Download PRESENTATIE_BARBARA

What is radiation therapy (RT)?
• Cancer treatment
• Tumor versus normal
tissues
• External photon beam RT
Intensity-modulated RT (IMRT)
• Brahme et al. 1982
– Fluence-modulated
beams
– Homogeneous, concave
dose distributions
• Better target dose
conformity and/or
better sparing of organs
at risk (OARs)
Imaging for RT
Anatomical imaging
• CT
• MRI
Biological imaging
•
•
•
•
PET
SPECT
fMRI
MRSI
Brain
Tumor
Tumor biology characterization
Radiotracer
Characterization
18F-FDG
Glucose metabolism
18F-FLT
DNA synthesis
11C-MET
Protein synthesis
60Cu-ATSM, 18F-FMISO
Hypoxia
Radiolabeled Annexin V
Apoptosis
Radiolabeled aVb3 integrin
antagonists
Angiogenesis
Apisarnthanarax and Chao 2005
Biological imaging for RT
• Improvement of diagnostic and staging
accuracy
• Guidance of target volume definition and
dose prescription
• Evaluation of therapeutic response
Target volume definition
• Gross tumor volume
(GTV)
• Clinical target volume
(CTV)
• Planning target volume
(PTV)
Biological target volume (BTV)
Ling et al. 2000
Dose painting
Dose painting by contours
Dose painting by numbers
Dose painting by numbers
Biologically
Conformal
Radiation
Therapy
Dose calculation algorithms
• Speed versus accuracy:
– Broad beam
– Pencil beam (PB)
– Convolution/superposition (CS)
– Monte Carlo (MC)
• Monte Carlo dose engine MCDE
Reynaert et al. 2004
Accuracy ↑
Speed ↓
MC dose calculation accuracy
• Cross section data
• Treatment beam modeling
• Patient modeling
– CT conversion
– Electron disequilibrium
– Conversion of dose to medium
to dose to water
• Statistical uncertainties
Implementation of BCRT:
Relationship between signal intensity
and radiation dose
Dose
Dhigh
D  Dlow
I  Ilow

(Dhigh  Dlow )
Ihigh  Ilow
for Ilow  I  Ihigh
Dlow
Ilow
Ihigh
Signal intensity
Implementation of BCRT:
Treatment planning strategy
Implementation of BCRT:
Biology-based segmentation tool
• 2D segmentation grid in template
beam’s eye view
– Projection of targets (+)
– Integration of signal intensities
along rayline (+)
– Projection of organs at risk (-)
– Distance
• Segment contours from iso-value lines
of segmentation grid
Implementation of BCRT:
Objective function
• Optimization of segment weights and
shapes (leaf positions)
• Expression of planning goals
• Biological:
– Tumor control probability (TCP)
– Normal tissue complication probability (NTCP)
• Physical:
– Dose prescription
 Ddev   1  Ddev  
  
  1
  Fi 
i
 Dmean i  2  Dmean i 
Relative volume (%)
Implementation of BCRT:
Treatment plan evaluation
100
80
1
QF   Qp  1
n p
60
40
QVH
20
0
0
0.5
1
Q Dp
Qp 
Dpresc
1.5
Implementation of BCRT:
Example
• [18F]FDG-PET guided BCRT for oropharyngeal
cancer
• PTV dose prescription:
Dlow = 2.16 Gy/fx
Ilow = 0.25*I95%
Dhigh= 2.5 and 3 Gy/fx
Ihigh = I95%
Implementation of BCRT:
Example
Implementation of BCRT:
Example
100
2.5 Gy/fx
Volume (%)
80
3 Gy/fx
60
40
20
0
0.85
0.9
0.95
1
Q
1.05
1.1
1.15
Implementation of BCRT:
Conclusions
• Technical solution
– Biology-based segmentation tool
– Objective function
• Feasibility
– Planning constraints OK
– Best biological conformity for the lowest level
of dose escalation
BCRT planning study:
Set-up
• BCRT or dose painting-by-numbers (“voxel
intensity-based IMRT”) versus dose
painting (“contour-based IMRT”)
• 15 head and neck cancer patients
• Comparison of clinically relevant dosevolume characteristics
– Between “cb250” and “vib216-250”
– Between “vib216-250” and “vib216-300”
BCRT planning study:
Target dose prescription
“cb250”
“vib216-250”
(cGy/fx) (cGy/fx)
PTVPET
“vib216-300”
(cGy/fx)
250
PTV69+PET
216 - 250
216 - 300
PTV69
216
PTV66
206
206
206
PTV62
194
194
194
PTV56
175
175
175
BCRT planning study:
“cb250” (blue) versus “vib216-250” (green)
100
Mandible PTV56
PTV
80
PTV66
Spinal cord
Volume(%)
62
PTV 69
60
40
PTV
PET
Spared parotid
PTV 69+PET
20
Surr
0
0
30
60
90
120
150
180
210
Fraction dose (cGy)
240
270
300
330
BCRT planning study:
“vib216-250” (green) versus “vib216-300” (orange)
100
Mandible PTV 56
PTV62
PTV66
Volume (%)
80
PTV 69
Spinal
cord
60
40
PTV
PET
Spared
parotid
20
PTV 69+PET
Surr
0
0
30
60
90
120
150
180
210
Fraction dose (cGy)
240
270
300
330
BCRT planning study:
Example
2.2 2.3
2.4
2.5
2.16
2.2
1.2
1.6
2.1
2.5
2.4
2.3
1.4
2.1
2.5
2.4
2.3
2.2
2.16
2.1
1.4
1.6
1.6
BCRT planning study:
QF
3.5
3
2.5
2
QF (%)
1.5
1
0.5
0
"cb250"
"vib216-300"
PTV69+PET
PTV69
"vib216-250"
"cb250"PTV69+PET
PTVPET
BCRT planning study:
Conclusions
• BCRT did not compromise the planning
constraints for the OARs
• Best biological conformity was obtained for
the lowest level of dose escalation
• Compared to dose painting by contours,
improved target dose coverage was
achieved using BCRT
MC dose calculations in the clinic
• Comparison of PB, CS and MCDE for lung
IMRT
• Comparison of 6 MV and 18 MV photons
for lung IMRT
• Conversion of CT numbers into tissue
parameters: a multi-centre study
• Evaluation of uncertainty-based stopping
criteria
• Feasibility of MC-based IMRT optimization
CT conversion: multi-centre study
• Stoichiometric calibration
• Dosimetrically equivalent
tissue subsets
• Gammex RMI 465 tissue
calibration phantom
• Patient dose calculations
• Conversion of dose to
medium to dose to water
CT conversion: example
CT conversion: conclusions
• Accuracy of MC patient dose calculations
• Proposed CT conversion scheme:
Air, lung, adipose, muscle, 10 bone bins
• Validated on phantoms
• Patient study:
Multiple bone bins necessary if dose is
converted to dose to water
Biologically conformal RT
• Technical solution
– Bound-constrained linear model
– Treatment plan optimization
• Biology-based segmentation tool
• Objective function
– Treatment plan evaluation
• Feasibility of FDG-PET guided BCRT for
head and neck cancer
MC dose calculations
• Individual patients may benefit from highly
accurate MC dose calculations
• Improvement of MCDE
– CT conversion
– Uncertainty-based stopping criteria
• Feasibility of MC-based IMRT optimization
• MCDE is unsuitable for routine clinical use,
but represents an excellent benchmarking
tool
Adaptive RT:
Inter-fraction tumor tracking
• Anatomical & biological changes during RT
• Re-imaging and re-planning
• Ghent University Hospital: phase I trial on
adaptive FDG-PET guided BCRT in head
and neck cancer
Summation of DVHs
CT 1 Dose 1
CT 2 Dose 2
Registration
Structure 1
Structure 2
Points
TPoints
P Doses
TP Doses
Total doses
Total
DVH
Summation of QVHs
PET 1 CT 1 Dose 1
Registration
Structure 1
PET 2 CT 2 Dose 2
Registration
Registration
Structure 2
Points
TPoints
Disregard TPoints
outside structure 2
P Q-values
TP Q-values
Total Q-values
Total
QVH
Fundamental research
in vitro, animal studies
Biological
imaging
•Tracers
•Acquisition,
reconstruction,
quantification
Treatment
planning and
delivery
•Biological
optimisation
•Adaptive RT
Clinical investigations
Treatment
outcome