Dynamic CT imaging (DCE-CT) in the anti-angiogenic response in Metastatic Renal Cell Carcinoma - PowerPoint PPT Presentation

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Dynamic CT imaging (DCE-CT) in the anti-angiogenic response in Metastatic Renal Cell Carcinoma

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Dynamic CT imaging (DCE-CT) in the anti-angiogenic response in Metastatic Renal Cell Carcinoma Prof. C A Cuenod , L Fournier, G Frija Laboratoire de Recherche en ... – PowerPoint PPT presentation

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Title: Dynamic CT imaging (DCE-CT) in the anti-angiogenic response in Metastatic Renal Cell Carcinoma


1
Dynamic CT imaging (DCE-CT) in the
anti-angiogenic response in Metastatic Renal
Cell Carcinoma
  • Prof. C A Cuenod ,
  • L Fournier, G Frija
  • Laboratoire de Recherche en Imagerie, Université
    Paris R Descartes.
  • Radiology, Hôpital Européen Georges Pompidou,
  • Paris
  • ESUR Munich 2008

2
Tumour angiogenesis is a major topic in oncology
  • 1971 Judah Folkman
  • New England Journal of Medecine

3
Tumour neo-angiogenesis
  •  Under the stimuli of malignant cells, the
    endothelial cells build a complete new network of
    capillaries 

R Jain
4
Tumor angiogenesis
Growth Factors
Folkman. NEJM 19712851182-1186
5
Avastin
Sorafenib / Nexavar
Endothelial Cell membrane
Sunitinib /Sutent
Sorafenib
Anti-angiogenic treatment
RAD001
Patel Br J Cancer 2006
6
Surrogate markers reflecting treatment efficacy
Surrogate markers reflecting treatment efficacy
  • Reference tumour size
  • RECIST Response Evaluation Criteria in Solid
    Tumors
  • Therasse P. et al, J Natl Cancer Inst
    200092205-16
  • Functional imaging measuring tumour
    vascularisation, target of anti-angiogenic drugs

7
RECIST Response Evaluation Criteria in Solid
Tumors
  • Therasse P. et al, J Natl Cancer Inst
    200092205-16

Measuring (and adding) the longest diameters in
targets
8
Lésions cibles ? 10 mm
Lésions non cibles
Nouvelles lésions
Stabilité
  • Progression
  • ? ? 20 de la taille des lésions cibles
  • OU ? des lésions non cibles
  • OU nouvelle lésion

Réponse ? ? 30 de la taille des lésions cibles
9
variation of the sum
Progressive disease PD
20
-30
Treatment cycles
0 BASELINE
1
2
3
4
5
10
variation of the sum
20
-30
Treatment cycles
1
2
3
4
5
11
Size variation in RCC under anti-angiogenic
treatment vs. placebo
Groupe placebo
Placebo Treatment
Groupe sous traitement
12
DCE-Imaging
  • Functional evaluation

13
precontrast
postcontrast
14
Regions of interest (ROIs) over time
15
Patients
  • PatientsMetastatic RCC
  • April 2004-May 2006
  • Clinical trials Sorafenib / Nexavar vs.
    placebo Sunitinib / Sutent vs. interferon

16
Acquisition
  • 1- First exam before IV (low dose) (for target
    selection) gt Functional target selection
  • 2 - Dynamic Acquisition low dose 80 mL contrast
    3x30s-breathholds, 1 image/s for 90 s
  • 3 - Standard whole-body acquisition (40mL)
  • -------------------
  • Total injection 120 mL (Xenetix, 350 mg I/mL)
  • 80kV Radiation dose supplement ? 200/2000
    mGy/cm

17
Choice of functional target
  • Size gt 2 cm
  • Minimal movementsRetroperitoneum gt mediastinum
    gt lung
  • Not liver or bone (medullary)

18
Results
19
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20
Main microvascular parameters
OUT
IN
21
Main microvascular parameters
Mean Transit time TTM VB/FT
22
Modélisation
Analyse compartimentale
k(2,1)
Capillaire Q cap 2
Artere q artere 1
k(0,2)
q Tumeur
23
  • Can we detect an effect on tumour vessels after a
    single cycle of treatment by anti-angiogenic
    drugs?

24
Variable () Placebo N8 Interferon N5 Anti-angiogenic N25
Tissue Blood flow (ml/min/100ml) -22.9 -27.3 -5.7 -6.1 -18.8 0.8 -50 -72-3
Tissue Blood volume () -4.2 -22.0 5.6 2.0 -5.5 18.0 -51 -67-24
Mean transit time (s) 17.0 7.4 28.5 -2.4 -10.2 16.6 5 -2273
Permeability surface area product (mL/min/100ml) -29.2 -47.4-14.5 16.4 -11.920.9 -34 -83 8
Sum of longest diameters (mm) 5.5 -1.0 11.8 -3.8 -16.5 -0.7 -17 -29.0 -7.0
Significant for Nexavar, not Sutent
25
Variable () Placebo N8 Interferon N5 Anti-angiogenic N25
Blood flow (ml/min/100ml) -22.9 -27.3 -5.7 -6.1 -18.8 0.8 -50 -72-3
Blood volume () -4.2 -22.0 5.6 2.0 -5.5 18.0 -51 -67-24
Mean transit time (s) 17.0 7.4 28.5 -2.4 -10.2 16.6 5 -2273
Permeability surface area product (mL/min/100ml) -29.2 -47.4-14.5 16.4 -11.920.9 -34 -83 8
Sum of longest diameters (mm) 5.5 -1.0 11.8 -3.8 -16.5 -0.7 -17 -29.0 -7.0
26
RCC metastasis under anti-angiogenic
therapy Good responder
01/12/04 BF 130
16/06/05 BF 18
27
RCC metastasis under anti-angiogenic
therapy Poor responder
03/01/05 BF 250
12/04/05 BF 230
28
DCE-CT vs morphology
Blood Flow maps
Baseline
Cycle 1 6 weeks
Cycle 4 30 weeks
29
  • Can baseline parameters as measured by functional
    imaging predict future tumour response?

30
Variable () Response N10 Stable N20 Progression N2 P (S vs. R)
Blood flow (mL/min/100ml) 245.3 130.3 453.5 119.5 74.1 224.3 190.5 162.5 218.5 0.04
Blood volume (mL/min/100ml) 15.5 9.0 24.5 8.2 5.6 14.9 9.6 9.2 10.1 0.02
Mean transit time (s) 5.6 3.5 9.5 9.0 5.0 13.6 5.4 5.1 5.7 0.07
Surface permeability product (mL/min/100ml) 9.9 9.1 21.1 7.3 6.0 13.2 9.0 8.7 9.3 0.12
Sum of longest diameters (mm) 104.0 76.0 252.0 155.0 91.0 198.5 73.0 50.0 96.0 0.18
31
Limits clinical study
  • Difficulties 50 of patient data incomplete or
    data analysis failed
  • 102 patients in clinical trial51 patients
    successful DCE-CT

32
DCE analysis failed
  • CT not injected (allergy, kidney failure) (N
    5, 10)
  • CT not performed at our institution (N 23,
    45)
  • Baseline perfusion acquisition not performed (N
    10, 18)
  • Failure of modeling movement, SNR (N 13,
    23)

33
AIF
34
Limits clinical study
  • Inter-investigator reproducibility
  • 2 investigators

35
Blood flow investigator 2
R 0.91 R² 0.82
Blood flow investigator 1
36
PS investigator 2
R 0.45 R² 0.20
PS investigator 1
37
Clinical study conclusions
  • DCE-CT can be used in a clinical context
  • Difficulties to implement the technique
    organisation motion (lung metastases)

38
IRM vs CT
39
Critères dynamiques
  • Profil   malignité  ..   bénignité 

Kuhl Eur. Radiol.20001046-58
57 des K 34 des K
9 des K 5 des
L.Bénignes 12 des LB
83 des LB
Kuhl Eur. Radiol.20001046-58
40
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41
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42
Remarques techniques
43
Correction des mouvements respiratoires
44
Arterial input function
True individual AIF Mean AIF Synthetic
AIF
45
Peak is missed
1 image/ 10 sec
1 image / 1 min
46
Tumor treatment
Tumor volume
Weeks
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