Future Proton Irradiation Facility at OncoRay

Seminar am Institut für Kern- und Teilchenphysik

Technische Universität Dresden

14. Juli 2011

Wolfgang Enghardt

OncoRay – National Center for Radiation Research in Oncology

Technische Universität Dresden, Germany

and

Helmholtz-Zentrum Dresden-Rossendorf, Dresden, GermanyInstitute of Radiation Physics

1

Outline

1. Radiotherapy

2. The technology platform at OncoRay

3. Scientific topics

2

1. RadiotherapyStatistics, Germany

• New cases of cancer p.a. 436.000

• Deaths p.a. 210.000

• Second rank in causes of death

• Surgery, radiation therapy, systemic therapy

• Radiation therapy applied to ≥ 60% of cancer patients

• Radiation therapy contributes to ≥ 50% of cures

3

4) Fractionated

therapeutic irradiation

1) Diagnostic

imaging

2) Dose prescription

1. RadiotherapyWorkflow

3) Treatment planning4

Electron

gun

Wave guide

Collimators

Scatter foil

Radiator

Electrons

Electrons

Photons

Electron linear accelerators:

photons and electrons

(~ 400 devices in Germany)

a-magnet

1. RadiotherapyElectron linear accelerators

Electrons

5

1. RadiotherapyCurrent technology: protons and light ions

Heidelberg Ion Therapy (HIT)

20 m

R(H2O) 30 cm

Particle energy:12C: E < 430 AMeV1H: E < 230 MeV

Magnetic rigidity:12C: Br < 6.6 Tm1H: Br < 2.3 Tm

Dose rate:

dD/dt 2 Gy/(min ·l)

Beam current:

I 5 nA

6

1. Radiotherapy Clinial results: Protons/ions vs. photons (I)

1. Chordoma of the skull base

3. Prostate carcinoma (side effects)

2. Bronchial carcinoma (stage I, inoperable)

Radiation modality 12C (GSI) Photons (FSRT)

5 years local tumour control 70 % 50 %

D. Schulz-Ertner et al.: Int. J. Radiat. Oncol. Biol. Phys. 68 (2007) 449

J. Debus et al.: Int. J. Radiat. Oncol. Biol. Phys. 47 (2000) 591

Radiation modality 12C (HIMAC) Photons (CRT)

5 years survival 42 - 60 % 10 - 32 %

Radiation modality 12C (HIMAC) Photons (IMRT)

Side effects genitourinary system (G2) 6 % 28 %

T. Miyamoto et al, Radiother. Oncol. 66 (2003) 127

H. Tsujii et al., Int. J. Radiat. Oncol. Biol. Phys. 63 (2005) 1153

M.J. Zelefsky et al., Int. J. Radiat. Oncol. Biol. Phys. 53 (2002) 1111

7

4. Nasopharyngeal carcinoma

Radiation modality Protons Photons (IMRT) p-value

3 years local tumour control 92 % 95 % 0.780

3 years survival 74 % 90 % 0.289

5. Paranasal and sinonasal carcinoma

Radiation modality 12C Protons Photons (IMRT) p-value

5 years local tumour control 49 % 88 % 66 % 0.035

5 years survival 71 % 52 % 0.323

6. Adenoid cystic carcinoma

Radiation modality 12C Protons Photons (CRT) p-value

5 years local tumour control 69 % 93 % 75 % -

5 years survival 70 % 77 % 73 % -

B.L.T. Ramaekers et al., Cancer Treat. Rev. (2010)

1. Radiotherapy Clinical results: Protons/ions vs. photons (II)

8

Advantage of proton/ion therapy not proven for most tumour entities:

• Lack of data quality and quantity

• Missing randomized clinical studies

• Technologically inadequate beam deliveries and equipment

1. Radiotherapy Clinical results: Conclusions

Schwere geladene Teilchen

(1H ... 12C ... 20Ne)

Rela

tive

eff

ektive

Dosis

%

Tiefe in Wasser / cm

Schwere geladene Teilchen

(1H ... 12C ... 20Ne)

Rela

tive

eff

ektive

Dosis

%

Tiefe in Wasser / cm

100

SOBP

Re

lative

do

se

/ %

Re

lative

eff

ective

do

se

/ %

Depth in water / cm Depth in water / cm

Electrons

E = 20 MeV

Photons

15 MV

9

2. The technology platform at OncoRayFunding, financing

SMWK: Landesexzellenzinitiative Sachsen (2008):

„Gemeinsames Zentrum für Strahlenforschung

in der Onkologie“

(Research building, technology platform)

Universitätsklinikum Carl Gustav Carus Dresden

(Proton irradiation facility: clinical equipment)

Helmholtz-Zentrum Dresden-Rossendorf(PET/MR)

BMBF: Zentren für Innovationskompetenz (2009):

Technical equipment of the junior research group:„High Precision Radiation Therapy“

Includes the research package of the proton

irradiation facility

HZDR: Laser PENELOPE‘10

2. The technology platform at OncoRayMain tasks

1. Research on compact accelerators (laser proton acceleration)

and beam deliveries (high field magnets)

2. Development of innovative medical techniques and technologies

for accessing the whole potential of proton therapy

• Particle therapy (PT) is an experimental therapy

• PT is not a simple substitute of photon therapy

• PT has to be performed on highest medical und technological level

e.g.: - motion compensation - in-vivo range measurement and dosimetry- biologically based treatment planning- image guidance

• Academic, no commercial approach

• Reasonable facility size (< 1000 patients p.a.)

• Careful patient recruitment

• International therapy register, local networking

11

2. The technology platform at OncoRayLocation

• Installation of the technology platform including a conventional proton therapy

facility on the campus of the university hospital Carl Gustav Carus in Dresden;

start of construction: May 2011, start of operation: 2014

• Integration into the department of radiooncology

Händelallee

Schubertstr.

12

2. The technology platform at OncoRayComponents

Infrastructure

• Radiobiological laboratories

• Physics laboratories

• Teaching rooms

• Offices

• Animal keeping facility

Laboratory for animal experiments

• Small animal CT

• Small animal PET

• Optical imaging

• Image guided, tumor conformalanimal irradiation facility

In vivo

dosimetry

• In-beam SPECT

Conventional proton therapy

• Clinical treatment roomwith isocentric gantry

• In-room PET

• Research cave

Petawatt high intensity laser

• Laser acceleratedproton beam

Molecular Imaging

• PET/CT

• PET/MRT

13

2. The technology platform at OncoRayThe proton irradiation unit: Layout

Conventional proton beam

acceleration and transfer

Therapy cave

Research cave

14

2. The technology platform at OncoRayThe proton irradiation unit: The cyclotron

Photo: Courtesy IBA

• Isochronous cyclotron

• Warm magnet

• d = 6 m

• E = 230 MeV

• I = 300 nA

15

2. The technology platform at OncoRayThe proton irradiation unit: The energy selection system

Photo: Courtesy IBA

• Degrader wheel with

graphite blocks of variing

thickness

• E = (70 – 230) MeV

• I = (2 – 50) nA

16

2. The technology platform at OncoRayThe proton irradiation unit: The beam transfer line

Photo: Courtesy IBA

17

2. The technology platform at OncoRayThe proton irradiation unit: The treatment site

Photo: Courtesy IBA

Therapy cave

(Capacity ~ 500 pat. p.a.)

• Isocentric gantrywith universal nozzle:

- single scattering

- double scattering

- pencil beam scanning

• Robotic patient table

18

2. The technology platform at OncoRayThe proton irradiation unit: In-room PET/CT

In-room PET/CT on rails:

CT: Patient positioning

PET:Range measurement

in-vivo

19

2. The technology platform at OncoRayThe proton irradiation unit: The potential of CT on rails

Before …

after position correction

20

2. The technology platform at OncoRayThe proton irradiation unit: Experimental cave (I)

Conventional proton

beam:

• Horizontal

• d < 10 mm (FWHM)

• E = (70 – 230) MeV

• I = (0.1 – 10) nA

21

2. The technology platform at OncoRayThe proton irradiation unit: Experimental cave (II)

Laser accelerated proton

beam:

?

22

2. The technology platform at OncoRayThe proton irradiation unit: Integration of the laser

Laser laboratory

Research cave

Gantry

Cyclotron

• PW laser: Polaris

DRACO

p

PW laser at HZDR

PENELOPEPW laser at OncoRay

23

2. The technology platform at OncoRayThe proton irradiation unit: Radiation protection calculations (I)

26

Sideview

Dose [Sv/a]

6e-10 6e-8 6e-6 6e-4 6e-2 6 6e+1 6e+3

On the roof: D < 1 mSv/a

In the experimental cave: D < 1 mSv/a

6 mSv/a

Footprint

G. Fehrenbacher, GSI, D. Kunath, WE24

28

2. The technology platform at OncoRayThe proton irradiation unit: Radiation protection calculations (II)

G. Fehrenbacher, GSI, D. Kunath, WE

Dose [Sv/a]

6e-7 6e-5 6e-3 6e-1 6 6e+2 6e+4 6e+6

On the roof: D < 1 mSv/a

In the

experimental

cave:

D < 1 mSv/a 6 mSv/a

Footprint

Side view

25

2. The technology platform at OncoRayThe proton irradiation unit: Status at July 4

26

3. Scientific topicsProton therapy

• Clinical studies

- bronchial carcinoma

- head and neck cancer

- paediatric cancer

• Precision therapy (image guidance)

• Motion compensation

• Biologically adaptive treatment

- individualization

- molecular targets

27

3. Scientific topicsProton therapy: Motion compensation

Beam off

Beam on

R. Perrin: High precision radiotherapy group 28

3. Scientific topicsLaser radiooncology (J. Pawelke, U. Schramm, T. Cowan)

p, He, C 2 m

Vision: Compact accelerators for proton/ionen therapy

• Dosimetry of ultra shortly (< 1 ps) pulsed particle beams

of high dose rate (1010 Gy/min)

• Radiobiology of ultra shortly pulsed particle beams

• Medical beam deliveries for laser accelerated particle beams

Layout

SIEMENS medical

29

3. Scientific topicsLaser radiooncology

Tumour cells head and neck (SKX)

Clonogenic cell survival DNA double strand brakes (24 h)

No significant RBE difference between laser accelerated, ultra-shortly pulsed

proton beams and tandem DC beams

Dose / Gy

Su

rviv

al

/

%

Dose / Gy

gH

2A

X/5

3B

P1

fo

ci

/

ce

ll■ DRACO laser protons

■ Tandem protons (reference)■ DRACO laser protons

■ Tandem protons (reference)

30

3. Scientific topicsIn-vivo dosimetry: motivation (F. Fiedler, WE)

The dose distribution deposited by ions is extremely sensitive to the ion range in vivo

The accuracy of the ion range is influenced by

(1) Systematic errors in the physical

beam model used for treatment

planning: R = R(HU)

(2) Random errors like

- mispositioning

- patient- or organ movement

- density changes within the

irradiated volume

- treatment mistakes and accidents

(3) Laser acceleration specific errors

- intensity fluctuations

- spectral uncertainties

Treatment planning

15. Therapy fraction

31

3. Scientific topicsIn-vivo dosimetry: physical basis

Nucleons

and particlesProjectile

Target nucleus

Projectile fragment

Target fragment

Fire ball

Prompt g-rays

Radionuclides

GS

I D

arm

sta

dt

MG

H B

osto

n

32

3. S

cie

nti

fic

to

pic

sIn

-viv

o d

osim

etr

y:

PE

T w

ork

flow

0.66 Gy

0.37 Gy

PET PET/CT

G. Shakirin: Phys. Med. Biol. 56 (2011) 1281 33

3. Scientific topicsIn-vivo dosimetry: workflow of in-beam PET

Treatment plan:

Dose distribution

b+-activity:

Prediction

b+-activity:

Measurement

Ion-Electron

Interaction

Ion –nucleus

interaction

12C-irradiation, GSI

W. Enghardt et al.: Strahlenther. Onkol. 175/II (1999) 33;

F. Pönisch et al.: Phys. Med. Biol. 48 (2003) 2419, Phys. Med. Biol. 49 (2004) 5217;

34

3. Scientific topicsIn-vivo dosimetry: motion compensation

Static and moving targets

Target movement:

- Sinusoidal (amplitude = 10 mm; period ≈ 3.5 s)

- Perpendicular to beam

Irradiation:- 295 AMeV 12C scanned pencil beam

- Motion compensation by tracking (magnetic beam

deflection and fast range difference compensation)

C. Bert et al.: Rad. Oncology 2 (2007) 4768

Reference (static) 4D-reconstruction 3D-reconstruction

PHD thesis: K. Laube 35

• Different path length per gate

• Attenuation correction may fail

3. Scientific topicsIn-vivo dosimetry: 4D-reconstruction

94 47894 29394 37495 75493 76792 28494 73494 95892 693

PhaseAmplitude

Coincidences:

134 500104 73275 25167 69165 43767 28476 960104 870134 065

Coincidences:

• Different number of coincidences per gate

• Different statistical errors

830 790 847 335

Gating

1. MLEM reconstruction of each gate addition: reconstruction artifacts

2. Spatial rearrangement of the lines of response reconstruction of the whole data 36

3. Scientific topicsIn-vivo dosimetry: automatisation of data evaluation

Beam direction

Range

enhanced

Range

as planned

Range

reduced

PHD thesis: S. Helmbrecht 37

3. Scientific topicsIn-vivo dosimetry: automatisation of data evaluation

38

• Long half lives of the positron emitters produced in tissue via nuclear reactions11C: T1/2 = 20 min15O: T1/2 = 2 min

• Low counting statistics → low quality images

• Washout of activity → no dosimetric information

• No real time capability → no adaptive radiotherapy (not suitable for lasers)

Protons

175 MeV

on PMMA

Co

nu

nt ra

te / s

-1

Time / s

K. Parodi et al.: IJROBP 68 (2007) 920

Dose b+-activity

3. Scientific topicsReal time in-vivo dosimetry: limits of in-beam PET

39

Nucleons

and particlesProjectile

Target nucleus

Projectile fragment

Target fragment

Fire ball

Prompt g-rays

Radionuclides

SPECT: Single Photon Emission Computed Tomography

Em

issio

n d

ensity o

f g-

rays:

Monte

-Carlo s

imula

tion

of irra

dia

tion a

nd

photo

n t

ransport

(G

eant4

)

Pro

ton tre

atm

ent

pla

n:

Bra

in t

um

our

CM

S T

PS

(E

lekta

)

AK

H a

nd M

ed.

Univ

. W

ien

3. Scientific topicsReal time in-vivo dosimetry: feasibility of in-beam SPECT (I)

A. Müller, Diploma thesis, TU Dresden, 2011 40

Do it yourself!

Photo: Siemens AG

99mTc: 140 keV

Treatment plan: brain tumor

• Total dose: 60 Gy, fractionated dose: 2 Gy

• 2 treatment fields: 1: 98 ... 135 MeV, 2: 82 ... 127 MeV

• 1,6 ∙ 1010 protons / fraction

Emission of g-rays

• 4 · 109 photons / fraction

• Photon energies: 0 – 15 MeV

Ph

oto

ns / (

Me

V p

)-1

Energy / MeV

3. Scientific topicsReal time in-vivo dosimetry: feasibility of in-beam SPECT (II)

41

•

3. Scientific topicsReal time in-vivo dosimetry: technical solution

Compton camera

gg rE

'

g1 g1‘

j1

j1

j1

g2‘

g2j2

j2

j2

Absorp

tion d

ete

cto

r

eerE

Coincidence

g-ra

y s

orc

e

Scatt

er

dete

cto

r2 photons

10 photons

300 photons

42

Proton beam

1. Scatter detector

2. Scatter detector

Absorption detector

T. Kormoll et al. NIM A 626-627 (2011) 114

• Installation

• Laboratory tests

• In-beam tests (KVI, GSI)

• Clinically applicable

system from 2013

Prototype

(2 × 2 cm2)

3. Scientific topicsReal time in-vivo dosimetry: in-beam SPECT

43

Backprojection of measured scatter events

22Na point source (511, 1275 keV)

2 cm camera distance

2000 events •

Scientific topicsReal time in-vivo dosimetry: prototype testing

First imaging: Apr. 7, 2011

Preliminary data

1 Event2 Events3 Events4 Events10 Events20 Events2000 Events

44

Scientific topicsReal time in-vivo dosimetry: clinical device (U. Dersch)

In-vivo dosimetry for new types of radiation | Dr. Uwe Dersch

Source: Company Siemens Healthcare

CZT cross strip detector

ASIC RENA3 (Nova R&D)

LSO block detector• Detector integration (commercial elements)

• Front-end-electronics

• Signal processingSystem performance

• Compton camera detector modules

• Photon energy: 1 – 15 MeV

• Operational in clinical environment

• Real time capability45

Acknowledgments

46

1. RadiotherapyIntensity modulated radiotherapy - IMRT

Dynamic multi-leaf collimator:

- pairwise W-leaves

- computer controlled movable

- approximation of the tumor contour

- inhomogeneous dose distributionsvia irradiation time

D

x

Photo: Varian

6

1. RadiotherapyOrgan motion compensation

• Bronchial carcinoma

• Breathing motion

• 4D CT

• Pressure belt

Beam off

Beam on F. Pönisch et al. Phys. Med. Biol. 53 (2008) N259 7

1. RadiotherapyImage guided radiotherapy - IGRT

e--linac

MV cone beam CT

In-room CT on rails

kV X-ray

position control

IR m

ovem

ent

trackin

g

8

3. Scientific topicsIn-vivo dosimetry: range monitoring with in-beam PET

Treatment plan:

Dose distribution

b+-activity:

Prediction

b+-activity:

Measurement

Planning-CT

New CT

38