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Purpose In modulated radiotherapy, breathing motion can lead to Interplay (IE) and Blurring (BE) effects that can modify the delivered dose. The aim of this work is to present the implementation, the validation and the use of an open-source Monte-Carlo (MC) model that computes the delivered dose including these motion effects. Methods The MC model of the Varian TrueBeam was implemented using GATE. The dose delivered by different modulated plans is computed for several breathing patterns. A validation of these MC predictions is achieved by a comparison with measurements performed using a dedicated programmable motion platform, carrying a quality assurance phantom. A specific methodology was used to separate the IE and the BE. The influence of different motion parameters (period, amplitude, shape) and plan parameters (volume margin, dose per fraction) was also analyzed. Results The MC model was validated against measurement performed with motion with a mean 3D global gamma index pass rate of 97.5% (3%/3 mm). A significant correlation is found between the IE and the period and the antero-posterior amplitude of the motion but not between the IE and the CTV margin or the shape of motion. The results showed that the IE increases D2% and decreases the D98% of CTV with mean values of +6.9% and −3.3% respectively. Conclusions We validated the feasibility to assess the IE using a MC model. We found that the most important parameter is the number of breathing cycles that must be greater than 20 for one arc to limit the IE.

Compositionally graded channel AlGaN/GaN high electron mobility transistors (HEMTs) offer a promising route to improve device linearity, which is necessary for low-noise radio-frequency amplifiers. In this work, we demonstrate different grading profiles of a 10-nm-thick Al xGa1− xN channel from x = 0 to x = 0.1 using hot-wall metal-organic chemical vapor deposition (MOCVD). The growth process is developed by optimizing the channel grading and the channel-to-barrier transition. For this purpose, the Al-profiles and the interface sharpness, as determined from scanning transmission electron microscopy combined with energy-dispersive x-ray spectroscopy, are correlated with specific MOCVD process parameters. The results are linked to the channel properties (electron density, electron mobility, and sheet resistance) obtained by contactless Hall and terahertz optical Hall effect measurements coupled with simulations from solving self-consistently Poisson and Schrödinger equations. The impact of incorporating a thin AlN interlayer between the graded channel and the barrier layer on the HEMT properties is investigated and discussed. The optimized graded channel HEMT structure is found to have similarly high electron density (∼ 9 [Formula: see text] cm−2) as the non-graded conventional structure, though the mobility drops from [Formula: see text] cm2/V s in the conventional to [Formula: see text] cm2/V s in the graded structure. The transconductance gm of the linearly graded channel HEMTs is shown to be flatter with smaller [Formula: see text] and [Formula: see text] as compared to the conventional non-graded channel HEMT implying improved device linearity.

We derive the coarse-graining (CG) equations of incompressible Hall magnetohydrodynamic (HMHD) turbulence to investigate the local (in space) energy transfer rate as a function of the filtering scale ℓ. First, the CG equations are space averaged to obtain the analytical expression of the mean cascade rate. Its application to three-dimensional simulations of (weakly compressible) HMHD shows a cascade rate consistent with the value of the mean dissipation rate in the simulations and with the classical estimates based on the "third-order" law. Furthermore, we developed an anisotropic version of CG that allows us to study the magnitude of the cascade rate along different directions with respect to the mean magnetic field. Its implementation on the numerical data with moderate background magnetic field shows a weaker cascade along the magnetic field than in the perpendicular plane, while an isotropic cascade is recovered in the absence of a background field. The strength of the CG approach is further revealed when considering the local-in-space energy transfer, which is shown theoretically and numerically to match at a given position x, when locally averaged over a neighboring region, the (quasi-)local dissipation. Prospects of exploiting this model to investigate local dissipation in spacecraft data are discussed.

Various exact laws governing compressible magnetohydrodynamic (MHD) and Hall-MHD (CHMHD) turbulence have been derived in recent years. Other than their fundamental theoretical interest, these laws are generally used to estimate the energy dissipation rate from spacecraft observations in order to address diverse problems related, e.g., to heating of the solar wind (SW) and magnetospheric plasmas. Here we use various $1024^3$ direct numerical simulation (DNS) data of free-decay isothermal CHMHD turbulence obtained with the GHOST code (Geophysical High-Order Suite for Turbulence) to analyze two of the recently derived exact laws. The simulations reflect different intensities of the initial Mach number and the background magnetic field. The analysis demonstrates the equivalence of the two laws in the inertial range and relates the strength of the Hall effect to the amplitude of the cascade rate at sub-ion scales. When taken in their general form (i.e., not limited to the inertial range) some subtleties regarding the validity of the stationarity assumption or the absence of the forcing in the simulations are discussed. We show that the free-decay nature of the turbulence induces a shift from a large scale forcing towards the presence of a scale-dependent reservoir of energy fueling the cascade or dissipation. The reduced form of the exact laws (valid in the inertial range) ultimately holds even if the stationarity assumption is not fully verified., 14 pages, 10 figures

Using an exact law for incompressible Hall magnetohydrodynamics (HMHD) turbulence, the energy cascade rate is computed from three-dimensional HMHD-CGL (bi-adiabatic ions and isothermal electrons) and Landau fluid (LF) numerical simulations that feature different intensities of Landau damping over a broad range of wavenumbers, typically $0.05\lesssim k_\perp d_i \lesssim100$. Using three sets of cross-scale simulations where turbulence is initiated at large, medium and small scales, the ability of the fluid energy cascade to "sense" the kinetic Landau damping at different scales is tested. The cascade rate estimated from the exact law and the dissipation calculated directly from the simulation are shown to reflect the role of Landau damping in dissipating energy at all scales, with an emphasis on the kinetic ones. This result provides new prospects on using exact laws for simplified fluid models to analyze dissipation in kinetic simulations and spacecraft observations, and new insights into theoretical description of collisionless magnetized plasmas., 10 pages, 9 figures

Resume Introduction Apres ligamentoplastie du ligament croise anterieur (LCA), la recuperation musculaire est souvent comparee aux asymetries lors des sauts monopodaux en longueur, mais rarement a des exercices fonctionnels avec deplacements verticaux. L’objectif de cette etude est d’analyser ces asymetries et de determiner les correlations avec la force musculaire. Materiel et methodes Nous avons inclus 12 sportifs ayant beneficie d’une ligamentoplastie isolee du LCA. Nous avons realise une analyse videographique 2D d’exercices fonctionnels avec des deplacements verticaux (montee de genoux, talon-fesse, saut monopodal vertical repete, squat jump). Nous avons egalement realise une mesure concentrique de la force musculaire isocinetique du quadriceps et des ischio-jambiers sur appareil Biodex a la vitesse de 90°/s et 240°/s. Nous avons cherche des correlations entre les asymetries videographiques et les asymetries de force musculaire. Resultats La reproductibilite de l’analyse videographique est tres satisfaisante. Le deficit de force musculaire du quadriceps est fortement correle a la difference entre les hauteurs de hanche lors du squat jump (valeurs maximales : r = 0,70 et amplitudes : r = 0,85) et l’amplitude d’angle du genou lors du squat jump (r = 0,71). Il existe une asymetrie de hauteur de hanche pour les exercices de sauts repetes et le squat jump avec une ascension verticale moins importante cote lese. L’articulation du genou du cote lese est moins mobile que du cote sain lors des montees de genoux (p = 0,01), des sauts repetes (p = 0,04) et du squat jump (p = 0,01). Conclusion Le deficit de force musculaire du quadriceps est correle aux asymetries lors des sauts de type squat jump. L’ascension verticale de la hanche est moins elevee du cote lese lors des sauts. Le genou du cote lese est moins mobile que du cote sain et c’est l’articulation la plus perturbee au niveau des tests.

Using mixed second-order structure functions, a compact exact law is derived for isothermal compressible Hall magnetohydrodynamic turbulence with the assumptions of statistical homogeneity, time stationarity and infinite kinetic/magnetic Reynolds numbers. The resulting law is written as the sum of a Yaglom-like flux term, with an overall expression strongly reminiscent of the incompressible law, and a pure compressible source. Being mainly a function of the increments, the compact law is Galilean invariant but is dependent on the background magnetic field if one is present. Only the magnetohydrodynamic source term requires multi-spacecraft data to be estimated whereas the other components, which include those introduced by the Hall term, can be fully computed with single-spacecraft data using the Taylor hypothesis. These properties make this compact law more appropriate for analysing both numerical simulations and in situ data gathered in space plasmas, in particular when only single-spacecraft data are available.

The role of supersonic turbulence in structuring the interstellar medium (ISM) remains an unsettled question. Here, this problem is investigated using a newexact law of compressible isothermal hydrodynamic turbulence, which involves two-point correlations in physical space. The new law is shown to have a compact expression that contains a single flux term reminiscent of the incompressible case and a source term with a simple expression whose sign is given by the divergence of the velocity. The law is then used to investigate the properties of such a turbulence at integral Mach number $4$ produced by a massive numerical simulation with a grid resolution of $10,048^3$ points. The flux (resp. source) term was found to have positive (resp. negative) contribution to the total energy cascade rate, which is interpreted as a direct cascade amplified by compression, while their sum is constant in the inertial range. Using a local (in space) analysis it is shown that the source is mainly driven by filamentary structures in which the flux is negligible. Taking positive defined correlations reveals the existence of different turbulent regimes separated by the sonic scale, which determines the scale over which the non-negligible source modifies the scaling of the flux. Our study provides new insight into the dynamics and structures of supersonic interstellar turbulence., 8 pages, 6 Figures

The first complete estimation of the compressible energy cascade rate $|\varepsilon_\text{C}|$ at magnetohydrodynamic (MHD) and sub-ion scales is obtained in the Earth's magnetosheath using Magnetospheric MultiScale (MMS) spacecraft data and an exact law derived recently for {\it compressible} Hall MHD turbulence. A multi-spacecraft technique is used to compute the velocity and magnetic gradients, and then all the correlation functions involved in the exact relation. It is shown that when the density fluctuations are relatively small, $|\varepsilon_\text{C}|$ identifies well with its incompressible analogue $|\varepsilon_\text{I}|$ at MHD scales but becomes much larger than $|\varepsilon_\text{I}|$ at sub-ion scales. For larger density fluctuations, $|\varepsilon_\text{C}|$ is larger than $|\varepsilon_\text{I}|$ at every scale with a value significantly higher than for smaller density fluctuations. Our study reveals also that for both small and large density fluctuations, the non-flux terms remain always negligible with respect to the flux terms and that the major contribution to $|\varepsilon_\text{C}|$ at sub-ion scales comes from the compressible Hall flux.

A comparison is made between several existing exact laws in incompressible Hall magnetohydrodynamic (IHMHD) turbulence in order to show their equivalence, despite stemming from different mathematical derivations. Using statistical homogeneity, we revisit the law proposed by Hellinger et al. (2018) and show that it can be written, after being corrected by a multiplicative factor, in a more compact form implying only flux terms expressed as increments of the turbulent fields. The Hall contribution of this law is tested and compared to other exact laws derived by Galtier (2008) and Banerjee & Galtier (2017) using direct numerical simulations (DNSs) of three-dimensional electron MHD (EMHD) turbulence with a moderate mean magnetic field. We show that the studied laws are equivalent in the inertial range, thereby offering several choices on the formulation to use depending on the needs. The expressions that depend explicitly on a mean (guide) field may lead to residual errors in estimating the energy cascade rate ; however, we demonstrate that this guide field can be removed from these laws after mathematical manipulation. Therefore, it is recommended to use an expression independent of the mean guide field to analyze numerical or in-situ spacecraft data., 8 pages, 3 figures. Submitted to Astrophysical Journal

The number of protontherapy facilities is still increasing rapidly with more than 30 ongoing projects and close to 60 currently under operation. Although the technology is now validated and robust, a proton facility cannot be considered as a standard radiation therapy equipment: its constraints in terms of building, services, project management are of paramount impact at the level of the hospital. Therefore, a protontherapy project must be carefully considered and prepared, which is mandatory for further fluid and efficient clinical operation.

International audience; PURPOSE: To report the outcomes of initial methylprednisolone pulse then oral prednisone in the treatment of birdshot chorioretinopathy (BSCR). METHODS: We retrospectively reviewed medical records of 21 BSCR patients, treated with initial methylprednisolone, prednisone, or immunosuppressive therapy. Main outcome measures were changes in visual acuity, intraocular inflammation, concomitant immunosuppressive drug or intravitreal steroid, and adverse events. RESULTS: In total, 14 patients were initially treated with methylprednisolone; four patients with prednisone; and three with immunosuppressive drug. Intraocular inflammation was controlled in 10 of 14 patients (71%) at 1 year, with a mean dose of 6.2 mg/day prednisone. Patients treated initially by methylprednisolone had improved visual acuity at 1 year, but it was not significantly different from patients treated initially by prednisone. CONCLUSIONS: Corticosteroid therapy, including initial methylprednisolone pulse then prednisone, was effective in stabilizing vision and decreasing inflammation in most patients with BSCR

Les carcinomes epidermoides de la tete et du cou (CETEC) sont majoritairement diagnostiques a un stade localement avance, et une majorite d’entre eux va echapper a leur prise en charge initiale et recidiver au niveau locoregional et/ou a distance. La prise en charge est pluridisciplinaire. L’inclusion dans un essai therapeutique est toujours privilegiee. Hors essai, l’association d’un sel de platine au 5-FU et au cetuximab est actuellement le standard en premiere ligne chez les patients en bon etat general. Apres echappement aux sels de platine, une monotherapie par taxanes, methotrexate intraveineux ou cetuximab peut etre proposee, les meilleurs soins de support (MSS) exclusifs etant une option. La meilleure connaissance de la biologie de ces tumeurs devrait permettre une amelioration de l’efficacite des traitements proposes.

The treatment of metastatic prostate cancer since the 1940s is based on the consideration of oncogenic addiction to its androgen receptor (AR). The significant improvement in survival outcomes over the past decade depends not only on the development of effective cytotoxic chemotherapy but also new molecules targeting the AR or decreasing testosterone levels, even in case of castration-resistant cancer. In this review, we summarize the structure and function of the RA, the mechanisms of androgen suppression, the concept of resistance to castration, historical targeted treatment on the AR and those recently marketed as abiraterone acetate and enzalutamide.

Introduction Treatment planning in the presence of metallic implants may lead to several issues from contouring to dose calculation. The aim of this study was to control if extended CT scale technique (−10240 UH; 30710 HU) is a suitable alternative to standard CT scale technique for dose calculation in presence of high-Zmaterials. Then the efficiencies of two commercially available dose prediction algorithms, Accuros XB™ (AXB) and Analytical Anisotropic Algorithm™ (AAA) (Varian Medical Systems) were compared in this condition. This work will use for implementation of spinal stereotactic body radiation therapy (SBRT) with metallic fixations. Methods First an extended scale Hounsfield units (HU) conversion curve to relative electron density and to mass density was created based on density phantom (CIRS model 062). Uniformity, noise, low contrast and spatial resolution were evaluated for extended CT scale technique with manufactured CT phantom (GE Healthcare). Images were analyzed with ImageJ. Then measurements were performed using a True Beam™ linac (Varian Medical Systems) with energies of 6 MV flattening filter and flattening filter free for static fields and VMAT. Deposited dose through a titanium implant included in a water-equivalent phantom was evaluated. Two dimensional measurements were also performed at different depths in RW3’s plates with the implant placed above it. Calculations dose were made with Eclispe TPS (Varian Medical Systems) using AXB and AAA. EBT3 radiochromic films (Gafchromic) and liquid-filled ionization chamber array SRS 1000 (PTW Freiburg) were used. Analyses were performed with FilmQAPro (Ashland) et VeriSoft (PTW Freiburg). Results The extended scale HU conversion curve to relative electron density and to mass density show a good agreement to standard scale with 2% maximum variance. Image quality was steady. However low contrast detectability slightly decreased without significant clinical influence. AXB agrees better with measurements than AAA in presence of metallic implant. Conclusions Using extended CT scale technique can potentially improve efficiency in presence of metallic implants in the treatment planning process. In this condition, AXB improves dose calculation in comparison to AAA.

The number of protontherapy facilities is still increasing rapidly with more than 30 ongoing projects and close to 60 currently under operation. Although the technology is now validated and robust, a proton facility cannot be considered as a standard radiation therapy equipment: its constraints in terms of building, services, project management are of paramount impact at the level of the hospital. Therefore, a protontherapy project must be carefully considered and prepared, which is mandatory for further fluid and efficient clinical operation.

The full-length sequence of HLA-C*18:02 differs from that of HLA-C*18:01 by a single nucleotide polymorphism.

The full-length nucleotide sequence of HLA-C*16:01:01:02 differs from that of HLA-C*16:01:01:01 with a SNP at 2996CT.

HLA-C*06:04:02 allele differs from HLA-C*06:02:01:01 with two nucleotide substitutions in exon 3 and 3' untranslated region (UTR_.

Resume Rationnel La chimiotherapie de seconde ligne (CSL) n’est pas validee dans le mesotheliome pleural malin (MPM). Dans notre experience, de nombreux patients en bon etat general au moment de la rechute sont pourtant candidats a un traitement de rattrapage. Methode Nous avons retrospectivement analyse notre experience en matiere de CSL dans le MPM dans deux centres parisiens de cancerologie thoracique (l’institut Gustave-Roussy, a Villejuif et l’hopital d’Instruction des Armees Percy, a Clamart). Resultats Pendant la periode du 1er janvier 2005 au 31 decembre 2006, nous avons collige 84 patients consecutifs, porteurs d’un MPM en progression apres une chimiotherapie de premiere ligne a base de pemetrexed. Un traitement de seconde ligne est administre a 44 patients (30 hommes et 14 femmes) qui presentent un âge moyen de 58 ans (extremes : 34 a 70 ans), un performance status (PS) inferieur ou egal a 1 dans 82 % des cas et une histologie epithelioide dans 91 % des cas. Le temps jusqu’a progression est egal a 6,1 mois. La mediane de survie est egale a 12,2 mois (extremes : deux a 72 mois). Secondairement, une troisieme et une quatrieme ligne de traitement ont ete realisees respectivement chez quatre et deux patients. Conclusions Dans notre experience, chez les patients ayant un MPM en rechute apres une premiere ligne standard a base de pemetrexed et en bon etat general, il est possible d’administrer un traitement de rattrapage. La CSL optimale n’est pas encore definie actuellement et des etudes prospectives sont necessaires dans ce cadre.

Hadron therapy (including protons and ions) is still expanding worldwide, although still limited by the cost and thus the number of available facilities. If the historical indications remain eye melanomas, skull base tumours and paediatric tumours for protontherapy; and salivary glands, paranasal sinus and nasal cavity tumours, and soft tissue sarcomas for carbon ions, no conclusion can be drawn about the role of these modalities for other tumours, such as prostate, lung cancers. Since 2013, more than 100 clinical trials are on-going, including comparisons between advanced photons modalities, protontherapy and carbon ions therapy. An important technological and scientific (physics, radiobiology) effort has been made in parallel in order to reduce the cost of the facilities and to fully take advantages of the beam properties: standardization of beam scanning, image guided treatment, robust and 4D planning. Furthermore, the increasing number of facilities, the development of hypofractionation and the selection of indications will contribute to find the true place of particle therapy, despite the "screening effect" of the cost. The long term effects assessment on large patient cohorts will allow or not to correlate adverse effects and dosimetric data, always evoked.

The market of particle therapy is still rapidly growing worldwide and this modality is now being considered as one modality of radiation therapy, in complementarity with other types of RT treatments. However, the number of facilities and patient treated remains negligible compared to photon RT (less than 1 mainly due to the complexity and therefore overall costs of the particle (proton and moreover ion) facility. Due to the current technology employed and the size/costs, a particle therapy project cannot be managed like a standard radiation therapy project. Nevertheless, from a medical physics point of view, many steps are common to any radiation therapy machine set-up and commissioning and the methodology and principles employed can therefore be adapted. From a project management point of view, a proton project reaches another dimension, on several aspects: – regarding the time frame, the standard duration is in years (2–3 years for one room) and not in months – the overall cost is in tens of millions (more than 30) for one single room and can reach hundreds of million for ion therapy centers, to be compared to several millions for a X ray RT project. Furthermore, a specific building has to be built and the constraints in terms of engineering (power supply, cooling…) exceed by far the standard constraints and have an impact on the whole infrastructure of the hospital. – the financial aspects and the clinical constraints put a much higher pressure on the starting and the ramp rate of the facility and have therefore to be carefully studied and guaranteed, especially from a staffing and training point of view. On the medical physics side, however, the traditional steps remain more or less the same, although modified by the specificity of the particles: beam acceptance and QA, TPS commissioning, daily QA, patient positioning, uncertainties management and robust planning. Nevertheless, three aspects are emphasized when addressing particle therapy: – radiation protection and activation, as the nuclear interactions and neutron production rates are much more important – treatment planning (beam modeling) and QA linked to inhomogeneities, motion and robust planning due to the required precision on the range of the clinical beams – education and training as, up to now, particle therapy is not completely part of the background of the vast majority of medical physicists. Regarding this aspect, upstream education program far before the facility acceptance, is mandatory for clinical teams. In conclusion, although industrial efforts and decades of treatment, a particle therapy facility is not a project like the others and the project management has to be adapted to this dimension. However, as it is no longer research centers but CE marked clinical machines, the methodology of x ray machines acceptance can be largely adapted.

The treatment of metastatic prostate cancer since the 1940s is based on the consideration of oncogenic addiction to its androgen receptor (AR). The significant improvement in survival outcomes over the past decade depends not only on the development of effective cytotoxic chemotherapy but also new molecules targeting the AR or decreasing testosterone levels, even in case of castration-resistant cancer. In this review, we summarize the structure and function of the RA, the mechanisms of androgen suppression, the concept of resistance to castration, historical targeted treatment on the AR and those recently marketed as abiraterone acetate and enzalutamide.

During metamorphic climax, anuran amphibians undergo dramatic changes as they pass from aquatic to terrestrial life. In particular, the digestive tract is completely modified. The pharyngeal filtering apparatus disappears. Striking transformations take place in the gastric region. The tadpole's glandular sheath regresses and ceases protruding from the gut wall. At the same time, a large permanent stomach is formed to replace the sheath, gastric glands develop, and the muscle layer thickens. The intestine also changes greatly. An overall shortening and rearrangement of its coils occurs. The histological changes that affect the intestine are largely confined to the epithelium. Degeneration occurs in the larval epithelium, while intense proliferation of stem cells results in the development of a new epithelium that is folded. During metamorphosis, the endocrine cells of the digestive tract are also redistributed. Such changes are associated with modifications in feeding behavior. Most tadpoles are microphago...

With over 70,000 patients treated worldwide, protontherapy has an evolution on their clinical applications and technological developments. The ballistic advantage of the Bragg peak gives the possibility of getting a high conformation of the dose distribution to the target volume. Protontherapy has accumulated a considerable experience in the management of selected rare malignancies such as uveal melanomas and base of the skull chordomas and chondrosarcomas. The growing interest for exploring new and more common conditions, such as prostate, lung, liver, ENT, breast carcinomas, as well as the implementation of large pediatric programs advocated by many experts has been challenged up to now by the limited access to operational proton facilities, and by the relatively slow pace of technical developments in terms of ion production, beam shaping and modelling, on-line verification etc. One challenge today is to deliver dynamic techniques with intensity modulation in clinical facilities as a standard treatment. We concentrate in this paper on the evolution of clinical indications as well as the potentialities of new technological concepts on ion production, such as dielectric walls and laser-plasma interactions. While these concepts could sooner or later translate into prototypes of highly compact equipments that would make easier the implantation of cost-effective hospital-based facilities, the feasibility of their clinical use must still be proved.

The role of second-line chemotherapy (SLC) has still not been established in malignant pleural mesothelioma (MPM) but SLC is increasingly used because many patients are still fit at the time of the progression of the disease.In this retrospective study, the authors reviewed their experience with SLC in pemetrexed-pretreated patients with MPM at two French thoracic oncology units (institut Gustave-Roussy, Villejuif, and hôpital d'Instruction des Armées Percy, Clamart).Between January 2005 and December 2006, 84 consecutive patients with progressing MPM after pemetrexed chemotherapy were enrolled. Forty-four patients received an SLC. There were 30 men and 14 women. The median age was 58 years (range: 34 to 76 years). Most patients had a performance status (PS) less than or equal to 1 (82%) and an epithelial histological subtype (91 %). The median time to progression (TTP) after first-line chemotherapy was 6.1 months. The SLC was a pemetrexed therapy in 21 patients and a new regime in 20 patients (gemcitabine alone or with oxaliplatin). The other three patients were enrolled in a phase I study. According to the Recist criteria, a partial response was observed in four patients and the disease was stabilised in six patients after SLC. The median TTP after SLC was 3.8 months. The median survival was 12.2 months (range: 2 to 72 months). Four of these 44 patients then received third-line (4.8 %) and two received fourth-line therapy (2.4 %).This experience indicates the feasibility of administering SLC in patients with MPM who are healthy at the time of the progression of the disease. The optimal treatment has not been defined to date and prospective trials are needed.

In hadron therapy centers that have only fixed horizontal beams (i.e. most carbon ions centers and protons centers of first generation), the angulations of the beam remain technically limited, especially for the treatment of children under general anaesthesia with posterior-oblique (40 degrees or so) beams in supine position. We have been developing recently an original positioning system allowing for treatment with posterior-oblique beams, either from right or left directions, by keeping the child in the adequate position.

In this paper, we present an iterative method for positioning a patient in protontherapy. The main difficulty in this kind of treatment is the unknown position of the treated volume during the set up of the patient. The positioning process is realized by a 6 degrees of freedom (DOF) industrial robot. This article explains how the positioning error of the treated volume can e minimized thanks to an external tracking system.

The Proton Therapy Center in Orsay (CPO) and CEA/DAPNIA launched the joint project on Monte Carlo modeling of a CPO beam line with the aim to achieve a prediction of dose distribution in all the calibration configurations (depth and the shape of the tumor) better than 2%. The calculation module is intended to be used for the absolute dosimetry of the clinical beam (patient Quality Assurance – QA), and in a second stage for predicting the dose distribution on a voxelized phantom constructed from the Computer Tomography (CT) patient’s data. The MCNPX code was used as a basic Monte Carlo simulation tool in this study. All the elements of a CPO beam line were modelled with sub-millimetric precision. To speed up the calculations of modulated dose profiles in water phantom, a routine simulating rotation of modulator wheel was created to save phase space of particle tracks crossing the modulator. The modeling of nuclear interactions, which contribute noticeably into the total absorbed dose in water phantom at the prescribed proton energy (average raw beam energy 201MeV), was improved by means of creation and implementation of the two new evaluated proton-induced nuclear data files up to 200MeV for 1H and 16O. Thus, the simulations of 3D dose profiles in water show excellent agreement with measured data allowing to move forward to the absolute dose calibrations.

Introduction Treatment of chestwall with lymph nodes (internal mammary and clavicular nodes) is achieved in most of the centers with conventional radiotherapy using photons and electrons beams with junctions. The aim of this study is to do a dosimetric comparative study between two technics using modulation irradiation: Tomotherapy and Rapid Arc (RA). Material and methods Seven patients (5 left, 2 right) were treated using Tomotherapy. For these patients a RA plan was prepared retrospectively. Patients were positioned supine with two arms above the head. The prescribed dose was 50 Gy for the chestwall and 46–50 Gy for the lymph nodes. Optimisation constraints were increased until the PTV coverage was acceptable. Tomotherapy plans were computed with a 2.5–5 cm collimation and a 0.287 pitch. RA plans were computed using a 5 mmbolus on the chestwall, 2 arcs (60–180°) and a +/-10° collimator rotation. Doses delivered to targets, heart and both lungs are reported. Results For the 7 patients the heart mean dose was 7.1–8.6 Gy (mean 7.5 Gy) with Tomotherapy and 4.4–18.1 Gy (mean 9.9 Gy) for RA. For the ipsilateral lung, the mean dose, V5, V20 and V30 were respectively 10.1–14.7 Gy, 56.4–85.7%, 14.8–25.9% and 6.2–16.6% for Tomotherapy. For RA, these values were 10.5–16.0 Gy, 65.3–96.0%, 14.8–30.0% and 6.2–16.6%. Conclusion For 5/7 patients RA plans were acceptable but the OAR doses were generally higher than Tomotherapy plans (in particular V5 of lungs and lung mean dose). For 2/7 patients (left side) RA plans were not acceptable.

To define prognostic factors for local control and survival in 100 consecutive patients treated by fractionated photon and proton radiation for chordoma of the skull base and upper cervical spine.Between December 1995 and August 2002, 100 patients (median age: 53 years, range: 8-85, M/F sex-ratio: 3/2), were treated by a combination of high-energy photons and protons. The proton component was delivered by the 201 MeV proton beam of the Centre de Protonthérapie d'Orsay (CPO). The median total dose delivered to the gross tumour volume was 67 Cobalt Gray Equivalent (CGE) (range: 60-71). A complete surgery, incomplete surgery or a biopsy was performed before the radiotherapy in 16, 75 and 9 cases, respectively.With a median follow-up of 31 months (range: 1-87), 25 tumours failed locally. The 2 and 4-year local control rates were 86.3% (+/-3.9%) and 53.8% (+/-7.5%), respectively. According to multivariate analysis, less than 95% of the tumour volume encompassed by the 95% isodose line (P=0.048; RR: 3.4 IC95% [1.01-11.8]) and a minimal dose less than 56 CGE (p=0.042; RR: 2.3 IC95% [1.03-5.2]) were independent prognostic factors of local control. Ten patients died. The 2 and 5-year overall survival rates were 94.3% (+/-2.5%) and 80.5% (+/-7.2%). According to multivariate analysis, a controlled tumour (P=0.005; RR: 21 IC95% [2.2-200]) was the lonely independent favourable prognostic factor for overall survival.In chordomas of the skull base and upper cervical spine treated by surgical resection followed by high-dose photon and proton irradiation, local control is mainly dependent on the quality of radiation, especially dose-uniformity within the gross tumour volume. Special attention must be paid to minimise underdosed areas due to the close proximity of critical structures and possibly escalate dose-constraints to tumour targets in future studies, in view of the low toxicity observed to date.

Neutrons have radiobiological characteristics, which differ from those of conventional radiotherapy beams (photons) and which offer a theoretical advantage over photons to fight radioresistance by the differential relative biological effect of them between normal and tumour tissues. Neutron therapy beneficed of great interest between 1975 and 1985. Many of phase III trials were conducted and indications have been definitively deducted of them. After briefly describing the properties of neutron beams, this review discusses the indication of neutron therapy on the basis of the clinical results. Salivary, prostate tumours and sarcomas are the main indications of neutron therapy. In concern to the prostate cancers, other alternative treatments reduce the neutron therapy field. For sarcomas, the lack of randomised trials limits the impact of the interest of neutrons. For other tumours, the ratio benefice/risk of neutron therapy is inferior to these obtained with photons and they could not be considered like classical indications.

Protons have physical characteristics, which differ from those of photons used in conventional radiotherapy. Better shielding of critical organs is obtained by using their particular ballistic (Bragg peak and lateral narrow penumbra). Some indications as ocular melanoma, chordoma and chondrosarcoma of the base of skull are now strongly accepted by the radiation oncologist community. Others are still in evaluation: meningioma, locally advanced nasopharynx tumor and paediatric tumors. The aim of this review is to present the clinical results of a technic which seems "confidential" because of the rarety and the cost of equipments.

Purpose- There is a relationship between the local control rate of the nasopharyngeal cancer and the total dose delivered within the tumoral volume. In contrast, the relation between the dose and the irradiated volume and the risk of complication is not clearly defined. That is why, in patients presenting with a locally advanced nasopharyngeal cancer, we compared the dose-volume distribution of irradiated tissues, obtained from two 3D conformal irradiation techniques. Patients and methods- Between January 2000 and June 2001, 5 patients, 3 males and 2 females, with a median age of 32 years and presenting with a T4N0M0 nasopharyngeal cancer received a chemoradiotherapy. Radiotherapy combined photons and protons beams and the platin-based chemotherapy was delivered in three intravenous injections at d1, 22, 43 of the irradiation. To calculate the dosimetry, a CT scan and a MRI were performed in all the patients. The gross tumor volume (GTV) was delineated from the imagery, three clinical tumor volumes were defined, the CTV1 was the GTV and the whole nasopharynx, the CTV2 was the CTV plus a 10 mm-margin and the CTV3 was the CTV2 and the nodes areas (cervical and subclavicular). Prophylactic dose within node areas was 44 Gy. Prescribed doses within CTV2 and GTV or CTV1 were 54 Gy/CGE (Cobalt Gy Equivalent, for an EBR = 1,1) and 70 Gy/CGE, respectively. Irradiation was delivered with fractions of 1.8 or 2.0 Gy/CGE, with 44 Gy or 54 Gy by photons and with 16 or 26 CGE by protons. According to dose-volume histograms obtained from the dosimetry planning by protons and photons and from the theoretical dosimetry by photons lonely, for the different volumes of interest, GTV, CTV2, and organs at risk (optic nerves, chiasm, internal ears, brainstem, temporal lobes), we compared the averages of the maximum, minimum and mean doses and the averages of the volumes of organs of interest encompassed by different isodoses.Results- Calculated averages of minimum, maximum and mean doses delivered within GTV were superior for the treatment with combined photons and protons than with photons alone. The average GTV encompassed by the 70 Gy/CGE isodose was larger by 65% with the association compared to photons alone. The conformation ratio (tissue volume encompassed by the 95% isodose/GTV encompassed by the 95% isodose) was 3.1 with the association compared to 5.7 with photons alone. For the CTV2, there were no differences in different criteria according to the both irradiation techniques. For the critical, radiosensitive organs, the comparison of the majority of the criteria was in favour of the association of protons and photons. Overall, 78% of the criteria were in favour of the association.Conclusion- For locally advanced nasopharyngeal cancer without clinical adenopathy, irradiation by photons and protons increases the tumor volume irradiated at the prescribed dose and decreases the volume or critical organs irradiated and the total dose delivered within them.

From October 1993 through July 1998, 48 assessable adult patients with non-resectable aggressive intracranial tumors were treated by a combination of high dose photon + proton therapy at the Centre de Protonthérapie d'Orsay.Grade 1 and 4 gliomas were excluded. Patients benefited from a 3D dose calculation based on high-definition CT and MRI, a stereotactic positioning using implanted fiducial markers and a thermoplastic mask. Mean tumor dose ranged between 63 and 67 Gy delivered in five weekly sessions of 1.8 Gy in most patients, according to the histological types (doses in Co Gy Equivalent, with a mean proton-RBE of 1.1).With a median 18-month follow-up (range: four-58 months), local control in tumors located in the envelopes and in the skull base was 97% (33/34), and in parenchymal tumors, 43% (6/14) only. Two patients (5%) presented with a clinically severe radiation-induced necrosis (temporal lobe and chiasm).In our experience, high-dose radiation combining photons and protons is a safe and highly efficient procedure in selected malignancies of the skull base and envelopes.