Precision of pre-sirt predictive dosimetry

Transcription

1 International Course on THERANOSTICS AND MOLECULAR RADIOTHERAPY Precision of pre-sirt predictive dosimetry Hugo Levillain Department of Nuclear Medicine Medical Physics Jules Bordet Institute, Université Libre de Bruxelles Brussels, Belgium

2 Imaging workflow pre-sirt 1 Patient s Selection Diagnostic MRI, CT, PET/CT, SPECT/CT 2 Patient stratification Hepatobiliary scintigraphy Dynamic Planar + SPECT/CT 3 3D CT Angiogram Cone Beam CT (CBCT) 99m Tc-MAA injection 99m Tc-MAA SPECT/CT Treatment Planning Prevent post-therapy complication and select patient with good potential outcome 1

3 3 Imaging workflow post-sirt CBCT 90 Y SIR-Spheres injection 90 Y SIR-Spheres PET/CT Treatment 7 to 15 days after simulation We see what We treat 4 Patients follow up 6-8 weeks after treatment Follow-up MRI, CT, PET/CT, SPECT/CT Response assessment 2

4 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

5 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

6 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

7 SIRT therapeutic window: therapeutic effect Progressive disease Threshold for response Response Partial Response / Stable disease SIRsphere Therasphere Cremonesi et al., 2014, frontiers in Oncology 6

8 TLG change % SIRT therapeutic window: therapeutic effect Dose-response relationship based on 99m Tc-MAA SPECT/CT for mcrc patients Flamen et al. 2008: R² = Simulated Absorbed Dose (Gy) Significant response (ΔTLG>50%) for D mean > 66 Gy No standardization of image acquisition and reconstruction Evolution of image modalities Flamen P. et al. 2008, Physics in Medicine and Biology 7

9 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

10 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 Bolch.W. et al. 2009, Journal of nuclear medicine : official publication, Society of Nuclear Medicine 9

11 Dosimetry methodology 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

12 Dosimetry methodology Personalized 3D dosimetry (Planet Onco 3.0, Dosisoft ) 90 Y SIR-Spheres PET/CT 99m Tc-MAA SPECT/CT 90 Y SIR-Spheres isodoses Convert to 90 Y-MS TIA map VSV Dose Volume Histogram (DVH) Dieudonné, A., 2011, Journal of Nuclear Medicine 11

13 Dosimetry methodology Personalized 3D dosimetry: Dose Volume Histograms 40 Gy 100% uniform 40 Gy 60% uniform 40 Gy 60% Heterogeneous 00 V (%) D (Gy)

14 Dosimetry methodology Personalized 3D dosimetry: Dose Volume Histograms 40 Gy 100% uniform 40 Gy 60% uniform 40 Gy 60% Heterogeneous 00 V (%) D (Gy)

15 Dosimetry methodology Personalized 3D dosimetry: Dose Volume Histograms 40 Gy 100% uniform 40 Gy 60% uniform 40 Gy 60% Heterogeneous 00 V (%) D (Gy)

16 Dosimetry methodology Jules Bordet Institute s pre-sirt dosimetry workflow I) Images selection 99m Tc-MAA SPECT/ CT (reference images) Diagnostic images (FDG PET/CT, SPECT CT, IRM, CT) Additional images: CBCT, hepatobiliary SPECT/CT 13

17 Dosimetry methodology Jules Bordet Institute s pre-sirt dosimetry workflow II) 99m Tc-MAA SPECT/ CT Liver delineation Manually Errors 14

18 Dosimetry methodology Jules Bordet Institute s pre-sirt dosimetry workflow III) Images rigid co-registration Automatic + visual inspection and manual corrections Errors 15

19 Dosimetry methodology Jules Bordet Institute s pre-sirt dosimetry workflow IV) 99m Tc-MAA treated liver delineation (e.g. right liver) Manually Validation with CBCT Errors 16

20 Dosimetry methodology Jules Bordet Institute s pre-sirt dosimetry workflow V)Lesions delineation Fixed threshold based on PERCIST Errors Wahl.R. et al., 2009, Journal of Nuclear Medicine 17

21 Dosimetry methodology Jules Bordet Institute s pre-sirt dosimetry workflow V (%) VI) Dosimetry using partition model 1) Safety Activity homogenous MAA distribution giving 40 Gy to the treated liver Prescribed activity = 987 MBq Lesion mean absorbed dose = 288 Gy D (Gy) 18

22 Dosimetry methodology 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 Before optimization 35 Gy-40% After optimization 40 Gy-40%

23 Dosimetry methodology 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 Simulation 99m Tc-MAA isodoses on baseline FDG PET/CT 20

24 Dosimetry methodology 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

25 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

26 Pre-SIRT dosimetry errors sources 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 90 Y SIR-Spheres activity 23

27 Response Side effects Response Side effects Precision and accuracy of pre-sirt dosimetry SIRT needs accurate/precise determination of administered 90 Y SIR-Spheres activity Affected by Stochastic and Systematic errors Systematic Accuracy Stochastic Precision Clinical dosimetry need first Precision 24

28 Response Side effects 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 Cross-validation of radionuclide calibrator with 90 Y SIR-Spheres PET/CT s calibration Constant 4 25

29 Quality assurance of activity administration in SIRT Evaluate the difference between administered 90Y SIR-Spheres activities: Computed A prepared A residual Quantified on 90 Y PET/CT images 26

30 Quality assurance of activity administration in SIRT Retrospective study based on 73 patients Single catheter position No quantifiable shunt to non-target organs Patients underwent 99m Tc-MAA SPECT/CT MAA perfusion volume (1-5% max) Activity prescription 90 Y SIR-Spheres PET/CT 27

31 Quality assurance of activity administration in SIRT Administered activity Computed (State of the art): A prepared A residual 1 Quantified on 90 Y PET/CT Corrected from nuclear decay 2 28

32 Quality assurance of activity administration in SIRT 1 Computed administered activity A prepared A residual 90 Y 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

33 Quality assurance of activity administration in SIRT 2 Quantified administered activity 90 Y SIR-Spheres PET/CT images GE-Healthcare Discovery 690 PET/CT 2 bed positions of 30min, voxel size: mm 3 Images reconstruction (QUEST phantom study) 3D OSEM, 18 iterations, 3 subsets, 13.7 Gaussian post-filtering Corrections: Attenuation, Diffusion, TOF, PSF inhomogeneity Willowson.K. et al., 2015, European Journal of Nuclear Medicine and Molecular Imaging 30

34 Quality assurance of activity administration in SIRT Quantified administered activity 2 Requires a volume 90 Y SIR-Spheres PET/CT volume delineation? No methods Noise Partial volume effect Utilize the MAA volume 90 Y SIR-Spheres PET/CT quantification Predictive power of MAA for the volume Willowson.K. et al., 2015, European Journal of Nuclear Medicine and Molecular Imaging Carlier.T. et al., 2016, Medical Physics 31

35 Quality assurance of activity administration in SIRT Quantified administered activity 2 Registration corrected by visual inspection 32

36 Quality assurance of activity administration in SIRT 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

37 Quantified 90 Y-MS activity (MBq) Quality assurance of activity administration in SIRT Quantified vs Computed administered activities R 2 =0.96 Computed 90 Y-MS activity (MBq) 34

38 Frequency Quality assurance of activity administration in SIRT Quantified vs Computed administered activities Mean relative difference=3.2±12.3% Relative difference (%) 35

39 Relative difference (%) Relative difference (%) Quality assurance of activity administration in SIRT Quantified vs Computed administered activities Treated Volume (cm3) Administered activity (MBq) 36

40 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

41 Conclusion Relative difference between computed and quantified administered activities is relatively low Good correlation of the 2 measurements: R 2 = 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

42 Conclusion Feasibility of a quality assurance process 90 Y 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

43 Perspectives 90 Y-MS PET/CT and 99m Tc-MAA distributions correlation Simulation 99m Tc-MAA isodoses On baseline FDG PET/CT Treatment 90 Y SIR-Spheres isodoses On baseline FDG PET/CT 40

44 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

45 International Course on THERANOSTICS AND MOLECULAR RADIOTHERAPY Thank you!