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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.

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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) )

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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

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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!!