Particle Therapy- Why? - TU Wieninfo.tuwien.ac.at/.../Dosanjh_HadronTherapyEU_compr.pdf ·...

Particle Therapy- Why?

X-RayTherapy

ProtonTherapy

Head, neck, Spinal cord Eyes, orbits Pelvis Prostate Lung PEDIATRIC

Kill tumour without affecting healthy cells

Photon IMRT Photon Proton

(Courtesy of IBA)AUSTRON – 15 March 2011 Manjit Dosanjh 2

First patient in Europe in 1957 Uppsala, Sweden

The Gustaf Werner Cyclotrone

First treatment of a patientwas performed in November 1957a woman with cervix cancer.Börje Larsson and Stig Stensson

During1976 - 1989 no patients were treated due to re-buldings

AUSTRON – 15 March 2011 Manjit Dosanjh 3

Uppsala ‐ 1957

4Mexico City ‐ 1 ‐ U. Amaldi

The modified synchrocyclotron

Alignment system for the treatment with 185 MeV protons

Bőrje Larsson “On the Application of a 185 MeV Proton Beam to Experimental Cancer Therapy and Neurosurgery: a Biophysical Study” Doctoral dissertation -1962

(1931-1998)

• First treatment of eye melanoma in April 1989(72 MeV beam with 54,5 Gy in four fractions)

• Arterio‐venous malformation, AMV

• Uveal melanomas and meningeomas in the brain (1991..)(100 MeV beam with 20 Gy in two fractions)

Continued proton treatment in Uppsala


• Prostate treatment started late 2002 by using a new special platform


• In 2008 The Swedish Childhood Cancer Foundation funded an adjustable treatment coach for children

3 crucial years

In the years 1992‐1994 the rate of progress changed:

– 1992 at Loma Linda first proton patient – 1993 MGH orders the first commercial protontherapy centre

– 1993 GSI starts the carbon ion ‘pilot project’– 1994 HIMAC first carbon ion patient

Manjit Dosanjh 7AUSTRON – 15 March 2011

Proton therapy is booming


Proton facilities in Europe

• GWI (Sweden) 1957-1976• TSL (Sweden) 1987-• Douglas, Clatterbridge, U.K. 1989• UCL, Louvain, Belgium 1991-1993• CAL, Nice, France 1991• CPO, Orsay, France 1991• PSI, Villigen, Switzerland 1996• HMI, Berlin, Germany 1998• …………………..


Why Heavier Charged Particle Beams?

• Precision Therapy Conformed to Tumour• Sparing of Normal Tissues• Increased DNA Damage in Tumor• Increased Effect on Hypoxic Tumors• Less Repair of Sub-lethal and Potentially Lethal

Damage in Cell Cycle• Short Overall Treatment Course• Use of Radioactive Beam Component for

Treatment Verification – in beam PET

Ultimate Goal: Heavy Ions & Therapeutic Gain

• Overcoming tumor radioresistance• Enhancing tumor cell killing• Protecting normal cells

Relative Biological Effectiveness(reference vs test radiation)

Dx____

Di

= RBE

• RBE varies not only with type of radiation but also with type of cell or tissue, biological effect under investigation, dose rate and fractionation.

• In general RBE increases with LET to reach a maximum RBE of 3 to 8 (dependent of the level of cell kill) at LET≈ 200 keVµm and then decreases.

• An increase in the RBE in itself offers no therapeutic advantage unless there is a differential effect making the RBE for normal tissue smaller than that for the tumour, increasing the relative level of tumour cell killing and the therapeutic ratio.

Radio Biological Effect : RBE


RBE and how does it vary

• Varies with type of radiation• Varies with type of cell/tissue• Varies with the biological effect under investigation• Varies with dose rate and fractionation• An increase in RBE in itself does not offer

therapeutic advantage unless there is differential effect between normal and tumour tissues

• OER (oxygen enrichment ratio) effects RBE• Effected by presence of other chemicals present

Carbon ion treatment in Europe

Carbon ion treatments of patients at the GSI started in 1997mostly head-and-neck and prostate cancer patients

Hiedelberg Ion-Beam Radiotherapy Center (HIT) started treating patents with carbon in clinical facility in 2009

New facilities in Europe under way, some will start very soon


The Darmstadt GSI ‘pilot project’ (1997‐2008)

16

450

G. Kraft

J. Debus

AUSTRON – 15 March 2011 Manjit Dosanjh

The PIMMS Collaboration

Collaboration was formed in 1996 following an agreement between Med‐AUSTRON (A) and TERA (I)

CERN agreed to host and support the study in PS


The study was later joined by ONKOLOGY 2000 (CZ) Close contacts were kept with GSI (D) Work started in January 1996 and continued for 4 years. Final report is available (CD ROM;CERN Yellow Report)

Schematic Layout of the PIMMS Design


Injection Chain

Treatment rooms

Main Accelerator

Slow Extraction

C-ionsourcedump

dumpprotonsource

C-ion linac

proton linac

Synchrotron

protons andC-ions

beamdiagnostic

p+C-ions

room 1

protongantry

room 2proton

horizontalroom 3protongantry

room 4

C-ionhorizontal

room 5C-iongantry

Conclusions

PIMMS is best suited to light‐ion therapy

Designed for high‐precision active scanning with a gantry

Extraction optimised for a smooth spill and (short treatments ~2 min)

Extraction lines exploit special properties of slow extracted beam

Modular design of extraction lines integrated withthe gantries


The European Ion Beam Facilities

WPE Essen

Orsay I & II Paris

HITHeidelberg

RPTC Munich

PSI Villingen

MedAustronWiener Neustadt

Kiel

Berlin

Marburg Asclepios

Caen GSI

Darmstadt

Aachen

WPE Essen

Orsay I & II Paris

HITHeidelberg

RPTC Munich

PSI Villingen

MedAustronWiener Neustadt

Kiel

Berlin

Marburg Asclepios

Caen GSI

Darmstadt

Aachen


Carbon ion facilities

• Light Ion Therapy Facilities


In Asia:

3 in operation: Chiba, Harima, Gunma (Japan)3 under construction: Shanghai (China), 2+ Japan

GSI/Siemens: Heidelberg

In Europe:HIT in operation, Heidelberg (Germany), CNAO Pavia (Italy) almost ready to treat patientsMarburg (Germany) nearly finishedKiel (Germany) in constuctionWiener Neustadt (Austria) construction starts tomorrow!ETOILE in Lyon, FranceARCHADE in Caen (France)

Miscellaneous662(20.9%)HAMT：403

Lung467(14.7%)HAMT: 17

Head & Neck408(12.9%)HAMT: 125

Prostate515(16.3%)HAMT: 242

Bone & Soft Tissue349(11.0%)HAMT: 175

Liver212(6.7%)HAMT: 15

Uterus115(3.6%)

CNS93(2.9%)

Rectum88(2.8%)HAMT: 50

Pancreas84(2.7%)

Skull Base46(1.5%)HAMT: 17

Esophagus47(1.5%)

Lacrymal Gl

12(0.4%)

Total3,178

HAMT:1,077

Eye70(2.2%)HAMT: 28

Tumor Sites in Carbon Ion RT (6.1994～2.2007)


56789

1011121314151617181920212223

1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006

年度

照射回数

１回の治療当り平均：１４回

Yr.

No.

Fra

ctio

ns

The Number of Fractions in Carbon Ion RT

The entire course of treatment Has been given by carbon ions alone.

Average No. of fractionsper patient is 12


Dose planning at GSI/HIT vs HIMAC carbon ion

• At GSI and HIT the dose planning for patients is based on the local effect model (LEM)

• At HIMAC, HIBMC and GMHC the dose planning is based on the neutron normal physical dose response

Future……..Dose planning for patients will also be considered using the microdosimetric-kinetic (MK) model in combination with different Monte Carlo (MC) codes e.g. GEANT2, PHITS, SHIELD-HIT and FLUKA, to provide clinical calculated absorbed and RBE weighted doses


European Network for Light Ion

Hadron Therapy


ENLIGHT

• Why did we need a network?• Why the timing 2001?• What was necessary for a network?• Which activities were needed to catalyse ENLIGHT?• Which were the key starting points?


ENLIGHT

– Create common multidisciplinary platform– Share knowledge– Share best practices – Harmonise data – Provide training, education– Identify challenges– Innovate– Lobbying for funding

Manjit Dosanjh 28AUSTRON – 15 March 2011 28

ENLIGHT was established to…

Challenges for a network

Multidisciplinary and cutting‐edge technologies:• Clinical Studies• Radiobiology • Treatment planning for Particle Therapy • Adaptive ion therapy and treating of moving organs • Novel imaging PET systems• Feasibility study for innovative gantry designs • Improved gantry design • ………………………………

Manjit Dosanjh 29AUSTRON – 15 March 2011 29

ENLIGHT++ challenges

• A heterogeneous group ‐many different disciplines• How to balance between basic research and the clinical needs?

• Many partners. How to give space to each and make progress with the main objectives?

• How to strike a balance between agenda of the single centres and the ENLIGHT++ goals?

• Can we show ion therapy is more effective?


The birth of ENLIGHT �

• ENLIGHT was launched at CERN in Feb 2002• In 2002, ENLIGHT was composed of

– ESTRO, the European Society for Therapeutic Radiology and Oncology

– ETOILE, Lyon, France– Karolinska Institute, Sweden– GSI/GHIP (German Heavy‐Ion Project), Germany– Med‐Austron, Austria– TERA, Italy– CERN, Switzerland

• ENLIGHT was funded as a network by the European Commission between 2002 ‐ 2005


Bridging the gap

A major achievement of ENLIGHT is bringing together of various communities so that clinicians, physicists, biologists and engineers interested in particle therapy are working together for research, funding and lobbying


From ENLIGHT…..…. ENLIGHT++

• In 2006 ENLIGHT became+ More than a network….research+ More inclusive ……..more institutions, more countries

• The network itself continued even without funding– Develop strategies for securing the funding for specific projects under the umbrella of ENLIGHT, along two major axes

- Research in areas needed for improving hadron therapy- Networking, to establish and implement common standards, protocols for treating patients, training and education

• Now we have >300 participants from 20 European countries


ENLIGHT is helping to get funding

In 2011, under the umbrella of ENLIGHT, there are now 4 EC funded projects:

– Three ongoing projects: PARTNER, ULICE and ENVISION with a total funding of 24 M Euros

• midterm PARTNER at Karolinska in Sept 2010

– The newest training project , ENTERVISION, started in February 2011 in Lyon


PARTNER

• 4‐year Marie Curie Training project – Funded by the EC

with 5.6 M Euros– Started in September

2008• Aims at the creation

of the next generation of experts


Particle Training Network for European Radiotherapy

• Brings together key academic institutes and research centres and the two leading European companies in particle therapy (IBA and Siemens)

• Research and training opportunities for 25 young biologists, engineers, physicians and physicists

PARTNER is funded by the European Commission under Grant Agreement Number 215840

The 3 pillars of ULICE

Joint Research Activities- aims at improving the

performance of hadron therapy facilities by research and development


Networking Activities– Communication

among the 20 partners and with the external world

Transnational Access– provides access for

external researchers to the recently opened ion therapy facilities

The ULICE project is co‐funded by the European Commission under FP7 Grant Agreement Number 228436

ENVISION: European Novel Imaging Systems for Ion Therapy

Accurate positioning is a crucial challenge for targeting moving organs during treatment


ENVISION aims at developing solutions for:• real‐time monitoring • quantitative imaging• precise determination of

delivered dose • fast feedback for optimal

treatment planning • real‐time response to

moving organs • Simulation studies

adapted from Parodi et al, IJROBP 68 (2007) 920-34

The ENVISION project is co-funded by the European Commission under FP7 Grant Agreement N. 241851

ENTERVISION

• ENTERVISION fills the need for reinforcing research and training of young researchers in all aspects of imaging

• Interdisciplinary and multinational initiative

• Many training courses open to external young researchers

• ENTERVISION brings together ten academic institutes and and the two leading European companies in particle therapy, IBA and Siemens.

• The network will train 16 Researchers during a 4‐year period.


Research Training in Imaging for Cancer Radiation Therapy

The ENTERVISION project is co-funded by the European Commission under FP7 Grant Agreement N. 264552

In conclusion…..

• ENLIGHT provides a powerful multidisciplinary European collaboration amongst interested partners

• ENLIGHT acts as a platform for defining research needs

• Developing projects and getting them funded

• Lobbying politically (e.g. France, Poland, UK)

• ENLIGHT is a useful resource for communities interested in hadron therapy and establishing facilities

Clear desire for continuing to collaborate on new and existing research topics and helping new initiatives….


• 1st proposed by Wilson in 1946• 1st proton therapy conducted by Lawrence in 1954• 1st treatment in Uppsala in 1957

• By 2010, 62 017 patients patients worldwide have been treated

• 56 854 protons, 7151 C‐ions

• In Europe 9 facilities: 20 166 patients (1957‐2009)

(Dr. Martin Jermann, PTCOG meeting, 2010)


Number of patients treated

Hadrontherapy goals

• Provide the irradiation technologies and the detection systems to optimally use the advantages of charged particles

• Optimize the dose to the tumour by beam scanning and adaptation of the delivery e.g. organ motion, respiration

• Treat around patients and perform clinical trials using low‐LET and high‐LET beams

• Conduct technical, physical, radiobiological and clinical R+D

tumour-conformaldose distribution

organs atrisk

tumour


Particle Therapy- Why? - TU Wieninfo.tuwien.ac.at/.../Dosanjh_HadronTherapyEU_compr.pdf ·...

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