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CANDIDATE THERAPEUTIC IONS:
a physics accountMary PW Chin
Giuseppe BattistoniTill Böhlen
Francesco CeruttiAlfredo Ferrari
Pablo Garcia OrtegaAndrea Mairani
Paola R Sala
CERN, CH-1211 Geneva, SwitzerlandCNAO, 27100 Pavia, Italy
INFN, 20133 Milano, ItalyICTR-PHE Feb/Mar 2012 Geneva1
overviewMonte Carlo simulation setup
a sample history
energy deposition & energy balance
fluence
escapes
treatment monitoring
rare interactions
2
energy deposition ➙ senescence
necrosis
apoptosis
mutation
chromosome damage
mitotic catastrophe
genetic instability
cell repair?
the scope of this work
A PHYSICS ACCOUNTapplicable to
present and futureradiobiological models
this work is not about selecting the best ionbut to provide a physics resume
probably no single ion is The Best, a mix is our best bet➙ Brahme 2010 Plans for Ion Radiation Therapy at Karolinska Institute and University Hospital
4th Japanese-European Joint Symp on Ion Cancer Therapy
3
MeV/uproton 104.8 ~ 107.8
4He 418.0 ~ 429.87Li 120.4 ~ 123.89Be 144.9 ~ 149.010B 176.2 ~ 181.212C 196.0 ~ 202.016O 232.0 ~ 239.0
20Ne 266.0 ~ 273.0
Monte Carlo code:FLUKA version 2012
energies chosen to form a hypothetical SOBP at 8.0 to 8.4 cm
depth, filling a voxel
so that dose profiles may be normalised for
sensible inter-ion comparisonwithout restricting the analysis to a
specific clinical target dimension
simulation setup: the beam
4
VIP-Man anthropomorphic voxel phantom segmented into 62 tissue types by
George Xu et al [Health Physics 78(5) 2000]
simulation setup: the phantom
Tissue type in each voxel was converted to density and elemental composition according to ICRP-89 and ICRU-44
5
⑤
④
③
②
①
ns MeV local target
① 0.800 3027 H, muscle
② 1.15 747 O, caudate nucleus
③ 1.32 463 C, white matter
④ 1.43 387 O, white matter
⑤ 827 0.00 O, caudate nucleus
16O THERAPY:A SAMPLE HISTORY
FROM FLUKA
6
ENERGY DEPOSITION ➙ treatment planning
ESCAPES ➙ treatment monitoring➙ radiation protection & shielding
7
0 2 4 6 8 10
1
2
3
4 x 10 9
8 8.5 9 9.5 10 10.5 110
0.5
1
1.5
2
2.5
3
3.5
4
4.5
x 10 10
depth (cm)
dose
(Gy)
0 1 2 3 4 50.8
0.9
1
1.1
1.2
1.3
1.4
x 10 9
depth (cm)
dose
(Gy)
monotonic increase with heavier ions
some cross-overat greater
depths
trends due to different fragments➙ next page
ratio of doses under SOBP due to one primary ion
ratio of doses under SOBP due to one primary ion
ratio of doses under SOBP due to one primary ion
ratio of doses under SOBP due to one primary ion
ratio of doses under SOBP due to one primary ion
ratio of doses under SOBP due to one primary ion
ratio of doses under SOBP due to one primary ion
ratio of doses under SOBP due to one primary ion
p 4He 7Li 9Be 10B 12C 16O 20Ne1 4 8 11 15 19 30 41
8
0 2 4 6 8 100
0.5
1
1.5
2
2.5
3
3.5
x 10 9
dose
(Gy)
primary
0 2 4 6 8 10
0.5
1
1.5
2
2.5x 10 10 alpha
0 2 4 6 8 10
1
2
3
4
5
6
7
8
x 10 11 helium 3
0 2 4 6 8 10
0.5
1
1.5
2
2.5
x 10 11
depth (cm)
triton
dose
(Gy)
0 2 4 6 8 10
0.5
1
1.5
2
2.5
x 10 11
depth (cm)
deuteron
0 2 4 6 8 10
1
2
3
4
5
x 10 11
depth (cm)
proton
20Ne16O12C10B9Be7Li4Hep
ENERGY DEPOSITED BY FRAGMENTSlighter ions exhibitdesirable shape
of an inverted ‘V’
heavier ions exhibitundesirable distal flatness
premature peaking, but biological effectiveness of protons is relatively low
by the two lightest ions studied
prematurepeaking
9
WHERE WAS THE REMAINING ENERGY SPENT% ENERGY SPENT p 7Li 12C 16O 20Ne
hadron dE/dx
nuclear binding
escapes
95.5 91.9 88.7 86.9 84.9
-1.7 -1.7 -1.4 -1.2 -1.1
0.7 4.2 6.1 7.5 9.2
TOTAL ENERGY DEPOSITED PER BEAM KINETIC ENERGYp 7Li 12C 16O 20Ne
1 0.96 0.95 0.94 0.92
10
0 5 10
0.02
0.04
0.06
0.08
0.1
part
icle
cm
2
heavy ion
0 5 10
0.02
0.03
0.04
0.05
0.06
photon
0 5 10
0.02
0.04
0.06
0.08
0.1
0.12
neutron
0 5 10
0.005
0.01
0.015
0.02
0.025alpha
0 5 10
1
2
3
4
5
6
x 10 3
part
icle
cm
2
depth (cm)
helium 3
0 5 10
1
2
3
4
5
6
7
8x 10 3
depth (cm)
triton
0 5 10
1
2
3
4
5
6
7
8
9
x 10 3
depth (cm)
deuteron
0 5 100
0.005
0.01
0.015
0.02
0.025
depth (cm)
proton
FLUENCE normalised to dose in target
heavier ions penetrate more
monotonic trend from 4He to 20Ne
light ions producemore neutrons
good behaviour
11
0E+00
4.3E-04
8.5E-04
1.3E-03
1.7E-03
muon- muon+ pion- pion+ neutrim aneutrim positron
p 7Li 12C 16O 20Ne
0E+00
5.5E-01
1.1E+00
1.7E+00
2.2E+00
heavyIon He-3 H-3 H-2 alpha electron proton photon neutron
ESCAPES normalised to dose in the target
fortreatmentmonitoring
coun
t
major source of
noise
➙ PET➙ prompt-gamma method
another potential
European Novel Imaging Systems for
Ion Therapy12
0 50 100 150 200 250 300 350
10 4
10 2
100
102
energy (MeV)
photon
part
icle
cm
2
0 100 200 300 400 500 600 700 800 900
10 4
10 2
100
energy (MeV)
proton
part
icle
cm
2
100 200 300 400 500 600 700 800 900
10 15
10 10
10 5
energy (MeV)
neutron
part
icle
cm
2
EXIT SPECTRAnormalised to dose in the target
13
ESCAPES for treatment monitoring
European Novel Imaging Systems for
Ion Therapy
Main challenges:
• beam-patient setup optimised not for
escapes (out of the body) but for
dose deposition (in the body)
• low SNR requires specialised detector setup,
backprojection and filtering (energy, angle, time)
14
3 LEVELS OF DEMAND on the spatial profile of exit particles
IA DISTINCT ICON
AT THE POSITION OF THE BRAGG PEAK
TO KNOW THE DEPTH OF
THE BRAGG PEAKACHIEVABLE
WITH SUFFICIENT FILTERING
II
A GRADIENT RISING AND DROPPING
IN UNISON WITH THE BRAGG CURVE
TO INFER ENERGY DEPOSITION
AT LEAST QUALITATIVELY
ACHIEVABLE WITH
SUFFICIENT FILTERING
IIIA CURVE
QUANTITATIVELY TRACING THE BRAGG CURVE
TO RECONSTRUCT DOSE DEPOSITION
IN THE BODY
TOO AMBITIOUS FOR NOW;
INEVITABLE EMPLOYMENT OF FUDGE FACTORS
15
muon+creation
inelastic decay7Li 2E-06 2E-0612C 3E-06 9E-0516O 1E-05 4E-04
20Ne 5E-05 9E-04per historyper historyper history
muon+interactions
decay7Li 2E-0612C 9E-0516O 4E-04
20Ne 9E-04per historyper history
pion+creation
inelastic7Li 3E-0612C 1E-0416O 6E-04
20Ne 1.5E-03per historyper history
pion+interactions
elastic inelastic decay7Li 2E-0612C 3E-06 4E-06 9E-0516O 2E-05 2E-05 4E-04
20Ne 6E-05 7E-05 9E-04per historyper historyper historyper history
16
WHAT’S RARE, WHAT’S NOT
many will stop at this pointwithout colliding non-elastically
% primaries which collide non-elastically% primaries which collide non-elastically% primaries which collide non-elastically% primaries which collide non-elastically% primaries which collide non-elastically
p 7Li 12C 16O 20Ne
11 34 40 47 53
17
PHYSICS & BEYOND
18
THE CASE FOR CARBON?-- BACK TO SQUARE ONE: HYPOXIA§
§ hypoxia is very interesting but beyond the scope of this talk
➙ molecular imaging ➙ 3γ PET: Variation of 3γ-to-2γ ratio from 18F in haemotological components measured using the GAMMASPHERE
Chin MPW et al 2009 Nucl. Instrum. Meth. A 604 (1) 331 19
This work is supported by the European Novel Imaging Systems for Ion Therapy
Grant Agreement 241851- ENVISION-COOPERATION as part of the
Seventh Framework Programme
20