Hadron Therapy
Rositsa Chankova, Dr. Scient trial lecture, 23 June, 2006
Content
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Facts about cancer
History
How it works - effect of the radiation
Conventional therapy
Charged particles therapy
– Standard approach
– Advanced Rasterscan systems
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Results
Facilities in the world
Situation
• More than 1 million get sick
from cancer every year in
Europe
2/3 patients suffer from a local
disease at the time of diagnosis
Methastatic
tumours 42%
5 % Chemotherapy
•In 18% local treatment
modalities fail=> 280.000
deaths/ year in the EC
•Protons and ions have the
potential to cure 30.000
patients/ year in the EC
Surgery
37 %
Palliative treatment
22 %
Radiotherapy
12 %
Failure of
local control
Surgery +
radiotherapy
6%
18 %
Localized tumours 58%
Organ location
Locations: brain and base of the
skull, prostate, liver, lung
Profile: deep-seated and radioresistant tumour close to organs
at risk
Tumour-conformal dose distribution
History
1903 - W.H. Bragg: Increase of ionization density with range
first described for -particles
1930 - H. Bethe:
1946 - R. Wilson:
Theory of stopping power
Increase of ionization density with range has
been confirmed for protons and heavier ions
1954 - Berkeley:
Proton therapy
1957 - Uppsala:
Proton therapy
1974 - Berkeley:
Heavy Ions (C, Ne,,,)
Energy loss of photons
The main interaction mechanisms which
contribute to μ(E) are:
•photoelectric effect ( Z5/E 3.5).
•Compton scattering ( (Z/E) ln E).
•pair-production ( Z2 ln E).
For energies typical for radioactive sources
(MeV) Compton scattering dominates.
The absorption profile of photons in matter
exhibits a peak close to
the surface followed by an exponential
decay.
X - the depth.
μ - the linear mass attenuation coefficient

Energy loss of charged particles
Bethe-Block formula
(Linear Energy Transfer):
dE 4e 4 z 2 ZN e  2mv 2 

ln

2
dx
me v
I 

•
The dominant part in the Bethe-Blochformula is 1/2 ==> increase in energy
loss with decreasing particle energy.
•
For heavy ions the energy loss is
essentially scaled by z2
Energy loss of different particles as function of the energy
Bragg curves for mono-energetic carbon beams with different
initial energies
Energy loss plotted over the penetration depth.
•The main differences between photons and particle beams is:
1.The depth dose profiles
2.The increased radiobiological efficiency (RBE) for heavy ions.
Relative biological efficiency
Defined in reference to sparsely ionizing
radiation, mostly 220 keV X-rays.
RBE is referred to a linear quadratic
reference curve ==> its value depends on
dose:
RBE is larger for low doses.
Definition of the relative biological effectiveness RBE,
illustrated for cell survival curves.
LET does not determine the
biological response alone
The local distribution of ionization density
inside the particle track is as important as
the total energy. The LET value gives
the total dose released and the radial
distribution of this dose depends on the
projectile energy.
The combination of LET and energy
determine the RBE and its position in
the LET spectrum.
Schematic comparison of RBE values for different atomic numbers.
How it works?
The effect of radiation is mainly on the DNA molecule
Typical dimensions of biological targets
Watson & Crick’s
model of DNA
•The target force killing is the DNA in the cell nucleus.
•DNA contains two strands containing identical information.
•The DNA damage is inherited through cell division, accumulating damage to the cancer cells.
The microscopic structure of proton and carbon tracks in water compared to a schematic
representation of a DNA molecule.
Protons and carbon ions are compared for the
same specific energy before, in and behind
the Bragg maximum [Krämer 1994]
•The size of the DNA-molecule compares
favourably well with the width of the ionisation
track of a heavy ion.
Conventional radiotherapy - Limitations
•
low energy x-rays the dose decreases
exponentially with depth.
•
higher energies as for Cobalt gamma
rays a build up effect shifts the
maximum dose below the skin.
•
For high energetic Bremsstrahlung the
maximum dose is located 3 cm below
the skin
•
==> higher energies intensitymodulated radiation therapy with
photons (IMRT)
1.17 MeV
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•
better depth dose profiles
reduced scattering
Comparison of the depth dose profiles of X-rays, Co-gamma
and Rentgen Bremsstrahlung with carbon ions.
Heavy charged particles give better dose
delivery than photons/electrons
Neutrons
The tumour is sensitized by a
boron compound, preferentially
deposited in the tumour region.
-particles
•very short range ( several mm)
•high biological effectiveness.
Epithermal Neutrons ( 1 keV)
produced by 5 MeV protons on
light targets (e.g. Be).
Comparison of depth-dose curves of neutrons, -rays, 200
MeV protons, 20 MeV electrons and 192 Ir  -rays (161 keV)
BUT: high amount of biologically very effective
damage in the healthy tissue around the tumour.
PRODUCTION OF PARTICLE BEAMS
Sketch of a typical set-up for the acceleration of heavy ions
The treatment of deep seated tumours requires charged particles of typically 100 to
400 MeV per nucleon, i.e. 100 to 400 MeV protons or 1.2 to 4.8 GeV 12C ions.
Beam shaping systems
•Passive devices - fixed E from the accelerator adjusted by:
Longitudinal direction - ridge filters
Lateral spread - scattering system
Compensator and apertures give the final shape of the beam
Advantage - intensity fluctuation do not influence the homogeneity of the dose
distribution
•Active devices
Range are changed via active energy variation
Laterally distributed by fast magnetic deflection
No material on the beam path
Advantage - much better conformity of the irradiated volume to the target volume
Passive devices
Distal edge shaping using a
bolus pulls dose back into
healthy tissue
Advanced Rasterscan system
The basic idea:
•Dose distributions of outmost tumor
conformity can be produced by superimposing
many thousands Bragg-peaks in 3D.
•Dissect the treatment volume in to
thousands of voxels.
dose distribution for individual energy
settings and the resulting total dose
•Use small pencil beams wit a spatial resolution of a few mm to fill
each voxel with a pre-calculated amount of stopping particles.
Advanced Rasterscan system
- Scanning of
focussed ion beams
in fast dipole
magnets.
- Active variation of
the energy, focus
and intensity in the
accelerator and
beam lines
- Utmost precision
via active position
and intensity
Intensity-controlled rasterscan technique@ GSI (Haberer et al.)
feedback loops
Raster scan technique
Controls and safety:
•intuitive user interface
•independent sequencer
•fail-safe characteristics
•diversity and redundancy
•beam intensity sampling
100000-times per second
•beam position sampling
10000-times per second
•real-time visualisation
Beam delivery system
Able to produce any
angle with respect too
the patient
•optimum dose application
•world-wide first ion gantry
•world-wide first integration of beam
scanning
•13m diameter
•25m length
•600to overall weight
•420to rotational
•0,5mm max. deformation
•prototype segment tested at GSI
HICAT / Scanning Ion Gantry
Positron emission tomography (PET)
Fragmentation of heavy ions leads to
the production of positron emitters.
For the 12C case
T1/2(11C)=20,38 min, T1/2(10C)=19.3 s
The positrons have a very short range,
typically below 1 mm.
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photons detected by PET
techniques
monitor the destructive effect of
heavy ions on the tumour tissue.
Hadron therapy results
Facilities in the world
Who
Where
Berkeley 184
CA. USA
Berkeley
CA. USA
Uppsala
Sweden
Harvard
MA. USA
Dubna
Russia
ITEP, Moscow
Russia
Los Alamos
NM. USA
St. Petersburg
Russia
Berkeley
CA. USA
Chiba
Japan
TRIUMF
Canada
PSI (SIN)
Switzerland
PMRC (1), Tsukuba
PSI (72 MeV)
Switzerland
Dubna
Russia
Uppsala
Sweden
Clatterbridge
England
Loma Linda
CA. USA
Louvain-la-Neuve Belgium
Nice
France
Orsay
France
iThemba LABS South Africa
MPRI (1)
IN. USA
UCSF – CNL
CA. USA
HIMAC, Chiba Japan
TRIUMF
Canada
PSI (200 MeV)
Switzerland
GSI Darmstadt Germany
HMI, Berlin
Germany
NCC, Kashiwa
Japan
HIBMC, Hyogo Japan
PMRC (2), Tsukuba
NPTC, MGH
MA. USA
HIBMC, Hyogo Japan
INFN-LNS, Catania
WERC
Japan
Shizuoka
Japan
MPRI (2)
IN. USA
What
p
He
p
p
p
p
πp
ion
p
ππJapan
p
p
p
p
p
p
p
p
p
p
p
C ion
p
p
C ion
p
p
p
Japan
p
C ion
Italy
p
p
p
Year of
first RX
1954
1957
1957
1961
1967
1969
1974
1975
1975
1979
1979
1980
p
1984
1999
1989
1989
1990
1991
1991
1991
1993
1993
1994
1994
1995
1996
1997
1998
1998
2001
p
2001
2002
p
2002
2003
2004
Year of
last RX
1957
1992
1976
2002
1996
1982
1992
1994
1993
1983
4066
1993
1999
Recent
patient total
30
2054
73
9116
124
3748
230
1145
433
145
367
503
2000
June 2004
191
418
1287
9282
21
2555
2805
446
34
632
1796
89
166
198
437
270
359
2001
800
30
2002
14
69
21
4511 ions
39612 protons
Totalt
Date
of total
June 2004
Apr. 2004
Apr. 2002
700
Nov. 2003
Jan. 2004
Dec. 2003
July 2004
Apr. 2004
Dec. 2003
Dec. 2003
June 2004
Feb. 2004
Dec. 2003
Dec. 2003
Dec. 2003
Dec. 2003
June 2004
June 2004
492
July 2004
Dec. 2002
77
Dec. 2003
July 2004
July 2004
45223
July 2004
June 2004
General layout of the Loma Linda facility (USA)
cork screw gantries.
synchrotron
accelerator
FUTURE FACILITY - HICAT
• compact design
• full clinical integration
• rasterscanning only
• treatments with
various ions, change within
minutes
• world - wide first scanning Ion
gantry
•1000 patients/year
HICAT / Scanning Ion Gantry
•Dedicated
positioning
•Integration of
PET and digital
X-ray systems
and stereo tactic
equipment
Advantages using hadron therapy
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Destroy malignant tissue with minimal dose exposure for the neighboring
tissue
•
Destroy tumor localized as deep as 30 cm with less side effects than
conventional surgery or therapy
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Do not expose energy beyond the Bragg peak. Can cure tumor a few mm
from critical organs.
•
Each treatment take 5 min and the number can be reduced from typically
30 to 15 times.
•
Painless, current only 10-9 (A)
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Heavy ions deposit more energy per volume and probability for destroying
the cancer cell increases
•
The technique of cross fire assures better energy deposition in the tumor.