The FFAG R&D and medical application project RACCAM

JACoW web site http://accelconf.web.cern.ch/AccelConf/e06/Pre-Press/WEPCH161.pdf WEPCH161International audienceThe RACCAM project (Recherche en ACCelerateurs et Applications Medicales) has recently obtained fundings, extending over three years (2006-2008), from the French National Research Agency (ANR). RACCAM is a tripartite collaboration, involving (i) the CNRS Laboratory IN2P3/LPSC, (ii) the French magnet industrial SIGMAPHI, and (iii) the nuclear medecine Departement of Grenoble Hospital. The project concerns fixed field alternating gradient accelerator (FFAG) research on the one hand, and on the other hand their application as hadrontherapy and biology research machines. RACCAM's goal is three-fold, (i) participate to the on-going international collaborations in the field of FFAGs and recent concepts of "non-scaling" FFAGs, with frames for instance, the Neutrino Factory (NuFact) and the EMMA project of an electron model of a muon FFAG accelerator, (ii) design, build and experiment a prototype of an FFAG magnet proper to fulfil the requirements of rapid cycling acceleration, (iii) develop the concepts, and show the feasibility, of the application of such FFAG beams to hadrontherapy and to biology research

Theoretical approach based on Monte-Carlo simulations to predict the cell survival following BNCT

International audienceWe present here a very preliminary work on BNCT Dosimetry. The approach is as follows:A full Monte Carlo calculation is used to separate all dose components and determine the corresponding physical dose fractions with a realistic clinical model.These dose fractions are then used as mixed fields to predict cell-survivals and RBE values for a specific cell-line, thanks to the radiobiological model NanOxTM

International Veterinary Epilepsy Task Force Consensus Proposal: Outcome of therapeutic interventions in canine and feline epilepsy

Common criteria for the diagnosis of drug resistance and the assessment of outcome are needed urgently as a prerequisite for standardized evaluation and reporting of individual therapeutic responses in canine epilepsy. Thus, we provide a proposal for the definition of drug resistance and partial therapeutic success in canine patients with epilepsy. This consensus statement also suggests a list of factors and aspects of outcome, which should be considered in addition to the impact on seizures. Moreover, these expert recommendations discuss criteria which determine the validity and informative value of a therapeutic trial in an individual patient and also suggest the application of individual outcome criteria. Agreement on common guidelines does not only render a basis for future optimization of individual patient management, but is also a presupposition for the design and implementation of clinical studies with highly standardized inclusion and exclusion criteria. Respective standardization will improve the comparability of findings from different studies and renders an improved basis for multicenter studies. Therefore, this proposal provides an in-depth discussion of the implications of outcome criteria for clinical studies. In particular ethical aspects and the different options for study design and application of individual patient-centered outcome criteria are considered

A step towards international prospective trials in carbon ion radiotherapy: investigation of factors influencing dose distribution in the facilities in operation based on a case of skull base chordoma

Background: Carbon ion radiotherapy (CIRT) has been delivered to more than 20,000 patients worldwide. International trials have been recommended in order to emphasize the actual benefits. The ULICE program (Union of Light Ion Centers in Europe) addressed the need for harmonization of CIRT practices. A comparative knowledge of the sources and magnitudes of uncertainties altering dose distribution and clinical effects during the whole CIRT procedure is required in that aim. Methods: As part of ULICE WP2 task group, we sent a centrally reviewed questionnaire exploring candidate sources of uncertainties in dose deposition to the ten CIRT facilities in operation by February 2017. We aimed to explore native beam characterization, immobilization, anatomic data acquisition, target volumes and organs at risks delineation, treatment planning, dose delivery, quality assurance prior and during treatment. The responders had to consider the clinical case of a clival chordoma eligible for postoperative CIRT according to their clinical practice. With the results, our task group discussed ways to harmonize CIRT practices. Results: We received 5 surveys from facilities that have treated 77% of the patients worldwide per November 2017. We pointed out the singularity of the facilities and beam delivery systems, a divergent definition of target volumes, the multiplicity of TPS and equieffective dose calculation approximations. Conclusion: Multiple uncertainties affect equieffective dose definition, deposition and calculation in CIRT. Although it is not possible to harmonize all the steps of the CIRT planning between the centers, our working group proposed counter-measures addressing the improvable limitations

Synchrotron radiation-based experimental determination of the optimal energy for cell radiotoxicity enhancement following photoelectric effect on stable iodinated compounds

This study was designed to experimentally evaluate the optimal X-ray energy for increasing the radiation energy absorbed in tumours loaded with iodinated compounds, using the photoelectric effect. SQ20B human cells were irradiated with synchrotron monochromatic beam tuned at 32.8, 33.5, 50 and 70 keV. Two cell treatments were compared to the control: cells suspended in 10 mg ml1 of iodine radiological contrast agent or cells pre-exposed with 10 mM of iodo-desoxyuridine (IUdR) for 48 h. Our radiobiological end point was clonogenic cell survival. Cells irradiated with both iodine compounds exhibited a radiation sensitisation enhancement. Moreover, it was energy dependent, with a maximum at 50 keV. At this energy, the sensitisation calculated at 10% survival was equal to 2.03 for cells suspended in iodinated contrast agent and 2.60 for IUdR. Cells pretreated with IUdR had higher sensitisation factors over the energy range than for those suspended in iodine contrast agent. Also, their survival curves presented no shoulder, suggesting complex lethal damages from Auger electrons. Our results confirm the existence of the 50 keV energy optimum for a binary therapeutic irradiation based on the presence of stable iodine in tumours and an external irradiation. Monochromatic synchrotron radiotherapy concept is hence proposed for increasing the differential effect between healthy and cancerous tissue irradiation

2012 Activity Report of the Regional Research Programme on Hadrontherapy for the ETOILE Center

2012 is the penultimate year of financial support by the CPER 2007-2013 for ETOILE's research program, sustained by the PRRH at the University Claude Bernard. As with each edition we make the annual review of the research in this group, so active for over 12 years now. Over the difficulties in the decision-making process for the implementation of the ETOILE Center, towards which all our efforts are focussed, some "themes" (work packages) were strengthened, others have progressed, or have been dropped. This is the case of the eighth theme (technological developments), centered around the technology for rotative beam distribution heads (gantries) and, after being synchronized with the developments of ULICE's WP6, remained so by ceasing its activities, coinciding also with the retirement of its historic leader at IPNL, Marcel Bajard. Topic number 5 ("In silico simulations") has suffered the departure of its leader, Benjamin Ribba, although the work has still been provided by Branka Bernard, a former postdoctoral fellow in Lyon Sud, and now back home in Croatia, still in contract with UCBL for the ULICE project. Aside from these two issues (and the fact that the theme "Medico-economical simulations" is now directly linked to the first one ("Medical Project"), the rest of the teams are growing, as evidenced by the publication statistics at the beginning of this report. This is obviously due to the financial support of our always faithful regional institutions, but also to the synergy that the previous years, the European projects, the arrival of the PRIMES LabEx, and the national France Hadron infrastructure have managed to impulse. The Rhone-Alpes hadron team, which naturally includes the researchers of LPC at Clermont, should also see its influence result in a strong presence in France Hadron's regional node, which is being organized. The future of this regional research is not yet fully guaranteed, especially in the still uncertain context of ETOILE, but the tracks are beginning to emerge to allow past and present efforts translate into a long future that we all want to see established. Each of the researchers in PRRH is aware that 2013 will be (and already is) the year of great challenge : for ETOILE, for the PRRH, for hadron therapy in France, for French hadrontherapy in Europe (after the opening and beginning of treatments in the German [HIT Heidelberg, Marburg], Italian [CNAO, Pavia] and Austrian [MedAustron, Wien Neuerstadt]) centers. Let us meet again in early 2014 for a comprehensive review of the past and a perspective for the future ..

The role of inflammation in epilepsy.

Epilepsy is the third most common chronic brain disorder, and is characterized by an enduring predisposition to generate seizures. Despite progress in pharmacological and surgical treatments of epilepsy, relatively little is known about the processes leading to the generation of individual seizures, and about the mechanisms whereby a healthy brain is rendered epileptic. These gaps in our knowledge hamper the development of better preventive treatments and cures for the approximately 30% of epilepsy cases that prove resistant to current therapies. Here, we focus on the rapidly growing body of evidence that supports the involvement of inflammatory mediators-released by brain cells and peripheral immune cells-in both the origin of individual seizures and the epileptogenic process. We first describe aspects of brain inflammation and immunity, before exploring the evidence from clinical and experimental studies for a relationship between inflammation and epilepsy. Subsequently, we discuss how seizures cause inflammation, and whether such inflammation, in turn, influences the occurrence and severity of seizures, and seizure-related neuronal death. Further insight into the complex role of inflammation in the generation and exacerbation of epilepsy should yield new molecular targets for the design of antiepileptic drugs, which might not only inhibit the symptoms of this disorder, but also prevent or abrogate disease pathogenesis

Synchrotron Radiation Therapy: ongoing development and long term prospect

International audienceTherapeutic applications of the Synchrotron Light (SL) are becoming a reality. As an experimental radiotherapy, the present principles of use remain rather close to the classical radiotherapy performed in oncology. For instance, the very first human application of SL, the ongoing SSRT trial (stereotactic synchrotron radiation therapy), is mostly mimicking stereotactic arctherapy and is applied to the same patients than those treated at the hospital [1]. However, this is only a transitory step allowing to go progressively from well known situations to more innovative ones.This presentation will address, first, the starting points of the different types of SL clinical study applications we could develop with the present type of patients we are recruiting at ESRF, namely pauci-brain-metastatic patients. Early medical exploration of SSRT and of MRT (micro beam radiotherapy) [2] will be described. Then, as a second generation of study, the first possibilities to address real orphan diseases able to be alleviate or hopefully cured by SL will be described. This could be particular forms of meningioma, very resistant life threatening epileptic conditions [3], diffuse brain micrometastatic evolution, etc. These rare diseases could be a reason for multicentric recruitment of the patients and for attractive international collaborations. Finally very innovative applications combining different possibilities, specific to SL, will be described as narrow spectra high dose rate therapy with nanoparticles for large target volumes; or very high dose rate “white” SL delivered as micro beams for small target volumes, both being fractionated. These items are presented as an introduction and an invitation for imagination and creativity about the use and the applications of SL, which is still in its infancy. From the selection of the most useful and applicable procedures could come more narrow definitions of specific machines [4] devoted to produce either monochromatic X ray or huge dose rate X ray beams or both!References[1] - Brauer-Krisch E, et al., Medical physics aspects of the synchrotron radiation therapies: Microbeam radiation therapy (MRT) and synchrotron stereotactic radiotherapy (SSRT), Physica Medica (2015), http://dx.doi.org/10.1016/j.ejmp.2015.04.016[2] - Bravin A, et al., SYRA3 COST Action - Microbeam radiation therapy: Roots and prospects, Physica Medica (2015), http://dx.doi.org/10.1016/j.ejmp.2015.06.002[3] - Studer F, et al., Synchrotron X-ray microbeams: A promising tool for drug-resistant epilepsy treatment, Physica Medica (2015), http://dx.doi.org/10.1016/j.ejmp.2015.04.005[4] - A. Variola et al., The ThomX project status, prepress WEPRO052, 5th International Particle Accelerator ConferenceIPAC’14 (Dresden, Germany, 15 - 20 june 2014).http://www.umr-lams.fr/spip.php?article16