of 7

Radiation Oncology, Physics, Total Body Irradiation ( TBI )

SomecentresimagethepatientwithaCTscanoftheentirebodyorcertainlevelswithinthepatienttoobtaininformationfor atreatmentplanningsystem(ifused)ortomanuallycalculateseparationanddeviseshieldingpositions.Xraysmayalsobe usedtomarkoutlungshieldingpositions. Itisimportanttonotethatwhendevisingshielding,thepatientshouldbescannedorxrayedinthetreatmentpositiondueto theshiftinanatomywhenlyingsupineorsideways,orstanding. MonitorUnits(MU)maybegeneratedusingatreatmentplanningsystemormanualcalculation.Insomecentres,MUisnot calculatedandthetreatmentdeliveryisbasedontheionchamberreadingatthepatientsgroin,correctedforambient pressure,temperatureandpatienttemperature.

Dosimetry
InvivodosimetryforTBIisofrelevanceinreportingthedosedeliveredandmostimportantly,thedosehomogeneityduring eachtreatmentfraction.Itisalsousedtoverifypatientpositionandthereproducibilityofthesetup5.Thereareseveral factorstoconsiderwhenchoosingadosimetertoperforminvivodosimetryforaTBIpatient.Theseconsiderationsare consistentwiththerequirementsofaninvivodosimeterforanytypeofpatientmeasurement. Someconsiderationsinclude:
I I I I I I I I I I I I

inherentbuildupinthedosimeter accuracy reproducibility doserate, fieldsize, angular, SSDand temperatureindependence linearity easeofuseandreadout postirradiationfading andphysicalsize20

Thermoluminescencedosimeters(TLDs)areoftenusedinTBIastheyconformwellwiththerequirementsofinvivodosimeters andhaveasmalluncertaintyofupto2.5%21.ThethicknessaTLDchipisrepresentativeofthesensitivelayersoftheskin. HoweverTLDsarelabourintensivetoprepare,readoutandcalibrate,andrequiresomephysicalspaceforthesupporting hardware 20. SemiconductorsarealsowidelyusedforTBIdosimetry,withmuchresearchstillbeingconductedtocontinuallyimprovetheir physicalandresponsecharacteristics.Metaloxidesemiconductorfieldeffecttransistors(MOSFETs)havebeenusedforTBI dosimetry.Reproducibilitywithin3%oftheentranceandexitdose,andagreementwithin3.9%ofTLDreadingshavebeen achieved20, 22 .Semiconductordiodesallowforimmediatedosereadings,howevercaremustbetakenduetotheirangular andenergydependence 23. Otherdosimetersincludeopticallystimulatedluminescence(OSL),whichhastheadvantageofbeingeasiertohandlethan TLDs,andtheselfdevelopingGAFchromicfilm(figure5).GAFchromicEBTfilmhasbeenfoundtoagreewithTLDresultswithin 6.7%foratypicalpatientmeasurement24.

(a)

(b)

Figure5:(a)CutpiecesofGAFchromicEBT2filmusedforinvivodosimetry(b)pointdensitometerusedtoreadoutfilm.
Dosimetersareplacedatsomeofthefollowingpositions:head,neck,sternalnotch,chest,abdomen,pelvisandankles. Dosimetersmayalsobeplacedbetweenthethighsnearthegroinasasubstituteforpatientmidline.Anionchambermayalso

Page 5 of 7

Radiation Oncology, Physics, Total Body Irradiation ( TBI )

beusedatthispositiontoallowdirectcomparisontoprescribeddose25(figure6).

(a) (b)

Figure6Anexampleofanionchamber(a)placedatgroinwithGAFchromicEBT2filmattached,and(b)connectedto electrometertomonitordosedelivered.

TBIonCobalt60
TBImaybeperformedonaCobalt60unit.Variousmethodsincludeusingastationarybeaminconjunctionwithamoving couch26,orplacingthepatientinastretcheronthefloor27.ThepatientassumesaproneandsupinepositionfortheAP/PA fields.

RadiationSafety
MostTBItreatmentsareperformedwithahighenergylinearaccelerator,withthegantryat90o or270o andthecollimatorat 45 o withjawsfullopentogivethemaximumfieldwidthpossible.Giventheextendedtreatmentdistance,therequirednumber ofMUtodelivertheprescribeddoseforTBIcanbeupto36timesmorethanifthepatientwereatisocentre28. WhilstscatterfromtheisocentreisnotaconcernforTBI,moreradiationwillbedirectlyincidentontheprimarybarrierbehind thepatient.AnextensiontotheNCRPbarrierdesignformulahasbeenproposed,whichseparatesdirect,leakageandscatter forthelinearacceleratorworkloadcomponents28.

References
1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. 17. Safwat,A.,Y.Bayoumi,H.Akkoush,etal.2004."AphaseIItrialofadjuvantlowdosetotalbodyirradiationin nonHodgkin'slymphomapatientsfollowingstandardCHOP."ActaOncol43(5):480485. Gratwohl,A.1990."Bonemarrowtransplantation:indicationsandtechnique."RadiotherOncol18Suppl1:39. "AustralianBoneMarrowDonorRegistry(ABMDR)."Linktoexternalarticle "ArrowBoneMarrowTransplantFoundation."Linktoexternalarticle Briot,E.,A.DutreixandA.Bridier.1990."Dosimetryfortotalbodyirradiation."RadiotherOncol18Suppl1:16 29. Gilson,D.andR.E.Taylor.1997."Totalbodyirradiation.ReportonameetingorganizedbytheBIROncology Committee,heldatTheRoyalInstituteofBritishArchitects,London,28November1996."BrJRadiol70 (840):12011203. Cosset,J.M.,T.Girinsky,E.Malaise,etal.1990."ClinicalbasisforTBIfractionation."RadiotherOncol18Suppl 1:6067. Bieri,S.,C.Helg,B.Chapuis,etal.2001."Totalbodyirradiationbeforeallogeneicbonemarrowtransplantation:is moredosebetter?"IntJRadiatOncolBiolPhys49(4):10711077. O'Donoghue,J.A.,T.E.WheldonandA.Gregor.1987."Theimplicationsofinvitroradiationsurvivalcurvesfor theoptimalschedulingoftotalbodyirradiationwithbonemarrowrescueinthetreatmentofleukaemia."BrJ Radiol60(711):279283. Hui,S.K.,R.K.Das,B.Thomadsen,etal.2004."CTbasedanalysisofdosehomogeneityintotalbodyirradiation usinglateralbeam."JApplClinMedPhys5(4):7179. Adkins,D.R.andJ.F.DiPersio.2008."Totalbodyirradiationbeforeanallogeneicstemcelltransplantation:is thereamagicdose?"CurrOpinHematol15(6):555560.Linktoexternalarticle Kornguth,D.G.,A.Mahajan,S.Woo,etal.2007."Fludarabineallowsdosereductionfortotalbodyirradiationin pediatrichematopoieticstemcelltransplantation."IntJRadiatOncolBiolPhys68(4):11401144. Khan,FM.2003.ThePhysicsofRadiationTherapy:Lippincott,Williams&Wilkins,USA.4thEd. Galvin,J.M.2001."AAPM2001MeetingReports."Linktoexternalarticle Kassaee,A.,Y.Xiao,P.Bloch,etal.2001."Dosesnearthesurfaceduringtotalbodyirradiationwith15MVX rays."IntJCancer96Suppl:125130. Shank,B.,R.J.O'Reilly,I.Cunningham,etal.1990."Totalbodyirradiationforbonemarrowtransplantation:the MemorialSloanKetteringCancerCenterexperience."RadiotherOncol18Suppl1:6881. Cheng,J.C.,T.E.SchultheissandJ.Y.Wong.2008."Impactofdrugtherapy,radiationdose,anddoserateon renaltoxicityfollowingbonemarrowtransplantation."IntJRadiatOncolBiolPhys71(5):14361443.

Page 6 of 7

Radiation Oncology, Physics, Total Body Irradiation ( TBI )

18. 19. 20. 21. 22. 23. 24. 25. 26. 27. 28. Oya,N.,K.Sasai,S.Tachiiri,etal.2006."Influenceofradiationdoserateandlungdoseoninterstitialpneumonitis afterfractionatedtotalbodyirradiation:acuteparotitismaypredictinterstitialpneumonitis."IntJHematol83 (1):8691.Linktoexternalarticle Greig,J.R.,R.W.MillerandP.Okunieff.1996."Anapproachtodosemeasurementfortotalbodyirradiation."IntJ RadiatOncolBiolPhys36(2):463468. Best,S.,A.RalstonandN.Suchowerska.2005."ClinicalapplicationoftheOneDosePatientDosimetrySystemfor totalbodyirradiation."PhysMedBiol50(24):59095919. Palkoskova,P.,H.Hlavata,P.Dvorak,etal.2002."Invivothermoluminescencedosimetryfortotalbody irradiation."RadiatProtDosimetry101(14):597599. Scalchi,P.andP.Francescon.1998."Calibrationofamosfetdetectionsystemfor6MVinvivodosimetry."IntJ RadiatOncolBiolPhys40(4):987993. Williams.J.R,Thwaites.D.R.2000.RadiotherapyPhysics:Inpractice:OxfordUniversityPress,USA. Su,F.C.,C.ShiandN.Papanikolaou.2008."ClinicalapplicationofGAFCHROMICEBTfilmforinvivodose measurementsoftotalbodyirradiationradiotherapy."ApplRadiatIsot66(3):389394. Lancaster,C.M.,J.C.CrosbieandS.R.Davis.2008."Invivodosimetryfromtotalbodyirradiationpatients (20002006):resultsandanalysis."AustralasPhysEngSciMed31(3):191195. Zabatis,Ch,T.Koligliatis,S.Xenofos,etal.2008."Dosimetryintranslationtotalbodyirradiationtechnique:a computertreatmentplanningapproachandanexperimentalstudyconcerninglungsparing."JBuon13(2):253 262. Evans,M.D.,R.X.Larouche,M.Olivares,etal.2006."Totalbodyirradiationwithareconditionedcobalt teletherapyunit."JApplClinMedPhys7(1):4251. Rodgers,J.E.2001."RadiationtherapyvaultshieldingcalculationalmethodswhenIMRTandTBIprocedures contribute."JApplClinMedPhys2(3):157164.

Thecurrencyofthisinformationisguaranteedonlyupuntilthedateofprinting,foranyupdatespleasecheckwww.eviq.org.au 02Apr2013

Page 7 of 7