Institute of Oncology & Radiobiology . Institute of Oncology - - PowerPoint PPT Presentation

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Institute of Oncology & Radiobiology . Institute of Oncology & Radiobiology . Havana, Cuba. Havana, Cuba.

INOR INOR

“ “Transition from 2 Transition from 2-

• D to 3

D to 3-

• D conformal radiotherapy

D conformal radiotherapy in high grade in high grade gliomas gliomas: our experience in Cuba : our experience in Cuba” ”

• Chon. I, MD
• Chon. I, MD -
• Chi.

Chi. D, MD D, MD -

• Alert.J, MD

Alert.J, MD-

• Alfonso.

Alfonso. R, PhD. R, PhD.-

• Ropero

Ropero. . R, MD. R, MD. Department of Radiotherapy Department of Radiotherapy Institute of Oncology & Radiobiology . Havana, Cuba. Institute of Oncology & Radiobiology . Havana, Cuba.

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• The aims of 3D

The 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

• f improving survival.
• f 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 tumours tumours 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 dose Firstly, 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 (3 dimension 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 (2 radiation therapy (2-

• D RT). All patients have high

D RT). All patients have high grade grade gliomas gliomas. . Secondly, to show the benefits of third dimension Secondly, to show the benefits of third dimension conformal radiation therapy (3 conformal radiation therapy (3-

• D CRT) as the

D CRT) as the treatment of choice for malignant treatment of choice for malignant gliomas gliomas in the in the postoperative stage. postoperative stage.

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Patients Patients and and Methods Methods: :

• A total

A total of

• f 45

45 patients patients with with supratentorial supratentorial high high grade grade gliomas gliomas were were included included from from 2004 2004 to to 2007 . 2007 . The The treatments treatments were were performed performed in in our

• ur radiotherapy

radiotherapy department department . .

• The

The inclusion inclusion/ /exclusion exclusion criteria criteria were were: :

• Anaplastic

Anaplastic Astrocytoma Astrocytoma (AA) (AA) and and Glioblastoma Glioblastoma Multiforme (GBM) Multiforme (GBM) histology histology. .

• Karnofsky

Karnofsky Performance Performance Score Score (KPS) (KPS) ≥ ≥70. 70.

• 18

18-

• 65

65 years years

• ld
• ld.

.

• Total

Total or

• r

subtotal subtotal macroscopic macroscopic surgical surgical resection resection. .

• No

No previous previous chemotherapy chemotherapy/ / inmunotherapy inmunotherapy treatment treatment. .

• Informed

Informed consent consent

• btained
• btained.

.

Control Control Group Group

• DTT : 60

DTT : 60 Gy Gy (2 (2 Gy Gy x 5d / x 5d / wk wk during during 6 6 weeks weeks) )

• The

The total total treated treated volume volume was was: tumor + : tumor + oedema

• edema +3

+3-

• 4cm

4cm

• f
• f margins

margins

• 2D

2D Conventional Conventional Radiotherapy Radiotherapy ( (local local fields fields) )

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Prospective Prospective Group Group

• DTT : 66

DTT : 66 -

• 70

70 Gy Gy (1,8 (1,8 Gy Gy x 5d/ x 5d/wk wk during during 7 7-

• 8

8 weeks weeks) )

• Treatment

Treatment Volumes Volumes (ICRU 50 & 62): (ICRU 50 & 62): * *GTV: GTV: enhanced enhanced contrast contrast lesion lesion defined defined by CT by CT or

• r

MRI. MRI. *CTV 1: *CTV 1: enhanced enhanced contrast contrast lesion lesion + + the the perilesional perilesional edema edema + + 3 3-

• 4

4 cm cm of

• f

margins margins. . *CTV 2: *CTV 2: enhanced enhanced contrast contrast lesion lesion + + 2cm 2cm of

• f

margins margins. . *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.

• Level

Level 2 ( 2 (the the European European Dynarad Dynarad Consortium Consortium) ) of

• f

3D 3D Conformal Conformal Radiotherapy Radiotherapy

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• Conventional

Conventional Simulator Simulator ( (Beam Beam geometry geometry determined determined by by fluoroscopic fluoroscopic simulation simulation) )

• Immobilization: Velcro strap, head support

Immobilization: Velcro strap, head support

• 2D treatment planning systems:

2D treatment planning systems:

– – Theraplan Theraplan Plus (Basic, non image based) Plus (Basic, non image based)

• Treatment Machine :

Treatment Machine :

– – Co Co 60 60 Theratronics Theratronics Phoenix Phoenix

2D CONVENTIONAL RADIOTHERAPY. .

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• Imaging Equipment

Imaging Equipment (multi (multi-

• slice CT

slice CT-

• Scanner)

Scanner)

• Immobilization: thermoplastic mask

Immobilization: thermoplastic mask

• 3D image based treatment planning systems:

3D image based treatment planning systems:

– – Theraplan Theraplan Plus (Advanced) Plus (Advanced) – – PrecisePLAN PrecisePLAN

• V. 2.12
• V. 2.12
• Treatment Machine

Treatment Machine

– – 2 2 Elekta Elekta Precise Precise linacs linacs

• (MLC

(MLC & EPID) & EPID)

• R&V System

R&V System and Networking and Networking

3D 3D Conformal Conformal Radiotherapy Radiotherapy

Network

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• Treatment

Treatment portals portals were were determined determined based based

• n
• n bony

bony landmarks landmarks, , where where the the target target was was the the tumor tumor and and peritumoral peritumoral tissue tissue. . Critical Critical structures structures were were avoided avoided or

• r not

not. .

• Limited

Limited information information was was obtained

• btained

about about isodose isodose distributions distributions such such as as the the minimum minimum and and the the maximum maximum tumor tumor and and normal normal tissues tissues doses doses received received

• Evaluation

Evaluation plan plan consisted consisted only

• nly in

in the the examination examination of

• f one
• ne or
• r a

a very very few few cross cross-

• sectional

sectional images images. .

• 2

2-

• D

D treatment treatment was was verified verified comparing comparing port port films films with with simulator simulator films films. .

• Treatment

Treatment planning planning is is based based

• n
• n

3 3-

• D

D anatomy anatomy, , designing designing beam beam geometries geometries and and treatment treatment portals portals according according to to the the extension extension of

• f target

target and and risk risk structures structures. .

• The

The plan plan evaluation evaluation was was done done through through the the 2D 2D isodose isodose curves curves for for Multiple Multiple Plannar Plannar Reconstruction Reconstruction (MPR), 3D (MPR), 3D isosurface isosurface and and Dose Dose Volumen Volumen Histogram Histogram (DVH). (DVH).

• 3

3-

• D

D treatment treatment is is verified verified comparing comparing DRR ( DRR (from from the the 3D CT data), 3D CT data), with with the the portal portal images images acquired acquired by by films films

• r
• r EPIDs

EPIDs. .

2 2-

• D

D 3 3-

• D

D

CLASSIFICATION OF CONFORMAL THERAPY

ACCORDING TO THE METHODOLOGY AND TOOLS ASSOCIATED WITH EACH STEP OF THE PROCEDURE (IAEA TECDOC 1588)

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3D 3D-

• CRT

CRT

1.

• 1. Patient data acquisition

Patient data acquisition ( (level level 2 2 reached reached) ) Immobilization Immobilization Customized thermoplastic masks. Customized thermoplastic masks. Imaging system Imaging system Non dedicated, multi Non dedicated, multi-

• slice CT

slice CT-

• scanner

scanner Digital fluoroscopic simulator, Digital fluoroscopic simulator, MR optional (provided by external institution) MR optional (provided by external institution) Reference marks for setup Reference marks for setup Radio Radio-

• opaque marks, ARPLAY frame optional
• paque marks, ARPLAY frame optional

Critical organs Critical organs 3D segmentation provided by 3D segmentation provided by TPSs TPSs Inhomogeneities Inhomogeneities Voxel Voxel based correction, automated for bone, based correction, automated for bone, manual contouring optional manual contouring optional Gross tumour volume Gross tumour volume-

• GTV

GTV Contouring every slice or interpolated Contouring every slice or interpolated. . Clinical target volume Clinical target volume-

• CTV

CTV Expanded from GTV using auto Expanded from GTV using auto-

• margin tools

margin tools Internal target volume (ITV) Internal target volume (ITV) Non relevant for intra Non relevant for intra-

• cranial targets

cranial targets

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3D 3D-

• CRT

CRT

2 2-

• Beam definition

Beam definition ( (level level 2 2 reached reached) ) Accounting for beam setting Accounting for beam setting uncertainty uncertainty 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 images images Type of radiation and beam Type of radiation and beam modifiers modifiers Photon beams, 6 MV, motorized wedges. Photon beams, 6 MV, motorized wedges. Beam incidence Beam incidence Several (including non coplanar) beams Several (including non coplanar) beams Isocentre Isocentre SAD technique (auto centred on target) SAD technique (auto centred on target) Beam limiting device Beam limiting device Elekta Elekta MLCi MLCi, 80 leaves , 80 leaves PTV PTV – – CTV margin CTV margin Only setup margins considered, based on Only setup margins considered, based on immobilization device and verification images immobilization device and verification images

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• 3. Dose calculation and optimization
• 3. Dose calculation and optimization (

(level level 2 2 reached reached) ) Calculation model Calculation model Pencil beam with Pencil beam with inhomogeneity inhomogeneity Evaluation of treatment plans Evaluation of treatment plans Isodoses Isodoses in MPR, in MPR, isosurface isosurface on 3D rendered

• n 3D rendered

volumens volumens and and DVHs DVHs Treatment plan optimization Treatment plan optimization Trial & error, PTV coverage, forward Trial & error, PTV coverage, forward planning planning

• 4. Treatment verification and execution
• 4. Treatment verification and execution (

(level level 2 2 reached reached) ) Verification simulation Verification simulation Conventional Conventional simulator simulator used used,

• rtogonal

,

• rtogonal

digital digital views views Immobilization Immobilization Same as during patient date acquisition, Same as during patient date acquisition, Thermoplastic Mask. Thermoplastic Mask. Aids for positioning Aids for positioning Isocentre Isocentre Lasers Lasers Patient positioning Patient positioning Displacements from anatomical landmarks Displacements from anatomical landmarks Verification reference image Verification reference image DRR and initial Electronic Portal Images DRR and initial Electronic Portal Images Record and Verify system Record and Verify system Elekta Elekta Precise Precise Desktop+iViewGT Desktop+iViewGT In vivo measurements In vivo measurements PTW PTW Si Si-

• diodes

diodes

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3-D CONFORMAL RADIOTHERAPY

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2D 3D

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2D 2D Conventional Conventional Radiotherapy Radiotherapy. . 3D 3D Conformal Conformal Radiotherapy Radiotherapy

• Fig. 1 Overall Survival Function

CNS High Grade Gliomas. INOR 2004-2007

TIME (MONTHS)

40 35 30 25 20 15 10 5

A c u m u l a t e d S u r v i v a l

1,0 ,9 ,8 ,7 ,6 ,5 ,4 ,3 ,2 ,1 0,0

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)

2 4 6 8 10 12 14 16 18 20

DISTRIBUTION OF COMPLICATIONS IN PATIENTS RECEIVING 2D AND 3D RT

2D 3D

COMPLICATIONS COMPLICATIONS F F R R E E Q Q U U E E N N C C Y Y

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Cox Cox Regression Regression. . Prognostic Prognostic Factors Factors in in High High Grade Gliomas Grade Gliomas

p p Exp(B Exp(B) ) 95,0% CI 95,0% CI Lower Lower Upper Upper Female Female 0,004 0,004 0,218 0,218 0,077 0,077 0,614 0,614 Age Age (39 (39-

• 50)

50) 0,259 0,259 Age Age (51 (51-

• 60))

60)) 0,327 0,327 2,016 2,016 0,496 0,496 8,203 8,203 Age Age (61 (61 and and older

• lder)

) 0,130 0,130 3,306 3,306 0,703 0,703 15,561 15,561

• A. A.
• A. A. Histology

Histology 0,820 0,820 0,894 0,894 0,341 0,341 2,343 2,343 Complete Complete Surgery Surgery 0,000 0,000 0,110 0,110 0,035 0,035 0,349 0,349 3D RT 3D RT Technique Technique 0,000 0,000 0,085 0,085 0,031 0,031 0,239 0,239

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RESULTS AND DISCUSSION RESULTS AND DISCUSSION

• Median age was 54 years

Median age was 54 years

• Median survival (Kaplan

Median survival (Kaplan-

• Meier method):

Meier method):

– – 3 3-

• D CRT patients: 16 months

D CRT patients: 16 months – – 2D RT patients: 9 months 2D 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 2 respectively; 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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CONCLUSIONS CONCLUSIONS

• 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 i

Escalating 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 tumours tumours, attaining a better control and maybe a potential cure. , attaining a better control and maybe a potential cure.

• High

High-

• dose 3D CRT had a better tolerance and no severe side

dose 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 dose

There is evidence of a dose-

• response relationship for hemispheric high

response relationship for hemispheric high grade grade gliomas gliomas. .

• Intensification of local radiotherapy with dose escalation is fe

Intensification 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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Thank Thank you you! !