adaptive radiotherapy of hnscc: advantages, limits and
TRANSCRIPT
Brescia
May 200 9
Adaptive radiotherapy of HNSCC:
advantages, limits and clinical applications
in the treatment of oropharyngeal carcinoma.
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
Brescia
May 200 9
Chemotherapy
Surgery
Surgery +radiotherapyRadiotherapy
not cure(local recurrence)
not cure(distal recurrence)
37%
18%
5%
22%
6%12%
Myths and facts in Oncology: the challenge
of local therapies
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May 200 9
Myths and facts in Oncology: the challenge
of local therapies in …HNSCC…
Chemotherapy
Surgery
Surgery + radiotherapy± chemo/biological
modifiers
Radiotherapy
± chemo/biological
modifiers
not cure(local recurrence)
not cure(distal recurrence)
˜ 10-15%
˜ 25-35%
0%
22%
>6%>>12%
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May 200 9
“My” vision of Radiation Oncology in 2009
and beyond …
• RO will be (even more) multidisciplinary…
• RO will be conformal (e.g. IMRT, proton, hadrons)…
• RO will be tailored (based on imaging and molecular
profiling) and adaptive …
• RO will be associated with targeted agents …
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“My” vision of Radiation Oncology in 2009
and beyond …
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Challenges in Head & Neck loco-regional
treatment
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“2D” Radiotherapy in oropharyngeal
cancers
Mendenhall et al., 2000
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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
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IMRT for Head and Neck Tumors
Oropharyngeal carcinomas
Lee, N. et al Head & Neck 2007
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Salivary flow rate inunstimulated gland
Parotid gland sparing in IMRT
From Eisbruch, 1996
Salivary flow rate instimulated gland
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Parotid gland sparing in IMRT for NPC
Kam, et al. J Clin Oncol; 2007
Stage I-II; 2DRT (66 Gy) >< IMRT (66 Gy); brachytherapy boost; no chemotherapy
**
**
*
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May 200 9
Relationship between radiation dose to the pharyngeal
constrictors and aspirationR
isk o
f A
spir
ati
on
on V
ideofl
uoro
scopy
Mean Dose to the Total Pharyngeal Constrictor
1/52/13 2/15
3/12
14/19
7/8
Feng & Eisbruch, 2008
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May 200 9
Osteoradionecrosis with “modern”
radiotherapy techniques
Ben-David, 2007
• n= 176 (86% ORO/OC)
• IMRT ± CH
• Primary RT + post-op RT
• Median FU of 35 months
No case of ORN
• Pre-IMRT dental care
• Daily fluorination
• Dental protective stent
• Post-RT prophylactic dental
care
Mandible doseMean V50: 62 ± 18%
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Challenges in H&N IMRT
Harari et al., 2005
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18F-FDGPET
NMR (T1)
CAT Scan
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May 200 9 Daisne et al, 2004
How far are we from the truth ?
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Impact of imaging modality on dose distribution
Image-Guided Radiation Therapy in HNSCC
CT-based target volume FDG PET-based target volume
Geets et al, 2006
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May 200 9
Validation protocol in locally advanced HNSCC
Apport de l'imagerie fonctionnelle par Tomographie
par Emission de Positrons (TEP) dans le ciblage biologique
par radiothérapie de conformation (3D-CRT)
et par modulation d'intensité (IMRT) de tumeurs ORL
Use of functional imaging with PET for target volume
delineation in 3D-CRT/IMRT for head and neck tumors
Prof. V. Grégoire, UCL St-Luc, Brussels, Belgium
Prof. E. Lartigau, COL, Lille, France
Dr. JF Daisnes, Cliniques St-Elisabeth, Namur, Belgium
Brescia
May 200 9 C. Monet, 1894The Cathedral of Rouen
4D-IMRT
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MVCT
kVCT
Geometric 4D-IMRT
Vaandering, 2006
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First five MVCTs: CTV to PTV margins
0,00
2,00
4,00
6,00
8,00
10,00
12,00
14,00
16,00
18,00
1 6 11 16 21 26 31 36 41 46 51 56 61 66 71
In itial CTV-P TV m a rgin
Correcte d CTV-PTV m a rgin
4 m m m a rgin
0,00
2,00
4,00
6,00
8,00
10,00
12,00
14,00
1 5 9 13 17 21 25 29 33 37 41 45 49 53 57 61 65 69 73
Initial C TV-PTV margin
Corrected CTV-PTV margin
4mm margin
0 , 0 0
2 , 0 0
4 , 0 0
6 , 0 0
8 , 0 0
1 0 ,0 0
1 2 ,0 0
1 4 ,0 0
1 7 1 3 1 9 2 5 31 3 7 4 3 4 9 5 5 6 1 6 7 7 3
Initial
C T V-PT V m argin
C or rec t ed C T V-PT V m argin
4m m m argin
• 75 patients
• total of 1481 MVCT
• CTV-PTV: (2*Σ + 0.7s )
Vaandering, 2007
CT
V t
o P
TV
mar
gin
Cranio-caudal directionMedio-lateral direction
Antero-posterior direction
Geometric 4D-IMRT
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May 200 9
Alternate week MVCTs: CTV-PTV margins
0 ,0 0
2 ,0 0
4 ,0 0
6 ,0 0
8 ,0 0
10 ,0 0
12 ,0 0
14 ,0 0
16 ,0 0
18 ,0 0
1 6 1 1 1 6 2 1 2 6 3 1 36 4 1 4 6 5 1 56 6 1 66 7 1
I nit ial CTV-P TV m a rg in
Co rrect ed CTV-PTV m a rg in
4 m m m a rg in
0 ,0 0
2 ,0 0
4 ,0 0
6 ,0 0
8 ,0 0
10 ,0 0
12 ,0 0
14 ,0 0
1 6 11 16 2 1 26 3 1 3 6 4 1 4 6 51 5 6 6 1 6 6 7 1
In itial CTV-P TV m a rgin
Correcte d CTV-PTV m a rgin
4 m m m a rgin
0 ,0 0
2 ,0 0
4 ,0 0
6 ,0 0
8 ,0 0
10 ,0 0
12 ,0 0
14 ,0 0
1 6 1 1 1 6 2 1 2 6 3 1 36 4 1 4 6 5 1 56 6 1 66 7 1
I nit ial CTV-P TV m a rg in
Co rrect ed CTV-PTV m a rg in
4 m m m a rg in
• 75 patients
• total of 1481 MVCT
• CTV-PTV: (2*Σ + 0.7s )
Vaandering, 2007
CT
V t
o P
TV
mar
gin
Cranio-caudal directionMedio-lateral direction
Antero-posterior direction
Geometric 4D-IMRT
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May 200 9
Residual deviations analysis
-- First five days protocol (FFD)
-- Alternate week protocol (AW)
0,0
0,1
0,2
0,3
0,4
0,5
0,6
0,7
0,8
0,9
1,0
0,0 1,0 2,0 3,0 4,0 5,0 6,0 7,0 8,0
Cu
mu
lati
ve
dis
trib
tuti
on
Residual deviations (mm)
H&N cancer patients:
Residual deviations in m-l direction
0,0
0,1
0,2
0,3
0,4
0,5
0,6
0,7
0,8
0,9
1,0
0,0 1,0 2,0 3,0 4,0 5,0 6,0 7,0 8,0
Cu
mu
lati
ve
dis
trib
tuti
on
Residual deviations (mm)
H&N cancer patients:
Residual deviations in c-c direction
0,0
0,1
0,2
0,3
0,4
0,5
0,6
0,7
0,8
0,9
1,0
0,0 1,0 2,0 3,0 4,0 5,0 6,0 7,0 8,0
Cu
mu
lati
ve d
istr
ibtu
tio
n
Residual deviations (mm)
H&N cancer patients:
Residual deviations in a-p direction
FFD(avg±1S) : -0,03 ± 0,8mm
AW(avg±1S) : -0,07 ± 0,6mm
FFD(avg±1S) : -0,3 ± 0,8mm
AW(avg±1S) : -0,1 ± 0,6mm
FFD(avg±1S) : -0,4 ± 1,2mm
AW(avg±1S) : -0,1 ± 0,6mm
Residual deviationsGeometric 4D-IMRT
Vaandering, 2008
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May 200 9
CT MRI (T2) FDG-PET
PRE-R/
WEEK 3
WEEK 5
(Week 2)
(Week 4)
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May 200 9 Geets et al, 2003
0 Gy
50 Gy
FDG-PET
Image-Guided Radiation Therapy in HNSCC The 4th dimension …
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May 200 9
Raw
im
age
Image processing Image segmentation
SBR
W&C
UG 4mm
BG 6mm + deconvolution
PET image segmentation during RxTh
J. Lee & X. Geets, 2005
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May 200 9
Image registration…
Week 0
Week 3
Rigid Registration (mutual information)
Differential dysplay
Castadot & Lee, 2006
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Differential dysplay
Image registration…
Parraga, Castadot & Lee, 2006
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May 200 9
Mean slope: -1.46% / treat day (p<0.05)
Medial shift: 0.91mm after 25# (p<0.05)
Mean slope: -2.55% / treat day (p<0.05)
Lateral shift: 1.52mm after 25# (p<0.05)
Variation in therapeutic CTVs during RT-CH…
Castadot & Lee, 2008
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May 200 9
Mean slope: -0.47% / treat day (p<0.05)
No shift
Mean slope: -0.41% / treat day (p<0.05)
Medial shift: 1.76mm after 25# (p<0.05)
Variation in prophylactic CTVs during RT-CH…
Castadot & Lee, 2008
Brescia
May 200 9
Mean slope: -0.93% / treat day (p<0.05)
Medial shift: 3.21mm after 25# (p<0.05)
Mean slope: -1.03% / treat day (p<0.05)
No shift
Variation in parotid volumes during RT-CH…
Castadot & Lee, 2008
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May 200 9
Impact on Target Volume delineation
P<0.001
Geets, 2007
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May 200 9
0 ? 14Gy 14 ? 25Gy 25 ? 35Gy 35 ? 45Gy 45 ? 69Gy
Total Dose really received by each volume element of the
patient
+
w2? w0
+
w3? w0
+
w4? w0
+
w5? w0
Castadot & Lee, 2008
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May 200 9
Classic CT-based planning Adaptive PET-based planning
58%67%73%98%100%99%Adaptive PET-based
81%82%83%98%99%99%Classic PET-based
66%80%85%100%100%99%Adaptive CT-based
100%100%100%100%100%100%Classic CT-based
V100V95V90V80V50V10Planning
P<0.001
Geets, 2007
Impact on dose distribution
SIB-IMRT
30x2.3 Gy
30x1.85 Gy
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May 200 9
Dose distribution after adaptive RT-CH (n=5)
Castadot & Lee, 2008
Brescia
May 200 9
Survival is non-flat
(higher in resistant areas)
Non-flat doseFlat dose
More similar survival
across entire tumor
Far m
ore effic
ient use
of do
se
Mean Tumor Dose = 2 Gy
Courtesy of D. De Ruysscher
“Dose painting” by number…
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May 200 9
Metabolism: 18F-FDG
11C-Met
Proliferation: 76Br-BFU
Hypoxia: 18F-EF3
Which biological pathways? …
Brescia
May 200 9 C. Monet, 1874
The Bridge
at
Argenteuil
Challenges in Head & Neck loco-regional
treatment
• Target selection and delineation
• Adaptive IMRT: geometrical, biological &
dosimetrical
•which imaging modalities??
•which biological pathways??
•which volume/dose registration algorithms??
•how frequently??
• Concomitant association with drugs and/or
“small molecules”
Brescia
May 200 9
Acknowledgements
• Communication and Remote Sensing Lab. Adriana PARRAGA, Eng.
Benoit MACQ,Eng., Ph.D.
• ENT and Head & Neck surgery Marc HAMOIR, M.D.
• Imaging Emmanuel COCHE, M.D.
Thierry DUPREZ, M.D.
Max LONNEUX, M.D.
• Oral & Maxillo-Facial surgery Pierre MAHY, M.D.
Hervé REYCHLER, M.D., D.M.D.
• Pathology Birgit WEYNAND, M.D.
• PET laboratory Anne BOL, Ph.D.
Daniel LABARE, Ph.D.
• Radiation Oncology Nicholas CHRISTIAN, M.D.
Pierre CASTADOT, M.D.
Xavier GEETS, M.D., Ph.D.
John LEE, eng., Ph.D.
Pierre SCALLIET, M.D., Ph.D.