Image Image- -Guided and Adaptive Guided and Adaptive - - PowerPoint PPT Presentation

Image Image-

• Guided and Adaptive

Guided and Adaptive Radiotherapy Radiotherapy Radiotherapy Radiotherapy

PMH 50 PMH 50th

th Conference

Conference A.

• A. Fyles

Fyles y

• Dept. of Radiation Oncology
• Dept. of Radiation Oncology

Princess Margaret Hospital Princess Margaret Hospital

IMRT for IMRT for Cervix Cancer Cervix Cancer

Four-field IMRT

• M. Milosevic, PMH-RMP IGRT, 25/1/2008

Challenges in IMRT for Cervix Cancer Challenges in IMRT for Cervix Cancer g

Target Identification MR CT

• MR vs CT
• Nodal targets
• Online image quality

Online image quality Organ motion

• Influence of

– Bladder filling – Rectal filling g – Normal uterus position

Workload Workload

PMH CTV Definition PMH CTV Definition

GT GTV

Cervix Vagina Uterus Cervix

CTV

g Parametria

• CTV = GTV (+0.7cm margin) + Cervix + parametria

+ lower 2cm uterus + upper 2cm vagina

• Nodal CTV as per Taylor et al

Nodal CTV as per Taylor et al

• Normal Organs at Risk
• rectum, bladder, sigmoid, bowel, bone etc.

Point of Interest Analysis in 16 Patients Point of Interest Analysis in 16 Patients Mean Values Mean Values Point of Interest Analysis in 16 Patients Point of Interest Analysis in 16 Patients – Mean Values Mean Values

14.0 mm 3.8 mm 6.2 mm 9.6 mm 1.7 mm 1.4 mm 1.6 mm 5.6 mm

INTERFRACTION INTRAFRACTION

+

Internal Uterine Fundus Internal Uterine Fundus Cervical Os Cervical Os

y + z

Point of Interest Analysis in 16 Patients Point of Interest Analysis in 16 Patients – – Mean Values Mean Values

14.0 mm 3.8 mm UB = UB = Uncertainty Uncertainty B d B d

Cranio Cranio-

• Caudal

Caudal (mm) (mm) Ant Ant-

• Post

Post (mm) (mm)

6.2 mm 9.6 mm 1.7 mm 1.4 mm 1.6 mm 5.6 mm Bounds Bounds (confidence (confidence limits) limits)

(mm) (mm) (mm) (mm) INTERFRACTION INTRAFRACTION Total Total Intra Intra Total Total Intra Intra Fundus UB Fundus UB 36.9 36.9 9.6 9.6 16.4 16.4 4.3 4.3

+

Internal Uterine Fundus Internal Uterine Fundus Cervical Os Cervical Os

Fundus UB Fundus UB 36.9 36.9 9.6 9.6 16.4 16.4 4.3 4.3 Os UB Os UB 14.8 14.8 3.6 3.6 24.8 24.8 4.0 4.0

y + z

Adapting to Change Adapting to Change

• Tumors are heterogeneous

Tumors are heterogeneous

• Position changes

Position changes

+

– Inter Inter-

• fraction, Intra

fraction, Intra-

• fraction

fraction

• Size and shape changes

Size and shape changes

• Biology changes

Biology changes

+ +

8 Gy Pre-Tx

Tumour Shrinkage & Deformation

20 Gy 28 Gy

• Influence of:

– Tumour factors

• Biology

– Hypoxia

T t t f t

38 Gy 48 Gy

– Treatment factors

• Chemo-radiation

Adaptive Image Adaptive Image-Guided RT Guided RT Adaptive Image Adaptive Image-Guided RT Guided RT

• Complex dynamics of

OAR & t t ti OAR & target motion

• Concerns:

M i ? – Margins? – Geographical miss – ↑ dose to normal tissues ↑ dose to normal tissues

• What you see is not

What you get

• Adaptive approach is

needed for treatment of intact cervix cancer intact cervix cancer

IMRT Lymph Node Plan IMRT Lymph Node Plan IMRT Lymph Node Plan IMRT Lymph Node Plan

Role for image- guided guided nodal targeting using g USPIO MR

Lymph Node Margins Lymph Node Margins

2 cm radial expansion around iliac vessels

Shih, 2005 Shih, 2005 Taylor, 2005 Taylor, 2005

LN Movement During RT LN Movement During RT

Coverage of Unified nCTV7

105 100 105 age

Day 1 CTV Summed CTV

95 entage Covera 85 90 Perce 85 4 8 12 16 20 2-mm Expansions of nCTV7

Chan and Dinniwell Chan and Dinniwell

4 mm PTV expansion encompasses 4 mm PTV expansion encompasses >90% of LN movement >90% of LN movement

• M. Milosevic, PMH-RMP IGRT, 25/1/2008

Delivered vs. Planned Dose Delivered vs. Planned Dose

Image at T=0 Image at T=1 Mesh-Based Biomechanical Model

• Motion

Motion

• Motion

Motion

• Deformation

Deformation

• Dose accumulation

Dose accumulation

• Adaptive re

Adaptive re-

• planning

planning

MORFEUS MORFEUS MORFEUS MORFEUS

Slide c/o Kristy Brock Slide c/o Kristy Brock

p p g p g

CT_0

BASELINE

WEEK 1 WEEK 2 WEEK 3 WEEK 4 WEEK 5 MRI_0 Contours Contours MRI_1 Contours Contours Contours Contours MRI_2 Contours Contours MRI_3 Contours Contours MRI_4 Contours Contours MRI_5 Sur Surface ace Sur Surface ace Meshes Meshes Meshes Meshes Sur Surface ace Sur Surface ace Meshes Meshes Meshes Meshes Sur Surface ace Sur Surface ace Meshes Meshes Meshes Meshes Sur Surface ace Sur Surface ace Meshes Meshes Meshes Meshes Sur Surface ace Sur Surface ace Meshes Meshes Meshes Meshes Sur Surface ace Sur Surface ace Meshes Meshes Meshes Meshes

Nominal Nominal Nominal Nominal Plan Plan Plan Plan Dose Dose Accumulated Accumulated Pl Pl

Meshes Meshes Meshes Meshes Meshes Meshes Meshes Meshes Meshes Meshes Meshes Meshes Meshes Meshes Meshes Meshes Meshes Meshes Meshes Meshes Meshes Meshes Meshes Meshes

Plans Plans

Acc Dose cc Dose Acc Dose cc Dose Acc Dose cc Dose Acc Dose cc Dose Acc Dose cc Dose Acc Dose cc Dose Acc Dose cc Dose Acc Dose cc Dose Acc Dose cc Dose Acc Dose cc Dose

Def Deformable Dose A rmable Dose Accumulation ccumulation Def Deformable Dose A rmable Dose Accumulation ccumulation Def Deformable Dose A rmable Dose Accumulation ccumulation Def Deformable Dose A rmable Dose Accumulation ccumulation

Dose Dose Dose Dose Accumulat Accumulated d Accumulat Accumulated d

Acc Dose cc Dose wk1 wk1 Acc Dose cc Dose wk1 wk1 Acc Dose cc Dose wk2 wk2 Acc Dose cc Dose wk2 wk2 Acc Dose cc Dose wk3 wk3 Acc Dose cc Dose wk3 wk3 Acc Dose cc Dose wk4 wk4 Acc Dose cc Dose wk4 wk4 Acc Dose cc Dose Wk5 Wk5 Acc Dose cc Dose Wk5 Wk5

Plans Plans Plans Plans Nominal Nominal Plan Plan Adaptive Adaptive Adaptive Adaptive Re Re-

• plan

plan

Initial IMRT strategy Initial IMRT strategy – 10 pts 10 pts Initial IMRT strategy Initial IMRT strategy – 10 pts 10 pts

• LM (large margin) plan
• SM (small margin) plan

– 1-2 cm PTV margin – Expectation

• little OAR sparing

– 0.5 cm PTV margin – Expectation

• Some OAR sparing

little OAR sparing

• Target always covered

Some OAR sparing

• Target missed

Initial IMRT strategy Initial IMRT strategy – 10 pts 10 pts Initial IMRT strategy Initial IMRT strategy – 10 pts 10 pts

• Adaptive re-plan

p p

– Union CTV of 1st 3 image sets (iCTV) – Expectation

M OAR i

• More OAR sparing
• Target coverage better
• Results

– LM plan covered most pts – SM plan seemed adequate for more pts than expected expected – Re-plan did not spare as much OAR as hoped

• WHY?

WHY?

WHY? WHY? WHY? WHY?

• Large CTV – tumour shrinkage did not influence

treatment volume as much as expected

• Organ motion – iCTV – resulted in even larger CTVs

than baseline than baseline

• Estimates of 3D margins too generous based on

previous POI data

• Influence of bladder / rectal filling

– Heterogeneous despite bowel & bladder prep Caused large displacements in CTV location in some pts – Caused large displacements in CTV location in some pts

• Influence of uterus position

2nd

nd Adaptive strategy

Adaptive strategy – 25 pts 25 pts 2 Adaptive strategy Adaptive strategy – 25 pts 25 pts

• Use of ultra-small PTV margins (0.3cm)

g ( )

• Assume perfect set-up daily (CBCT)
• Separate out pts into consistent & variable

Separate out pts into consistent & variable bladders

• Adaptive re-plan – after 2nd wk treatment, use

p p ,

• nly imaging at that time point, no union CTV.

25pts 25pts

98% of the PTV to be covered by the 95% isodose for all plans 98% of the PTV to be covered by the 95% isodose for all plans Plan evaluation criteria: Plan evaluation criteria: 98% of GTV received 5000cGy; 98% HRCTV received ≥ 4900cGy 98% of GTV received 5000cGy; 98% HRCTV received ≥ 4900cGy

Dose Accumulation with Inter Dose Accumulation with Inter-

• Fraction Motion Applied

Fraction Motion Applied

Consistent Bladders Consistent Bladders

Dose Accumulation with Inter Dose Accumulation with Inter Fraction Motion Applied Fraction Motion Applied

Variable Bladders Variable Bladders

Nom SM Nom SM Acc SM Acc SM Acc AM Acc AM

GTV GTV (D98)

(D98)

5036 5036 5014 5014 5031 5031 HRCTV HRCTV (D98)

(D98)

4923 4923

4858 4858 4858 4858

4909 4909

Nom SM Nom SM Acc SM Acc SM Acc AM Acc AM

GTV GTV (D98)

(D98)

5024 5024 4987 4987 5008 5008 HRCTV HRCTV (D98)

(D98)

4911 4911

4783 783 4783 783 4780 780 4780 780

HRCTV HRCTV (D98)

(D98)

4923 4923

4858 4858 4858 4858

4909 4909 Rectum Rectum

(V45) (V45)

54 54 51 51

41 41 41 41

Sigmoid Sigmoid 59 59 61 61

39 39 39 39

HRCTV HRCTV (D98)

(D98)

4911 4911

4783 783 4783 783 4780 780 4780 780

Rectum Rectum (V45)

(V45)

52 52 50 50

41 41 41 41

Sigmoid Sigmoid (V45)

(V45)

61 61 67 67 51 51 Sigmoid Sigmoid

(V45) (V45)

59 59 61 61

39 39 39 39

Bladder Bladder

(Mean) (Mean)

4002 4002 4103 4103

3963 3963 3963 3963

Bladder Bladder

(Mean) (Mean)

4065 4065 3960 3960 3930 3930

P < P < 0.05 0.05 P < P < 0.05 0.05 compared to Nominal SM plan

Conclusions of MR Study Conclusions of MR Study

• Tumour & organ dynamics within the

pelvis is complex

• Inter-fraction motion is a major issue in

cervix cancer, supporting IGRT S ll i t f ti d LN

• Small inter-fraction and LN

motion/deformation

• Tumour regression during treatment

g g suggests adaptive IGRT

• Conventional plan ≠ Delivered dose
• Daily image-guidance and adequate

bladder prep is essential

• Adaptive strategy may be successful for

Adaptive strategy may be successful for some patients

Cervical Stump Carcinoma Cervical Stump Carcinoma Cervical Stump Carcinoma Cervical Stump Carcinoma

• 45 year old woman,

y , previous sub-total hysterectomy for fibroids

• MR

– 6 cm. tumor replacing cervix, small pelvic nodes p – sigmoid looped

• ver over tumor

IMRT Boost Treatment IMRT Boost Treatment IMRT Boost Treatment IMRT Boost Treatment

• 5-10% of patients -
• Boost to 70 - 75 Gy

unsuitable for brachytherapy

• Gross nodal disease may

be treated to 65-70 Gy

• Cervical stump
• Sidewall or nodal disease

that receives less than 60

• Other means of radiation

boost St d d EBRT that receives less than 60 Gy (EBRT and IC)

• PMH IMRT dose of 25.2

– Standard EBRT

• Limited by normal

tissue tolerance Gy in 14 fractions tissue tolerance (dose of 60-65 Gy)

IMRT Boost IMRT Boost - Issues Issues IMRT Boost IMRT Boost - Issues Issues

• Boost Volume
• Cervix alone – simulating IUA brachytherapy
• Cervix and pelvic sidewall(s)
• Organ movement.

I l di bl dd d t l ti

• Including bladder and rectal preparation
• Set-up reproducibility

I bili ti

• Immobilization

IMRT Boost Spares Normal Organs IMRT Boost Spares Normal Organs

Bladder/Rectum Femoral heads

Para Para-aortic Radiation aortic Radiation Para Para-aortic Radiation aortic Radiation

• Positive pelvic

Positive pelvic nodes and/or small PAN or recurrence

• Concurrent

cisplatin

• Risk of toxicity

GI, hematologic

Para Para-

• aortic Radiation with Simultaneous

aortic Radiation with Simultaneous Integrated Boost Integrated Boost Integrated Boost Integrated Boost

Dose-Volume Histogram

Kidneys/Small Bowel

Histogram

Bowel

Post Post-

• Operative Adjuvant Pelvic IMRT

Operative Adjuvant Pelvic IMRT

• Recent RTOG Phase

II trial of feasibility

• Toxicity decreased
• esp. GI
• Possible benefit if

chemo-radiation

• Target motion issues

Target motion issues minimized with ITV (simulation bladder t d f ll) empty and full)

• Cone-beam imaging

for bone matching for bone matching

MR Image MR Image Guided Guided MR Image MR Image-Guided Guided Brachytherapy Brachytherapy for Cervix Cancer for Cervix Cancer for Cervix Cancer for Cervix Cancer

• Adapt to changing volume

Adapt to changing volume p g g p g g

• IR

IR-

• CTV

CTV: Tumor at diagnosis Tumor at diagnosis 20 Gy 20 Gy

• HR

HR-

• CTV

CTV: Residual tumor at BT Residual tumor at BT 40 Gy from BT 40 Gy from BT 40 Gy from BT 40 Gy from BT

• Reduced toxicity

Reduced toxicity

• Identification of

Identification of “non “non responders” responders” “non “non-responders” responders”

• M. Milosevic, PMH-RMP IGRT, 25/1/2008

Image Image-

• Guided Brachytherapy

Guided Brachytherapy

Std brachytherapy is not optimal for all patients Std brachytherapy is not optimal for all patients y py p p y py p p

90 100 70 80

%)

40 50 60

Volume (%

HR-CTV 20 patients

10 20 30

V

Standard plans MR-dosimetry

(Zwahlen)

V100

10 20 40 60 80 100 120 140 160 180 200

Dose (%)

Image Image-

• Guided Brachytherapy

Guided Brachytherapy

30 30 30

g y py y py

20 25

me (cm 3)

20 25

me (cm 3)

20 25

me (cm 3)

HR-CTV 20 patients Standard plans

15

wall volum

Rectum

15

wall volum

Rectum

15

wall volum

Rectum

MR-dosimetry

(Zwahlen)

5 10

Rectal w

D2cm3

5 10

Rectal w

5 10

Rectal w

D2cm3

1000 2000 3000 4000 5000

D2cm

1000 2000 3000 4000 5000 1000 2000 3000 4000 5000

D2cm

Dose (cGy) Dose (cGy) Dose (cGy)

• M. Milosevic, PMH-RMP IGRT, 25/1/2008

Optimized IG Optimized IG-

• Brachytherapy

Brachytherapy

D2cm3 OAR Tumor size Conventional (Gy) Optimized (Gy) Change (%) All

Optimization Optimization

All tumors 25 ±8.7 22 ±6.6

• 14%*

Small 26 ±3.2 19 ±5.7

• 32%*

Sigmoid colon Large 25 ±7.4 24 ±6.7

• 3%

20 cases 20 cases HR HR-

• CTV

CTV > >40 Gy 40 Gy IR IR CTV CTV >20 G 20 G

Large 25 ±7.4 24 ±6.7 3% All tumors 16 ±6.2 16 ±6.7 Small 16 ±7.8 14 ±7.6

• 14%*

Rectum

IR IR-CTV CTV >20 Gy 20 Gy Point A Point A < <40 Gy 40 Gy

Large 17 ±4.5 19 ±4.5 +14%* All tumors 31 ±9.2 30 ±9.8

• 2%

Small 30 ±8.7 26 ±9.6

• 12%*

Bladder Large 32 ±9.9 34 ±8.6 +6%

Daniel Zwahlen, 2007 Daniel Zwahlen, 2007

• M. Milosevic, PMH-RMP IGRT, 25/1/2008

Optimized IG Optimized IG-

• Brachytherapy

Brachytherapy p y py y py

145 patients 145 patients

Local control

T1b/2a 15% T1b/2a 15% T2b/3a 59% T2b/3a 59%

Local control CSS

T3b 26% T3b 26% >5 cm 54% >5 cm 54%

OS

LN 39% LN 39% RT RT+ +CT CT

Late Toxicity Late Toxicity

• Gr. 3
• Gr. 3-4 GI 4%

4 GI 4%

Optimized BT Optimized BT 80 80-

• 85 Gy

85 Gy

G 3 G 3 G % G % GU 4% GU 4% Vaginal 5% Vaginal 5%

Potter, 2007 Potter, 2007

• M. Milosevic, PMH-RMP IGRT, 2008

Optimized IG Optimized IG-

• Brachytherapy

Brachytherapy p y py y py

145 patients 145 patients

Local control Small tumors

T1b/2a 15% T1b/2a 15% T2b/3a 59% T2b/3a 59%

Local control CSS Large tumors Small tumors

T3b 26% T3b 26% >5 cm 54% >5 cm 54%

OS

LN 39% LN 39% RT RT+ +CT CT

Late Toxicity Late Toxicity

• Gr. 3
• Gr. 3-4 GI 4%

4 GI 4%

Local Control

Optimized BT Optimized BT 80 80-

• 85 Gy

85 Gy

G 3 G 3 G % G % GU 4% GU 4% Vaginal 5% Vaginal 5%

Potter, 2007 Potter, 2007

• M. Milosevic, PMH-RMP IGRT, 2008

What Next? What Next? What Next? What Next?

• Work by our group &

th

• Contouring

l t &

• thers

– poor correlation between rectal & bladder volumes and cervix position

nomenclature & guidelines (e.g. GEC- ESTRO and Post-op RTOG)

and cervix position

• Look at influence of

uterus position on target ti RTOG)

– International collaboration – RTOG group in June 08

motion

• Simple class solution /

margin recipe unlikely

group in June 08

• Any adaptive strategy

needs to be i di id li d g y given complexity of target motion & deformation individualised

• At present IMRT not

ready for intact cervix y

What next? What next? What next? What next?

• Validate modeled findings with independent

g p cohort of pts with more frequent imaging

– 2-3 MR scans per wk – Initial bladder full & bladder empty MRIs – CBCT during treatment

E l f ibili f i CBCT

• Explore feasibility of contouring on CBCT

images Ulti t l ti d ti

• Ultimate goal – propose prospective adaptive

IMRT strategy for cervix patients

Princess Margaret Hospital Princess Margaret Hospital

Radiation Oncology: Radiation Oncology: M. Milosevic, K. Lim, P. Chan, D. Zwahlen, R. Dinniwell, W.

• M. Milosevic, K. Lim, P. Chan, D. Zwahlen, R. Dinniwell, W.

Levin, L. Manchul Levin, L. Manchul Medical Physics: Medical Physics: Y Y-

• B Cho, K. Brock, J. Jezioranski, I. Yeung, T. Craig,

B Cho, K. Brock, J. Jezioranski, I. Yeung, T. Craig, A Beiki A Beiki Ardakani J Stewart J Moseley M Sharpe D Jaffray Ardakani J Stewart J Moseley M Sharpe D Jaffray

• A. Beiki
• A. Beiki-Ardakani, J. Stewart, J. Moseley, M. Sharpe, D. Jaffray

Ardakani, J. Stewart, J. Moseley, M. Sharpe, D. Jaffray Medical Imaging: Medical Imaging:

• M. Haider
• M. Haider

Radiotherapy: Radiotherapy:

• V. Kelly, J. Paterson
• V. Kelly, J. Paterson

Biostatistics: Biostatistics: M Pintilie G Lockwood M Pintilie G Lockwood Biostatistics: Biostatistics:

• M. Pintilie, G. Lockwood
• M. Pintilie, G. Lockwood

RaySearch Laboratories AB RaySearch Laboratories AB

• A. Lundin, H. Rehbinder, J. L
• A. Lundin, H. Rehbinder, J. Lö

öf f

Supported by: Supported by:

National Cancer Institute of Canada through the Terry Fox Run National Cancer Institute of Canada through the Terry Fox Run Giovanni and Concetta Guglietti Family Trust Giovanni and Concetta Guglietti Family Trust

• M. Milosevic, PMH-RMP IGRT, 25/1/2008