Med-1 Protontherapy 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 Proposed workplan for 2013 Collaboration matters Extend and evaluate Geant4 performance for protontherapy and microdosimetry in the context of protontherapy Proposed workplan for 2013 Evaluate Geant4 performance for protontherapy Modelling of geometries for plasmid irradiation Perform irradiation of pBR322 plasmids at NCC with 230 MeV protons at NCC Continue verification & validation of Geant4-DNA physics models Collaboration matters

Med 1 triangular collaboration IN2P3/CENBG Geant4 “low energy” EM Geant4-DNA NCC Protontherapy MC simulation & track structure modeling Experiments on proton beam IN2P3/LPC Clermont GATE/Geant4-DNA modeling for protontherapy Biology experiments

1) Geant4 perfomance for protontherapy simulation

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 Proton therapy room 3D water phantom with moving Markus chamber

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, QBBC Int. J. Rad. Biol. 88, 171-175 (2012)

Example of longitudinal profiles Measurement using water phantom Geant4 simulation Background in entrance water phantom Model of nozzle: we don’t dd components, when we measure the beam there is some contamination from shielding (not simulated) secondary particles not simulated Zebra = hospital = better than wtaer phantom for range measurement Measurements with the multi layer ionisation chamber – one dimensional profile (range) markus chamber + water phantom = 3D moving chamber in water pantom Water phantom more convenine Beam delivery Pencil beam: Beam nozzle, many parts, can give secondary particles Enlargement of lateral profile

Preliminary results Geant4 water phantom simulation Validation Measurement Percent Depth Dose Depth profile Simulation of 53000 protons Physics:QGSP_BIC,EMstandardOpt3,… Using NCC proton nozzle simulation with Geant4 9.6

Regional comparison Comparison in beam entrance region Comparison in Bragg peak region Measurement Geant4

Preliminary results Lateral dose distribution from water phantom measurement 2D dose distribution comparison between Simulation and Measurement Depth (cm) Percent Depth Dose Depth profile lateral profile lateral profile Percent Depth Dose

2D dose distribution comparison between Simulation and Measurement near Bragg peak

2) Verification & validation of Geant4-DNA

Verification Liquid water Adenine 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 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 http://sandwalk.blogspot.com

Plasmid irradiation pBR322 4361 base pairs Two irradiation conditions 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 project

Measurement of DNA damage in plasmids M. Davidkova, NPI Degraded SSB DSB Supercoiled Circular relaxed Linear *SSB DNA plasmids 0.5 - 10 kbp in size Diferent plasmid conformations after irradiation can be easily separated by agarose gel electrophoresis

Agarose gel electrophoresis M. Davidkova, NPI The DNA is stained with a fluorescent dye (ethidium bromide, SYBR green) Direction of migration 1 2 3 Well relaxed linear supercoiled + - relaxed linear supercoiled 1 2 3 The full biology protocol will be established on June 21st at Toulouse / Paul Sabatier U. Supercoiled Circular relaxed Linear Increasing dose Plasmid dimer

Simple parametrized 300 bp circular Example of Geant4-DNA plasmid geometry Simple parametrized 300 bp circular Simple description using two tube segments per nucleotide. Such volume-based model will only be used for direct effect evaluation. Nucleotide model needs improvements. V. Stepan – CENBG ESA BioRad II

3) Outreach

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 KISTI, 2012

Med-1 collaboration matters

Participants France Korea V. Breton LPC Clermont J. H. Jeong NCC C. Champion CENBG S. B. Lee M. Karamitros S. J. Park L. Maigne J. I. Shin Y. Perrot P. Trung

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).

Geant4 International Conference at the Physics-Medicine-Biology frontier http://geant4.in2p3.fr/2013/ 7-11 October 2013 Bordeaux France Takashi Sasaki - KEK Se Byeong Lee – NCC Representing Japan and Korea Full papers in Phys. Med. Biol.

Thank you National Center for Cancer Prevention and Early Detection NCC Proton Therapy Center Research Institute Hospital