precision of pre-sirt predictive dosimetry...precision of pre-sirt predictive dosimetry...

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

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

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

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

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

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

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

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

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

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

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

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

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)

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

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)

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

Jules Bordet Institute’s pre-SIRT dosimetry workflow

II) 99mTc-MAA SPECT/ CT Liver delineation

Manually

14

Dosimetry methodology

Errors

Jules Bordet Institute’s pre-SIRT dosimetry workflow

III) Images rigid co-registration

Automatic + visual inspection and manual corrections

15

Dosimetry methodology

Errors

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

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

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)

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

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

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

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

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

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

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

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

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

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

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

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

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

Quantified administered activity

Registration corrected by visual inspection

32

Quality assurance of activity administration

in SIRT

2

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

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

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

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)

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

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

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

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

40

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

41

Thank you!

International Course on THERANOSTICS AND MOLECULAR RADIOTHERAPY