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

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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

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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

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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

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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

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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

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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

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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

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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

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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)

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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

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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

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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

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PHYSICS & BEYOND

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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

mary.chin@cern.ch

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