Future Proton Irradiation Facility at OncoRay
Seminar am Institut für Kern- und Teilchenphysik
Technische Universität Dresden
14. Juli 2011
Wolfgang Enghardt
OncoRay – National Center for Radiation Research in Oncology
Technische Universität Dresden, Germany
and
Helmholtz-Zentrum Dresden-Rossendorf, Dresden, GermanyInstitute of Radiation Physics
1
Outline
1. Radiotherapy
2. The technology platform at OncoRay
3. Scientific topics
2
1. RadiotherapyStatistics, Germany
• New cases of cancer p.a. 436.000
• Deaths p.a. 210.000
• Second rank in causes of death
• Surgery, radiation therapy, systemic therapy
• Radiation therapy applied to ≥ 60% of cancer patients
• Radiation therapy contributes to ≥ 50% of cures
3
4) Fractionated
therapeutic irradiation
1) Diagnostic
imaging
2) Dose prescription
1. RadiotherapyWorkflow
3) Treatment planning4
Electron
gun
Wave guide
Collimators
Scatter foil
Radiator
Electrons
Electrons
Photons
Electron linear accelerators:
photons and electrons
(~ 400 devices in Germany)
a-magnet
1. RadiotherapyElectron linear accelerators
Electrons
5
1. RadiotherapyCurrent technology: protons and light ions
Heidelberg Ion Therapy (HIT)
20 m
R(H2O) 30 cm
Particle energy:12C: E < 430 AMeV1H: E < 230 MeV
Magnetic rigidity:12C: Br < 6.6 Tm1H: Br < 2.3 Tm
Dose rate:
dD/dt 2 Gy/(min ·l)
Beam current:
I 5 nA
6
1. Radiotherapy Clinial results: Protons/ions vs. photons (I)
1. Chordoma of the skull base
3. Prostate carcinoma (side effects)
2. Bronchial carcinoma (stage I, inoperable)
Radiation modality 12C (GSI) Photons (FSRT)
5 years local tumour control 70 % 50 %
D. Schulz-Ertner et al.: Int. J. Radiat. Oncol. Biol. Phys. 68 (2007) 449
J. Debus et al.: Int. J. Radiat. Oncol. Biol. Phys. 47 (2000) 591
Radiation modality 12C (HIMAC) Photons (CRT)
5 years survival 42 - 60 % 10 - 32 %
Radiation modality 12C (HIMAC) Photons (IMRT)
Side effects genitourinary system (G2) 6 % 28 %
T. Miyamoto et al, Radiother. Oncol. 66 (2003) 127
H. Tsujii et al., Int. J. Radiat. Oncol. Biol. Phys. 63 (2005) 1153
M.J. Zelefsky et al., Int. J. Radiat. Oncol. Biol. Phys. 53 (2002) 1111
7
4. Nasopharyngeal carcinoma
Radiation modality Protons Photons (IMRT) p-value
3 years local tumour control 92 % 95 % 0.780
3 years survival 74 % 90 % 0.289
5. Paranasal and sinonasal carcinoma
Radiation modality 12C Protons Photons (IMRT) p-value
5 years local tumour control 49 % 88 % 66 % 0.035
5 years survival 71 % 52 % 0.323
6. Adenoid cystic carcinoma
Radiation modality 12C Protons Photons (CRT) p-value
5 years local tumour control 69 % 93 % 75 % -
5 years survival 70 % 77 % 73 % -
B.L.T. Ramaekers et al., Cancer Treat. Rev. (2010)
1. Radiotherapy Clinical results: Protons/ions vs. photons (II)
8
Advantage of proton/ion therapy not proven for most tumour entities:
• Lack of data quality and quantity
• Missing randomized clinical studies
• Technologically inadequate beam deliveries and equipment
1. Radiotherapy Clinical results: Conclusions
Schwere geladene Teilchen
(1H ... 12C ... 20Ne)
Rela
tive
eff
ektive
Dosis
%
Tiefe in Wasser / cm
Schwere geladene Teilchen
(1H ... 12C ... 20Ne)
Rela
tive
eff
ektive
Dosis
%
Tiefe in Wasser / cm
100
SOBP
Re
lative
do
se
/ %
Re
lative
eff
ective
do
se
/ %
Depth in water / cm Depth in water / cm
Electrons
E = 20 MeV
Photons
15 MV
9
2. The technology platform at OncoRayFunding, financing
SMWK: Landesexzellenzinitiative Sachsen (2008):
„Gemeinsames Zentrum für Strahlenforschung
in der Onkologie“
(Research building, technology platform)
Universitätsklinikum Carl Gustav Carus Dresden
(Proton irradiation facility: clinical equipment)
Helmholtz-Zentrum Dresden-Rossendorf(PET/MR)
BMBF: Zentren für Innovationskompetenz (2009):
Technical equipment of the junior research group:„High Precision Radiation Therapy“
Includes the research package of the proton
irradiation facility
HZDR: Laser PENELOPE‘10
2. The technology platform at OncoRayMain tasks
1. Research on compact accelerators (laser proton acceleration)
and beam deliveries (high field magnets)
2. Development of innovative medical techniques and technologies
for accessing the whole potential of proton therapy
• Particle therapy (PT) is an experimental therapy
• PT is not a simple substitute of photon therapy
• PT has to be performed on highest medical und technological level
e.g.: - motion compensation - in-vivo range measurement and dosimetry- biologically based treatment planning- image guidance
• Academic, no commercial approach
• Reasonable facility size (< 1000 patients p.a.)
• Careful patient recruitment
• International therapy register, local networking
11
2. The technology platform at OncoRayLocation
• Installation of the technology platform including a conventional proton therapy
facility on the campus of the university hospital Carl Gustav Carus in Dresden;
start of construction: May 2011, start of operation: 2014
• Integration into the department of radiooncology
Händelallee
Schubertstr.
12
2. The technology platform at OncoRayComponents
Infrastructure
• Radiobiological laboratories
• Physics laboratories
• Teaching rooms
• Offices
• Animal keeping facility
Laboratory for animal experiments
• Small animal CT
• Small animal PET
• Optical imaging
• Image guided, tumor conformalanimal irradiation facility
In vivo
dosimetry
• In-beam SPECT
Conventional proton therapy
• Clinical treatment roomwith isocentric gantry
• In-room PET
• Research cave
Petawatt high intensity laser
• Laser acceleratedproton beam
Molecular Imaging
• PET/CT
• PET/MRT
13
2. The technology platform at OncoRayThe proton irradiation unit: Layout
Conventional proton beam
acceleration and transfer
Therapy cave
Research cave
14
2. The technology platform at OncoRayThe proton irradiation unit: The cyclotron
Photo: Courtesy IBA
• Isochronous cyclotron
• Warm magnet
• d = 6 m
• E = 230 MeV
• I = 300 nA
15
2. The technology platform at OncoRayThe proton irradiation unit: The energy selection system
Photo: Courtesy IBA
• Degrader wheel with
graphite blocks of variing
thickness
• E = (70 – 230) MeV
• I = (2 – 50) nA
16
2. The technology platform at OncoRayThe proton irradiation unit: The beam transfer line
Photo: Courtesy IBA
17
2. The technology platform at OncoRayThe proton irradiation unit: The treatment site
Photo: Courtesy IBA
Therapy cave
(Capacity ~ 500 pat. p.a.)
• Isocentric gantrywith universal nozzle:
- single scattering
- double scattering
- pencil beam scanning
• Robotic patient table
18
2. The technology platform at OncoRayThe proton irradiation unit: In-room PET/CT
In-room PET/CT on rails:
CT: Patient positioning
PET:Range measurement
in-vivo
19
2. The technology platform at OncoRayThe proton irradiation unit: The potential of CT on rails
Before …
after position correction
20
2. The technology platform at OncoRayThe proton irradiation unit: Experimental cave (I)
Conventional proton
beam:
• Horizontal
• d < 10 mm (FWHM)
• E = (70 – 230) MeV
• I = (0.1 – 10) nA
21
2. The technology platform at OncoRayThe proton irradiation unit: Experimental cave (II)
Laser accelerated proton
beam:
?
22
2. The technology platform at OncoRayThe proton irradiation unit: Integration of the laser
Laser laboratory
Research cave
Gantry
Cyclotron
• PW laser: Polaris
DRACO
p
PW laser at HZDR
PENELOPEPW laser at OncoRay
23
2. The technology platform at OncoRayThe proton irradiation unit: Radiation protection calculations (I)
26
Sideview
Dose [Sv/a]
6e-10 6e-8 6e-6 6e-4 6e-2 6 6e+1 6e+3
On the roof: D < 1 mSv/a
In the experimental cave: D < 1 mSv/a
6 mSv/a
Footprint
G. Fehrenbacher, GSI, D. Kunath, WE24
28
2. The technology platform at OncoRayThe proton irradiation unit: Radiation protection calculations (II)
G. Fehrenbacher, GSI, D. Kunath, WE
Dose [Sv/a]
6e-7 6e-5 6e-3 6e-1 6 6e+2 6e+4 6e+6
On the roof: D < 1 mSv/a
In the
experimental
cave:
D < 1 mSv/a 6 mSv/a
Footprint
Side view
25
2. The technology platform at OncoRayThe proton irradiation unit: Status at July 4
26
3. Scientific topicsProton therapy
• Clinical studies
- bronchial carcinoma
- head and neck cancer
- paediatric cancer
• Precision therapy (image guidance)
• Motion compensation
• Biologically adaptive treatment
- individualization
- molecular targets
27
3. Scientific topicsProton therapy: Motion compensation
Beam off
Beam on
R. Perrin: High precision radiotherapy group 28
3. Scientific topicsLaser radiooncology (J. Pawelke, U. Schramm, T. Cowan)
p, He, C 2 m
Vision: Compact accelerators for proton/ionen therapy
• Dosimetry of ultra shortly (< 1 ps) pulsed particle beams
of high dose rate (1010 Gy/min)
• Radiobiology of ultra shortly pulsed particle beams
• Medical beam deliveries for laser accelerated particle beams
Layout
SIEMENS medical
29
3. Scientific topicsLaser radiooncology
Tumour cells head and neck (SKX)
Clonogenic cell survival DNA double strand brakes (24 h)
No significant RBE difference between laser accelerated, ultra-shortly pulsed
proton beams and tandem DC beams
Dose / Gy
Su
rviv
al
/
%
Dose / Gy
gH
2A
X/5
3B
P1
fo
ci
/
ce
ll■ DRACO laser protons
■ Tandem protons (reference)■ DRACO laser protons
■ Tandem protons (reference)
30
3. Scientific topicsIn-vivo dosimetry: motivation (F. Fiedler, WE)
The dose distribution deposited by ions is extremely sensitive to the ion range in vivo
The accuracy of the ion range is influenced by
(1) Systematic errors in the physical
beam model used for treatment
planning: R = R(HU)
(2) Random errors like
- mispositioning
- patient- or organ movement
- density changes within the
irradiated volume
- treatment mistakes and accidents
(3) Laser acceleration specific errors
- intensity fluctuations
- spectral uncertainties
Treatment planning
15. Therapy fraction
31
3. Scientific topicsIn-vivo dosimetry: physical basis
Nucleons
and particlesProjectile
Target nucleus
Projectile fragment
Target fragment
Fire ball
Prompt g-rays
Radionuclides
GS
I D
arm
sta
dt
MG
H B
osto
n
32
3. S
cie
nti
fic
to
pic
sIn
-viv
o d
osim
etr
y:
PE
T w
ork
flow
0.66 Gy
0.37 Gy
PET PET/CT
G. Shakirin: Phys. Med. Biol. 56 (2011) 1281 33
3. Scientific topicsIn-vivo dosimetry: workflow of in-beam PET
Treatment plan:
Dose distribution
b+-activity:
Prediction
b+-activity:
Measurement
Ion-Electron
Interaction
Ion –nucleus
interaction
12C-irradiation, GSI
W. Enghardt et al.: Strahlenther. Onkol. 175/II (1999) 33;
F. Pönisch et al.: Phys. Med. Biol. 48 (2003) 2419, Phys. Med. Biol. 49 (2004) 5217;
34
3. Scientific topicsIn-vivo dosimetry: motion compensation
Static and moving targets
Target movement:
- Sinusoidal (amplitude = 10 mm; period ≈ 3.5 s)
- Perpendicular to beam
Irradiation:- 295 AMeV 12C scanned pencil beam
- Motion compensation by tracking (magnetic beam
deflection and fast range difference compensation)
C. Bert et al.: Rad. Oncology 2 (2007) 4768
Reference (static) 4D-reconstruction 3D-reconstruction
PHD thesis: K. Laube 35
• Different path length per gate
• Attenuation correction may fail
3. Scientific topicsIn-vivo dosimetry: 4D-reconstruction
94 47894 29394 37495 75493 76792 28494 73494 95892 693
PhaseAmplitude
Coincidences:
134 500104 73275 25167 69165 43767 28476 960104 870134 065
Coincidences:
• Different number of coincidences per gate
• Different statistical errors
830 790 847 335
Gating
1. MLEM reconstruction of each gate addition: reconstruction artifacts
2. Spatial rearrangement of the lines of response reconstruction of the whole data 36
3. Scientific topicsIn-vivo dosimetry: automatisation of data evaluation
Beam direction
Range
enhanced
Range
as planned
Range
reduced
PHD thesis: S. Helmbrecht 37
3. Scientific topicsIn-vivo dosimetry: automatisation of data evaluation
38
• Long half lives of the positron emitters produced in tissue via nuclear reactions11C: T1/2 = 20 min15O: T1/2 = 2 min
• Low counting statistics → low quality images
• Washout of activity → no dosimetric information
• No real time capability → no adaptive radiotherapy (not suitable for lasers)
Protons
175 MeV
on PMMA
Co
nu
nt ra
te / s
-1
Time / s
K. Parodi et al.: IJROBP 68 (2007) 920
Dose b+-activity
3. Scientific topicsReal time in-vivo dosimetry: limits of in-beam PET
39
Nucleons
and particlesProjectile
Target nucleus
Projectile fragment
Target fragment
Fire ball
Prompt g-rays
Radionuclides
SPECT: Single Photon Emission Computed Tomography
Em
issio
n d
ensity o
f g-
rays:
Monte
-Carlo s
imula
tion
of irra
dia
tion a
nd
photo
n t
ransport
(G
eant4
)
Pro
ton tre
atm
ent
pla
n:
Bra
in t
um
our
CM
S T
PS
(E
lekta
)
AK
H a
nd M
ed.
Univ
. W
ien
3. Scientific topicsReal time in-vivo dosimetry: feasibility of in-beam SPECT (I)
A. Müller, Diploma thesis, TU Dresden, 2011 40
Do it yourself!
Photo: Siemens AG
99mTc: 140 keV
Treatment plan: brain tumor
• Total dose: 60 Gy, fractionated dose: 2 Gy
• 2 treatment fields: 1: 98 ... 135 MeV, 2: 82 ... 127 MeV
• 1,6 ∙ 1010 protons / fraction
Emission of g-rays
• 4 · 109 photons / fraction
• Photon energies: 0 – 15 MeV
Ph
oto
ns / (
Me
V p
)-1
Energy / MeV
3. Scientific topicsReal time in-vivo dosimetry: feasibility of in-beam SPECT (II)
41
•
3. Scientific topicsReal time in-vivo dosimetry: technical solution
Compton camera
gg rE
'
g1 g1‘
j1
j1
j1
g2‘
g2j2
j2
j2
Absorp
tion d
ete
cto
r
eerE
Coincidence
g-ra
y s
orc
e
Scatt
er
dete
cto
r2 photons
10 photons
300 photons
42
Proton beam
1. Scatter detector
2. Scatter detector
Absorption detector
T. Kormoll et al. NIM A 626-627 (2011) 114
• Installation
• Laboratory tests
• In-beam tests (KVI, GSI)
• Clinically applicable
system from 2013
Prototype
(2 × 2 cm2)
3. Scientific topicsReal time in-vivo dosimetry: in-beam SPECT
43
Backprojection of measured scatter events
22Na point source (511, 1275 keV)
2 cm camera distance
2000 events •
Scientific topicsReal time in-vivo dosimetry: prototype testing
First imaging: Apr. 7, 2011
Preliminary data
1 Event2 Events3 Events4 Events10 Events20 Events2000 Events
44
Scientific topicsReal time in-vivo dosimetry: clinical device (U. Dersch)
In-vivo dosimetry for new types of radiation | Dr. Uwe Dersch
Source: Company Siemens Healthcare
CZT cross strip detector
ASIC RENA3 (Nova R&D)
LSO block detector• Detector integration (commercial elements)
• Front-end-electronics
• Signal processingSystem performance
• Compton camera detector modules
• Photon energy: 1 – 15 MeV
• Operational in clinical environment
• Real time capability45
Acknowledgments
46
1. RadiotherapyIntensity modulated radiotherapy - IMRT
Dynamic multi-leaf collimator:
- pairwise W-leaves
- computer controlled movable
- approximation of the tumor contour
- inhomogeneous dose distributionsvia irradiation time
D
x
Photo: Varian
6
1. RadiotherapyOrgan motion compensation
• Bronchial carcinoma
• Breathing motion
• 4D CT
• Pressure belt
Beam off
Beam on F. Pönisch et al. Phys. Med. Biol. 53 (2008) N259 7
1. RadiotherapyImage guided radiotherapy - IGRT
e--linac
MV cone beam CT
In-room CT on rails
kV X-ray
position control
IR m
ovem
ent
trackin
g
8
3. Scientific topicsIn-vivo dosimetry: range monitoring with in-beam PET
Treatment plan:
Dose distribution
b+-activity:
Prediction
b+-activity:
Measurement
Planning-CT
New CT
38