AAPM

Aug. 2011

This house believes that the use of

Functional Imaging for treatment

planning of head and neck tumors

needs to be carefully considered.

Vincent GREGOIRE, M.D., Ph.D., Hon.

FRCR

Head and Neck Oncology Program, Radiation Oncology Dept.

& Center for Molecular Imaging and Experimental

Radiotherapy, Université Catholique de Louvain, St-Luc

University Hospital, Brussels, Belgium AAPM

Aug. 2011

Oropharyngeal SCC

T2-N0-M0

SIB-IMRT: 30x2.3 Gy

30x1.85 Gy

PRV Spinal cord

Left parotidRight parotid

Larynx

PTV 55.5 Gy

PTV 69 Gy

IMRT for Head and Neck Tumors

AAPM

Aug. 2011

This house believes that …

• RO will be (even more) multidisciplinary…

• RO is conformal (e.g. IMRT, proton, hadrons)…

• RO will be tailored (individualized) (based on imaging

and molecular profiling) and adaptive …

• RO will be associated with targeted agents …

AAPM

Aug. 2011

Heterogeneity in H&N TV

delineation

Harari et al., 2004

AAPM

Aug. 2011

Betrayal of

imagesThis is not an

apple…

R. Magritte

Target selection and delineation

AAPM

Aug. 2011

Segmentation methods: one by

lab…!

Histogram-based

Fixed threshold (SUV, %)

Adaptive threshold (SBR)

Soft thresholding (probabilistic)

Manual delineation

Visual interpretation

Subjective approach!

Feature-based

(Fuzzy) clustering

Clustering of TAC

Image-based

Probabilistic modeling

Gradient based NO CONSENSUS∆ Experimental conditions

∆ Data sets

∆ Validation studies

Visual rendering

Complex model – unrecoverable target

AAPM

Aug. 2011 Schinagl et al., 2007

Variability in PET image segmentation

for H&N tumors …

AAPM

Aug. 2011

5 c

m5 c

m5 c

m

18F-FDGPET

CAT Scan

Macroscopy

Daisne et al, 2003

AAPM

Aug. 2011

From PET image to tumor: a fixed

threshold?

55.917.226.5*13.3mean

56.53039.924.39

67.528.341.815.48

5925.535.917.37

43.26.69.78.66

70.919.237.95.65

575.384.14

38.621.729.730.93

55.76.710.95.22

55.111.823.38.31

50%40%SurgicalSpecimen

Patient

GTV (ml)

Geets et al, 2006AAPM

Aug. 2011 Geets et al, 2003

0 Gy

50 Gy

FDG-PET

Image-Guided Radiation Therapy in HNSCC The 4th dimension …

AAPM

Aug. 2011

Raw

im

ag

e

Image processing Image segmentation

SBR

W&C

UG 4mm

BG 6mm + deconvolution

PET image segmentation during

RxTh

J. Lee & X. Geets, 2005AAPM

Aug. 2011

NSCLC with atelectasis

Pathological correlation? Clinical validation?

Deruysscher, 2007

PET in radiotherapy planning for NSCLC

AAPM

Aug. 2011 Werner-Wasik et al., 2011

NSCLC digital MC PET phantom

Different segmentation methods …

AAPM

Aug. 2011

PET in radiotherapy planning for NSCLC

Wanet et al., Radioth. Oncol. 2011

AAPM

Aug. 2011

PET in radiotherapy planning for NSCLC

Wanet et al., Radioth. Oncol. 2011AAPM

Aug. 2011

Objective evaluation of the available

segmentation methods

Pathology validated patient images

Imag

es

Meth

ods

Fig

ure

s o

f m

eri

t

Gradient detection

Accuracy

Reproducibility/robustness

AAPM TG211, 2011

Simulated PET images (MC)

Statistical methods

Precision

Shape/volume

+ =+

Scanner model

3D phantom

NCAT

Zubal

3D tumor model

Clinical image used as an exampleand associated segmentation

NURBS surface

Simulated 3D PET

AAPM

Aug. 2011

PET imaging: a wide range of

molecular probes

• Glucose metabolism18F-FDG

• Protein synthesis11C-MET

18F-FET

• Proliferation18F-FLT

• Hypoxia18F-FMISO

18F-FAZA

• Receptors18F-FES

68GA-Traztuzumab (HER2)

64Cu-DOTA-panitumumab (EGFR)

Courtesy of Geets, 2011AAPM

Aug. 2011

proliferation

hypoxia

perfusion

A word of caution …

From Kaanders., 2001

5 µm

AAPM

Aug. 2011

[18F]-FDG TEP Registered

autoradiography

Résolution 2.3 mm Résolution 0.1 mm

N. Christian, 2010

Biological heterogeneity

AAPM

Aug. 2011

AR 100 µm

Effect of resolution

1,5 mm

2,0 mm

2,5 mm 2,7 mm

3,0 mm

3,5 mm

N. Christian, 2010

AAPM

Aug. 2011

SiHa UT-SCC-33

In Vivo experimental set-up

PET-tracer, Hoechst

PimonidazoleTumor

sectioning

Autoradiography

(2-D distribution of FAZA)

Micro PET

Immuno-fluorescence

microscopy

(hypoxia, vessels, perfusion) Busk et al Acta Oncol, 2008;47:1201-1210

Busk et al IJRBOP 2008;70:1202-12AAPM

Aug. 2011

FAZA autoradiogram & pimonidazol

SiHa SCCVII

Busk et al Acta Oncol;, 2008;47:1201-1210Busk et al Acta Oncol, 2008;47:1201-1210

Busk et al IJRBOP 2008;70:1202-12

AAPM

Aug. 2011

Tumor: FSA II

Mouse n° 2_1

Tum Volume: 2.30 ml18F-FDG – 300 µCi

Volume corresponding to the

highest 10 percent of activity

PET Volume

AR Volume

Mismatch (/)

Scaling issue…

N. Christian, 2010AAPM

Aug. 2011

FSA II (n=5)

SCC VII (n=5)

FSA II + RT (n=5)

10 20 30 40 50 60 70 80 90 100

10

20

30

40

50

60

70

80

90

100

0

% of Overall Tumor Volume

Dic

e S

imila

rity

Index

(%)

Scaling issue…

N. Christian, 2007

AAPM

Aug. 2011

Mosaic PET

0.88

0.84

0.86

0.87

0.86

0.84

r ²

Effect of resolution

% vol

0.0 7.0 8.7 10.0 11.0 12.1 12.7 13.1 13.9 14.5 15.0

Mouse T ø

0.0 13.9 17.5 20.1 22.1 23.8 25.3 26.6 27.8 28.9 30.0

Human T ø

N. Christian, 2010AAPM

Aug. 2011

PET imaging: a wide range of

molecular probes

• Glucose metabolism18F-FDG

• Protein synthesis11C-MET

18F-FET

• Proliferation18F-FLT

• Hypoxia18F-FMISO

18F-FAZA

• Receptors18F-FES

68GA-Traztuzumab (HER2)

64Cu-DOTA-panitumumab (EGFR)

Courtesy of Geets, 2011

AAPM

Aug. 2011

Comparison 18F-FDG / 14C-EF3

N. Christian, 2010AAPM

Aug. 2011

Comparison 18F-FDG / 14C-EF3

Anova: p = 0.19

N. Christian, 2010

AAPM

Aug. 2011

Survival is non-flat

(higher in resistant areas)

Non-flat doseFlat dose

More similar survival

across entire tumor

Mean Tumor Dose = 2 Gy

Courtesy of D. De Ruysscher

“Dose painting” by number…

AAPM

Aug. 2011

“Dose painting” : the physics issue

AAPM

Aug. 2011

Molecular imaging dose painting by number

Deveau et al., 2010

• Tomotherapy Hi-Art

• H&N SCC:

T4N2bM0

• 60 Gy + SIB of 30

Gy

• Hypoxia (Cu-ATSM)

AAPM

Aug. 2011

Dose escalation protocol …

Duprez et al., 2010

• DPBN based on FDG-

PET

• Median dose of 80.9

Gy (n=7) et 85.9 Gy

(n=14)

• No grade 4 acute

toxicity

Molecular imaging dose painting by number

AAPM

Aug. 2011 C. Monet, 1874

The Bridge

at

Argenteuil

Functional imaging for H&N

treatment planning

• Great potential … but …

• Don’t trust your physician …

• Rely on user’s independent methods

…

• Be aware of the various conceptual

limitations …

• Never forget the clinical knowledge …

• At the end, the proof is in the pudding

…