tumor therapy therapy with with ion ion beams...

D. Schardt / GSI-DLMarch 2012

Tumor Tumor therapytherapy withwith ionion beamsbeams Dieter Dieter SchardtSchardt

GSI DarmstadtGSI Darmstadt

1.

Introduction

(Radiation

therapy and particle

therapy)

2. Physical characteristics of ion beams in tumor therapy

3.

Technical

developments Accelerators, Beam

scanning

4.

Radiobiological

aspects

5.

Dose verification

techniques

6.

Clinical

results

Today

only

protons and light ions (4He,12C,20Ne) are

of practical

importance(neutrons, pions, antiprotons)XXX

???


Historical development of radiation therapyHistorical development of radiation therapy

1895 Discovery of X-rays

(Roentgen) 1896 Production

of X-ray

tubes

by

RGS Erlangen (later

Siemens)

1896 Discovery of Radioactivity

(Bequerel)1898 Radium (Curie) 226Ra, α

and γ

186 keV

(Brachytherapy)

Conventional radiotherapy (photons and electrons)1950 60Co ( γ

1 MeV) 137Cs ( γ

661 keV)

Betatron Electrons

up to 20 MeV + conv.target

(Photons)

1970 Linear accelerators

Electrons

6-25 MeV (Photons)

1985 IMRT (Intensity-Modulated

Radiation

Therapy)

→ about

1950: Development

of Particle

Therapy


ElektronElektron--LinacLinac


DepthDepth--dose profiledose profile

Photon-Irradiation

Rotation & Intensity Modulation

IMRTInverse Planning

Multifield-Irradiation

100%


IMRT TechniquesIMRT Techniques

Intensity-Modulated Radiation Therapy

IMRT

Treatment headVARIAN Systems


DepthDepth--dose profile dose profile –– charged particlescharged particles

Heavy charged particlesProtons / Light Ions

100%


Ion Ion BeamsBeams in in RadiotherapyRadiotherapy

1946 R.R. Wilson, Radiology 47,487

"…potential benefits

of heavy

chargedparticles

in radiotherapy"

R.R. Wilson at Harvard mid

1940s†2000

1954 First

proton

treatments

at 184“

cyclotronLBL BerkeleyJohn and Ernest Lawrence, C. Tobias, J. Castro

"…

for

a given

range, the

straggling

and the

angular

spread

of alpha particles willbe

one-half

as much

as for

protons.Heavier

nuclei, such as very

energeticcarbon atoms , may

eventually

becometherapeutically

practical."

Today: 32 clinical

proton

facilities

83,000 patients

treated6 carbon

ion

9,200


Ion Ion BeamsBeams in in RadiotherapyRadiotherapy

New projects planned or under construction …see PTCOG Newsletter http://ptcog.web.psi.ch/

Beam scanning

First clinical HI-facility

patients

1957 -

92 4He 184-inch SC Berkeley / USA 2054

1975 -

92 20Ne BEVALAC Berkeley / USA 433

1997 -

2008 12C SIS-18 Darmstadt / Germany 440 G. Kraft

Beam scanning

1994 12C HIMAC Chiba / Japan 5497

2003 12C,p HIBMC Hyogo

/ Japan 638

2009 12C IMPCAS Lanzhou / China 126

2010 12C,p HIT Heidelberg /Germany 400

2010

12C GHMC Gunma

/ Japan 454

2011 12C,p CNAO Pavia / Italy

5


Proton and Ion-Therapy in Europe

Protons

Light Ions

Centers in Operation

Under construction

Under discussion

?

x Marburg / Kiel(stopped)

Berlin

HIT

PSI

CPO

CNAO

ITEP

Gatchina

Uppsala Dubna

Krakow

Vienna

Prague

?

?

?

Clatterbridgex

x

Catania

RPTCMunich

Kiel

Berlin

Marburg


Cancer situation in EuropeCancer situation in Europe

Lokalisierte Tumore: 58% Metastasierende Tumore: 42%

Operation: 22%

Radiotherapie: 12%

Chemotherapie: 5%

Palliative Behandlung: 37%

Operation+Radiotherapie: 6%

Versagen bei der lokalen Kontrolle: 18%

(Tubiana

1992)

> 10.000 Patients/year could be treated better with particle therapy

In Germany about

480,000 new

cancer

incidences

per year

Localized

Tumors 58% Metastatic

Tumors 42%

Surgery

22%Chemotherapy

5%

Palliative treatment

37%

Surgery

22%

Radiotherapy

12%

Surgery

+ RT 6 %

Failure

of local

control

18%


HeavyHeavy--ionion therapytherapy isis an an interdiscplinaryinterdiscplinary fieldfield

Physics

Radiobiology

Engineering

Energy deposition, depth-dose

profile,particle

field, physical

model

Biological

effect

(RBE)cell

killing

& repair

mechanismsbiological

model

Accelerator, beam

delivery, scanning, Control

system, safety

aspectsIn-vivo

range

verification

(PET)

Clinical application

Indications, treatment

planning, fractionation

scheme, clinical

studies

...

Treatment planning


PhysicalPhysical characterizationcharacterization of of ionion beamsbeams

Energy deposition

Depth-dose distribution (Bragg curve)

Nuclear fragmentation

Lateral scattering


Definition

J/kg] 1 Gy [1

mED

AbsorbedAbsorbed DoseDose

Lethal

Dose:LD50/30 = 3-4 Gy (Human)

1000 Gy (Wasp)

Radation

therapy: ~ 40-60 Gy in target

volume

1 Gy is

a very

small

amount

of energy

(0,0002388 kcal/kg) (1 Gy heats 1 Liter Water by 0.0002 deg)

Radiation

effects

are

not

due

to heat

!


Inverted depth-dose profile (Bragg curve)

Unmodified Bragg peak

Typically

30 energy

steps

needed

for

a ripple

< 5%

Extended target volume

Tumor region

Normal tissue

Depth-dose profile


SpecificSpecific energyenergy lossloss

2

2p

cr

eZF

dtFp c

Energy loss per unit path length ? Niels Bohr 1913Semi-classical treatment

Ion

br

Momentum

Energy transferred

to 1 Elektron

Interaction goverened

by

inelastic collisions(99,9%)

222 22

)(

vbeZ

mmpE p

ee

Coulomb-Force

→ Integration over

all impact

parameters

0 -

∞gives

dE/dx

Slow particles produce a larger momentum than fast ones !


StoppingStopping of of energeticenergetic heavyheavy ionsions in matterin matter

Specific energy lossStopping power

2

2

22e

T22e

42eff

.el )1(Icm2lnZ

cm

eZN4

dxde 3/2

ppeff Z125exp1ZZ Barkas-Formula

mean

ionization

potential

dE/dx ~ Zp2 / v2

Bragg

Maximum: v ≈

Zp2/3

v0

(c/137)

Protons ≈

100 keVPb ions

≈

10 MeV/u

Bohr 1913, Bethe-Bloch Formula (1930)

Stopping

in tissue


BraggBragg curvescurves of of 1212C in C in waterwater

peak-width and height are affected by–

straggling –

fragmentation

increasing tail dose


Mechanical accuracy:10 μm for

relative thickness0.2 mm absolute

BraggBragg curvecurve measurementsmeasurements

IC2/IC1


particle flux fluence F =

tAbsorbed dose

erg/g] 100 Gy [1 mED

1

dxdEF106.1D 9

[Gy] [cm-2

keV/m g/cm3]Specific energy loss

m][keV/ xElim

dxdE

0x

Example:

12C ions

300 MeV/u de/dx=13 keV/mF=108

/cm2

Dose in water: 2 Gy

LET (linear energy

transfer)

ParticleParticle dosedose


Significance of nuclear fragmentation Significance of nuclear fragmentation in RT with light ionsin RT with light ions

Carbon

ion

therapy100-400 MeV/u

I. Pshenichnov

High-energy carbon beam stopping in water

Nuclear

fragmentation Loss

of primary

ions

depth-dose, RBE

Total reaction

cross section

1-2 b

Buildup

of secondary

fragments

dose-tail, lateral dose

Exp. Investigations (physical characterization)–

LBL Berkeley Ne 670 MeV/u

1970’s W. Schimmerling–

NIRS/HIMAC Chiba C, light ions 1990’s T. Kanai –

GSI Biophysics C, light ions 1990’s


NuclearNuclear fragmentationfragmentation reactionsreactions

Peripheral

collisions

at high energies

Fragment spectrum

„Geometrical“

reaction

cross section23/1

t3/1

p20tot )bAA(r

Brad-Peters (1950)

xne)0()x( ; ndxd

x


Loss of carbon Ions bynuclear reactions

E. Haettner

et al., GSI 2005

Buildup

of secondary fragments

Surviving fraction

Attenuation of primary flux and Attenuation of primary flux and buildupbuildup of of secondary fragmentssecondary fragments


HowHow nuclearnuclear fragmentationfragmentation affectsaffects thethe BraggBragg curvescurves

Model calculations (HIBRAC-code)Lembit

Sihver

GSI, 1997semi-empirical

cross section

formula

Depth in water [cm]

Range 2.6 cm

Range 36 cm

Today

powerful

Monte-Carlo codes

likeFLUKA, GEANT4, PHITS etc.are

able

to simulate

all atomic

and nuclearInteractions

and reproduce

the

Bragg

curves


RangeRange--Straggling protons vs. carbon ionsStraggling protons vs. carbon ions

Mstraggl

1 ~

3.4 C

p

WW


Lateral Lateral beambeam profileprofile

Moliére

theory

(1948)

Highland-Formula (Gaussian

approxim.)

[rad] Ldlog

911

LdZ

pc/MeV1.14

RRp


ComparisonComparison of lateral of lateral beambeam spreadspread

Protons

12C ions0 cm 15 cm

Film dosimetry, LBL Berkeley

Ion beam


Beam spread Beam spread -- protons vs. carbon ionsprotons vs. carbon ions

Bea

m w

idth

FWH

M

[mm

]

0

5

10

15

20

25

30

Distance from exit window [cm]

0 20 40 60 80 100 120 140 160

nozzle

50 MeV

80

100 150

200

250

491 386

92

285

148 186

protons12C ions

waterair

MeV/u

≈

1mPatient

Multiple scattering–

nozzle

elements–

patient

tissue

Molière theory


Comparison of Carbon Ions vs. Protons

C-12 (GSI)

Protons (Capetown/SA)

Heavy ions offer higher precision close to organs at risk


PhysicalPhysical characteristicscharacteristics of of ionion beamsbeams relevant relevant forfor tumortumor therapytherapy

„Inverted“

depth-dose

profile

(Bragg

curve)major

advantage

for

treating

deep-seated

tumors

Nuclear

fragmentation

is

a significant

effectfor

heavy

ions

(tail

dose)

Lateral scattering

significant

for

protons

tumor therapy therapy with with ion ion beams...

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