F. Trompier

Mesenchymal stem cells home to injured tissues when co-infused with hematopoietic cells to treat a radiation-induced multi-organ failure syndrome

Recent studies have suggested that ex vivo expansion of autologous hematopoietic cells could be a therapy of choice for the treatment of bone marrow failure. We investigated the potential of a combined infusion of autologous ex vivo expanded hematopoietic cells with mesenchymal (MSCs) for the treatment of multi‐organ failure syndrome following irradiation in a non‐human primate model.

Emerging therapy for improving wound repair of severe radiation burns using local bone marrow‐derived stem cell administrations

The therapeutic management of severe radiation burns remains a challenging issue today. Conventional surgical treatment including excision, skin autograft, or flap often fails to prevent unpredictable and uncontrolled extension of the radiation‐induced necrotic process. In a recent very severe accidental radiation burn, we demonstrated the efficiency of a new therapeutic approach combining surgery and local cellular therapy using autologous mesenchymal stem cells (MSC), and we confirmed the crucial place of the dose assessment in this medical management. The patient presented a very significant radiation lesion located on the arm, which was first treated by several surgical procedures: iterative excisions, skin graft, latissimus muscle dorsi flap, and forearm radial flap. This conventional surgical therapy was unfortunately inefficient, leading to the use of an innovative cell therapy strategy. Autologous MSC were obtained from three bone marrow collections and were expanded according to a clinical‐grade protocol using platelet‐derived growth factors. A total of five local MSC administrations were performed in combination with skin autograft. After iterative local MSC administrations, the clinical evolution was favorable and no recurrence of radiation inflammatory waves occurred during the patients 8‐month follow‐up. The benefit of this local cell therapy could be linked to the “drug cell” activity of MSC by modulating the radiation inflammatory processes, as suggested by the decrease in the C‐reactive protein level observed after each MSC administration. The success of this combined treatment leads to new prospects in the medical management of severe radiation burns and more widely in the improvement of wound repair.

Small fields output factors measurements and correction factors determination for several detectors for a CyberKnife® and linear accelerators equipped with microMLC and circular cones.

PURPOSE The use of small photon fields is now an established practice in stereotactic radiosurgery and radiotherapy. However, due to a lack of lateral electron equilibrium and high dose gradients, it is difficult to accurately measure the dosimetric quantities required for the commissioning of such systems. Moreover, there is still no metrological dosimetric reference for this kind of beam today. In this context, the first objective of this work was to determine and to compare small fields output factors (OF) measured with different types of active detectors and passive dosimeters for three types of facilities: a CyberKnife(®) system, a dedicated medical linear accelerator (Novalis) equipped with m3 microMLC and circular cones, and an adaptive medical linear accelerator (Clinac 2100) equipped with an additional m3 microMLC. The second one was to determine the kQclin,Qmsr (fclin,fmsr) correction factors introduced in a recently proposed small field dosimetry formalism for different active detectors. METHODS Small field sizes were defined either by microMLC down to 6 × 6 mm(2) or by circular cones down to 4 mm in diameter. OF measurements were performed with several commercially available active detectors dedicated to measurements in small fields (high resolution diodes: IBA SFD, Sun Nuclear EDGE, PTW 60016, PTW 60017; ionizing chambers: PTW 31014 PinPoint chamber, PTW 31018 microLion liquid chamber, and PTW 60003 natural diamond). Two types of passive dosimeters were used: LiF microcubes and EBT2 radiochromic films. RESULTS Significant differences between the results obtained by several dosimetric systems were observed, particularly for the smallest field size for which the difference in the measured OF reaches more than 20%. For passive dosimeters, an excellent agreement was observed (better than 2%) between EBT2 and LiF microcubes for all OF measurements. Moreover, it has been shown that these passive dosimeters do not require correction factors and can then be used as reference dosimeters. Correction factors for the active detectors have then been determined from the mean experimental OF measured by the passive dosimeters. CONCLUSIONS Four sets of correction factors needed to apply the new small field dosimetry formalism are provided for several active detectors. A protocol for small photon beams OF determination based on passive dosimeters measurements has been recently proposed to French radiotherapy treatment centers.

Lessons from recent accidents in radiation therapy in France

Many accidents in radiotherapy have been reported in France over the last years. This is due to the recent legal obligation to declare to the national safety authorities any significant incident relative to the use of ionising radiation including medical applications. The causes and consequences of the most serious events in radiotherapy are presented in this paper. Lessons can be learned from possible technical dysfunctions, from human errors or organisational weaknesses as to how such events can be prevented. The technical aspects are addressed here: in particular, dosimetric issues.

Radiation Accident Dosimetry On Glass By Tl And Epr Spectrometry

Retrospective dosimetry using glass has been investigated. Radiation-induced signals have been surveyed for a large number of watch glasses and display windows of mobile phones with TL and EPR techniques in order to study the variability of dosimetric properties among the different types of samples. Dose response, signal stability, and effects of storage conditions are presented.

Radiation accident dosimetry on electronic components by OSL.

In the event of large-scale radiation accidents and considering a growing terrorism concern, non-invasive and sufficiently accurate retrospective dosimetry methods are necessary to carry out a fast population triage in order to determine which radiation-exposed individuals need medical treatment. Retrospective dosimetry using different electronic components such as resistors, capacitors, and integrated circuits present on mobile phone circuit boards have been considered. Their response has been investigated with luminescence techniques (OSL, IRSL, and TL). The majority of these electronic components exhibit radiation-induced luminescence signals, and the OSL technique seems the most promising for these materials. Results concerning three types of components that present the most interesting OSL characteristics (in terms of signal annealing and sensitivity) and that are the most often present on mobile phone circuit boards are presented. Preheating effects on OSL signal, sensitization, and dose-response curves from 0.7 to 27 Gy for resistors and from 0.7 to 160 Gy for capacitors and integrated circuits, dose recovery tests, and signal stability 10 h after irradiation have been studied and interests and limits of their use evaluated.

Realising the European network of biodosimetry: RENEB—status quo

Creating a sustainable network in biological and retrospective dosimetry that involves a large number of experienced laboratories throughout the European Union (EU) will significantly improve the accident and emergency response capabilities in case of a large-scale radiological emergency. A well-organised cooperative action involving EU laboratories will offer the best chance for fast and trustworthy dose assessments that are urgently needed in an emergency situation. To this end, the EC supports the establishment of a European network in biological dosimetry (RENEB). The RENEB project started in January 2012 involving cooperation of 23 organisations from 16 European countries. The purpose of RENEB is to increase the biodosimetry capacities in case of large-scale radiological emergency scenarios. The progress of the project since its inception is presented, comprising the consolidation process of the network with its operational platform, intercomparison exercises, training activities, proceedings in quality assurance and horizon scanning for new methods and partners. Additionally, the benefit of the network for the radiation research community as a whole is addressed.

Fingernail dosimetry: current status and perspectives.

A summary of recent developments in fingernail EPR dosimetry is presented in this paper. Until 2007, there had been a very limited number of studies of radiation-induced signals in fingernails. Although these studies showed some promising results, they were not complete with regard to the nature of non-radiation signals and the variability of dose dependence in fingernails. Recent study has shown that the two non-radiation components of the EPR spectrum of fingernails are originated from mechanical stress induced in the samples at their cut. The mechanical properties of fingernails were found to be very similar to those of a sponge; therefore, an effective way to eliminate their mechanical deformation is by soaking them in water. Stress caused by deformation can also significantly modify the dose response and radiation sensitivity. Consequently, it is critically important to take into account the mechanical stress in fingernail samples under EPR dose measurements. Obtained results have allowed formulating a prototype of a protocol for dose measurements in human fingernails.

Measurement of stray radiation within a scanning proton therapy facility: EURADOS WG9 intercomparison exercise of active dosimetry systems

PURPOSE To characterize stray radiation around the target volume in scanning proton therapy and study the performance of active neutron monitors. METHODS Working Group 9 of the European Radiation Dosimetry Group (EURADOS WG9-Radiation protection in medicine) carried out a large measurement campaign at the Trento Centro di Protonterapia (Trento, Italy) in order to determine the neutron spectra near the patient using two extended-range Bonner sphere spectrometry (BSS) systems. In addition, the work focused on acknowledging the performance of different commercial active dosimetry systems when measuring neutron ambient dose equivalents, H(∗)(10), at several positions inside (8 positions) and outside (3 positions) the treatment room. Detectors included three TEPCs--tissue equivalent proportional counters (Hawk type from Far West Technology, Inc.) and six rem-counters (WENDI-II, LB 6411, RadEye™ NL, a regular and an extended-range NM2B). Meanwhile, the photon component of stray radiation was deduced from the low-lineal energy transfer part of TEPC spectra or measured using a Thermo Scientific™ FH-40G survey meter. Experiments involved a water tank phantom (60 × 30 × 30 cm(3)) representing the patient that was uniformly irradiated using a 3 mm spot diameter proton pencil beam with 10 cm modulation width, 19.95 cm distal beam range, and 10 × 10 cm(2) field size. RESULTS Neutron spectrometry around the target volume showed two main components at the thermal and fast energy ranges. The study also revealed the large dependence of the energy distribution of neutrons, and consequently of out-of-field doses, on the primary beam direction (directional emission of intranuclear cascade neutrons) and energy (spectral composition of secondary neutrons). In addition, neutron mapping within the facility was conducted and showed the highest H(∗)(10) value of ∼ 51 μSv Gy(-1); this was measured at 1.15 m along the beam axis. H(∗)(10) values significantly decreased with distance and angular position with respect to beam axis falling below 2 nSv Gy(-1) at the entrance of the maze, at the door outside the room and below detection limit in the gantry control room, and at an adjacent room (<0.1 nSv Gy(-1)). Finally, the agreement on H(∗)(10) values between all detectors showed a direct dependence on neutron spectra at the measurement position. While conventional rem-counters (LB 6411, RadEye™ NL, NM2-458) underestimated the H(∗)(10) by up to a factor of 4, Hawk TEPCs and the WENDI-II range-extended detector were found to have good performance (within 20%) even at the highest neutron fluence and energy range. Meanwhile, secondary photon dose equivalents were found to be up to five times lower than neutrons; remaining nonetheless of concern to the patient. CONCLUSIONS Extended-range BSS, TEPCs, and the WENDI-II enable accurate measurements of stray neutrons while other rem-counters are not appropriate considering the high-energy range of neutrons involved in proton therapy.

Overview of physical and biophysical techniques for accident dosimetry

From feedback experience from recent radiation accident cases, in addition to biological dosimetry and physical dosimetry based on Monte Carlo calculations or experimental means, there is a need for complementary methods of dosimetry for radiation accident. Electron paramagnetic resonance (EPR) spectrometry on bones or teeth is considered as efficient but is limited by the invasive character of the sampling. Since 2005, Institute for Radiological Protection and Nuclear Safety (IRSN) develops some new approaches and methodologies based on the EPR and luminescence techniques. This article presents the overview of the different studies currently in progress in IRSN.