Estro_revised brachy therapy cervical .ppt

Estro brachy therapy

1. RecommendationsfromGynaecological
(GYN)GEC-ESTROWorkingGroup*(I):
conceptsandtermsin3Dimagebased3D
treatmentplanningincervixcancer
brachytherapywithemphasisonMRI
assessmentofGTVandCTV

2. Background and purpose:
•Brachytherapy(BT)playsacrucialrolein
themanagementofinvasivecervixcancer
fromstageItoIV.
•Intracavitarytechniquesarebasedon
afterloadingdevices,withdifferenttypesof
applicators.

3. CTand/orMRIcompatibleapplicators
allowasectionalimagebasedapproach
withabetterassessmentofgrosstumour
volume(GTV)anddefinitionand
delineationoftargetvolume(CTV)
comparedtotraditionalapproaches.

4. Accurateandreproducibledelineationof
GTV,CTVandPTV,aswellasofcritical
organshasadirectimpactonBTtreatment
planning,especiallyifitispossibletoadapt
thepear-shapeisodosebyoptimisation
usingDVHanalysis.Whenintroducinga
3DimagebasedapproachforGTVand
CTVassessment,thereisaneedfora
commonlanguagetodescribetheconcepts
andtodefinethetermswhicharetobe
used.

5. •In2000,GEC-ESTROdecidedtosupport
3Dimagingbased3Dtreatmentplanning
approachincervixcancerBTwiththe
creationofaWorkingGroup.
•Thetaskwastodescribebasicconcepts
andtermsandtoworkoutaterminology
enablingvariousgroupsworkinginthis
advancedfieldtouseacommonlanguage.

6. Therecommendationsdescribedinthis
reportwereproposedbasedonclinical
experienceanddosimetricconceptsof
differentinstitutions(IGR,Leuven,Vienna)
andwerestepwisevalidatedagainstthe
backgroundofdifferentclinicalexperience.

7. 3D image based approach: change of GTV
during treatment
•TheprocedureisstraightforwardifBTisthesolemethodof
treatmentasinearlydiseaseorinapreoperativeapproachinlimited
disease.
•However,mostpatientsarenowadaystreateddefinitelywitha
combinationofexternalbeamtherapywithsimultaneous
chemotherapyandBT.
•AsGTVandtopographychangesignificantlyduringexternalbeam
therapy(withorwithoutchemotherapy)therearisesaclearneedfor
asystematicdescriptionofGTVandCTVinitsspecifictopographic
relationatdiagnosisandattimeofBT,whichisusuallyattheendof
externalbeamtherapy.

8. AstherearedifferentGTVsinachangingtopography—atdiagnosis,
duringandattheendoftreatment—different,andindividually
adaptedCTVsmaybedefinedandevaluatedaccordingtosizeand
configurationofGTVandtopographyatagiventime.

9. Clinical approaches in treatment planning
and performance
ThefirstapproachismainlyrepresentedbyIGRandisbasedon
clinicalassessmentofGTVatdiagnosis(GTVassessmentbeing
helpedbyavaginalimpressionatthetimeofdiagnosisandafter
externalirradiation)anddefinitionofCTVadaptedtoindividualtumour
configurationatdiagnosis.Thisprocessissupportedbyindividual
vaginalmoulddesign.
Treatment planning prior to1998 was, based on radiographs. A dose
of 60 Gy was prescribed to this CTV as defined on clinical examination
reported on radiographs. Individual 3D treatment planning in a (virtual)
3D space defined by clinical tumour volume assessment reported on
the radiographs was performed. Dimensions and volume of the 60 Gy
reference volume were reported as well as doses to specific reference
points including those recommended by ICRU 38.

10. From1998,systematicMRIbased
treatmentplanningwasintroduced
allowingamoreindividualdoseadaptation
tothetargetvolume,integratingclinical
andMRItumourvolumeassessment.

11. ThesecondapproachismainlyrepresentedbytheViennaGroupandis
basedondosespecificationatpointA,standarddosedistributions,anduse
ofstandardapplicators.GTVisassessedatdiagnosisandattimeofBTand
CTVisindividuallyadaptedaccordingtotumourconfigurationattimeofBT
takingintoaccounttumourextensionatdiagnosis.Treatmentplanningwas
basedonradiographs,supplementedbysectionalimages(firstCT,later
MRI).Individual3Dtreatmentplanningina(virtual)3Dspacebasedon
standarddosedistributions(pointA)andonpointsdefinedonradiographs
wasperformedtakingintoaccountdimensionsofGTVaccordingtoclinical
andimageassessment.
Adoseof80–90GywasprescribedtopointA(until1999/2000)(laterto
CTV,usuallynearpointA).DimensionsandVolumeofthetreatedvolume
(80–90Gy)werereported(forcomparisonalso60Gyreferencevolume)
anddosetospecificpointsasdefinedonradiographs.SystematicMRI
basedtreatmentplanningbasedonthisapproachwasintroducedin
1998/1999

12. Protocol development 2001–2002: first steps
Thefirstquestionnaire(2001)wasdesignedtoprospectivelycollectinformation
onfollowing:
•DimensionsandvolumesofGTV,CTVasdefinedbyclinicalexamination
andbyMRI:
–attimeofdiagnosis
–attimeofBT(afterexternalirradiation);
•Dimensionsandvolumesofreferencevolume(60,75,90,and120Gy);
•VolumeofisodosegoingthroughpointA;
•Treatedvolume(prescribeddose);
•CoverageinpercentrelatedtoCTVandGTV;
•DVHanalysisforfixeddosesandcertaincoveragepercentageofGTVand
CTV;
•DosestopointsAandB,rightandleft,mean;
•Dosevolumeparametersfororgansatrisk(nodetailshere);
•Radiobiologicalmodeling(linear-quadraticmodel).

13. Steps taken
Two workshops were conducted
GTVandCTVdelineationworkshopI:
Vienna7/2003
GTVandCTVdelineationworkshopII:
Vienna12/2003

14. Duringjointdiscussionofthesefindings(atnextmeetingVienna
12/2003)withevaluationofimages,itbecameclearthatlargest
variationswerefoundforfollowingsituations:
*Clinicalinformationwasnotsufficientlyaccurate
*Interpretationofimagefindingswasnotstraightforward
*Classicalimagesliceorientation(axial,sagittal,coronal)
made delineationdifficultbecauseof‘oblioblique’
representationofapplicatorandtopography:delineationof
vaginalextensionwithoutpara-axialorientationofimages
(parallel/orthogonaltoapplicatoraxis)
*Superimposinganatomo-pathologicalinformationin
parametriafromimagestakenatdiagnosisonimagestakenat
BTfordelineationofCTVID

15. *Understandingandidentifyingbordersofparametrium
(post.,ant.,lateral,infer.,superior):delineationof
potentialmicroscopicresidualdisease(CTVID)onMRI
wasfoundnottobestraightforwardandeasily
reproducible.
FirstexperiencecollectedontheoccasionofGTVand
CTVdelineationworkshopIIin12/2003showedthat
determinationofGTV,CTVHRandCTVIRasdescribed
belowwasveryconsistentbetweenthreeexperts(Fig.2)
andevaluationusingdosevolumeparametersdidnot
showsignificantdifferencesforanyofthelisted
parameters(Table1)

18. Definition and delineation of GTV and CTV: final
concept
Thefollowingrecommendationswereproposedbasedonclinical
experienceanddosimetricconceptsofdifferentinstitutions(IGR,
Leuven,Vienna)andbasedonvalidationmethodologyasdescribed
indetailabove.Thesetargetdefinitionstakeintoaccount
differencesinBTtargetdefinitionapproacheswithclinicaltraditions
basedonassessmentofdiseaseatdiagnosisandothersmore
basedonextentofdiseaseasitpresentsattimeofBT.
•TheapproachderivedfromusingpointAasareferencepointstarts
mainlyfromtumourextension(GTV)asitpresentsattimeofBT
takingintoaccountextensionatdiagnosis,anddefinesCTVforBT,
incaseofmajorresponselimitedtocervixandadjacentstructures
withpresumedresidualdisease(~30–60cc).Theintentistogivea
significanttotaldosetothisCTVasappropriatewithregardtostage
andrisk:e.g.80–90Gyindefinitiveradiotherapyinadvanced
disease.ThisdoseiscomparablewithdosetopointA.

19. •TheapproachusingICRU38recommendationsstartsmainlyfrom
GTVatdiagnosisfordefiningCTVattimeofBTandarrivesata
CTVincludinganatomicallytargetedsafetymarginswithregardto
dimensionsofGTVatdiagnosis(~150–300cc).Totaldose
prescribedtothisCTVis60Gyatadose-rateof50cGyperhour.
Thisdose(rate)isnotcomparabletodose(rate)inpointA,whichis
significantlylarger.
•Inordertotakeintoaccountthesemajorconceptsthatarebasically
different,buthavebothasignificantclinicalbackground,twoCTVs
areproposed:
1)A‘highrisk’CTV(HRCTV)withamajorriskoflocal
recurrencebecauseofresidualmacroscopicdisease.The
intentistodeliveratotaldoseashighaspossibleand
appropriatetoeradicateallresidualmacroscopictumour.
2)An‘intermediaterisk’CTV(IRCTV)withamajorriskof
localrecurrenceinareasthatcorrespondtoinitial
macroscopicextentofdiseasewithatmostresidual
microscopicdiseaseattimeofBT.Theintentistodelivera
totalradiationdoseappropriatetocuresignificant
microscopicdiseaseincervixcancer,whichcorrespondsto
adoseofatleast60Gy.

20. Terms and concepts definition (GYN GEC-ESTRO
protocol version 2004)
•ThetargetconceptasproposedhereisbasedinprincipleonthreeCTVs
accordingtotumourloadandhencetotheriskforrecurrence:ahighrisk
CTVwithamacroscopictumourloadandanintermediateriskCTV
representingsignificantmicroscopicdisease.Inaddition,alowriskCTV
includingpotentialmicroscopictumourspreadcanbedistinguished.Thelow
riskCTVistreatedbysurgeryand/orbyexternalbeamradiotherapy

21. •Grosstumourvolume(diagnosis)(GTVD)includesmacroscopic
tumourextensionatdiagnosisasdetectedbyclinicalexamination
(visualisationandpalpation)andasvisualisedonMRI:highsignal
intensitymass(es)atfastspinechosequences(FSE)T2in
cervix/corpus,parametria,vagina,bladderandrectum.
•Grosstumourvolume(BT)(GTVB1,GTVB2,GTVB3,.)forBT
includesmacroscopictumourextensionattimeofBTasdetectedby
clinicalexaminationandasvisualisedonMRI:Highsignalintensity
mass(es)(FSE,T2)incervix/-corpus,parametria,vagina,bladder
andrectum.InpatientstreatedwithupfrontBTorwithBTalone,
GTVBisidenticalwithGTVD.

22. HighriskCTVforBT(HRCTVB1,HRCTVB2,.)carryinga
hightumourload,includesGTVB1,B2,.,alwaysthewhole
cervixandthepresumedextracervicaltumourextensionat
timeofBT.InlimiteddiseaseGTVBisidenticalwithGTVD.
Inadvanceddisease,thepresumedtumourextensionisdefined
bymeansofclinicalexamination(visualisationandpalpation)
andbyMRIfindingsattimeofBTGTVB,takingintoaccount
tumourspreadatdiagnosisasindicatedonclinical
examinationandinitialMRIforstaging(GTVD).Pathologic
residualtissue(s)asdefinedbypalpableindurationsand/or
residualgreyzonesinparametria,uterinecorpus,vaginaor
rectumandbladderonMRIareincludedinHRCTVB.No
safetymarginsareadded.

23. •AtotalradiationdoseisprescribedtothishighriskCTVappropriate
toeradicatemacroscopicdisease.Doseisselectedaccordingto
tumourvolume,stageofdiseaseandtreatmentstrategy(BT
alone/combinationtreatment).
•IntermediateriskCTVforBT(IRCTVB1,IRCTVB2,.)carryinga
significantmicroscopictumourload,encompasseshighriskCTV
withasafetymarginof5mm.Amountofsafetymarginischosen
accordingtotumoursizeandlocation,potentialtumourspread,
tumourregressionandtreatmentstrategy.
1)Inlimiteddisease(tumoursize<4cm),BTmaybe
performedaloneorasacombinationtreatment:theIRCTVB
encompassestheHRCTV(includingGTVDandthewhole
cervix)anddifferentsafetymarginsareaddedaccordingto
potentialspread.

24. Inanterior–posteriordirection,asafetymarginofupto5mmis
taken,limitedbythenaturalanatomicalbordersoftherectaland
bladderwall.Asafetymarginof10mmisusedcraniallyintothe
uterinecorpusandcaudallybelowthecervicalosintothevagina.In
lateraldirection,a10mmsafetymarginisappliedintoboth
parametria,usuallyrepresentingtheinternalthirdofthe
parametrium.Incaseofendocervicalorlateralmacroscopictumour
growth,anadditionalmarginof5mmisapplied,intothedirectionof
potentialspread.
2)Inmoreextensivedisease,patientsaretreatedwithacombinationof
externalbeamirradiationandBT:IRCTVBisbasedonmacroscopic
tumourextensionatdiagnosis(GTVD)whichissuperimposedon
theanatomicalareaasitpresentsattimeofBTtakingoriginal
anatomicaltumourspreadasreference.

25. Differentsafetymarginsareuseddependingontheextentof
diseaseatdiagnosisandontheregressionattimeofBT.These
marginsareconfinedbytheanatomicalbordersofrectaland
bladderwallifthesearenotinvolved.Incaseofinvasion,the
marginsshouldberestrictedtotherectalandbladderwallonly(no
lumenincluded).Incaseofcompleteremission,theIRCTV
includestheHRCTVandtheinitialmacroscopictumourextension
atdiagnosissuperimposedontopographyattimeofBT,withoutany
safetymargins.

26. •Incaseofgoodremission,theIRCTVincludestheHRCTVandthe
initialtumourextensionatdiagnosisfig.Incaseofpoortumour
remissionlessthan10mmincludingextracervicalresidualdisease
(e.g.parametria),asafetymarginofminimum10mmintothe
directionofpotentialspread(parametria,vagina,uterus)isaddedto
theHRCTV(Fig).
•Incaseofstabledisease,asafetymarginof10mmisaddedtothe
initialtumourextensionatdiagnosiswhichissuperimposedonthe
anatomyasitpresentsattimeofBT(Fig).
•AtotalradiationdoseisprescribedtothisintermediateriskCTV
appropriateforeradicatingsignificantmicroscopicdisease.Doseis
selectedaccordingtotumourvolume,stageofdiseaseand
treatmentstrategy(BTalone/combinationtreatment).
•Itisassumedthatnoextramarginsareneededneitherforpatient
relateduncertainties(e.g.organmovement)norforsetup
uncertainties.Therefore,thePTVisidenticaltotheCTV.

27. •MRIhasbeenclearlydemonstratedtobesuperiortoanyother
imagingprocedureincervixcancerallowinganaccuratedefinition
ofthetumour.Thissuperiorityhasalsobeenreportedinliterature
whencomparingMRIbasedtreatmentplanningtoradiography
basedconventionaltreatmentplanningapproaches.
•TherecommendationsondefinitionanddelineationofGTVand
CTVarebasedonclinicalexperienceanddifferentdosimetric
concepts.Developmentof3Dimagebased3Dtreatmentplanning
includesacomprehensiveapproachwithsystematicdescriptionof
GTVandtopographyatdiagnosisandattimeofBT,takinginto
accountitsevolutionovertime.
•Theaimisnottomodifyclinicalanddosimetricexperiencebutto
assessthefeasibility,thevalueandthereproducibilityofsuch
volumesofinterest.
•Thiswillallowamoreappropriateunderstandingofdosevolume
relationsfordifferenttargetsandtheircorrelationtoclinicaloutcome.
Furtherdevelopmentoftechniqueandmethodoftreatmentwill
becomepossiblefordefinedandselectedclinicalsituationsalso
includingdoseescalationforcertainindications

28. Dose prescription
•Historically,doseprescriptionwasbasedoncertainsystemswith
dedicatedrules.
•DosehasbeenprescribedasmilligramperhourofradiumorTRAK
andiscurrentlymainlyprescribedtospecificwell-definedpoints
(e.g.pointA)ortoareferencevolume.
•Withtheintroductionof3Dimaging,moreandmorecentreswill
prescribetoatargetvolume.Whenprescribingtoatarget,the
prescriptiondoseistheplanneddosetocoverthistargetas
completelyaspossible.
•Image-guidedbrachytherapyallowsmoreconsistencyinregardto
thetarget(andorgansatrisk).
•Theprescribeddoseisalwaysrelatedtothetarget,whiletheactual
coveragecanbeevaluatedwiththeuseofDVHparameters.
•Normalisationandreferencedosepointsareatoolfortreatment
planningandallowtheachievementofreproducibledwelltime
weightingsandisodosedistributions.

29. •Whenconsideringadaptingthedoseprescriptiontoanimage-based
CTV,thefollowingprocedureisrecommended,atleastfora
significanttransitionperiod:
a)Patientsareinvestigatedwith3DimagesandtheCTVis
delineatedontheimagesasdescribedrecently.
b)Thetraditionaldoseprescriptionsystemisalsoapplied.
c)Correlationsareinvestigatedbetweentraditionaldose
prescriptions(e.g.atpointAorfor60Gyreferencevolume)andthe
imagebasedtargetcoverage.Inthenextphase,dosecoverageof
thetargetcanbeimprovedstartingfromthe
•Standarddoseprescriptionsystemasappliedbeforeandcareful
adaptationofloadingpatternanddwelltimes.
•Finally,dosecanbeprescribedtoanimage-basedtarget.
•Inordertofacilitatecomparison,dosereportingshouldrefertothe
prescribeddosetotheimage-basedtarget(dosecoverage
parameters)andtothetraditionalsystem.

30. Dose heterogeneity within target volumes
•TheGTVandCTVinintracavitarybrachytherapyareclosetothesources,usually
within15–40mm,andaredependentonthepositionoftheapplicator,sizeand
locationofthetumour,cervixandonthemethodappliedforCTVdetermination(HR
CTV/IRCTV).
•Duetothesteepdosefalloffclosetothesources,thereisasignificantchangein
doseanddose-ratethroughoutthetargetvolumes.
•Theclosertothesource,themorepronouncedthiseffect:thedosealonganaxis
perpendiculartotheintrauterinesourceatthelevelofpointAdecreasesfrom
approximately200to100%ofthedosetopointAwhengoingfrom10to20mmfrom
thesource,whereasdosedecreasesfrom100%toapproximately60%from20to30
mm.Asnotonlydosebutalsodoseratefollowsthegradienteffect,oneshouldbe
awarethatthegradientisevensteeperintermsofbiologicallyequivalentdose.This
doseinhomogeneityiscertainlyofmajorimportanceforthebiologicaleffectof
intracavitarybrachytherapy.

32. Definition of dose volume parameters
•Dosevolumeparametersfortargetvolumescanbederivedfromcumulative
dosevolumehistogram(DVH)analysis.
•DVHsfortheGTVandtheCTVinintracavitarybrachytherapyhavea
plateau,whichindicates100%dosecoverageofthevolumeofinterest.This
plateaugoesdownsmoothlyindicatingdecreasingpercentageofdose
coveragewithincreasingdose.
•Certaindosecoveragevaluescanbedefinedtodescribethespecificshape
ofsuchaDVH,e.g.D100andD90,definingtheminimumdosedeliveredto
100and90%ofthevolumeofinterest,respectively.Alsoparameters
describingavolume(withregardtotheGTVorCTV)receivingacertain
biologicallyweightedequivalentdoseEQDcanbedefined,eitherasan
absolutenumber(e.g.V(85GyEQD),V(60GyEQD))oraspercentage(e.g.
V100).

34. Potential and limitations of dose volume parameters
Therearesomespecificconsiderationsconcerningdosevolume
analysisofintracavitarybrachytherapy.
TheminimumtargetdoseD100bearsatleastonepracticallimitationin
accuracyasthereporteddosevalueisextremelydependentontarget
delineation.Duetothesteepdosegradient,smallspikesinthecontour
causelargedeviationsinD100.
D90islesssensitivetotheseinfluencesandisthereforeconsideredto
beamore‘stable’parameter.Althoughtheirclinicalrelevancehasnot
beenprovenyet,D100andD90arebothhighlyrecommendedfor
reporting:theycaneasilybecalculatedfromaDVHandconvertedto
biologicallyweightedEQDdoses,whichmakesthemsuitablefor
correctplancomparisonofalldoseratetechniques.
V100describeshowcloselytheintendedtreatmentcouldbeachieved
intermsoftargetcoverage,providinginformationindirectlyonthe
proportionoftheunderdosedarea.

35. High dose volumes
•Sincetheintrauterinetandemisplacedwithinornearthe
macroscopictumour,thedosetotheGTVishigherthanthedoseto
theCTV.Therefore,theD100andD90fortheGTVconsequently
implyrelevantinformationaboutthehighdoseregionswithintheHR
andtheIRCTV.
•ParameterssuchasV150/V200,thevolumereceivingatleast1.5/2
timestheprescribedphysicaldosearerecommended,butshouldbe
usedwithcaution:amultiplyingfactoroftheprescribedphysical
doseisapplied,therefore,thedoseandthebiologicallyweighted
valuesofthereportedhighdosevolumesareonlyapplicablefor
intercomparisonforaspecificdoseprescriptionandwithina
specificdoserateandfractionationschedule.
•Theycannotbeusedforintercomparisonofdifferenttreatment
concepts.

36. Applicator volume
•WhenanalysingDVHparameters,somepartofthetargetvolumes
evaluatedconsistofapplicatorvolume.Thevolumeoftheapplicator
doesnotinfluencetheevaluatedparameterstoomuchaslongas
largevolumescomparedtotheapplicatorvolumeareinvestigated.
•Dosevolumeparametersforwhichsmallvolumesareconsidered,
suchase.g.D30(30%oftargetvolume),mayincludetoomuchof
theapplicatorvolumetobeameaningfulparameter.
•Currently,itisnotclearifandhowtheapplicatorvolumeshouldbe
takenintoaccount.Thisissueneedsfurtherinvestigation.However,
whenreportingDVHparametersitshouldbealwaysmentionedif
theapplicatorisincludedintheconsideredvolumeornot.

37. Reference volume for applicator systems
•Thereferencevolumeisthevolumeencompassedbythereference
isodose,selectedandspecifiedintermsofdimensionsandabsolutevolume
tocomparetreatmentsperformedindifferentcentresusingdifferent
techniques.
•InICRUReport38,areferencedoselevelof60Gydeliveredatthe
classicallowdoserate(50cGy/h)isrecommended.Thisisthedose
appropriatetocuremicroscopicdiseaseincervixcancercorrespondingto
theIntermediateRiskCTVindefinitivetreatment.
•Thedosecurrentlyemployedtocuremacroscopicdiseasecorrespondingto
theHighRiskCTVrangesbetween75and90GyEQD(andabove).
Therefore,inadditiontothe60Gyreferencevolume,higherreferencedose
levels(e.g.85GyEQD)havebeenproposedrecently.
•Thereferencevolumeinthecontextof3Dimage-basedcervixcancer
brachytherapyisrecommendedtobeonlyusedtodescribethedimensions
ofitswidth,thicknessandheightwhichcanbecoveredbyacertaindose
(60,85GyEQD)withacertainapplicatorandacertaintypicalloading
pattern.

38. Dose volume parameters for organs at risk
•Incervicalcancer,thelocationoforgansatriskclosetothe
brachytherapysources(rectum,sigmoid,bladder)significantly
influencesthetreatmentplanningprocessandthedosethatcanbe
prescribed.Thevaginashouldbetakenintoconsideration.Other
partsofbowelmayalsoreceiveasignificantdose.
•DosevolumeparametersforOARareintroducedanddemonstrated.
Inaddition,aschematicdiagramindicatesthedosevolume
parameters,andadosevolumehistogramtheevaluationofa
treatmentplanfordifferentOARs.

39. High density tumour mass with invasion of both parametria (white
arrowheads).

40. Tumour (white arrowheads) is limited to the cervix without invading the uterine
corpus. Bladder impression by the anteflected uterus (grey arrowheads).

41. c) On the coronal view tumour growth to the medial third of both parametria
(white arrowheads).

42. Clinical examination prior to therapy revealed invasion of both
parametria (left & right), as seen on axial and coronal drawings.

43. Intracervical high signal intensity residual tumour mass (black star).

44. On para-sagittal view tandem and ring of the applicator are displayed with low
signal intensity.

45. g) Black arrowheads are indicating parametrial borders.

46. At time of brachytherapy, there is only slight invasion of the left parametrium on
clinical examination. Bladder (B), uterine corpus (C), rectum (R), fluid in the
uterine corpus (F), sigmoid colon (S), cervical canal (black arrowheads),
lymphocele after lymph node staging (LC), applicator: ring (Ri), balloon of foley
catheter (F), vaginal packing (VP), tandem (white stars).

48. Point doses versus dose volume parameters
•Sofar,ingynaecologicbrachytherapycorrelationbetweenthe
radiationdoseandthenormaltissueeffectshavebeenassessed
usingpointdoses.Since1985,thesepointshavebeendefined
usingthestandardizeddosespecificationpointsproposedinthe
ICRU38report.Thereisgeneralagreementthatcorrelationof
radiationpointdosesanddosevolumeeffectsisinferiorto
correlationofdosevolumerelationsanddosevolumeeffectsinany
givenorgan.
•However,forgynaecologicbrachytherapy,thiscorrelationcould
hardlybeinvestigateduntilnow,asconventionalorthogonalfilm
basedtreatmentplanningforbrachytherapywasbasedonpoint
dosesandnotondosevolumerelations.Acomprehensive
assessmenthasonlyrecentlybecomefeasiblewhenintroducing
crosssectionalimage-basedtreatmentplanningforbrachytherapy
usingCTorMRI.

49. •Dose heterogeneity in organs at risk
•Withexternalbeamtherapy,itispresumedthatahomogeneousdoseis
deliveredtotheorgansatriskwithasharpdosegradientatthefieldedges.
Withintracavitarybrachytherapy,thereisaninhomogeneousdose
distribution,especiallyinthetissuesadjacenttothesources.
•Theadjacentorgansatriskarehollow,withthetypicalorganwallconsisting
ofmucosal,submucosal,andmuscularlayers.Theconfigurationand
thicknessofthedifferentorganwalls(variationfrom2–3upto6–8mm)is
dependentonthedegreeoffilling,theimpactofwhichismostpronounced
inthebladder,rectosigmoid,andvagina.Theorganwallsadjacenttothe
applicator(sources),liketheanteriorrectalandsigmoidwalls,inferior–
posteriorbladderwall,orthevaginalwalladjacenttothecervix,are
irradiatedbythebrachytherapysourceswithahighinhomogeneousdose
(>20–40Gy),whereastheorganwallsfurtheraway,liketheposterior
rectosigmoidwalls,thesuperior–anteriorbladderwall,ortheinferiorvagina,
areirradiatedwithmuchlowerdoses(<5–10Gy).
•Withdefinitiveirradiation,thisinhomogeneousdosedeliveredwith
brachytherapytodifferentpartsoftheorganwalls,iscombinedwiththe
dosefromexternalbeamappliedtolargepartsoftheorganwalls(e.g.45–
50Gyto75–95%ofrectumandsigmoid,to60–90%ofbladderandto50–
90%ofvagina).Thesepartsirradiatedbyexternalbeamalsoinclude
portionsofthewall,whichareirradiatedwithalowermorehomogenous
dosefrombrachytherapy(e.g.posteriorrectalwall).

50. Fig. 3. MRI based 3D treatment plan with
relevant dose volume parameters for GTV,
HR/IR CTV and OAR (at time of
brachytherapy (patient, Fig. 1). Pelvic MRI
at time of brachytherapy and treatment
plan in (a) transverse, (b) parasagittal, and
(c) paracoronal orientation with MRI
compatible applicator in place

51. Assumptions when combining external beam therapy
and several brachytherapy fraction doses
Inordertobeabletomatchdosevolumerelationsfromboth
externalbeamandbrachytherapy,itisnecessarytomatcheach
tissuevolumeelement(voxel)irradiatedbyexternalbeamwiththe
correspondingvoxelirradiatedbybrachytherapy.
Fromclinicalexperience,itcanbeconcludedthattheorganwalls
adjacenttotheapplicatorreceivingahighinhomogeneousdoseare
alwaysirradiatedwiththefulldoseofexternalbeamtherapy.As
theseareasarelocatedneartheICRUreferencepoint,inaccuracies
shouldnotbelargerthan±5%forthedoseofexternalbeam
therapy.Suchanassumptionisnotnecessarilyvalidforthepartsof
organwallsatalargerdistancefromtheapplicator,asthisvalue
dependsontheexternalbeamtechniqueaswellastheamountof
changeintopographyduetotumourremissionanddueto
introductionoftheapplicator.

52. •Furthermore,infractionatedbrachytherapy,thelocationofthehigh
doseregionfrombrachytherapymaynotbeidenticalforeach
fraction.Astumoursshrinkduringthecourseofradiation,thereisa
changeintumourvolumeandconfigurationovertimeand
consequentlyachangeinnormaltissuetopographyovertime.
•Inaddition,thebrachytherapyapplicatorchangesnormaltissue
topographysignificantly,eachtimeitisinserted.Whenaddingdose
volumerelations,however,ithastobeassumed,thatthelocationof
theregionofinterestisidenticaleachtime.
•Finally,duetotheshapeofagivenorganwall,ahighdoseregion
maybecontiguousornon-contiguous.Non-contiguoushighdose
volumesaretypicallyseeninthebladderwall,duetothefilled
lateralrecessus(horns)

53. Definition of dose volume parameters
•Analysingthe3Ddosedistributioninanorganatriskhasbeen
basedonthehypothesisthatclinicallyusefulinformationhasto
includevolumeinformationobtainedwithcumulativedosevolume
histogram(DVH)analysis.
•TwomainapproacheshavebeendescribedforDVHanalysis,one
referringtorelativeorgan(wall)volumes(widelyappliedinEBT),
andtheotherreferringtoabsoluteorgan(wall)volumes.Typical
adverseeffectsfrombrachytherapysuchaslocalinflammation,
fibrosis,ulceration,necrosisandfistulasoccurmainlyinlimited
volumesadjacenttotheapplicatorirradiatedwithhighdoses(>70–
80Gy),whereaswholeorgansideeffectslikeoverallorgan
inflammation,fibrosisoccurmainlyafterwholeorganirradiationwith
intermediateorhighdoses(60–70cGy).Astheseorgansofinterest
arehollow,thefillingstatusoftherespectiveorganshouldbe
clearlystated,especiallyforthebrachytherapycomponent.The
mostconstantfillingstatuspossibleisadvisedforvalidandreliable
datacollection,especiallyforthebladder,asthismaychange
withinshorttimeperiods.Whenassessinglateeffectsfrom
brachytherapy,smallorgan(wall)volumesirradiatedtoahighdose
seemtobeofmajorinterest.Asthereisrapiddosefall-offnearthe
sources,inparticularinadjacentsmallorgan(wall)volumes,the
doseassessmenthastorefertoone(ormore)defineddose
point(s)intheselimitedvolumes.

54. •Theminimumdoseinthemostirradiatedtissuevolumeadjacentto
theapplicator(0.1,1,2and5cm
3
)isrecommendedforrecording
andreporting,ashasbeenproposedbyseveralauthorspreviously
(Figs.5and6).Whenassumingawallthicknessof5mmthese
volumescorrespondto‘wallplanes’of5mmx4mm(0.1cm
3
),1.4
cmx1.4cm(1cm
3
),2cmx2cm(2cm
3
),and3.3cmx3.3cm(5
cm
3
).
•Inordertoindicatethedoserangeinthesesmallvolumes,itis
recommendedtoreportatleasttwovalueswhichshouldbe1and2
cm
3
.

56. •Organ contouring
Whenusingorganwallvolumesforrecordingandreporting
-theorganwallshavetobedelineatedslicebyslice
-majorpracticaldifficultiesoftheverysmalldimensionsandtheinability
tohaveautomaticallygeneratedsecondcontoursatselecteddistancesbythe
treatmentplanningsystem.
Thesefactorsrepresentmajoruncertaintiesandmayleadtomajor
inaccuracies.
Forpracticalreasons,itshould,therefore,betakenintoconsideration,thatfor
organwallvolumesupto2–3cm
3
,organandorganwallcontouringleadto
almostidenticalnumericalresults,whichallowsfororgancontouringonly.
Iflargerorganwallvolumesareconsidered,organwallcontouringhastobe
performed.Thechoiceofthemostappropriate3Dimagingsystemfor
delineationisofmajorimportancebecausevariationsindelineationwithina
fewmillimetresleadtosignificantvariationofdoseduetotheinversesquare
law.WhereasthereisnodoubtthatMRIissuperiortoCTforthe
discriminationofGTVandadjacentnormal(uterine)tissue,CTandMRI
providebasicallysimilarqualityfordiscriminationofthebladder,rectum,
sigmoid,bowelandvagina.
However,inpracticedelineationseemstobemoreaccuratewhenusingMRI:
delineationoforgansatriskinrelationtotheMRIcompatibleapplicatorwas
excellentinonestudyinmorethan90%ofcases.

57. Radiobiological modeling of doses
Whenapplying3Ddosevolumeassessments,eachfractionhasto
beevaluatedandabiologicallyweighteddose(EQD2or50cGy/h)
hastobecalculated.
Thedifferentfractionscanthenbeaddedarrivingatacumulative
biologicallyweighteddose.
Thiscumulativevaluefrombrachytherapyistobeaddedtothedose
fromexternalbeamtherapy,alsobiologicallyweighted.Thissum
thenrepresentsthetotalbiologicallyweighteddose(fordose
rate/doseperfraction)whichwasappliedtothevolumeofinterest,
e.g.theminimumin2cm
3
rectum,intheGTVorintheHRCTV.

58. Integration of new parameters
•Three-dimensionaltoolsfordosevolumeassessmentshouldbe
prospectivelyusedforshortandlongtermevaluation,inordertoestablish
valuableclinicalinformationcorrelatedto3Ddosevolumerelations.
•Appropriatemethodsformorbidityassessmenthavetobeintegratedfor
differentorgansystems(French–ItalianGlossary,LENTSOMA,CTCAE
3.0).
•These3Dtoolsshouldbeused(inatransitionperiod)inparallelwithfilm-
basedreferencepointsasproposedbyICRU38andsomefurtherpointsas
proposedintheliteratureinthepast(maximumbladderpoint,meanand
maximumrectumpoint,etc.).
•Whenassessingthesedosevolumerelationsbasedontraditional
performanceofbrachytherapy,dosevolumeconstraintscanbeexpectedto
begeneratedwhicharemorevalidandreliableandthusclinicallyrelevant
thanthoseinthepastbasedonlyonpointsdosesandICRUreference
volumes.However,thesenewdosevolumeconstraintsshouldbe
discussedintheframeoftraditionalexperience.Forsigmoid(smallbowel,
ovary)meaningfuldosevolumeconstraintsareexpectedtobegenerated.

59. Recommendations for reporting