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High Precision Radiation Therapy for Cancers of the Upper Abdomen - - PowerPoint PPT Presentation
High Precision Radiation Therapy for Cancers of the Upper Abdomen - - PowerPoint PPT Presentation
High Precision Radiation Therapy for Cancers of the Upper Abdomen Laura A Dawson M D Laura A. Dawson, M.D. Princess Margaret Hospital, University of Toronto, Toronto Ontario Canada Toronto, Ontario, Canada Elekta Oncology Disclosures
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Outline: RT for Upper Abdominal Ca pp
Historical (dismal) role of RT Overcoming challenges Example – RT for hepatocellular carcinoma Future (promising) role of RT
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Historical (Dismal) Role of RT – Why?
- Challenging to select appropriate patients
– Local, regional and distant occult metastases
- Tumorcidal dose RT not possible to deliver
– Tumor delineation – Moving organs – Many critical normal tissues
- Normal tissue toxicity
– Parallel fn organs – liver, kidneys S i l f t h ll b l i l d – Serial fn organs - stomach, small bowel, spinal cord… – Low whole organ RT tolerances – Partial organ tolerances not established Partial organ tolerances not established
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Potential Toxicities
- Hepatic injury
– Radiation induced liver disease (RILD)
A i t i it h t l l
- Anicteric ascites, hepatosplenomegaly
- Elevated liver enzymes (ALP > AST/ALT)
– Non-RILD hepatic toxicity Non RILD hepatic toxicity
- Elevation of transaminases
- Reactivation of viral hepatitis
- Liver decompensation
- Liver decompensation
- Biliary stricture
- Renal failure
- Renal failure
- Stomach, duodenal, colon bleeding, obstruction,
fistula, … fistula, …
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How to Deliver RT Safely
- Requires RT technological advances
– Imaging – Breathing motion management – Planning I id – Image guidance
- Understand normal tissues tolerances
A i t ti t l ti
- Appropriate patient selection
- Improve integration of RT with other therapies
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Technological Advances
- Improved imaging
– Tumor definition – Image fusion (CT, MRI) – Respiratory sorting – Motion measurement
- Conformal, computer aided RT planning
- Breathing motion management
- Image guided radiotherapy (IGRT)
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Imaging Imaging
- Multi-modal imaging: CT MR PET
- Multi-modal imaging: CT, MR, PET
- Multi-phasic imaging: CT, MR
– Arterial - HCC Venous - portal vein thrombus – Arterial - HCC, Venous - portal vein thrombus
- Image registration and fusion
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Radiation Planning
- Geometric conformation of dose
- Intensity modulated radiation therapy
Intensity modulated radiation therapy
- Automated computer optimization
Volume to be irradiated Prescription dose 50% dose
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Breathing Motion Management Breathing Motion Management
- Breathing motion measurement (1 – 3 cm)
– Fluoroscopy, cine MR, respiratory sorted CT
- Motion management strategies
– Increase volume irradiated – Breath hold G ti b
Planning target
– Gating beam – Track beam
volume, PTV
Free breathing Breath hold RT
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Image Guided Radiation Therapy, IGRT Image Guided Radiation Therapy, IGRT
- IGRT = Daily imaging immediately before or
during RT delivery to position patient more accurately and precisely accurately and precisely
- Changes in upper abdo
Changes in upper abdo
- rgan position day-to-day
– Free breathing – Breath hold
- IGRT increases likelihood of dose being delivered
- IGRT increases likelihood of dose being delivered
as planned
– Improved tumor control & less toxicity p y
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IGRT Is Not New
1951 Johns & Cunningham, Canada Co60 & xray designed 1958 Co60-xray implemented 1958 Lokkerbol, Netherlands Li & t t bl t b d i d Linac & retractable xray tube designed 1961 Linac-xray implemented
Canadian stamp demonstrating image guided Cobalt from 1951
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IGRT Is Not New
1951 Johns & Cunningham, Canada Co60 & xray designed 1958 Co60-xray implemented 1958 Lokkerbol, Netherlands Li & t t bl t b d i d Linac & retractable xray tube designed 1961 Linac-xray implemented Why didn’t IGRT catch on previously?
- Not efficient
- Less rationale, since other challenges
limited RT doses
Canadian stamp demonstrating image guided Cobalt from 1951
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IGRT 2008
MV EPID kV Fl k Ult d kV CT MV EPID kV Fluoroscopy + markers Ultrasound kV CT MV CT kV Cone beam CT MV cone beam CT MV CT kV Cone-beam CT beam CT
Dawson, Jaffray, JCO, 2007
MR Integration, …
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R i t S t d kV
4D (Temporal) IGRT
kV Fl Respiratory Sorted kV Cone Beam CT kV Fluoroscopy
Free Breathing Free Breathing CBCT CBCT CBCT CBCT
- Improved accuracy
- Improved precision
Planned doses = delivered doses
Exhale Exhale Inhale Inhale
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Understanding Normal Tissue RT Tolerances
Liver Toxicity
0 8 1.0
Veff
Liver volume irradiated
Liver Toxicity
0.6 0.8
Veff
3/3 2/3 1/3
icity
irradiated
0.4
1/3
- f Toxi
0.2
Risk
0.0 20 40 60 80 100 120
Dose (G ) 1 5 G bid
Dose (Gy)
Dose (Gy), 1.5 Gy bid
Dawson LA et al. IJROBP 2002
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Understanding Normal Tissue RT Tolerances
- Collaboration and consensus
Michigan, hyper# Colorado, 3 # Liver DVHs with no liver toxicity
Pan, Kavanaugh, Dawson et al, QUANTEC IJROBP, 2008
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HCC Radiotherapy
Planning CT at simulation kV cone beam CT at treatment treatment
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Hepatocellular Carcinoma Hepatocellular Carcinoma
- HCC - third cause of global cancer mortality
- Increasing in N America w increasing Hepatitis C
g g p
– 18 000 cases / year US in 2006
- Local therapy can cure
– Resection 50% 5 yr survival – Transplant 70% 5 year survival
- Predominantly hepatic recurrence
- < 15% of patients have resection/ transplant
- Overall 5 year survival < 10%
WHO and American Cancer Statistics 2003-2006
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Carbon Ions for HCC: Japan n=69
Ph II St d HCC 52 8 G / 4 # / 4 d
- Phase II Study HCC: 52.8 Gy/ 4 # / 4 days
- Med follow-up of 5.4 years
Local control 94%
< 3 cm 100% LOCAL CONTROL 94%
1
3-5 cm 90% 5-10 cm 93% >10 cm 100%
.6 .8
< = 5 cm (n=53) > 5 cm (n=16)
>10 cm 100%
G 3 t i it 3
.2 .4
- Gr. 3 toxicity n=3
Time (years)
1 2 3 4 5 6
Courtesy of H Tsujii, Japan Kato H, Tsujii H, et al: ICLA 06 2007, Barcelona; Tsuji et al, New Journal of Physics 10, 2008
(y )
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Carbon Ions for HCC: Japan n=69
Ph II St d HCC 52 8 G / 4 # / 4 d
- Phase II Study HCC: 52.8 Gy/ 4 # / 4 days
- Med follow-up of 5.4 years
Survival 3yr 5yr < 5 cm 62% 36%
OVERALL SURVIVAL
8 1
5 cm 62% 36% > 5 cm 64% 17%
4 .6 .8
< = 5 cm
.2 .4
> 5 cm
Time (years)
1 2 3 4 5 6
(y )
Courtesy of H Tsujii, Japan Kato H, Tsujii H, et al: ICLA 06 2007, Barcelona; Tsuji et al, New Journal of Physics 10, 2008
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PMH Phase I Study
- 41 patients
– 31 HCC (52% portal vein thrombosis) – 10 intrahepatic cholangiocarcinoma (IHC)
- Median volume 172 cc ( 9 – 1913)
- Individualized therapy
– Breath hold, IGRT, SBRT
M di d 36 G (24 54 G ) 6 f ti
- Median dose 36 Gy (24 – 54 Gy), 6 fractions
- No radiation induced liver disease (RILD)
Tse, JCO, 2008
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Toxicity: PMH
G d 3 / iti 1
- Grade 3 nausea/vomiting
1
- Grade 3 platelets
1 R di ti Li Di RILD
- Radiation Liver Disease, RILD
- Grade 3 liver enzymes
10 (8 preexisting) Decline in Child score 7 (5 with PD)
- Decline in Child score
7 (5 with PD)
- 1 small bowel obstruction: 24 mo post RT
p
- 1 duodenal perforation: 15 mo post RT
Pre RT 15 mo post RT Pre RT 15 mo post RT Tse, JCO, 2008
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45 y o man – Hepatocellular carcinoma 36 Gy/ 6 #
Response: PMH
45 y.o. man Hepatocellular carcinoma, 36 Gy/ 6 #
Baseline 9 months
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Overall Survival: PMH
1.0
- Med. Surv
95% CI Cholangioca 15.0 mo 6.5 - 29.0
0.8
urvival
HCC
11.7 mo 9.2 - 21.6
0.6
ability of Su
Survival
0 2 0.4
Proba
S
0.0 0.2 CH HCC
HCC Cholangiocarcinoma
5 10 15 20 25 30 35
Months
Months
Tse, JCO, 2008
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Future (Promising) Role of RT
- Biologic & image based improved patient selection
– Micro-metastases identification Treatment predictive biologic signatures – Treatment predictive biologic signatures
- Tumorcidal doses of RT to high risk targets only
– Biologic highest risk tumor delineation – Individualized doses – Multiple strategies to control organ motion – Multiple strategies to control organ motion
- Avoidance of normal tissue toxicity
- Improved integration of RT with other therapies
I d t f bd i l
- Improved outcomes for upper abdominal cancers
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