Research and development at the Proton Therapy Center

 

Since 2018 the Institut Curie - Protontherapy center is member of a community of European research centers (H2020 program, project INSPIRE : INfraStructure in Proton International REsearch) promoting access to European researchers (physicists, biologists, students) to infrastructures providing high energy proton beams. For more information and apply for translational access, you can visit this page. For all inquiries about it thank you to contact us at comex.cpo@curie.fr

The teams at the Proton Therapy Center have recognized expertise in several areas of research and development. Research in particular revolves around three main areas: clinics, physics and radiobiology.

An experimental line of research is being introduced (delivery scheduled for 2020). It will allow access to the beam for research teams wishing to study the use of protons for medical applications, with direct transfer to the proton therapy treatment, in physics (medical and nuclear) and in biology of radiation.

This will complete the activities underway, the main themes of which are presented below.

Accelerator & beam

The Proton Therapy Center is equipped with a particle accelerator (cyclotron) which produces a proton beam with the characteristics needed for their medical application. The teams at the center are invested in R&D programs for improvement of performance of the machine and quality of treatment.

The cyclotron (proton beam with maximum energy of 230 MeV, reducible to 70 MeV depending on the locations to be treated) is equipped with a beam production system, the source of ions, which delivers the protons. The extracted beam, with millimetric dimensions, is channeled to the treatment rooms via a transport system using magnets. It is shaped in relation to the geometry of the tumor either via diffusion systems that broaden the size of the beam, paired with elements that alter the spread longitudinally (Double Scattering - DS), or via magnets (Pencil Beam Scanning - PBS). The teams at the center and IBA (supplier of the accelerator) have produced and continue to develop appropriate tools to check the performance of the machine and ensure that it is reliable, and to guarantee delivery of the dose to the patient. In particular, the shaping of the beam using the PBS technique is one of the major aspects of investigation (2017 thesis on scanning of the tumor using a continuous beam, rather than the routine technique which is known as spot scanning). The other developments are linked closely to research projects in radiobiology (shaping of the beam for pre-clinical experiments “FLASH” and “pMBRT”).

The individuals working on the topic

Annalisa Patriarca, engineer, PhD
J.D. Bocquet, assistant engineer
S. Meyroneinc, engineer
C. Nauraye, medical physicist, PhD

Imaging & robotics

In 1991 the Proton Therapy Center introduced robotic and imaging systems in its treatment rooms to allow the patient to be placed opposite the proton beam. Since then robotics and medical imaging have continued to be developed and improved in our center to benefit patients at Institut Curie and at other centers.

To ensure that the dose is correctly delivered during a proton therapy treatment, the placement of the patient must be accurate to the closest millimeter. In the 1990s, the patient positioning systems available in radiotherapy were not adequate to satisfy this need. The Proton Therapy Center therefore turned to robotics to adapt it to its field, developing and introducing the world’s first medical robotic positioners. Since then, medical robotics has become increasingly widespread in radiotherapy and the Proton Therapy Center continues developments in this field to improve this discipline and make it available in other centers worldwide.

This increased need for precision has also required major progress in the field of medical imaging to define, quantify and validate the various steps in a proton therapy treatment. To achieve this, for many years the Proton Therapy Center has been developing imaging tools to help manage proton therapy sessions.

 

The individuals working on the topic

J. Assuli, Engineer
I. Pasquié, medical physicist
L. De Marzi, medical physicist, PhD

Radiobiology

Radiobiology is the discipline that aims to understand the effects of ionizing radiation on living organisms. It is a highly interdisciplinary field where research revolves around two main areas, namely treatment of cancer and radioprotection.

Historically, protons were chosen to treat cancers due to the physical specificities of these beams. Indeed, this type of beam reduces the dose administered to the healthy tissues surrounding the tumor.

Thus the effects of protons on the living organism are less well-known, via the information generated by the scientific community, than those of more conventional ionizing radiation (X-rays, electrons). These gaps in knowledge are due partly to the rarity of this type of installation and to the difficulties experienced by the research teams in using these installations.

The main areas of research in radiobiology in this field aim to understand the differences in the biological effects observed between X-rays and protons (cellular toxicity, side effects, etc.), to improve the effectiveness of proton treatments (proton/chemotherapy combinations, development of new treatment protocols, etc.), to assess the effects of secondary particles emitted in the trace of the beam.

In particular, a collaboration is underway with the CNRS - IMNC/NARA (Y. Prezado - research associate) on development of an innovative radiation technique based on the use of spatial fractioning of the dose (project on “Proton minibeam radiation therapy (pMBRT): a new therapeutic approach” - Plancancer 2014-2019).

Collaborations between the hospital and the Institut Curie Research Center are underway to characterize the biological effects of proton beams, such as for example the difference between diffused and scanned beam techniques, the variation of biological effectiveness related to protons in the tissues (F. Megnin-Chanet - INSERM U1196/UMR9187 CMIB), as well as on the properties of high-dose proton beams (FLASH project - C. Fouillade and V. Favaudon - CNRS, INSERM, UMR3347, U1021, and PROMUFLASH – P. Verrelle – Institut Curie).

 

The individuals working on the topic

V. Calugaru, oncological radiotherapist, MD, PhD
R. Dendale, oncological radiotherapist
C. Nauraye, medical physicist, PhD
L. De Marzi, medical physicist, PhD
A. Patriarca, engineer, PhD
F. Pouzoulet, manager of the experimental radiotherapy platform, Radexp

Information system

When the Proton Therapy Center opened in 1991, there were no IT systems adapted to this discipline. Thus the teams at the center developed a variety of software programs to manage both the equipment and the data necessary to perform treatments.

The information systems are now very widespread. The same applies to proton therapy. From patient identification data to invoicing the health insurance administration, including the parameters needed to deliver personalized treatment suited to the patient’s pathology; all of this information is exchanged digitally.

Some of the software programs used at Orsay have been specially developed internally to suit the specificities of the discipline. This is the case for the center’s two “historic” rooms, but also for the OIS (Oncology Information System), the software at the heart of the information system, which exchanges with both the identity management application and the cyclotron control system to guide the beam to one of the treatment rooms. This software is regularly upgraded so that it remains suited to the needs of users and the other software programs with which it communicates.

 

The individuals working on the topic

Frédéric Martin, engineer
Caroline Devalckenaere, engineer

Digital simulation

Digital simulation of high-energy proton beams and of the geometry of treatment lines is based on calculation, analytical or Monte Carlo methods. Since it was formed in 1991, our team has been developing models for the treatment planning system (TPS), to prepare, check and analyze the effects of beams on patients, in particular for scattered beam techniques.

 

▲ Example of treatment planning: scanned proton minibeams (PBS) (Single Field Uniform Dose technique, Isogray® software, from Dosisoft, France), comparison with the so-called Monte Carlo simulation and passive scattering technique.

Our work on simulations is used to establish libraries (databases) of our treatment machines (beam line), for quality control of clinical beams and also for modeling of the biological effects of ionizing radiation (primary beams or secondary particles such as neutrons). Indeed special attention is given to the long-term consequences of proton therapy, particularly in children. In order to optimize the modern double scattering (DS) techniques from this point of view, or the intensity modulation techniques (IMPT) already used at the Proton Therapy Center in Orsay, studies on anthropomorphic phantoms are being conducted, as well as an intensive calculation via Monte Carlo simulation.

All the treatment lines were modeled precisely using the MCNPX or GATE/GEANT4 calculation tools in collaborations between Institut Curie and the CEA (IRFU, INCa-ANR2009 project), the IRSN or Dosisoft (PROUESSE project ANR2009). A calculation cluster (eight nodes) was installed (sponsored by AREVA 2012-2015) and helps to significantly reduce calculation time. The development of simulations toward the minibeam scanning technique is currently part of a research project (DEDIPRO project, AAP Physicancer 2014-INSERM).

 

The individuals working on the topic

L. De Marzi, engineer, medical physicist, PhD
S. Delacroix, medical physicist, PhD
C. Nauraye, medical physicist, PhD

 

The latest publications

Prezado Y, Jouvion G, Hardy D, Patriarca A, Nauraye C, Bergs J, Gonzales W, Guardiola C, Juchaux M, Labiod D, Dendale R, Jourdain L, Sebrie C and Pouzoulet F. (2017). Proton minibeam radiation therapy spares normal rat brain: Long-Term Clinical, Radiological and Histopathological Analysis. Scientific Reports 7, Article number: 14403

Fouillade C, Favaudon V, Vozenin MC, Romeo PH, Bourhis J, Verrelle P, Devauchelle P,  Patriarca A, Heinrich S, Mazal A, Dutreix M, (2017), Les promesses du haut débit de dose en radiothérapie, 4747(1), Bulletin du cancer

Marsolat F, De Marzi L, Pouzoulet F and Mazal A; (2016) , Analytical linear energy transfer model including secondary particles: Calculations along the central axis of the proton pencil beam , Phys. Med. Biol. 61 740–757

Marsolat F, De Marzi L, Patriarca A, Nauraye C, Moignier C, Pomorski M, Moignau F, Heinrich S, Tromson D, Mazal A (2016), Dosimetric characteristics of four PTW microDiamond detectors in high-energy proton beams, Phys Med Biol. 61(17):6413-29

Peucelle C, Nauraye C, Patriarca A, Hierso E, Fournier-Bidoz N, Martínez-Rovira I and Prezado Y (2015), Proton minibeam radiation therapy: Experimental dosimetry evaluation. Med. Phys., 42: 7108–7113

Bonfrate A, Farah J, De Marzi L, Delacroix S, Constant E, Hérault J and Clairand I (2016) Benchmarking Monte Carlo simulations against experimental data in clinically relevant passive scattering proton therapy beamline configurations. Radioprotection 51(2), 113-122

Farah J, Bonfrate A, De Marzi L, De Oliveira A, Delacroix S, Martinetti F, Trompier F, Clairand I (2015) Configuration and validation of an analytical model predicting secondary neutron radiation in proton therapy using Monte Carlo simulations and experimental measurements. Phys Med.Biol. 31(3) :248-256