11
Institute of Oncology & Radiobiology .Institute of Oncology & Radiobiology . Havana, Cuba.Havana, Cuba.
INORINOR
““Transition from 2Transition from 2--D to 3D to 3--D conformal radiotherapy D conformal radiotherapy in high grade in high grade gliomasgliomas: our experience in Cuba: our experience in Cuba””
Chon. I, MD Chon. I, MD --
Chi.Chi.
D, MD D, MD --
Alert.J, MDAlert.J, MD--
Alfonso.Alfonso.
R, PhD.R, PhD.--
RoperoRopero..
R, MD.R, MD.
Department of RadiotherapyDepartment of RadiotherapyInstitute of Oncology & Radiobiology . Havana, Cuba.Institute of Oncology & Radiobiology . Havana, Cuba.
33
The aims of 3DThe aims of 3D--CRT are to achieve conformity of CRT are to achieve conformity of the high dose region to the target volume and the high dose region to the target volume and consequently to reduce the dose reaching the consequently to reduce the dose reaching the surrounding normal tissues. This should reduce both surrounding normal tissues. This should reduce both acute and late morbidity. If the adverse effects of acute and late morbidity. If the adverse effects of treatment can be reduced in this way, the dose of the treatment can be reduced in this way, the dose of the target volume can be increased with the expectation target volume can be increased with the expectation of improving survival.of improving survival.
It is now the standard practice in developed It is now the standard practice in developed countries, treating many types of countries, treating many types of tumourstumours with with curative intent.curative intent.
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THE GOALS OF THE PRESENT STUDY ARE:THE GOALS OF THE PRESENT STUDY ARE:
Firstly, to compare the effects of radiation doseFirstly, to compare the effects of radiation dose-- escalation in adult patients, treated with third escalation in adult patients, treated with third
dimension conformal radiation therapy (3dimension conformal radiation therapy (3--D CRT) D CRT) with those patients who had just the second dimension with those patients who had just the second dimension radiation therapy (2radiation therapy (2--D RT). All patients have high D RT). All patients have high grade grade gliomasgliomas. . Secondly, to show the benefits of third dimension Secondly, to show the benefits of third dimension conformal radiation therapy (3conformal radiation therapy (3--D CRT) as the D CRT) as the treatment of choice for malignant treatment of choice for malignant gliomasgliomas
in the in the
postoperative stage.postoperative stage.
55
PatientsPatients andand MethodsMethods::
A total A total ofof 45 45 patientspatients withwith supratentorialsupratentorial highhigh grade grade gliomas gliomas werewere includedincluded fromfrom 2004 2004 toto 2007 . 2007 . TheThe treatmentstreatmentswerewere performedperformed in in ourour radiotherapyradiotherapy departmentdepartment ..
TheThe inclusioninclusion//exclusionexclusion criteriacriteria werewere::--AnaplasticAnaplastic
AstrocytomaAstrocytoma
(AA) (AA) andand
GlioblastomaGlioblastoma
Multiforme (GBM) Multiforme (GBM) histologyhistology. . --KarnofskyKarnofsky
PerformancePerformance
ScoreScore
(KPS) (KPS) ≥≥70.70.
--1818--65 65 yearsyears
oldold..--Total Total oror
subtotal subtotal macroscopicmacroscopic
surgicalsurgical
resectionresection..
--No No previousprevious
chemotherapychemotherapy/ / inmunotherapyinmunotherapy
treatmenttreatment..--InformedInformed
consentconsent
obtainedobtained..
Control Control GroupGroup
DTT : 60 DTT : 60 GyGy(2 (2 GyGy
x 5d / x 5d / wkwk
duringduring
6 6 weeksweeks))
TheThe total total treatedtreated volumevolume waswas: tumor + : tumor + oedemaoedema +3+3--4cm 4cm ofof marginsmargins
2D 2D ConventionalConventional RadiotherapyRadiotherapy ((local local fieldsfields) )
77
ProspectiveProspective GroupGroup••DTT : 66 DTT : 66 --
70 70 GyGy
(1,8 (1,8 GyGy
x 5d/x 5d/wkwk
duringduring
77--8 8 weeksweeks) )
•• TreatmentTreatment
VolumesVolumes
(ICRU 50 & 62):(ICRU 50 & 62):
**GTV: GTV: enhancedenhanced
contrastcontrast
lesionlesion
defineddefined
by CT by CT oror
MRI.MRI.*CTV 1: *CTV 1: enhancedenhanced
contrastcontrast
lesionlesion
++
thethe
perilesionalperilesional
edema edema ++
33--4 4 cmcm
ofof
marginsmargins..*CTV 2: *CTV 2: enhancedenhanced
contrastcontrast
lesionlesion
+ + 2cm 2cm ofof
marginsmargins..
*PTV 1: CTV1*PTV 1: CTV1+ 10+ 10--15mm margins when technique is uncertain.15mm margins when technique is uncertain.*PTV2: *PTV2: CTV2 CTV2 + margin of 10+ margin of 10--15mm when technique is uncertain.15mm when technique is uncertain.
•• LevelLevel
2 (2 (thethe
EuropeanEuropean
DynaradDynarad
ConsortiumConsortium) ) ofof
3D 3D ConformalConformal RadiotherapyRadiotherapy
88
99
ConventionalConventional Simulator Simulator ((BeamBeam
geometrygeometry
determineddetermined
by by
fluoroscopicfluoroscopic
simulationsimulation))
Immobilization: Velcro strap, head support Immobilization: Velcro strap, head support
2D treatment planning systems: 2D treatment planning systems: ––
TheraplanTheraplan
Plus (Basic, non image based)Plus (Basic, non image based)
Treatment Machine : Treatment Machine : ––
CoCo
60 60 TheratronicsTheratronics
PhoenixPhoenix
2D CONVENTIONAL RADIOTHERAPY..
1010
Imaging EquipmentImaging Equipment(multi(multi--slice CTslice CT--
Scanner)Scanner)
Immobilization: thermoplastic maskImmobilization: thermoplastic mask
3D image based treatment planning systems: 3D image based treatment planning systems: ––
TheraplanTheraplan
Plus (Advanced)Plus (Advanced)––
PrecisePLANPrecisePLAN
V. 2.12V. 2.12
Treatment MachineTreatment Machine––
2 2 ElektaElekta
Precise Precise linacslinacs(MLC (MLC & EPID)& EPID)
R&V System R&V System and Networkingand Networking
3D 3D ConformalConformal RadiotherapyRadiotherapy
Network
1111
TreatmentTreatment portalsportals werewere determineddeterminedbasedbased onon bonybony landmarkslandmarks,, wherewherethethe targettarget waswas thethe tumor tumor andandperitumoralperitumoral tissuetissue. . CriticalCritical structuresstructureswerewere avoidedavoided oror notnot. . LimitedLimited informationinformation waswas obtainedobtainedaboutabout isodoseisodose distributionsdistributions suchsuch as as thethe minimumminimum andand thethe maximummaximumtumor tumor andand normal normal tissuestissues dosesdosesreceivedreceivedEvaluationEvaluation plan plan consistedconsisted onlyonly in in thetheexaminationexamination ofof oneone oror a a veryvery fewfewcrosscross--sectionalsectional imagesimages. . 22--D D treatmenttreatment waswas verifiedverifiedcomparingcomparing portport filmsfilms withwith simulatorsimulatorfilmsfilms..
TreatmentTreatment planning planning isis basedbased onon33--D D anatomyanatomy,, designingdesigning beambeamgeometriesgeometries andand treatmenttreatment portalsportalsaccordingaccording toto thethe extensionextension ofof targettargetandand riskrisk structuresstructures..TheThe plan plan evaluationevaluation waswas done done throughthrough thethe 2D 2D isodoseisodose curves curves forforMultipleMultiple PlannarPlannar ReconstructionReconstruction(MPR), 3D (MPR), 3D isosurfaceisosurface andand DoseDoseVolumen Volumen HistogramHistogram (DVH).(DVH).33--D D treatmenttreatment isis verifiedverified comparingcomparingDRR (DRR (fromfrom thethe 3D CT data), 3D CT data), withwiththethe portal portal imagesimages acquiredacquired by by filmsfilmsoror EPIDsEPIDs..
22--DD 33--DD
CLASSIFICATION OF CONFORMAL THERAPY
ACCORDING TO THE METHODOLOGY AND TOOLS
ASSOCIATED WITH EACH STEP OF THE PROCEDURE
(IAEA TECDOC 1588)
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3D3D--CRTCRT
1. 1. Patient data acquisitionPatient data acquisition ((levellevel 2 2 reachedreached))
ImmobilizationImmobilization Customized thermoplastic masks.Customized thermoplastic masks.
Imaging systemImaging system Non dedicated, multiNon dedicated, multi--slice CTslice CT--scannerscannerDigital fluoroscopic simulator,Digital fluoroscopic simulator,MR optional (provided by external institution) MR optional (provided by external institution)
Reference marks for setupReference marks for setup RadioRadio--opaque marks, ARPLAY frame optionalopaque marks, ARPLAY frame optional
Critical organsCritical organs 3D segmentation provided by 3D segmentation provided by TPSsTPSs
InhomogeneitiesInhomogeneities VoxelVoxel based correction, automated for bone, based correction, automated for bone, manual contouring optionalmanual contouring optional
Gross tumour volumeGross tumour volume--GTV GTV Contouring every slice or interpolatedContouring every slice or interpolated..
Clinical target volumeClinical target volume--CTV CTV Expanded from GTV using autoExpanded from GTV using auto--margin toolsmargin tools
Internal target volume (ITV)Internal target volume (ITV) Non relevant for intraNon relevant for intra--cranial targets cranial targets
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3D3D--CRTCRT
22--Beam definitionBeam definition ((levellevel 2 2 reachedreached))Accounting for beam setting Accounting for beam setting uncertaintyuncertainty
3D margins based on evaluation of setup 3D margins based on evaluation of setup errors by repeated simulator and portal errors by repeated simulator and porta l imagesimages
Type of radiation and beam Type of radiation and beam modifiersmodifiers
Photon beams, 6 MV, motorized wedges.Photon beams, 6 MV, motorized wedges.
Beam incidenceBeam incidence Several (including non coplanar) beamsSeveral (including non coplanar) beamsIsocentreIsocentre SAD technique (auto centred on target)SAD technique (auto centred on target)Beam limiting deviceBeam limiting device ElektaElekta MLCiMLCi, 80 leaves, 80 leavesPTV PTV ––
CTV marginCTV margin Only setup margins considered, based on Only setup margins considered, based on
immobilization device and verification imagesimmobilization device and verification images
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3. Dose calculation and optimization 3. Dose calculation and optimization ((levellevel 2 2 reachedreached))
Calculation modelCalculation model Pencil beam with Pencil beam with inhomogeneityinhomogeneity
Evaluation of treatment plansEvaluation of treatment plans IsodosesIsodoses in MPR, in MPR, isosurfaceisosurface on 3D rendered on 3D rendered volumensvolumens and and DVHsDVHs
Treatment plan optimizationTreatment plan optimization Trial & error, PTV coverage, forward Trial & error, PTV coverage, forward planningplanning
4. Treatment verification and execution4. Treatment verification and execution ((levellevel 2 2 reachedreached))
Verification simulationVerification simulation ConventionalConventional simulatorsimulator usedused, ortogonal , ortogonal digital digital viewsviews
ImmobilizationImmobilization Same as during patient date acquisition, Same as during patient date acquisition, Thermoplastic Mask.Thermoplastic Mask.
Aids for positioningAids for positioning IsocentreIsocentre LasersLasers
Patient positioningPatient positioning Displacements from anatomical landmarks Displacements from anatomical landmarks
Verification reference imageVerification reference image DRR and initial Electronic Portal ImagesDRR and initial Electronic Portal Images
Record and Verify systemRecord and Verify system ElektaElekta Precise Precise Desktop+iViewGTDesktop+iViewGT
In vivo measurementsIn vivo measurements PTW PTW SiSi--diodesdiodes
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3-D CONFORMAL RADIOTHERAPY
1717
2D 3D
1818
2D 2D ConventionalConventional RadiotherapyRadiotherapy..
3D 3D ConformalConformal RadiotherapyRadiotherapy
Fig. 1 Overall Survival Function
CNS High Grade Gliomas.
INOR 2004-2007
TIME (MONTHS)
4035302520151050
Acu
mulated
Surviva
l
1,0
,9
,8
,7
,6
,5
,4
,3
,2
,10,0
Mean = 15 95% CI (11, 18) months
Median= 7 95% CI (5, 9) months
2D RT Mean = 10 95% CI ( 6,13) Median = 6 95% CI (5,7)
3D RT Mean = 18 95% CI (13, 23) Median = 18 95% CI (7, 29)
0
2
4
6
8
10
12
14
16
18
20
DISTRIBUTION OF COMPLICATIONS IN PATIENTS RECEIVING 2D AND 3D RT
2D3D
COMPLICATIONSCOMPLICATIONS
FF RR EE QQ UU EE NN CC YY
2222
Cox Cox RegressionRegression..PrognosticPrognostic FactorsFactors in in HighHigh Grade GliomasGrade Gliomas
pp Exp(BExp(B))95,0% CI95,0% CI
LowerLower UpperUpperFemaleFemale 0,0040,004 0,2180,218 0,0770,077 0,6140,614AgeAge (39(39--50)50) 0,2590,259AgeAge (51(51--60))60)) 0,3270,327 2,0162,016 0,4960,496 8,2038,203AgeAge (61 (61 andand olderolder)) 0,1300,130 3,3063,306 0,7030,703 15,56115,561
A. A. A. A. HistologyHistology 0,8200,820 0,8940,894 0,3410,341 2,3432,343Complete Complete SurgerySurgery 0,0000,000 0,1100,110 0,0350,035 0,3490,349
3D RT 3D RT TechniqueTechnique 0,0000,000 0,0850,085 0,0310,031 0,2390,239
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RESULTS AND DISCUSSION RESULTS AND DISCUSSION
Median age was 54 yearsMedian age was 54 years
Median survival (KaplanMedian survival (Kaplan--Meier method):Meier method):––
33--D CRT patients: 16 monthsD CRT patients: 16 months
––
2D RT patients: 9 months2D RT patients: 9 months
Survival at 1 and 2 years for 3D group was 51% and 28% Survival at 1 and 2 years for 3D group was 51% and 28% respectively; 28% and 16% for 2respectively; 28% and 16% for 2--D RT. D RT.
No significant toxicities were observed, only mild acute. No significant toxicities were observed, only mild acute.
( p<0,0001). ( p<0,0001).
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CONCLUSIONSCONCLUSIONS
Patients with total resection and 3D CRT had a better median Patients with total resection and 3D CRT had a better median survival. survival.
Escalating doses we can increase local control and potentially iEscalating doses we can increase local control and potentially improve mprove global survival. It could help to change the treatment approach global survival. It could help to change the treatment approach in some in some CNS CNS tumourstumours, attaining a better control and maybe a potential cure., attaining a better control and maybe a potential cure.
HighHigh--dose 3D CRT had a better tolerance and no severe sidedose 3D CRT had a better tolerance and no severe side--effects effects compared to 2D group.compared to 2D group.
There is evidence of a doseThere is evidence of a dose--response relationship for hemispheric high response relationship for hemispheric high grade grade gliomasgliomas..
Intensification of local radiotherapy with dose escalation is feIntensification of local radiotherapy with dose escalation is feasible for asible for some selected patients with GBM or AA.some selected patients with GBM or AA.
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ThankThank youyou!!