Early prediction of response

Functional imaging

Microarrays

Proteomics

FDG SUVmax

0

10

20

30

Before RT During RT After RT

FMISO/FDG SUVmax

0

10

20

30

Before RT During RT After RT

SU

V m

ax

FDG/FLT SUVmax

0

10

20

30

SU

V m

ax

N=15 N=10 N=5

Before RT

During RT

After RT

Before RT During RT After RT Before RT During RT After RT

FDG 17 10 5 18 11,5 4,5 14 8 3

FMISO 5 3 3

FLT 8 3 1,5

tumour evolution: SUVmax

RECTUMGELATINE

Rectum resection

Styrofoam boxOrientation sticks

-20°C

Formol

scan

4 mm slices

Validation of tumor delineation

Validation of Tumor Delineation

T

T

T

MR CT FDG PET FLT PET

Resection specimen Pathology

metabolism tracer proliferation tracer

before therapy

during therapy

after therapy

MR FDG FMISO FLT Pathology

cc cc cc cc cc

P1 7,76 3,54 1,45 1,37

P2 5,77 0,53 3,09 0,05

P3 20,36 12,95 8,98 11,19

P4 8,79 1,02 1,38 0,77

P5 7,15 3,61 0 pCR

P6 3,59 0 0 0,55

P7 6,99 2,92 0 0,43

P8 3,2 0 0 pCR

P9 18,29 3,18 1,87 2,25

P10 3,45 2,05 0,52 pCR

P11 2 7,09 3,05 0,32

P12 4,08 0 5,14 pCR

P13 0,48 0,35 2,26 pCR

P14 1,32 0 0 pCR

P15 8 5,4 0 0,13 T

P

Validation tumour volume MR-FDG with APO

FDG-PET TVs delineated with the gradient-based method matched closer with the pathological TV than MR-based TV

Translational research in rectal cancer

SSURGERY

W 12-13

T0 T1 T2

Blood/ tissue samples

Pathological response according to tumor regression grading

Chemoradiation Cetuximab* + capecitabine

(n=37)

Oxaliplatin* + capecitabine

(n=36)

5-FU alone (n=35)

pCR

2 (5%)

5 (14%)

4 (11%)

> 2 mm mesorectal margin

27 (73%)

30 (83%)

Translational research in rectal cancer

Micro-arraysImmunohistochemistr

y

FISH

GENES PROTEINS

ELISA

Phase II study with cetuximab in rectal cancer

TGF-α

EGFR

Fibro-inflammatory

changes

Ki67

Debucquoy et al, unpublished results

Effect of Bevacizumab on tumour responseMarked response in all 6 patients

Only microscopic disease in 5 patients

Willett et al. J Clin Oncol 2005

Effect of bevacizumab on tumour vasculature

Pretreatment

Day 12

Patient

IFP (

mm

Hg

)

0

4.5

9.0

13.5

18.0

22.5

3 4 5 6IFP = interstitial fluid pressure

Willett et al. Nat Med 2004