HIT Betriebs GmbH amUniversitätsklinikum Heidelbergmit beschränkter Haftung

www.med.uni-heidelberg.de/hit

Ion- and proton-beams: Experience with Monte Carlo Simulation

Katia Parodi, Ph.D.

Heidelberg Ion Therapy Centre, Heidelberg, Germany(Previously: Massachusetts General Hospital, Boston, USA)

Workshop on Monte Carlo usage in the medical fieldRome, Italy,07.12.2007

Massachusetts General Hospitaland Harvard Medical School

The advantages of ion therapy

Physical validation of the FLUKA MC tool

Examples of clinical applications (from dose calculations to PET monitoring)

Conclusion and outlook

Overview

The physical advantages of ion beams

The „Inverse“ depth-dose distribution (BP)

The physical advantages of ion beamsThe reduced lateral scattering (for Z > 1)

Courtesy of T. Haberer, HIT

The physical advantages of ion beamsIMRT Protons

Courtesy of A. Trofimov and A. Chan, MGH Boston

The physical advantages of ion beamsIMRT: 9 Fields Carbon ions: 2 Fields

Courtesy of O. Jäkel, DKFZ Heidelberg

The role of MC in ion therapy

In clinical practice: validation of critical TPS dose calculations (e.g., inhomogeneous tissue, metallic implants)

In commissioning of new facilities: specification of the beam parameters and generation of TPS input data ( meas. time)

In dedicated applications: powerful tools for nuclear reaction related issues, like PET monitoring of ion treatment

Long computational time Realistic representation of physical interactions in complextargets, e.g., patient ☺

The FLUKA MC code(http://www.fluka.org)

Reliable nuclear models

Already applied to proton therapy for dosimetricand radiobiological studies (Biaggi et al NIM B 159, 1999)

Import of raw CT scans with optimized algorithms for efficient transport in voxel geometries(Andersen et al Radiat. Prot. Dosimetry 116, 2005)

Huge efforts for ion transport in connection with NASAgrant since 2000

Promising results from initial studies of ion beam fragmentation in water (Sommerer et al PMB 51, 2006)

Recent improvements for therapeutic ion applications:BME generator for low energy nucleus-nucleus reactions (Cerutti et al Proc. VII LASNPA Conf., Cusco, Peru, 2007)

The

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Experimental validation: Protons Protons (160 Protons (160 MeV/uMeV/u) on ) on MultiLayerMultiLayer

Faraday Cup (CHFaraday Cup (CH22))

Exp. Data (points):H. Paganetti et al.,

Medical Physics, 2003 Simulations: A. Mairani, INFN Pavia

Prelim

inary

Exp. Data (points) taken at HIT(!): D. Schardt, P. Steidl,

K. Parodi, S. Brons et al.

Preliminary

Protons (182 Protons (182 MeV/uMeV/u) in Water) in Water

Exp. Data (points): Haettner et al, Rad. Prot. Dos. 2006Simulations: A. Mairani, Ph.D. Thesis, 2007

FLUKA

Depth-dose distribution (BP)

1212C ions @ 400 C ions @ 400 MeV/uMeV/u in in WaterWaterExperimental validation: 12C6+

1212C ions @ 400 C ions @ 400 MeV/uMeV/u in Water in Water

Exp. Data (points): Haettner et al, Rad. Prot. Dos. 2006

Simulations: A. Mairani, Ph.D. Thesis

Carbon Beam Attenuation

FLUKA

Build-up of secondary fragments

FLUKA

Experimental validation: 12C6+

Experimental validation: 12C6+

Preliminary exp. Data: E.Haettner (Diploma thesis) and D.Schardt, GSI Simulations A.Mairani Ph.D. thesis

1212C @ 400 C @ 400 MeV/uMeV/u in waterin water

Carbon angular distribution at different depths

Experimental validation: 12C6+

Heavy Fragment angular distribution at 31.2 cm

1212C @ 400 C @ 400 MeV/uMeV/u in waterin water

Preliminary exp. Data: E.Haettner (Diploma thesis) and D.Schardt, GSI Simulations A.Mairani Ph.D. thesis

Two examples of clinical dose calculations

I. For protons @ MGH Boston II. For 12C @ GSI Darmstadt

I. Beam input informationPassively formed p treatments @ MGH

At MGH: FLUKA coupled with beam phase-space from a Geant4 MC-calculation of nozzle and beam modifiers

Paganetti et al,Med. Phys. 2004

Example of set-up(Tsukuba)

The general principles of Passive Modulation

I. Beam input informationPassively formed p treatments @ MGHR

elat

ive

Dos

e in

Wat

er

Depth (mm)

Parodi et al, Med Phys 34 2007

SOBPMC vs. IC meas.:80% and 90% fall-off positionagree within 1 mm

II. Beam input informationActive rasterscan system for 12C treatments @ GSI

Haberer et al, NIMA 1993

Intensity- andPosition- controlledmagnetic scanning

Active variationof beam energy, focus and intensityfrom accelerator

II. Beam input informationActive rasterscan system for 12C treatments @ GSI

Experimental data (points) from S.Brons (HIT)Simulations: A. Mairani, Ph.D. Thesis

SOBP MC vs IC meas

FLUKA coupled with control file of raster scanning system and modeling ridge filter(F. Sommerer presented at MC Workshop, Ghent 2006, http://www.ewg-mctp.ugent.be )

FLUKAData

Lateral Profiles

CT segmentation into 27 materials (Schneider et al PMB 45, 2000, extended to include Ti in Parodi et al, Med. Phys. 34, 2007)

Soft tissue

Air, Lung,Adipose tissue

Skeletal tissue

I-II. Using the information from the patient CT

Nominal mean density for each HU interval(Jiang and Paganetti MP 31, 2004)

I-II. Using the information from the patient CT

Schneider et alPMB 45, 2000

But real density varies continuously with HU value

I. Adaptation of FLUKA to follow the TPS (XiO/CMS) calibration curve for p @ MGH

HU dependent adjustment of nuclear and electromagnetic processes, reproducing same calibration curve as TPS

(similar to Jiang and Paganetti MP 31, 2004)

Parodi et al MP 34, 2007, Parodi et PMB 52, 2007

1000

Ti

II. Adaptation of FLUKA to follow the TPS (TRiP) calibration curve for 12C @ GSI

O. Geiß et al, GSI Scientific Report 1997O. Jäkel et al, Med. Phys. 28 2001

A. Mairani Ph.D. thesis

FLUKATRiP

12C (270 MeV/u) on CT phantoms

I. Proton therapy @ MGH: MC vs XiO/CMS

Clivus Chordoma PatientXiO/CMS FLUKA

Prescribed dose: 1 GyEMC : ~ 5.5 106 protons in 10 independent runs

(11h each on Linux Cluster mostly using 2.2GHz Athlon processors)

Parodi et al, JPCS 74, 2007

mGy mGy

XiO/CMS FLUKAmGy mGy

I. Proton therapy @ MGH: MC vs XiO/CMS

FLUKAXiO/CMS

mGy mGy

FLUKA mGy

Prescribed dose: 2 GyEMC : ~ 7.4 107p in 12 independent runs (~ 130h each on 2.2 GHz Linux cluster)

XiO/CMS

metallic implants

K. Parodi et al, IJROBP 2007

mGy I. Proton therapy @ MGH: MC vs XiO/CMS

Paraspinal tumor with metallic implants

II. Carbon ion therapy: MC vs TRiP

Clivus Chordoma Patient(physical dose calculations)

A. Mairani, Ph.D. Thesis

TRiPmGy

FLUKA

mGyFLUKA

TRiP

A. Mairani, Ph.D. Thesis

II. Carbon ion therapy: MC vs TRiP

TRiP FLUKAmGymGy

mGyFLUKA

mGyTRiP

TRiP

FLUKA

Two examples of application at the upcomingHeidelberg Ion Therapy Center (HIT)

Ion species• low-LET: Protons

(later He)• high-LET: Carbon

(Oxygen)Beam delivery• Rasterscanning with

active energy variation(like GSI)

• Required parameters:255 Energy steps4 (6) Foci10 IntensitiesFLUKA simulations

HIT, Heidelberg, Germany

Two examples of dedicated, fragmentation-related applications

PET/CT @ MGH Radiology

Siemens Biograph 16

I. PET/CT after proton therapy II. In-beam PET during 12C therapy

In-beam PET @ GSIFZ Rossendorf

The principle of PET monitoring in ion therapy

Production of positron emitters (15O, 11C, 13N..., T1/2 ~ 2, 20 and 10min...) as a by-product of irradiation

Before collision After collisionProton

Target fragment

Proton

Atomic nucleusof tissue

16O 15O Neutron

Before collision After collisionProjectilefragment

Target fragment

Projectile12C ion

Atomic nucleusof tissue

16O 15ONeutrons

C12 11C

15O 15N + e+ + νeT1/2

180°Δt = 0

Eγ = 511 keV

InIn--vivo, nonvivo, non--invasive detection invasive detection of irradiation induced of irradiation induced ββ++--activityactivityby means of PETby means of PET

Courtesy of W. Enghardt, FZ Rossendorf

The motivation for PET and Monte Carlo

⇒⇒ Measured activity compared with MC calculation as for 12C therapy at GSI Darmstadt, Germany (Enghardt et al, NIMA 525, 2004)

K. Parodi et al, IEEE MIC CR, 200212C ions, E=212 A MeVProtons, E=110 MeV

11C,10C

15O, 11C, ...

15O, 11C, ...

A(A(rr) ) ≠≠ D(D(rr))

I. PET/CT@MGH: β+-activity calculation

FLUKA simulations using1. Initial beam and CT information as for dose calculations 2. Runtime folding of experimental cross-sections with p fluence

3. Biological decay (animal studies: Mizuno et al, PMB 48, 2003)4. Convolution of activity with 3D Gaussian kernel (~7mm FWHM)

∫ →Φ

∝ EEEEN YXY d)(

d)(d σ

+ other reaction channels on C, N, O, Ca yielding, e.g., 13N, 38K, …(Parodi et al PMB 52 2007)

Data from IAEA Nuclear Data SectionParodi et al, PMB 45 2002

I. PET/CT@MGH: Head

mGy mGyClival Chordoma, 0.96 GyE / field Planned dose

I. PET/CT@MGH: HeadClival Chordoma, 0.96 GyE / field, ΔT1 ~ 26 min, ΔT2 ~ 16 min

Bq / ml Bq / ml

Parodi et al., IJROBP 68(3) 2007

Agreement within 1-2 mmFor position of distal max.And 50 % fall-off

Average Activity

1 Field

2 Field

I. PET/CT@MGH: Spine

T-spine Chondrosarcoma, 0.6 GyE1.2 GyE

mGy

mGy

Planned dose

I. PET/CT@MGH: Spine

Average Activity

Bq / ml

Bq / ml

Parodi et al., IJROBP 68(3) 2007

T-spine Chondrosarcoma, 0.6 GyE DT1 ~ 22 min,1.2 GyE DT2 ~ 16 min

1 Field

2 Field

Points: MeasSolid line: FitDotted line: Simu

Activity evolution over time

I. PET/CT@MGH: Spine

Parodi et al., IJROBP 68(3) 2007

FLUKAMeasurementF. Sommerer et al PMB 51 2006, PhD Thesis, Wien 2007

260 MeV/u 12C ion on Graphite, backprojections

II. In-beam PET imaging of heavier ionsOngoing work on:

Application of FLUKA to PET monitoring of ions (e.g. 12C, 16O) based on internal nuclear modelsSimulation of imaging process (β+-decay, propagation of e+ and annihilation photons, detection) same as for measured data

Exact replica of the experimental setup, PET heads includedFLUKA irradiation+decay features exploitedMC γ’s detection converted to list-mode data by modified PETSIM1

Backprojection with same routines as in experiment 1Pönisch et al. PMB 49 2004

In-beam PET phantom experiments @ GSI

II. In-beam PET imaging of heavier ions

12C 260 MeV/A on PMMA, during irradiation

16O 350 MeV/A on PMMAafter irradiation

NORMALIZED TO THE SAME AREA

,

Incorporating time course of irradiation and acquistion as in meas. …(F. Sommerer, PhD Thesis)

Conclusion and outlookMC tools are increasingly spread in ion therapy to support

Analytical TPS (validation in water /CT, input data generation)Special applications (e.g., PET monitoring)

FLUKA is a good candidateGenerally good agreement of p / 12C dose calculations vs.

experimental data and established TPS systemsDifferences to TPS mainly because of large inhomogeneities(e.g., metallic implants) and dose-to-water / dose-to-tissue Reasonable predictions of nuclear reactions and, inparticular, fragmentation (key factor for heavier ions!)

Still ongoing…Several activities in connection with HIT / FLUKA team Optimization of computational time… MC TPS???

Acknowledgement

CERN Geneva:A. Ferrari, F. Sommerer, F. Cerutti

HIT Heidelberg:S. Brons, T. Haberer, P. Heeg, J. Naumann

INFN Pavia:A. Mairani

MGH Boston:H. Paganetti, T. Bortfeld, H. Shih

FZ Rossendorf:W. Enghardt