predictive dosimetry: bsa vs. partition model...predictive dosimetry: bsa vs. partition model s....

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Predictive dosimetry:

BSA vs. Partition Model S. Gnesin

Institute of Radiation Physics,

Lausanne University Hospital, Lausanne, Switzerland

Theragnostic, Bruxelles, 4 October 2017

SPECT 99mTc-MAA PET 90Y TOF

NTV

TV TV

NTV

Contents

• Why dosimetry ?

- Scientific evidences

• Which dosimetry ?

- BSA and mBSA

- Partition Model dosimetry

- Predictive vs. post treatment dosimetry

• Conclusion

Liver

Catheter-guided

microsphere injection

Selective tumor

vascularization

Introduction to Y-90 Radioembolization

Yttrium-90 microsphere radioembolization is a valuable therapeutic option in

unresectable hepatocellular carcinoma (HCC).

Tumor vs. non-tumor differential vascularization

microsphere dose deposition

on the radiation cross-fire region

Tumor cell killing

not irradiated cells

tumour proliferation

Radioembolization of hepatic tumors, A. Kennedy, J Gastrointest Oncol 2014;5(3):178-189

2 107 resin-spheres/GBq

Two devices are clinically available

Resin-Spheres glass-spheres

Similar size (~ 30 mm)

Different specific activity

4 105 glass-spheres/GBq

! Differences in activity deposition heterogeneity

and embolic effect !

Different microsphere density

SIRTeX SIR-Spheres® Therasphere®

Liver

Catheter-guided


Selective tumor

vascularization

30 mm

Radioembolization of hepatic tumors

A. Kennedy, J Gastrointest Oncol 2014;5(3):178-189

Liver

Catheter-guided


Selective tumor

vascularization

Therapy preparation via Tc-99m MAA

administration

Catheter fluoroscopy guided

procedure

PET 90Y TOF

NTV

TV TV

NTV

Post-treatment 90Y TOF PET acq.

Tumour (TV) and non-tumour

volume (NTV) delineation

Average signal in:

TV (STV) and NTV (SNTV)

Tum. to Non-Tum. Ratio (TNR)

TNR = STV/SNTV

SPECT 99mTc-MAA

Tc-99m MAA SPECT/CT acq.

TV

NTV

Post-treatment;

- 90Y Bremmsstrahlung SPECT/CT acq.

For target deposition and possible

extrahepatic shung assessment

Why dosimetry?

• Radiobiological effects are dose dependent

• Response to treatment :

Lesion response (efficacy): dose/response correlation

Spare healthy tissue and/or avoid/limit toxicity (safety)

The aim is to treat the tumor

while preserving the liver function

Scientific evidences (1)

> 120 Gy

< 120 Gy

the treatment was well tolerated

Tumour regression was found to be dose

related.

Progressive or static disease occurred in a

higher proportion of patients whose tumours

received 120 Gy

We conclude that yttrium-90 microsphere

therapy is:

safe

tumour response is dose related.

A tumour dose of > 120 Gy is recommended.

HCC patients

Resins spheres

C. Chiesa et al, Eur J Nucl Med Mol Imaging (2015) 42:1718–1738 Radioembolization of hepatocarcinoma with 90Y glass microspheres: development of an individualized treatment planning strategy based on dosimetry and radiobiology

Efficacy: Dose-response correlation

(HCC/glass spheres)

Safety: Normal Tissue Complication

Probability (HCC/glass spheres)

Normal tissue complication probability (NTCP)

as a function of the mean absorbed dose D (target

volume)

Acceptable LD risk of 15 % corresponds to the main

planning limit of 75 Gy to whole parenchyma

EASL response

Increase with dose to the lesion


E. Garin et al, Eur J Nucl Med Mol Imaging (2013) Boosted selective internal radiation therapy with 90Y-loaded glass microspheres (B-SIRT) for

hepatocellular carcinoma patients: a new personalized promising concept.

Conclusion: Dosimetry based on MAA SPECT/CT was able to accurately predict

response and survival in patients treated with glass microspheres

SIRT 90Y on HCC: Time to progression (TTP)

and overall survival (OS)

Response (TTP, OS) stratification according to

lesion delivered dose


Dose–Response correlation in colorectal cancer liver metastases (Resin spheres, administered activity according to BSA)

AF. van den Hoven et al. J Nucl Med 2016; 57:1014–1019

Insights into the Dose–Response Relationship of Radioembolization with Resin 90Y-Microspheres:

A Prospective Cohort Study in Patients with Colorectal Cancer Liver Metastases

TLG decrease > 50%

TLG decrease < 50%

Dose to tumor TLG

D> 60 Gy

D < 60 Gy


Conclusions: Lesions receiving an average dose greater than 50 Gy are likely

to have a significant response.


Dosimetry of 90Y (self S-Factor from Olinda)

0%

25%

50%

75%

100%

0 20 40 60 80 100 120 140 160 180 200

90Y radioembolization : Which dosimetry?

only morphologic input data (CT, MR) + patient size Body Surface Area (BSA)

Resin-spheres dosimetry: BSA

fractional tumor burden

Liver involvement (mBSA)

TV

NTV V tot liver = 2000 mL

V RL = 1500 mL (75% of total liver)

V TV = 450 mL (30% of the target volume =RL)

Patient of 1.8m and 80 kg Patient BSA = 2m2

V NTV = 1050 mL

Target: right liver (RL)

TNR =STV/STV = 3

A BSA = ( (2-0.2) + (450/1500) ) x 0.75 = 1.575 GBq

D mean,RL = (50 Gy/GBq.kg x 1.575 GBq)/(1.5x1.04 kg) =50.5 Gy

D in 1kg / GBq A BSA (GBq) m RL (GBq) D TV = 94 Gy

D NTV = 31.3 Gy

SPECT 99mTc-MAA

TV

NTV Partition model (TV,NTV, RTV/NTV, L) 99mTc-MAA SPECT data

90Y radioembolization : Which dosimetry?

Resin-spheres dosimetry: Partition Model

V tot liver = 2000 mL

V RL = 1500 mL (75% of total liver)


APM with a limit of 40 Gy to NTV

V NTV = 1050 mL

TV

NTV


TNR =STV/STV = 3 A PM,40Gy = 2.01 GBq

D mean,RL =64 Gy D TV = 120 Gy D NTV =40 Gy

TV

NTV V tot liver = 2000 mL

V RL = V Target =1500 mL (75% of total liver)


V NTV = 1050 mL


Recommended DTarget =[80-150] Gy not account for TV, NTV and RTV/NTV

Glass-sphere dosimetry

only morphologic input data (CT, MR)

A Target,120Gy = 120x1500x1.03/50= 3.71GBq

D TV =225 Gy D Target = 120 Gy D NTV =75 Gy

A Target,80Gy = 80x1500x1.03/50= 2.47GBq

D TV =150 Gy D Target = 80 Gy D NTV =50 Gy

Vol target 1500 mL

TV=30% 450 mL

RTF = 3 Aadmin D TV D NTV D target A PM/A BSA

BSA 1.57 94 31.3 50.1

PM 40 2.01 120 40 64 1.28

Glass 80 2.47 150 50 80

Glass 120 3.71 225 75 120

Vol target 1500 mL

TV=10% 150 mL


BSA 1.42 113.2 37.7 45.3

PM 40 1.51 120 40 48.1 1.06

Glass 80 2.47 200 67 80

Glass 120 3.71 300 100 120

Vol target 1500 mL

TV=50% 750 mL


BSA 1.72 82.3 27.4 54.8

PM 40 2.51 120 40 80 1.46

Glass 80 2.47 120 40 80

Glass 120 3.71 180 60 120

Vol target 1500 mL

TV=5% 75 mL


BSA (2m2) 1.38 120 40 44

PM 40 1.38 120 40 44 1.00

Glass 80 2.47 218 73 80

Glass 120 3.71 327 109 120

T

V

NTV

TNR =STV/STV = 3

T

V

NTV

TV

NTV

TV

NTV

T

V

NTV

T

V

NTV

TV

NTV

TV

NTV

TNR =STV/STV = 6

Vol target 1500 mL

TV=5% 75 mL


BSA (2m2) 1.38 121 35 44

PM 40 1.57 240 40 50 1.14

Glass 80 2.47 384 64 80

Glass 120 3.71 576 96 120

Vol target 1500 mL

TV=10% 150 mL


BSA 1.42 180 30 45

PM 40 1.88 240 40 60 1.32

Glass 80 2.47 320 53 80

Glass 120 3.71 480 80 120

Vol target 1500 mL

TV=30% 450 mL


BSA 1.57 120 20 50

PM 40 3.14 240 40 100 2.00

Glass 80 2.47 192 32 80

Glass 120 3.71 287 48 120

Vol target 1500 mL

TV=50% 750 mL


BSA 1.72 94 16 55

PM 40 4.4 240 40 140 2.56

Glass 80 2.47 137 22.8 80

Glass 120 3.71 205.8 34.3 120

0

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Tumour to Non-tumour liver Ratio (TNR)

Mean: 4.4

Median: 3.5

frequency

TNR

CHUV cohort

50 treatment sessions

APM/ABSA

frequency

0

2

4

6

8

10

12

14

16

18

APM / ABSA

Mean: 1.47

Median: 1.39

CHUV cohort

85 treatment sessions

Dose to target volume: tumor and non tumor volumes

dose-response in TV

safety of the treatment DNTV vs. Toxicity

Predictive dosimetry based on 99mTc-MAA SPECT/CT is used to predict:

SPECT 99mTc-MAA

TV

NTV

PET 90Y TOF

NTV

TV

Quantitative agreement between predictive dosimetry based on 99mTc-MAA

SPECT/CT and post-treatment dosimetry based on 90Y TOF PET/CT for

both TV and NTV in HCC patients

Experience with both resin- and glass-sphere devices

Y-90 Liver Radioembolisation:

Predictive vs. post-treatment dosimetry

Concordance: predictive vs. post-treatment

dosimetry in TV and NTV

TV NTV

S.Gnesin et al., J Nucl Med. 2016 Nov;57(11):1672-1678.

(Efficacy) (safety)

S.Gnesin et al., J Nucl Med. 2016 Nov;57(11):1672-1678.

Concordance: predictive vs. post-

treatment dosimetry in TV and NTV

Tumor volumes : On average good agreement for tumor dose deposition

But some case showed important discrepancy

Non-tumor volumes : very good agreement (safety)

Conclusions Scientific evidence support the need of dosimetry in Y-90 radioembolisation

Dosimetry aims

Efficacy : tumoricidal effect of radiation response in tumors

Safety : Preserve hepatic function and avoid/limit toxicity

Dosimetry approaches:

BSA: safely used in many clinical trials

- Easy to implement (only radiology data are needed)

- Tends to underdosage large tumors and large livers

and overdose small tumors and small livers.

mBSA: Incorporates the treated lobe volume (including tumor) into

the formula.

- suited for lobar/segmental treatment approach

Partition model:

- Includes emission data from Tc-99m MAA SPECT/CT (Tumor-to-nontumor ratio and

lung shunt)

- Need clear tumor/non tumor delineation

- Results on average higher administered activities (compared do BSA and mBSA)

- Potential benefits in terms of efficacy on tumors with simultaneous dose control on

non-tumor parenchyma

23/53

Tj

Thanks to:

John O. Prior

Niklaus Shaefer

Ariane Boubaker

Pierre Bize

Alban Denys

Sebastien Baechler

Laurent Canetti

Francis R. Verdun

Marina Silva Monteiro

Michael Da Mota

Cherbuin Nicolas

Thank you for your attention

Theranostic, Bruxelles, 4 October 2017

predictive dosimetry: bsa vs. partition model...predictive dosimetry: bsa vs. partition model s....

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