precision of pre-sirt predictive dosimetry...precision of pre-sirt predictive dosimetry...
TRANSCRIPT
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Precision of pre-SIRT predictive dosimetry
International Course on THERANOSTICS AND MOLECULAR RADIOTHERAPY
Department of Nuclear Medicine – Medical Physics
Jules Bordet Institute, Université Libre de Bruxelles
Brussels, Belgium
Hugo Levillain
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Imaging workflow pre-SIRT
Treatment Planning
3D CT Angiogram
Cone Beam CT (CBCT) 99mTc-MAA injection
99mTc-MAA SPECT/CT
Prevent post-therapy complication and select patient with good potential
outcome
3
1
Patient’s Selection
Diagnostic MRI, CT, PET/CT, SPECT/CT
1
Hepatobiliary scintigraphy Dynamic Planar + SPECT/CT
Patient stratification
2
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Imaging workflow post-SIRT
CBCT
90Y SIR-Spheres injection
Treatment 7 to 15 days after
simulation
90Y SIR-Spheres PET/CT
Patients follow up 6-8 weeks after treatment
Follow-up MRI, CT, PET/CT, SPECT/CT
3
4
We see what We treat
2
Response
assessment
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Personalized pre-SIRT predictive dosimetry
& SIRT therapeutic window
Optimize the therapeutic efficacy
Minimize the dose to organs at risk: Safety
Maximize the dose delivered to the tumor
3
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Problems
Therapeutic window
To be defined according to cutoffs definitions
Which dosimetry methodology?
Personalized pre-SIRT predictive dosimetry
Which dosimetry methodology?
Predictive power?
Precision and accuracy of pre-SIRT predictive
dosimetry
4
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Problems
Therapeutic window
To be defined according to cutoffs definitions
Which dosimetry methodology?
Personalized pre-SIRT predictive dosimetry
Which dosimetry methodology?
Predictive power?
Precision and accuracy of pre-SIRT predictive
dosimetry
5
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SIRT therapeutic window: therapeutic
effect
6 Cremonesi et al., 2014, frontiers in Oncology
Progressive disease
Threshold for response
Response
Partial Response / Stable disease
SIRsphere
Therasphere
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SIRT therapeutic window: therapeutic effect
Dose-response relationship based on 99mTc-MAA
SPECT/CT for mCRC patients
Flamen et al. 2008:
Significant response (ΔTLG>50%) for Dmean > 66 Gy
No standardization of image acquisition and reconstruction
Evolution of image modalities
7
R² = 0.26
-200-180-160-140-120-100
-80-60-40-20
020406080
100
0 20 40 60 80 100 120 140 160 180
TL
G c
han
ge
%
Simulated Absorbed Dose (Gy)
Flamen P. et al. 2008, Physics in Medicine and Biology
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Problems
Therapeutic window
To be defined according to cutoffs definitions
Which dosimetry methodology?
Personalized pre-SIRT predictive dosimetry
Which dosimetry methodology?
Predictive power?
Precision and accuracy of pre-SIRT predictive
dosimetry
8
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Dosimetry methodology
Medical Internal Radiation Dose (MIRD) formalism
Procedure guidelines based on MIRD model
Cumulated Activity (biological data): 3D quantification
S Factor (Physical data): Energy deposition into target volume
Organ/sub-organ level
Hypothesis: uniform distribution
9
Bolch.W. et al. 2009, Journal of nuclear medicine : official publication, Society of Nuclear Medicine
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Personalized 3D dosimetry (Planet Onco 3.0, Dosisoft®)
MIRD at voxel scale
Time Integrated Activity (TIA) map at voxel scale
Voxel S values (VSV) (Dieudonne et al., 2011)
Dieudonné, A., 2011 , Journal of Nuclear Medicine
10
Dosimetry methodology
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Personalized 3D dosimetry (Planet Onco 3.0, Dosisoft®)
Dose Volume Histogram (DVH)
Dieudonné, A., 2011 , Journal of Nuclear Medicine
11
90Y SIR-Spheres PET/CT 99m Tc-MAA SPECT/CT
VSV ⊗
Convert to 90Y-MS TIA map
90Y SIR-Spheres isodoses
Dosimetry methodology
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Personalized 3D dosimetry: Dose Volume Histograms
Dosimetry methodology
40 Gy – 100% uniform
40 Gy – 60% Heterogeneous
40 Gy – 60% uniform
20
40
60
80
100
0 40 60 80 100
V (%)
0 40 60 80 100 0 40 60 80 100
D (Gy)
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Personalized 3D dosimetry: Dose Volume Histograms
Dosimetry methodology
40 Gy – 100% uniform
40 Gy – 60% Heterogeneous
40 Gy – 60% uniform
20
40
60
80
100
0 40 60 80 100
V (%)
0 40 60 80 0 40 60 80 100
D (Gy)
100
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Personalized 3D dosimetry: Dose Volume Histograms
Dosimetry methodology
40 Gy – 100% uniform
40 Gy – 60% Heterogeneous
40 Gy – 60% uniform
20
40
60
80
100
0 40 60 80 100
V (%)
0 40 60 80 100 0 40 60 80 100
D (Gy)
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Jules Bordet Institute’s pre-SIRT dosimetry workflow
I) Images selection
99mTc-MAA SPECT/ CT (reference images)
Diagnostic images (FDG PET/CT, SPECT CT, IRM, CT)
Additional images: CBCT, hepatobiliary SPECT/CT
13
Dosimetry methodology
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Jules Bordet Institute’s pre-SIRT dosimetry workflow
II) 99mTc-MAA SPECT/ CT Liver delineation
Manually
14
Dosimetry methodology
Errors
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Jules Bordet Institute’s pre-SIRT dosimetry workflow
III) Images rigid co-registration
Automatic + visual inspection and manual corrections
15
Dosimetry methodology
Errors
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Jules Bordet Institute’s pre-SIRT dosimetry workflow
IV) 99mTc-MAA treated liver delineation (e.g. right liver)
Manually
Validation with CBCT
16
Dosimetry methodology
Errors
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Wahl.R. et al., 2009 , Journal of Nuclear Medicine
Jules Bordet Institute’s pre-SIRT dosimetry workflow
V)Lesions’ delineation
Fixed threshold based on PERCIST
17
Dosimetry methodology
Errors
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Jules Bordet Institute’s pre-SIRT dosimetry workflow
VI) Dosimetry using partition model
1) Safety
homogenous MAA distribution
Activity giving 40 Gy to the treated liver
18
Dosimetry methodology
Prescribed activity = 987 MBq
Lesion mean absorbed dose = 288 Gy 20
40
60
80
100
0 50 100 150 200 250 300
V (%)
D (Gy)
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20
40
60
80
100
Jules Bordet Institute’s pre-SIRT dosimetry workflow
VI) Dosimetry: Personalized 3D dosimetry (Planet Onco 3.0,
Dosisoft®)
2) Optimization
Dose volume histogram based
Activity giving 40% of the treated liver receive less than 40 Gy
EBRT safety criteria transformed using BED
19
Dosimetry methodology
Before optimization 35 Gy-40%
0 20 40 60 80 100 120 140 160
100
After optimization 40 Gy-40%
20
40
60
80
0 50 100 150 200
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Jules Bordet Institute’s pre-SIRT dosimetry workflow
VI) Dosimetry: Personalized 3D dosimetry (Planet Onco 3.0,
Dosisoft®)
2) Validation
Lesion mean absorbed dose = 339 Gy (+50 Gy)
Prescribed activity
20
Dosimetry methodology
Simulation 99mTc-MAA isodoses on baseline FDG PET/CT
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Jules Bordet Institute’s pre-SIRT dosimetry workflow
Pre-SIRT predictive dosimetry
Minimize the dose to the liver
Maximize the dose delivered to the tumor
Personalized activity prescription
21
Dosimetry methodology
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Problems
Therapeutic window
To be defined according to cutoffs definitions
Which dosimetry methodology
Personalized pre-SIRT predictive dosimetry
Which dosimetry methodology
Predictive power?
Precision and accuracy of pre-SIRT predictive
dosimetry
22
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Biology Vascularization
Hemodynamics
Dosimetry MAA as a surrogate of microspheres distribution?
Same catheter position?
Dosimetry methodology
Prepared vs prescribed activities?
Administered vs prescribed activities?
SIRT needs precise/accurate determination of
administered 90Y SIR-Spheres activity
Pre-SIRT dosimetry errors sources
23
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Precision and accuracy of pre-SIRT
dosimetry
SIRT needs accurate/precise determination of
administered 90Y SIR-Spheres activity
Affected by Stochastic and Systematic errors
Clinical dosimetry need first Precision
24
Re
spo
nse
Si
de
eff
ect
s
Re
spo
nse
Si
de
eff
ect
s
Stochastic Precision Systematic Accuracy
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Precision and accuracy of pre-SIRT
dosimetry
Dealing with accuracy
No gold-standard applicable in clinical routine
Expensive
Radionuclide calibrator and/or sources transport for calibration
4
Re
spo
nse
Si
de
eff
ect
s
Constant
Cross-validation of radionuclide
calibrator with 90Y SIR-Spheres
PET/CT’s calibration
25
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Quality assurance of activity administration
in SIRT
Evaluate the difference between administered
90Y SIR-Spheres activities:
Computed 𝐴𝑝𝑟𝑒𝑝𝑎𝑟𝑒𝑑 − 𝐴𝑟𝑒𝑠𝑖𝑑𝑢𝑎𝑙
Quantified on 90Y PET/CT images
26
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Retrospective study based on 73 patients
Single catheter position
No quantifiable shunt to non-target organs
Patients underwent
99mTc-MAA SPECT/CT
MAA perfusion volume (1-5% max)
Activity prescription
90Y SIR-Spheres PET/CT
27
Quality assurance of activity administration
in SIRT
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Administered activity
Computed (State of the art): 𝐴𝑝𝑟𝑒𝑝𝑎𝑟𝑒𝑑 − 𝐴𝑟𝑒𝑠𝑖𝑑𝑢𝑎𝑙
Quantified on 90Y PET/CT
Corrected from nuclear decay
28
Quality assurance of activity administration
in SIRT
1
2
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Computed administered activity 𝐴𝑝𝑟𝑒𝑝𝑎𝑟𝑒𝑑 − 𝐴𝑟𝑒𝑠𝑖𝑑𝑢𝑎𝑙
90Y SIR-Spheres activity to inject
Prepared in accordance to the prescription
Measured with radionuclide calibrator CRC-15R Capintec
Residual activity
Pre/Post-injection box doses’ rates measurements
29
Quality assurance of activity administration
in SIRT
1
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Quantified administered activity
90Y SIR-Spheres PET/CT images
GE-Healthcare Discovery 690 PET/CT
2 bed positions of 30min, voxel size: 2.7×2.7×3.3mm3
Images’ reconstruction (QUEST phantom study)
3D OSEM, 18 iterations, 3 subsets, 13.7 Gaussian post-filtering
Corrections: Attenuation, Diffusion, TOF, PSF inhomogeneity
30
Quality assurance of activity administration
in SIRT
2
Willowson.K. et al., 2015 , European Journal of Nuclear Medicine and Molecular Imaging
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Willowson.K. et al., 2015 , European Journal of Nuclear Medicine and Molecular Imaging
Carlier.T. et al., 2016 , Medical Physics
Quantified administered activity
Requires a volume
90Y SIR-Spheres PET/CT volume delineation?
No methods
Noise
Partial volume effect
Utilize the MAA volume
90Y SIR-Spheres PET/CT quantification
Predictive power of MAA for the volume
31
Quality assurance of activity administration
in SIRT
2
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Quantified administered activity
Registration corrected by visual inspection
32
Quality assurance of activity administration
in SIRT
2
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Quantified vs Computed administered activities
Univariate linear regression
Agreement between computed and quantified activities
Relative difference between the 2 measurements
Mean ± SD
Plot of errors as a function of treated volume size
Plot of errors as a function of the amount of injected activity
33
Quality assurance of activity administration
in SIRT
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Quantified vs Computed administered activities
34
R2=0.96
Qu
anti
fied
90Y-
MS
acti
vity
(M
Bq
)
Computed 90Y-MS activity (MBq)
Quality assurance of activity administration
in SIRT
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Quantified vs Computed administered activities
35
Mean relative difference=3.2±12.3%
Freq
ue
ncy
Relative difference (%)
Quality assurance of activity administration
in SIRT
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Quantified vs Computed administered activities
36
Quality assurance of activity administration
in SIRT
Rel
ativ
e d
iffe
ren
ce (
%)
Rel
ativ
e d
iffe
ren
ce (
%)
Treated Volume (cm3) Administered activity (MBq)
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Problems
Therapeutic window
To be defined according to cutoffs definitions
Which dosimetry methodology
Personalized pre-SIRT predictive dosimetry
Which dosimetry methodology
Predictive power
Precision and accuracy of pre-SIRT predictive
dosimetry
37
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Conclusion
Relative difference between computed and
quantified administered activities is relatively low
Good correlation of the 2 measurements: R2 = 0.96,
mean relative difference = 3.2 ± 12.3%
Knowledge of the precision of the correlation
Importance of images’ registration and segmentation
No correlation with the amount of injected activity or
with treated volume size
38
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Conclusion
Feasibility of a quality assurance process
90Y SIR-Spheres PET/CT can be used directly to
measure the administered activity
Demonstration of the predictive power of pre-SIRT
predictive dosimetry at liver scale
39
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Perspectives
90Y-MS PET/CT and 99mTc-MAA distributions’
correlation
Treatment 90Y SIR-Spheres isodoses
On baseline FDG PET/CT
Simulation 99mTc-MAA isodoses
On baseline FDG PET/CT
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Take home message
Therapeutic Window
Predictive dosimetry : treatment outcome
optimization
Personalized 3D Dosimetry workflow
Volume delineation and image registration
Safety: 40 Gy to the treated volume
Optimization: 40 Gy 40% based on DVH
Validation
Personalized activity prescription
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Thank you!
International Course on THERANOSTICS AND MOLECULAR RADIOTHERAPY