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Transition from 2D to 3D Brachytherapy in Cervical Cancers: The Vienna Experience

Richard Pötter MD

BrachyNext, Miami, 2014

DisclosuresRichard Pötter, MD, does not have any financial relationships or products or devices with any commercial interest related to the content of this activity of any amount during the past 12 months.

The Medical University of Vienna receives financial and equipment support for training and research activitiesequipment support for training and research activities from Nucletron, an Elekta Company and Varian Medical.

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Driving forces for the evolution from point (A) to 3D/4D image guided adaptive approach

Improvement of local control in advanced diseasepImprovement of cure

Decrease of adverse side effects/improvement in QoL(rectosigmoid, bladder, vagina, bowel, fatigue…)

Not accepting the „mystery“ of point A-based intracavitary brachytherapy

Implementation of 3D/4D Radiotherapy into Gynaecol.

2D Image based brachytherapy (100 years)

Applicator insertionClinical examination

3D/4D drawing

Dose delivery

Standard dose plan

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Vienna 1918 Clinical Evaluation

Drawing DiagramVienna 1918

Radiography

Since ~1983MRI Since 1998

Adler: Strahlentherapie 1918

CT i 1983

Painting

CT since 1983

Image-guided adaptive Brachytherapy

3D/4D imaging

Applicator insertionRepetitive Imaging

diagnosis, EBRT/ChT

3D/4D imaging

Contouring

Repetitive clin exam

+3D/4D drawing

Applicator Reconstruction

3D dose planning

Dose delivery

g

4

EBRTfrom 2D

to 3D

Avoidance of

„geographicalmiss“* posterior field

border * anterior field

border

Gerstner et al. R&O 1999 Zunino et al. IJROBP 1999

Technology Development: Higher conformity through IMRTBetter sparing of OAR (bowel/bladder)Higher chance for geographical miss

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Treatment Planning 2D vs 3D gIn Brachytherapy

Point A (since 1938)

2cm2cm

2cm 2cm

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Point A / target dose

84 Gy

84 Gy

60 Gy

D90 = 65 Gy

Point A / target dose

84 Gy

84 Gy

84 Gy

~ 500 Gy

D90 = 90 Gy

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Standard loading pattern

Optimized loading pattern

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Standard loading pattern

Optimized loading pattern

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Pattern of tumor regression: up to mid parametrium

Kirisits et al. IJROBP 2006

Dimopoulos et IJROBP 2007

The Vienna Applicator

IJROBP 2007

130

140

Median volume = 32 cm3 75 patients

80

90

80

90

100

110

120

HR

-CT

V D

90

sta

nd

ard

Standard

Target dose (Gy)

60 70 80 90 100 110 120

Sig

moi

d do

se

40

50

60

70

85 GyEQD2

50

60

70

0 10 20 30 40 50 60 70 80 90 100 110

Volume HR CTV, cm3

Violation of OAR constraint Tanderup 2007/2010

EQD2=10Gy

Dose constraint

10

140

O ti i d

Median volume = 32 cm3 75 patients

90

80

90

100

110

120

130

R-C

TV

D90

op

tim

ized

Optimised

Target dose (Gy)

60 70 80 90 100 110 120

Sig

moi

d do

se

40

50

60

70

80

85 GyEQD2

50

60

70

0 10 20 30 40 50 60 70 80 90 100 110

Volume HR CTV, cm3

HR

Violation of OAR constraint Application of needles

(Tanderup et al.2007/2010)

EQD2=10Gy

Dose constraint

Imaging And g gTarget Definition

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Stage IIB

At diagnosis

Pathology and TopographyStage IIB

Target Definition

Change of GTV and CTV with time (4D RT)

TumourCervixUterusParametriaOrgans at Risk

Stage IIB

At brachytherapy

Contouring and Dose Volume Assessment

Pathology and Topography

MRI: Initial tumour extension (3D RT)pattern of response (4D RT)

for adaptive MRI based planning

61,060

70

6 ,0

7,99,010,516,3

0

10

20

30

40

50

prior to therapy 1. brachytherapy 2. brachytherapy 3. brachytherapy 4. brachytherapy

Abs

olut

e V

ol (

cm³)

Dimopoulos et al., Strahlentherapie 2009

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„BT-Preplanning in cervical cancer: Different imaging modalities Max Schmid, Vienna University

Target delineation on CT with help of MRI and 3D clinical examination(Federico et al. ABS 2012)Analysis with respect to the overall study cohort:

Volume [ccm] CT/MR volume ratio

Median Median

HR-CTV1 57.62 1.58

HR-CTV2 46.19 1.26

HR-CTV3 37.55 1.09

HR-CTV MRI 30.09

~32%p ≤0.05

~17%p ≤0.05

normalized median volume reduction

HR CTVClinical

Drawings

HR CTVPre-BT

MRI

HR CTV FIGO

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3D Dose Reportingp gAnd Clinical Outcome

Overview of adaptive target concepts in cervix cancer

ICRU/GEC ESTRO report 88punder publicationFig. 5.9-11

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14

90

100

110

GTV

59 Gy 69 Gy 82 Gy

70 Gy 87 Gy 125 Gy

Total dose =10 Gy

Fig.10

Cumulative Dose Volume Histograms for GTV, HR CTV, IR CTVfor 45 Gy EBT (1.8 Gy/f) and 4x7 Gy HDR BT in HR CTV*

D90

D100D98

40

50

60

70

80

Vo

l [%

]

HR CTV

IR CTV

D90

D50 132 Gy

20

30

40

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14

Dose per fraction [Gy]

50 cGy/h

*GYN GEC ESTRO Recommendations (II) Radioth. Oncol. 2006

3D based dose volume constraints OAR

• Classical Maximum Dose • In 3D no clinical relevant endpoint

Bladder

Rectum

GTV

Sigmoid

• fixed volume ~ tolerance dose (total dose)„minimum dose to the most exposed tissue“*

0.1 cc: 3D „maximum dose“: ulceration (fistula)

1 cc/2 cc: teleangiectasia (20 mm x 20 mm x 5 mm)

2cc1cc

0.1cc

ICRU 38 Ref. Points

0 1 cm3(20 mm x 20 mm x 5 mm)

(>5 cc: fibrosis endpoint)*GYN GEC ESTRO Recommendations (II) Radioth. Oncol. 2006

0.1 cm3

2 cm3

15

50

60

70

80

90

Rectum

Bladder

7

8

9

10

Bladder

D2cc

D1cc

D0.1cc

Total dose /=3 Gy

Cumulative Dose Volume Histograms for Bladder, Sigmoid, Rectumfor 45 Gy EBT (1.8 Gy/f) and 4x7 Gy HDR BT in HR CTV*

0

10

20

30

40

Rectum

Sigma

2

3

4

5

6

7

Vo

l [c

m³]

Sigmoid

R t

61 Gy 66 Gy 84 Gy

0

1

3,5 4 4,5 5 5,5 6 6,5 7

Dose per fraction [Gy]

Rectum

64 Gy

67 Gy

69 Gy

78 Gy

89 Gy

99 Gy

*GYN GEC ESTRO Recommendations (II) Radioth. Oncol. 2006

represents the represents the minimal doseminimal dose for the for the most irradiated Volumemost irradiated Volume of x cm³of x cm³

LOCAL CONTROL - CLINICAL DATA

DOSE AT POINT A vs. D90 IN IMAGE BASED HR-CTV

DOSE

Pt A / D90 HR

BEST STANDARDS AIM

EARLY DISEASE 75 Gy / 95+ Gy 90-95% 100%

ADVANCED

DISEASE

IIB<5cm 80 Gy / 90+ Gy 70-85% 95-100%y y

IIB/IIIB>5cm 85 Gy / 85+ Gy 50-65% 85-90%

Expected Improvement through Image Guided Adaptation: 5-40%: IB: 5-10%; IIB lim: 10-20%; IIb ext, IIIB: 20-40%

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MRI based Treatment Planning

• Major Learning Period: 98-2000 (73 consecutive patients)no systematic prospective protocol (point A/ICRU points OAR)

• Systematic prospective protocol since 2001 (72 consecutive pts.)HR CTV concept GTV, HR CTV + OAR contouringBiological modelling (linear-quadratic model)Dose Volume constraints: OAR (2 cm3): 75/90 Gy(EQD2, α/β=3Gy)

Prescription: HR CTV (D90): 85+ Gy(EQD2 /β 10G )Prescription: HR CTV (D90): 85+ Gy(EQD2, α/β=10Gy)

´

Intracavitary + interstitial Brachytherapy, if D90 < 85 Gy

Prospective 3D image based optimisation

Linking DVH-parameters to clinical outcomeD90 for the HR CTV

Analysis (n=141, FIGO: IB-IVA, median follow-up=51 months)D90 for the HR-CTV and probability of local control

1

0.9 Entire population (n=141)

abili

ty o

f loc

al c

ontr

ol

0 3

0.5

0.4

0.9

0.7

0.6

0.8 Tumours > 5cm (n=76)

D90 HR CTV 90 Gy EQD2 90% probability for local control

D90 HR CTV 70 Gy EQD2

Pro

ba

0 10 20 30 5040 90 1007060 80 110 120 130 1400

0.1

0.2

0.3

D90 (HR CTV)Dimopoulos et Radioth & Oncol 2010

D90 HR CTV 70 Gy EQD2 65% probability for local control

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Image guided adaptive brachytherapy (IGABT) cervix cancer

local control and cancer specific survival (1998-2003)

TREATMENT PERIOD (-/+ IGABT) AND TUMOUR SIZE

18%

22%

Pötter R. et al. Radiother Oncol 2007mean 81 Gy vs. 90 Gy in CTVHR

c) d)156 patients MRI guided BT, Vienna 2001-2008, mean D90 to HR CTV 92 Gy

7/156 with G3 and 4/156 G4 toxicity (LENT SOMA) Radioth & Oncol 2011

Pötter et al, Radiotherapy&Oncology ,2011

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S >

3

60

70

80

90

100Dose volume effectsfor rectal morbidityapplying GEC ESTRO recommendations

(P. Georg et al. IJROBP 2011)

Inci

den

ce V

RS

0

10

20

30

40

50

60

> 2 80

90

100

D2 ccmD1 ccm

D0.1 ccmDICRU

GEC ESTRO recommendations

VRS: Vienna RectoscopyScore

N = 35 patients with rectosigmoidoscopy

Dose [Gy]

30 40 50 60 70 80 90 100 110 120 130 140

Inci

denc

e L

EN

T/S

OM

A >

0

10

20

30

40

50

60

70

Clinical late EffectsLENT SOMA score

Georg et al. Radioth&Oncol 2009

„New“ Paradigm Image guided adaptive brachytherapy:

Adaptation of target in space (3D) and time (4D)

• macroscopic tumour response plus change of overall topography

• adaptation of high risk Clinical Target Volume in 3D (space) and 4D (time) [each fraction]

• enables high radiation doses (up to >90 Gy)in limited volumes (HR CTV 15-80 ccm)

• prospective application of dose volume constraints 3D/4Dfor high risck CTV and organs at risk [each fraction]