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

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

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 Life.Sciences@cern.ch KT-LS 26 May 2011 4

Cancer incidence increases with age

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

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.

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

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

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

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

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

PET/CT (David Townsend)

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

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

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

Two opposite photon beams 80 30 50

Two opposite photon beams 110 100

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

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

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 1996-2000 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

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

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

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 held @ CERN, 2010 KT-LS 26 May 2011

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)

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

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

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………. Life.Sciences@cern.ch

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

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

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.

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

Status & Perspectives in Particle Therapy – A. Mazal Worldwide Patients Statistics 26.02.2012 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

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

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

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

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

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