1. From Physics to Medicine: Hadron Therapy
CERN – Bulgarian Industry
November 2012
Manjit Dosanjh, KT-LS

2. Knowledge and Technology Transfer
KT is an integral part of CERN’s mission
PP technologies relevant to key societal issues e.g. Health
CERN involved in the last years in health applications
few CERN resources
attracted significant external funding (EC, MS…)
raises impact and profile
beyond the particle physics arena
large number of collaborating institutes
including medical institutes & hospitals
Collaborators appreciate facilitation by CERN

3. CERN Technologies and innovation
accelerators, detectors and IT to fight cancer
Detecting
particles
Accelerating particle beams
Large-scale computing (Grid)
CANCER
Manjit Dosanjh
First Bern Cyclotron Symposium - June 5-6, 2011 3

4. Why Cancer ? Every year >3 millions new cases in Europe
About one third of us will have cancer
Number of patients needing treatment is increasing as people are living longer
Main cause of death between the ages of 45 and 65 in Europe
Second most common cause of death in Europe, Canada, USA after heart-disease
KT-LS 26 May 2011 4

5. Cancer incidence increases with age

6. Contribution from CERN is timely
Cancer is a large and growing challenge Need: Earlier diagnosis, better control, fewer side-effects
How?
new technologies
Imaging, dosimetry, accelerator & detector technology
Better understanding – genetics, radiobiology…
Advanced healthcare informatics …
international collaboration
If progress is to be maintained
Although cancer is a common condition, each tumour is individual
personalised approach
Large patients data to understand the key drivers of the disease
Contribution from CERN is timely

7. Catalysing collaboration in health field
Challenges:
Bring together physicists, biologists, medical physicists, doctors
Cross-cultural at European and global level
Why is CERN well placed to do this?
It is widely acknowledged as a provider of technologies and as a catalyst for collaboration.
It is international, non-commercial, not a health facility.
ULICE Kick-off in 2009
ENVISION approval in 2009
Enlight meeting leading to subm. Of ENTERVISION
PARTNER: 21 researchers recruited last year.

8. 4 Pillars: 3 are the key technologies
4th pillar: catalysing and facilitating collaboration
4 Pillars: 3 are the key technologies
Particle Therapy
Tumour Target
Accelerating particle beams
Detecting particles
Medical imaging
Large scale computing (Grid)
Grid computing for medical data management and analysis

9. Accelerator technologies and health
PIMMS (coordinated by CERN) has led to:
Treatment centre in Pavia, Italy.
First patient treated in Sept 2011
Treatment centre in Wiener Neustadt, Austria,
foundation stone 16 March 2011, will be ready in 2015
Looking forward:
LEIR facility: requested by community (>20 countries, >200 people)
Medicis (ISOLDE) exotic isotopes for future R&D
Minicyclotron: commonly used isotopes

10. Detector Technologies
Detector technology – improved photon detection and measurement: Crystal Clear, PET, PEM, Axial PET
Electronics and DAQ – high performance readout: (Medipix)
Multimodality imaging: PET-CT (proposed by Townsend, future with PET-MRI) CT
PET
PET-CT

11. Positron Emission Tomography
Idea of PET
Photon detection used for calorimetry
PET
today
CMS

12. PET (Positron Emission Tomography)
Detects pairs of photons emitted by an injected positron- emitting radionuclide
Images tracer concentration within the body
Reflects physiological activity
Reconstructed by software
LHC detector systems used in PET Systems 12

13. PET/CT (David Townsend)

14. In-beam-PET for Quality Assurance: real time
MC simulated
measured
On-line determination of the dose delivered
Modelling of beta+ emitters:
Cross section
Fragmentation cross section
Prompt photon imaging
Advance Monte Carlo codes
In-beam-PET
GSI- Darmstadt

15. Computing Technologies
GRID – data storage, distributed, safe and secure computing
MammoGrid: European-wide database of mammograms and support collaboration
Health-e-Child: combining various types (clinical, imaging…) of data and share in distributed, clinical arena.
HISP: Hadrontherapy Information Sharing Platform

16. Conventional Radiotherapy in 21st Century
3 "Cs" of Radiation
Cure (~ 45% cancer cases are cured)
Conservative (non-invasive, few side effects)
Cheap (~ 5% of total cost of cancer on radiation)
(J.P.Gérard)
There is no substitute for RT in the near future
The rate of patients treated with RT is increasing
Present Limitation of RT:
~30% of patients treatment fails locally
(Acta Oncol, Suppl:6-7, 1996) 16

17. Two opposite photon beams80 30 50

18. Two opposite photon beams
110
100

19. How to decrease failure rate?
Physics technologies to improve treatment: higher dose
Imaging: accuracy, multimodality, real-time, organ motion
Data: storage, analysis and sharing (confidentiality, access)
Biology: fractionation, radio-resistance, radio-sensitization
Working together: multidisciplinary
Raymond Miralbell, HUG 19

20. Hadrontherapy: all started in 1946
In 1946 Robert Wilson:
Protons can be used clinically
Accelerators are available
Maximum radiation dose can be placed into the tumour
Proton therapy provides sparing of normal tissues
Depth in the body (mm)
Conventional: X-Rays Ion Radiation 20

21. Proton & Ion Beam Therapy: a short history
Proposed by R.R. Wilson
MedAustron (Austria)
1st patient treated at Berkeley, CA
CNAO, Pavia (Italy)
1st patient in Europe at Uppsala
HIT (carbon), Heidelberg (Germany)
1984
1989
1990
1991
1992
1993
1994
2002
1946
1954
1957
2009
2011
2014
PIMMS
PSI, Switzerland
Eye tumours, Clatterbridge, UK
ENLIGHT
ENLIGHT
10th year
GSI carbon ion pilot, Germany
CPO (Orsay), CAI (Nice), France
Loma Linda (clinical setting) USA
Boston (commercial centre) USA
NIRS, Chiba (carbon ion) Japan

22. ENLIGHT CERN collaboration philosophy into health field
Common multidisciplinary platform
Identify challenges
Share knowledge
Share best practices
Harmonise data
Provide training, education
Innovate to improve
Lobbying for funding
Coordinated by CERN, 80% MS involved
> 150 institutes
> 400 people
> 25 countries
(>80% of MS involved) 22

23. EU funded projects Infrastructures for hadron therapy Marie Curie ITN
Wide range of hadron therapy projects: training, R&D, infrastructures
A total funding of ~24 M Euros
All coordinated by CERN,(except ULICE coordinated by CNAO
Under the umbrella of ENLIGHT
Marie Curie ITN
12 institutions
Infrastructures for hadron therapy
20 institutions
R&D on medical imaging for hadron therapy
16 institutions
Marie Curie ITN
12 institutions

24. First workshop on physics for health applications held @ CERN, 2010
Preparing for the Future……
review the progress in the domain of physics applications for health
identify the most promising areas for further developments
explore synergies between physics and physics spin-offs
catalyse dialogue between doctors, physicists, medical physicists……
First workshop on physics
for health applications CERN, 2010
KT-LS 26 May 2011

25. February 27 – March 2, 2012 at CICG, Geneva
International Conference on Translational Research in Radio-Oncology & Physics for Health in Europe
February 27 – March 2, 2012 at CICG, Geneva
2 days devoted to physics, 2 days to medicine, 1 common day
Over 600 people registered, nearly 400 Abstracts
Chairs: Jacques Bernier (Genolier) and Manjit Dosanjh (CERN)
Four physics subjects :
Radiobiology in therapy and space
Detectors and medical imaging
Radioisotopes in diagnostics and therapy
Novel technologies
Target (PTV)
Normal tissue
Sensitive
structure
(OAR)

26. 3 CERN Initiatives arising from PHE2010
Biomedical Facility
creation of a facility at CERN that provides particle beams of different types and energies to external users
Medical Accelerator Design
coordinate an international collaboration to design a low-cost accelerator facility, which would use the most advanced technologies
Radio Isotopes
Establish a virtual European user facility to supply innovative radioisotopes (produced at ISOLDE-CERN, ILL, PSI, Arronax,..) for R&D in life sciences

27. Future Biomedical Facility @ CERN
Using LEIR (low energy ionising ring) 0)) for:
European facility for radiobiology
basic physics studies
radiobiology
fragmentation of ion beam
dosimetry
test of instrumentation
Biomedical facility requested by ENLIGHT Community (> 20 countries, >200 people )
LEIR

28. CERN contribution Provider of Know-how and Technologies
Design studies for Hadron Therapy facilities
Scintillating crystals for PET scanners
Fast detector readout electronics for counting mode CT
Grid middleware for Mammogrid, Health-e-Child
Driving force for collaboration
Coordinator of the European Network for Light Ion Hadron Therapy (ENLIGHT) Platform
Training centre
Coordinator of large EC-ITN funded programs, e.g. Particle Training Network for European Radiotherapy (PARTNER), ENTERVISION
New ideas being proposed……….

29. Thank you for your attention manjit.dosanjh@cern.ch

31. R&D isotopes for “Theranostics”
149Tb-therapy
152Tb-PET
161Tb-therapy
& SPECT
155Tb-SPECT
#177: C. Müller et al., Center for Radiopharmaceutical Sciences ETH-PSI-USZ
#177: C. Müller

32. Preparing Innovative Isotopes
ISOLDE - MEDICIS
Preparing Innovative Isotopes
1.4GeV protons for spallation & fission reactions on diverse target materials
Providing a wide range of innovative isotopes such as 61,64,67Cu & rare earth metals such as 47Sc, 149Tb
1hr – 1 week t1/2
Will utilise CERN/EPFL patented nanostructured target material
Inventory of isotopes produced in a natural Zr target after proton beam irradiation.

33. Cancer Treatment Options…
Surgery
Radiotherapy
Chemotherapy and others
X-ray, IMRT, Brachytherapy, Hadrontherapy
Hormones; Immunotherapy; Cell therapy; Genetic treatments; Novel specific targets (genetics..)
Local control
Local control
Limited Local control
Survival Quality of life

34. Status & Perspectives in Particle Therapy – A. Mazal
Worldwide
Patients
Statistics
M.Jermann
A.Mazal
PTCOG
Protons are an (expensive) clinical tool at an institutional level,
Ions are today an (even more expensive) tool for clinical research at a national or multinational level
There is a need for interdisciplinary R&D and synergy with the photon world

35. Radiobiology in therapy and space : a highlight
Local effects of microbeams of hadrons seen by fluorescent proteins which repair DNA
10 µm
55 MeV carbon
5 × 5 µm² matrix
20 MeV protons
randomly distributed
117 protons per spot
Günther Dollinger - Low LET radiation focused to sub-micrometer shows enhanced radiobiological effectiveness (RBE)
Carbon ions have higher radiobiological effectiveness than protons

36. Detectors and medical imaging: a highlight
Detectors for Time-Of-Flight PET: the limit of time resolution
With 20 picosecond
Δx = 4 mm:
no track
reconstruction
is needed
D. Schaart: Prospects for achieving < 100 ps FWHM coincidence
resolving time in Time-Of-Flight PET

37. Novel technologies: a roadmap for particle accelerators
Marco Schippers
What we need to be able to provide beams for therapy

38. Actions needed … Establish an appropriate framework @CERN
Identify and secure resources (inside and outside)
Develop the necessary structure
Facilitate increased cooperation
between disciplines
physics, engineering, chemistry … (physical sciences)
medicine, biology, pharmacology… (life sciences)
within Europe
globally

39. Needs for a radiation facility
Increase radiobiological knowledge:
Cell response to different dose fractionations
Early and late effects on healthy tissue
Irradiation of cell at different oxygenation levels
Differing radio-sensitivity of different tumours/patients
Simulations:
Ballistics and optimization of particle therapy treatment planning
Validation of Monte Carlo codes at the energies of treatment and for selected ion-target combinations
Instrumentation tests:
Providing a beam line to test dosimeters, monitors and other detectors used in hadron therapy