Hadrontherapy in France and the ARCHADE programme

WS NuPECC, GANIL, October 9, 2015

Daniel GUERREAU, Cyclhad (Chairman)Daniel CUSSOL, LPC Caen

CYCLHAD

The Archade programme is aiming at

- The creation in Caen of a treatment and research center in Hadrontherapy( protons and carbon ions) using innovative technologies- The emergence of an industrial sector for the manufacture, marketing and using of medical accelerators for hadrontherapy treatments

THE ARCHADE PROGRAMME

Why ARCHADE IN CAEN?Competences

HospitalsResearch centers

What is ARCHADE?Different facetsOrganizationStatus

Research program around ARCHADE

GANIL

LPC CIMAP

LARIA

Multiple competences within 1km distance: Medical doctors and scientists from various fields concerned by

hadrontherapy (physicists, biologists, radiobiologists…)Collaborations

France-Hadron

Research Institutes

Curie Institute (Paris-Orsay)

NIRS (Japan)

…..

Industrial Partners

Archade: a pluridisciplinary project in Caen

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ORGANIZATION: 3 entities

CONSTRUCTION OF THE HADRONTHERAPY

CENTERBuilding constructionEquipments (accelerators) for cancer treatment and

R&D

----------------------------------------------------------------------------------IN PARALLEL, DEVELOPMENT AND CONSTRUCTION OF C400 N° 1

to be purchased by CYCLHAD

(followed later by the development of an industrial sector)

----------------------------------------------------------------------------------

RESEARCH DEVELOPMENTDevelopement of experimental equipments

MANAGEMENT BODY-----------------------------

SAS CYCLHAD

----------------------------

SAS NORMANDYHADRONTHERAPY

--------------------------ARCHADE ASSOCIATIONResearch InstitutesLaboratories

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ACCELERATORS, Treatment rooms, experimental areas

**

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Compact IMPT solution

*Subject to review by Competent Authorities (FDA, European Notified Bodies, et al.) before being put on the market.

COMPACTRobust compact

gantry & accelerator design

INTEGRATEDSoftware, Dosimetry

&Training

TREATMENT ROOMMost precise treatments

PBS allowing IMPT

PHASE 1 Proteus®ONE

(IBA)

SC Synchrocyclotron

S2C2 230 MeV p

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October 2014 Creation of CYCLHAD Society

December 2014 Contract signatures ( civil engineering, Proteus One)

September 2015 Construction permits

December 2015 Start of building construction

July 2018 First patient treatments with the Proteus OneOperated by the Cancer Institute François Baclesse

Financing of phase 1: 76.5 M€ Total cost of the project 129 M€

PHASE 1 SCHEDULE

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A 2nd generation equipment:

Preliminary design study realized by IBA Validation by international expert

committees (last in 2013 in Caen run by Archade)

Lower cost purchase (compared to synchrotron)

More compact and low operational cost

PHASE 2: C400, a new generation SC medical cyclotron

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Prospective investors for the consortium

ONGOING CONSTITUTION OF NORMANDY HADRONTHERAPY (Nha)the operational centre for the development and implementation of the prototype External

collaborations

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Estimated schedule

• 2016 (semester 1) Creation of Normandy Hadrontherapy Consortium

• 2016-2017 Finalization of Detailed Design Study, Execution order file

• 2018 Construction starts

• 2021 C400 into operationpurchased by Cyclhad

PHASE 2: CONSTRUCTION OF C400

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RESEARCH PROGRAMME: THE ACTORS

National Institutes CEA, CNRS, INSERM

National programso France-Hadron

o Gathers french laboratories around hadrontherapy studies (physics, biologogy, medicine)

o Nodes : CPO, CAL Nice, GANIL, ARCHADE, PERICLES, ETOILE

o IN2P3-Joint Research Group « MI2B »o Gathers french nuclear physics laboratories around hadrontherapy studieso « Poles » : Imaging, Radio-Biology, Therapy, Radio-Nucleides.

Local Actorso LPC Caeno CIMAPo LARIAo ISTCT/CYCERONo ToxeMAC-ABTEo CHU Caeno Centre François Baclesse

Local Institutionso ENSICAENo CHU Caeno Centre François Baclesseo Normandy Universityo GANILo Nucleopolis

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WP1 : Clinical research

WP2 : Physics-Chemistry

leaders : D. Cussol & J.C. Poully

WP3 : Hadronbiology

leaders : C. Laurent & Y. Saintigny

WP4 : R&D for treatment improvement

leaders : S. Valable & J.M. Fontbonne

THE ARCHADE SCIENTIFIC PROGRAMME

leader : J.L. Habrand

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Skin

Brain

Brain tumours

Cranium

Tumour

Gazeous monitorsSolid monitors

Secondary fragments production

Induced structural effectsInduced chemical effects

In line controls

Clinical imaging

WP2WP3WP4

Beam Monitors(pre-check)

Secondary particles detectors

(post-check)

Toxicity on healthy tissuesEfficiency on tumoral tissues

IRRADIATION WITH CARBON IONS

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CLINICAL RESEARCH

Clinical testing for different pathologieso Radio-resistant non-operable tumours (head and neck)o Pediatric cancers

Optimizing treatment protocols :o Best particleso Best dose delivery sequence

Long term side effects :o Functionnal disorderso Radio-induced pathologies

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C, p, 4

He

p, 4

He, 6

Li, 10

B, 12

C, 14

N, 16

O, 18

F, 20

Ne

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C, p, 4

He

Need for instrumentation for monitoring the delivered dose and control the irradiation process

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HADRON-BIOLOGY

Toxicity on healty tissues : o Skino Brain (astrocytes)o Craniumo Cartilages (chondrocytes)o Bystander effects

Efficiency on tumoral tissues :o Brain tumours (glioblastomas)o Cartilage tumour (chondrosarcoma)

Influence of physico-chemical quantities :o Doseo Dose rateo LETo Secondary electrons energy distributiono Additional drugs (chemicals, nano-particles)

Irradiation on cells and small animals

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C, p, 4

He, 6

Li, 10

B, 14

N, 16

O, 18

F, 20

Ne

12

C, 14

N, 16

O, 18

F, 20

Ne

Need for instrumentation

for measuring and monitoring these

quantities

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PHYSICS, CHEMISTRY & INSTRUMENTATION

Basic data : o Secondary particles production cross sections (FRACAS)o b+ emitters production cross sectionso Damages on the DNA baseso Production of chemical toxic species

Dose monitors :o Gazeous (IC2/3)o Diamondso Dose monitors for radio-biology experiments (Dosion III)

In-line control of the dose deposition :o «Prompt» go In line PETo Interaction Vertex Imaging

Clinical Imaging :o p-CT, C-CTo Tissues chemical composition imagingo Tumour identificationo Image Guided Irradiation, moving organs

Need for basic nuclear physics data

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Thank you for your attention !

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1919

GEANT4 simulations

Pathogenic mutationsFunctional damages

p, , B

Pathogenic mutationsFunctional damages

12C

Tumoral control12C

SECONDARY PARTICLES EFFECTS

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BEAM MONITORS

PBS beam control

X(64)I1

I2Y(64)

gap ~10mm

LPC CAEN – IBA Collaboration

2009 : experiments in ESSEN

« Westdeutsches Protontherapiezentrum

Essen »

Charlotte Courtois PhD october 2011C. Courtois, et al., Nuclear Instruments & Methods in Physics Research A (2013), Patent IBA 28/12/2009Inventors : J.M.Fontbonne & J.Perronnel

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FRACAS (LPC Caen, IPHC Strasbourg)

Yvan Merrer

Samuel Salvador

Z, v

, q j

A

REC-Hadron

France-Hadron

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CONTROL IMAGINGS

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2015 2016 2017 2018 2019 2020 2021 2022 2023

France-Hadron ARCHADE

Proto Beam Line (Nice)

Design and building of FRACAS Nuclear physics experiments (FRACAS)

Preparing the radio-chemistry experiments

Beam monitors, Controls, Imageries

Radio-chemistry experiments

Experiments at GANIL, Orsay, Nice Moving

set-u

ps

Radio-biology experiments Hadronbiology experiments

Rec-Hadron (XRays)

~ 300 to 500 h/year ~ 1 900 h/year

CALENDAR

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Segmentation et taille du marché accessible

50 centres opérationnels en proton thérapie, 6 centres en ions de Carbone et 27 projets en planification : Japon est le leader mondial,Fin 2013, on a identifié 6 centres d’ions de Carbone et 6 autres en planification, 70000 patients traités par Hadron thérapie (Proton + ions Carbone),15 pathologies possibles à date pour la thérapie par ions carbone.

Commentaires

16 centres opérationnels en proton thérapie8 projets en planification

US

Proton thérapie:15 centres opérationnelsDont 2 en FranceIons Carbone:2 centres opérationnels (700 patients / ans pour ~600 séances) et1 Project ARCHADE

Europe

Proton thérapie:6 centres opérationnels3 en planification

Ions Carbone:3 centres opérationnels5 en projets

Japon

Prix du traitement

NHa

Analyse Marché pour la constitution du BP