Med-1Protontherapy and

microdosimetry with the Geant4 toolkit

Se Byeong Lee – National Cancer Center, Goyan, Korea

Sébastien Incerti – IN2P3/CENBG, France

on behalf of the Med-1 team

TYL-FKPPL Joint Workshop, Seoul, June 4-6, 2013

Outline• Context

– Extend and evaluate Geant4 performance for protontherapy and

microdosimetry

in the context of protontherapy

• Proposed workplan for 2013

1. Evaluate Geant4 performance for protontherapy

2. Modelling of geometries for plasmid irradiation

3. Perform irradiation of pBR322 plasmids at NCC with 230 MeV protons

at NCC

4. Continue verification & validation of Geant4-DNA physics models

• Collaboration matters2

Med 1 triangular collaboration

NCC

Protontherapy MC simulation &

track structure modelingExperiments on proton

beam

IN2P3/CENBG

Geant4 “low energy” EM

Geant4-DNA

IN2P3/LPC Clermont

GATE/Geant4-DNA modeling for protontherapy

Biology experiments 3

1) Geant4 perfomance for protontherapy

simulation

4

Proton beam facility in National Cancer Center

IBA Proteus 235

Weight : 220 ton Height : 210 cm

Diameter : 434 cm

Energy : 230 MeV

Max. extracted beam current : 300 nA

RF frequency : 106 MHz

Evaluate for Geant4 perfomance

for protontherapy simulation• Objectives

– Deliver benchmark data for Bragg peak profiles

• in liquid water,

• longitudinal & lateral profiles, at entrance, near peak and tail

• at a selection of proton energies

– Perform monthly regression tests for the non-public monthly

releases of Geant4

• NCC joined the Geant4 collaboration in September 2012, in the

“Low Energy EM WG”

• Prior to public Geant4 releases (twice a year)

Measurements at NCC

3D water phantom

with moving Markus

chamber

Proton therapy room

Simulation application• Simulation application based on the Geant4 electromagnetic test

#44 for Bragg peak simulations (non-public)

• Easy to modify in order to implement a simple nozzle geometry

and General Particle Source feature for the generation of incident

beam phase space

• This application will be maintained on a monthly basis from the

CERN SVN repository

• Allows to study the impact of Physics components combination

using modular physics list:

– Electromagnetic : Option_0, 3 and 4, Livermore, Penelope

– Hadronic: FTFP_BERT, QBBCInt. J. Rad. Biol. 88, 171-175 (2012)

Example of longitudinal profiles

0 20 40 60 80 100 120 140 160 1800

20

40

60

80

100

Depth along Z axis (mm)

Measurement using water phantomGeant4 simulation

Enlargement of lateral profile

Preliminary resultsGeant4 water phantom

simulation

Validation

10

Geant4MeasurementPerce

nt Depth Dose

Depth profile

Simulation of 53000 protonsPhysics:QGSP_BIC,EMstandardOpt3

,…

Using NCC proton nozzle simulation

with Geant4 9.6

Regional comparisonComparison in beam

entrance region

Comparison in Bragg peak

region

11

Measurement

Geant4

Preliminary resultsLateral dose distribution

from

water phantom measurement

2D dose distribution

comparison between

Simulation and Measurement

12

lateral profile

Percent Depth Dose

lateral profile Percent Depth Dose

Depth profile

Depth(cm)

2D dose distribution comparison between Simulation and Measurement

near Bragg peak

13

2) Verification & validation of Geant4-

DNA

Verification• Verification = comparison to recommendations &

other simulation software

• During Med 1 activity, we recently published CTMC

cross section models for protons and hydrogen in

liquid water and DNA bases (A, T, G, C)

– Protons : single capture, single ionization, transfer ionization (new

process), double ionization (new process)

– Neutral hydrogen : single ionization, stripping

• We are now comparing

– stopping powers

– ranges

– mean deposted & transferred energies

– in liquid water and DNA material

– Once verified, the models will be made publicly available

in Geant4-DNA

15

Liquid water

Adenine

Nucl. Instrum. Meth. B in press (2013)

Validation• Validation = comparison to experimental results

• Geant4-DNA physics and physico-chemistry modelling

capabilites should be validated experimentally on ‘simple’

biological targets

– made of liquid water and/or DNA material

– in dry and hydrated conditions

• We propose to irradiate DNA plasmids at NCC

with few hundred MeV protons

– a circular double-stranded DNA purified

– grown from bacteria

• This will allow the experimental quantification of DNA

damages (SSBs & DSBs) and comparison to Geant4-DNA

simulations 16

http://sandwalk.blogspot.com

Plasmid irradiation• pBR322

• 4361 base pairs

– Fully known base sequence

• Two irradiation conditions

– Irradiation of dry DNA layers

→ direct effects

– Irradiation of DNA plasmids in water buffer

→ indirect + direct effects

• 230 MeV protons at NCC

• Irradiation protocol developed at Nuclear Physics Institute

of Prague

(M. Davidkova et al.) for the ESA AO7146 project17

Diferent plasmid conformations after irradiation can be easily separated by agarose gel electrophoresis

DNA plasmids0.5 - 10 kbp in size

Measurement of DNA damage in plasmids

Degraded

SSB DSB

SSBSSB

DSB

DSB

Supercoiled

Circularrelaxed

Linear

*SSB

*SSB

M. Davidkova, NPI

relaxedlinear

supercoiled

1

2

3

Direction of migration

1 2 3Well

relaxed

linear

supercoiled

+

-

Supercoiled

Circular relaxed

Linear

Increasing dose

Plasmid dimer

Agarose gel electrophoresisThe DNA is stained with a fluorescent dye (ethidium bromide, SYBR green)

M. Davidkova, NPI

The full biology protocol will be established on June 21st at Toulouse / Paul Sabatier

U.

Simple parametrized 300 bp circular

V. Stepan – CENBGESA BioRad II

Example of Geant4-DNA plasmid geometry

3) Outreach

21

Outreach• 51th Particle Theraphy Co-

operative Group (PTCOG)

conference in Seoul on May 14-

19th, 2012

– 3 communications on GATE/Geant4 &

Geant4-DNA

• Strong support of FKPPL to the

organization of reular Geant4 and

GATE tutorials in Korea : 2009,

2010, 2011

• Recent tutorial

– Geant4 Tutorial - October 29 –

November

2, 2012 - KISTI, Seoul, S. Korea

• A new Geant4 tutorial will be

organized in 2013 in Seoul : dates

to be selected

22

KISTI, 2012

Med-1 collaboration matters

Participants

France Korea

V. Breton LPC Clermont J. H. Jeong NCC

C. Champion CENBG S. B. Lee NCC

M. Karamitros CENBG S. J. Park NCC

L. Maigne LPC Clermont J. I. Shin NCC

Y. Perrot LPC Clermont

P. Trung LPC Clermont

24

Budget request for 2013• Request from France to FKPPL

– 2 French visitors to NCC (a week)

– 1 Korean visitor to CENBG (a month)

– Participation of Dr Jeong to Geant4 2013 International Conference at the Physiqcs-

Medicine-Biology frontier in Bordeaux

• Request from Korea made to NCC

– 1 participation to the Geant4 2013 collaboration meeting (Sevilla, Spain – September

2013)

• Note: we already benefit from funding by CampusFrance PHC STAR

« PROTEUS » project (2012-2013, coord.: S. Incerti) for 3 visits of French

collaborators to Korea in 2013 (6.5 keuros).

25

Geant4 International Conference at the

Physics-Medicine-Biology frontierhttp://geant4.in2p3.fr/2013/

7-11 October 2013Bordeaux

France

Full papers in Phys.

Med. Biol.

Takashi Sasaki - KEKSe Byeong Lee – NCCRepresenting Japan and Korea

Thank you

Hospital

Research Institute

National Center for Cancer Prevention and Early Detection

NCC Proton Therapy Center