From Physics to Medicine: Hadron Therapy

CERN – Bulgarian Industry 28 - 29 November 2012

Manjit Dosanjh, KT-LS

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 10-15 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

Knowledge Transfer | Accelerating Innovation

CERN Technologies and innovation accelerators, detectors and IT to fight cancer

Detecting particles

Large-scale computing (Grid)

Accelerating particle beams

CANCER

Knowledge Transfer | Accelerating Innovation Manjit Dosanjh

First Bern Cyclotron Symposium - June 5-6, 2011

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Why Cancer ? •

Every year >3 millions new cases in Europe

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About one third of us will have cancer

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Number of patients needing treatment is increasing as people are living longer

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Main cause of death between the ages of 45 and 65 in Europe

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Second most common cause of death in Europe, Canada, USA after heart-disease Knowledge Transfer | Accelerating Innovation

[email protected]

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KT-LS 26 May 2011

Cancer incidence increases with age

Knowledge Transfer | Accelerating Innovation

Cancer is a large and growing challenge Need: Earlier diagnosis, better control, fewer side-effects

How? • new technologies •

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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 Knowledge Transfer | Accelerating Innovation

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.

Knowledge Transfer | Accelerating Innovation

4th pillar: catalysing collaboration 4 Pillars: 3 areand thefacilitating key technologies Accelerating particle beams

Particle Therapy Tumour Target

Detecting particles

Large scale computing (Grid)

Knowledge Transfer | Accelerating Innovation

Medical imaging

Grid computing for medical data management and analysis

Accelerator technologies and health PIMMS 2000 (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 Knowledge Transfer | Accelerating Innovation

Detector Technologies •

Detector technology – improved photon detection and measurement: Crystal Clear, PET, PEM, Axial PET

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Electronics and DAQ – high performance readout: (Medipix)

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Multimodality imaging: PET-CT (proposed by Townsend, future with PET-MRI)

CT Knowledge Transfer | Accelerating Innovation

PET

PET-CT

Positron Emission Tomography

Idea of PET

Photon detection used for calorimetry PET today

CMS Knowledge Transfer | Accelerating Innovation

PET (Positron Emission Tomography) • Detects pairs of photons emitted by an injected positronemitting radionuclide • Images tracer concentration within the body • Reflects physiological activity • Reconstructed by software

LHC detector systems used in PET Systems

Knowledge Transfer | Accelerating Innovation

PET/CT (David

Townsend)

CT

Knowledge Transfer | Accelerating Innovation

PET

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 Knowledge Transfer | Accelerating Innovation

In-beam-PET

GSI- Darmstadt

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

Knowledge Transfer | Accelerating Innovation

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) Knowledge Transfer | Accelerating Innovation

Two opposite photon beams

80

50

Knowledge Transfer | Accelerating Innovation

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Two opposite photon beams

110

100

Knowledge Transfer | Accelerating Innovation

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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

Knowledge Transfer | Accelerating Innovation

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

Conventional: X-Rays

Depth in the body (mm)

Knowledge Transfer | Accelerating Innovation

Ion Radiation

Proton & Ion Beam Therapy: a short history Proposed by R.R. Wilson

MedAustron (Austria)

1st patient treated at Berkeley, CA 1st patient in Europe at Uppsala

CNAO, Pavia (Italy) HIT (carbon), Heidelberg (Germany)

1984 1989 1990 1991 1992 1993 1994 1996-2000 2002 1946

2009

1954 1957

2011 2014

PIMMS

PSI, Switzerland Eye tumours, Clatterbridge, UK GSI carbon ion pilot, Germany CPO (Orsay), CAI (Nice), France Loma Linda (clinical setting) USA Boston (commercial centre) USA NIRS, Chiba (carbon ion) Japan Knowledge Transfer | Accelerating Innovation

ENLIGHT

ENLIGHT 10th year

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

> 150 institutes > 400 people

Coordinated by CERN, 80% MS involved

> 25 countries

(>80% of MS involved) Knowledge Transfer | Accelerating Innovation

EU funded projects •

Wide range of hadron therapy projects: training, R&D, infrastructures

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A total funding of ~24 M Euros All coordinated by CERN,(except ULICE coordinated by CNAO Under the umbrella of ENLIGHT

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Marie Curie ITN 12 institutions

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R&D on medical imaging for hadron therapy 16 institutions

Knowledge Transfer | Accelerating Innovation

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Infrastructures for hadron therapy 20 institutions

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Marie Curie ITN 12 institutions

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 held @ CERN, 2010 Knowledge Transfer | Accelerating Innovation KT-LS 26 May 2011

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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 Knowledge Transfer | Accelerating Innovation

Normal tissue Sensitive structure (OAR)

Target (PTV)

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

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Medical Accelerator Design coordinate an international collaboration to design a low-cost accelerator facility, which would use the most advanced technologies

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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

Knowledge Transfer | Accelerating Innovation

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 )

Knowledge Transfer | Accelerating Innovation

LEIR

CERN contribution •

Provider of Know-how and Technologies • • • •

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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 •

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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………. Knowledge Transfer | Accelerating Innovation

Life.Sciences@c

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Thank you for your attention [email protected]

Knowledge Transfer | Accelerating Innovation

Knowledge Transfer | Accelerating Innovation

R&D isotopes for “Theranostics” 149Tb-therapy

161Tb-therapy

& SPECT

Knowledge Transfer | Accelerating Innovation

152Tb-PET

155Tb-SPECT

#177: C. Müller et al., Center for Radiopharmaceutical #177: C. Müller Sciences ETH-PSI-USZ

ISOLDE - MEDICIS

Preparing Innovative Isotopes -

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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

Knowledge Transfer | Accelerating Innovation

Inventory of isotopes produced in a natural Zr target after proton beam irradiation.

Cancer Treatment Options… Surgery

Local control

Radiotherapy

Chemotherapy and others

X-ray, IMRT, Brachytherapy, Hadrontherapy

Hormones; Immunotherapy; Cell therapy; Genetic treatments; Novel specific targets (genetics..)

Local control

Survival Quality of life Knowledge Transfer | Accelerating Innovation

Limited Local control

Status & Perspectives in Particle Therapy – A. Mazal Worldwide 100 000 Patients 80 000 Statistics 26.02.2012 60 000

M.Jermann A.Mazal PTCOG Total

40 000

Protons

20 000 0 2006

2007

2008

2009

2010

2011

2012

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 Knowledge Transfer | Accelerating Innovation

Radiobiology in therapy and space : a highlight Local effects of microbeams of hadrons seen by fluorescent proteins which repair DNA 55 MeV carbon 5 × 5 µm² matrix

20 MeV protons randomly distributed

10 µm

10 µm

20 MeV protons 5 × 5 µm² matrix 117 protons per spot 10 µm

Günther Dollinger - Low LET radiation focused to sub-micrometer shows enhanced radiobiological effectiveness (RBE) Carbon ions have higher radiobiological effectiveness than protons Knowledge Transfer | Accelerating Innovation

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 Knowledge Transfer | Accelerating Innovation

Novel technologies: a roadmap for particle accelerators

Marco Schippers

WhatKnowledge we need to| Accelerating be ableInnovation to provide beams for therapy Transfer

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

Knowledge Transfer | Accelerating Innovation

Needs for a radiation facility •

Increase radiobiological knowledge: • • •

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Simulations: • •

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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 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

Knowledge Transfer | Accelerating Innovation