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International audience; PURPOSE: Stereotactic body radiation therapy has been proposed as a salvage treatment for recurrent prostate cancer after irradiation. One crucial issue is choosing appropriate dose-volume constraints (DVCs) during planning. The objectives of this study were to (1) quantify the proportion of patients respecting the DVCs according to the Urogenital Tumor Study Group GETUG-31 trial, testing 36 Gy in six fractions, (2) explain geometrically why the DVCs could not be respected, and (3) propose the most suitable DVCs. METHODS AND MATERIALS: This retrospective dosimetric analysis included 141 patients treated for recurrent prostate cancer with Cyberknife (Accuray), according to GETUG-31 DVCs: V(95%) ≥ 95% for the planning target volume (PTV), V(12Gy) < 20% and V(27Gy) < 2 cc for the rectum, and V(12Gy) < 15% and V(27Gy) < 5 cc for the bladder. The percentage of patients not respecting the DVCs was quantified. Correlations between the DVCs and anatomic structures were examined. New DVCs were proposed. RESULTS: Only 19% of patients respected all DVCs, with a mean PTV of 18.5 cc (range, 3-48 cc), although the mean PTV was 40.5 cc (range, 3-174 cc) in the whole series. A total of 98% of the patients with a clinical target volume (CTV)/prostate ratio >0.5 could not respect the DVCs in the organs at risk. The target coverage and organ-at-risk sparing decreased significantly with increase in the values of PTV, CTV, CTV/prostate ratio, the overlapping volume between the PTV and bladder wall and between the PTV and rectal wall. Threshold values of PTV, >20 cc and 40 cc, allowed for the PTV and bladder DVCs, respectively. To improve DVC respect in case of large target volume, we proposed the following new DVCs: V(12Gy) < 25% and 25% and V(27Gy) < 2 cc and 5 cc for the rectum and bladder, respectively. CONCLUSIONS: GETUG-31 DVCs are achievable only for small target volumes (CTV more than half of the prostate). For a larger target volume, new DVCs have been proposed.

International audience; Purpose: Ethical questions are poorly investigated specifically in radiation oncology. The objective of the study was to identify and understand the main ethical issue in radiation oncology. Materials and methods: A quantitative analysis was based on the answers to a questionnaire of 200 professionals from 22 radiation oncology departments. The questionnaire mainly aimed to characterize the main ethical issue. A monocentric qualitative analysis was based on semi-structured interviews focused on the main identified ethical issue, carried out with eight technologists, and 20 patients undergoing radiotherapy. Results: The main ethical issue was the understanding and/or acceptance of the treatment by the patients (71 %), which frequently arises (more than once a month) (52 %), and corresponds to an ethical tension between the principles of respect for autonomy and beneficence (the good as viewed by the patient) as defined by Beauchamp and Childress. The technologists, wish the patient to be fully involved in his treatment, with the even possibility of refusing it. However, excluding paternalism and autonomic relentlessness, the technologists have the feeling of acting for the good of the patients by treating them with radiation, even if the patients are not always aware of it, because they are within a situation of vulnerability. If the hierarchy of principles is a compromise alternative, this problem is finally well resolved by the effective implementation of an ethic of consideration and solicitude, restoring the patient capabilities, i.e. the maximum development of his potentialities in his situation of vulnerability. Beyond the legal dimension, patient information is crucial and must consider the specific temporality of the patient. Conclusion: The main ethical issue in radiation oncology is the understanding and/or acceptance of the treatment involving the development of an ethic of consideration and solicitude.

International audience; Background The choice between different diffusion-weighted imaging (DWI) techniques is difficult as each comes with tradeoffs for efficient clinical routine imaging and apparent diffusion coefficient (ADC) accuracy.Purpose: To quantify signal-to-noise-ratio (SNR) efficiency, ADC accuracy, artifacts, and distortions for different DWI acquisition techniques, coils, and scanners.Study Type: Phantom, in vivo intraindividual biomarker accuracy between DWI techniques and independent ratings.Population/Phantoms: NIST diffusion phantom. 51 Patients: 40 with prostate cancer and 11 with head-and-neck cancer at 1.5 TField Strength/Sequence: Echo planar imaging (EPI): 1.5 T and 3 T Siemens; 3 T Philips. Distortion-reducing: RESOLVE (1.5 and 3 T Siemens); Turbo Spin Echo (TSE)-SPLICE (3 T Philips). Small field-of-view (FOV): ZoomitPro (1.5 T Siemens); IRIS (3 T Philips). Head-and-neck and flexible coils.Assessment: SNR Efficiency, geometrical distortions, and susceptibility artifacts were quantified for different b-values in a phantom. ADC accuracy/agreement was quantified in phantom and for 51 patients. In vivo image quality was independently rated by four experts.Statistical Tests: QIBA methodology for accuracy: trueness, repeatability, reproducibility, Bland–Altman 95% Limits-of-Agreement (LOA) for ADC. Wilcoxon Signed-Rank and student tests on P

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International audience; Cultural aversion to microbes, healthiness or desire for safe bathing, the applications for water disinfection are varied and the technologies used to achieve this goal are numerous.The authors looked at a simple solution to implement: the use of a reagent called performic acid. Consequently, more than two years of applied research, observations and analyzes were necessary to demonstrate its harmlessness towards the natural environment.The strength of the demonstration lies in the cross-vision of many researchers and scientists from different backgrounds who shared their studies and observations.The strength of this testimony also lies in the diversity of the application cases, including notable and sensitive receiving environments as different as the Seine, the Atlantic Ocean or the Venice lagoon.Through its intentions and results, this work is a step, moving forward the 2030 Agenda for Sustainable Development, particularly SDG 6 “clean water and sanitation” relying on the lever of SDG 17 “partnerships for the goals”.

International audience; The development of immunotherapy has recently modified the anti-tumor therapeutic arsenal ; particularly, immune checkpoint inhibitors have led to a significant increase in overall survival. The current challenge is now to select good responder patients by identifying early biomarkers to propose therapeutic combinations that potentiate the efficacy of the therapy. Here we report the case of a 60-year-old man with superficial melanoma treated with high-dose hypo fractionated radiotherapy (H-SRT) combined with a single dose of anti-PD1 immunotherapy (Nivolumab) for a metastatic lymph node recurrence due to cancer progression. In this study, we present the results obtained regarding the activation of the Th1 immune response after H-SRT treatment followed by anti PD-1 therapeutic protocol. These results were correlated with clinical data to identify potential immunological biomarkers of treatment efficacy. This exceptional case report shows that a combination of H-SRT with a single dose of anti-PD1 immunotherapy may allow a better activation of the immune response in favor of a complete clinical response.

Copyright © 2020 by the authors. The test methods that currently exist for the identification of thyroid hormone system-disrupting chemicals are woefully inadequate. There are currently no internationally validated in vitro assays, and test methods that can capture the consequences of diminished or enhanced thyroid hormone action on the developing brain are missing entirely. These gaps put the public at risk and risk assessors in a difficult position. Decisions about the status of chemicals as thyroid hormone system disruptors currently are based on inadequate toxicity data. The ATHENA project (Assays for the identification of Thyroid Hormone axis-disrupting chemicals: Elaborating Novel Assessment strategies) has been conceived to address these gaps. The project will develop new test methods for the disruption of thyroid hormone transport across biological barriers such as the blood–brain and blood–placenta barriers. It will also devise methods for the disruption of the downstream effects on the brain. ATHENA will deliver a testing strategy based on those elements of the thyroid hormone system that, when disrupted, could have the greatest impact on diminished or enhanced thyroid hormone action and therefore should be targeted through effective testing. To further enhance the impact of the ATHENA test method developments, the project will develop concepts for better international collaboration and development in the area of thyroid hormone system disruptor identification and regulation. EU Horizon 2020 programme, grant number 825161

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International audience; PURPOSE:Limited pelvic nodal relapse of prostatic cancer is a paramount challenge for locoregional salvage treatments. Salvage whole pelvis radiotherapy as considered in the BLINDED trial, is an attractive option but with concerns about its toxicity. This article describes early toxicity with the technique.METHODS AND MATERIALS:BLINDED was a prospective multi-center phase II trial investigating high-dose salvage pelvic irradiation with an additional dose to the fluorocholine-based positron-emission-tomography (FCH-PET)-positive pelvic lymph nodes (PLN), combined with six-month androgen blockade. The prescribed dose was 54 Gy in 1.8 Gy fractions with up to 66 Gy in 2.2 Gy fractions to the pathological PLN. Early toxicity was defined until one year after radiotherapy. Patients quality of life was assessed using the EORTC questionnaires (QLQ-C30 and QLQ-PR25).RESULTS:Seventy-four patients were recruited in fifteen French radiation oncology departments between August 2014 and July 2016. Seven were excluded before treatment because of violation of the inclusion criteria. The intention-to-treat analysis therefore included sixty-seven patients. Half of them had received prior prostatic irradiation. Median age was 67.7 ± 6.5 years. Grade 2 acute urinary toxicity was observed in 9/67 patients (13.4%) and grade 2 one-year toxicity in 4/67 patients (6%). Three patients (4.4%) had grade 3 urinary toxicity. Grade 2 acute digestive toxicity was observed in 10/67 patients (14.9%) and grade 2 one-year toxicity in 4/67 patients (6%). Patients with prior prostate bed irradiation did not exhibit increased urinary or digestive toxicity. EORTC questionnaire scores at one year did not worsen significantly.CONCLUSIONS:The acute and one-year toxicity of the BLINDED protocol was satisfactory, even in patients with a past history of prostatic irradiation.

There is increasing interest in applying bioassays for water quality monitoring. However, information about the effects of individual micropollutants in bioassays, such as pharmaceuticals, pesticides and industrial compounds, as well as their contribution to the overall mixture effect in a sample, is often limited. In the current study, a bioanalytical test battery with both cell-based and whole organism assays was applied to fingerprint the effects of 34 micropollutants, which were selected based on their environmental presence, hazard quotients and mode of action. The bioassays were selected to cover different steps of the cellular toxicity pathway, such as induction of xenobiotic metabolism and receptor-mediated effects, as well as both specific and apical effects in whole organisms. All studied chemicals were active in at least one assay, with the industrial compound bisphenol A active in 70% of the applied assays. While many more chemicals were active in assays indicative of apical effects, the chemicals that had a response in the specific assays typically triggered an effect at much lower concentrations. The generated effect data were applied to existing mixture toxicity modelling of water samples to determine if and how the studied chemicals contributed to the biological effect. A slight increase in the fraction of the effect could be explained by detected chemicals. However, the fraction explained was still less than 1% for some assays, which suggests that many more chemicals contribute to the effect than those that are typically monitored by chemical analysis. This emphasises the need for a complementary approach of chemical analysis and bioanalysis for water quality monitoring.

Publications associées non citées dans la thèse: 1) Pasquier D, Lacornerie T, Vermandel M, Rousseau J, Lartigau E, Betrouni N. Automatic segmentation of pelvic structures from magnetic resonance images for prostate cancer radiotherapy. Int J Radiat Oncol Biol Phys. 2007 Jun 1;68(2):592-600. 2) Pasquier D, Lacornerie T, Betrouni N, Vermandel M, Rousseau J, Lartigau E. [Dosimetric evaluation of an automatic segmentation tool of pelvic structures from MRI images for prostate cancer radiotherapy]. Cancer Radiother. 2008 Sep;12(5):323-30. 3) Pasquier D, Betrouni N, Vermandel M, Lacornerie T, Lartigau E, Rousseau J. MRI alone simulation for conformal radiation therapy of prostate cancer: technical aspects. Conf Proc IEEE Eng Med Biol Soc. 2006;1:160-3. Biol Soc. 2006;1:160-3.; Radiotherapy is a curative treatment of malignant tumours. Radiotherapy techniques considerably evolved last years with the increasing integration of medical images in conformal radiotherapy. This technique makes it possible to elaborate a complex ballistics conforming to target volume and sparing healthy tissues. The examination currently used to delineate volumes of interest is Computed Tomography (CT), on account of its geometrical precision and the information that it provides on electronic densities needed to dose calculation. Magnetic Resonance Imaging (MRI) ensures a more precise delineation of target volumes in many locations, such as pelvis and brain. For pelvic tumours, the use of MRI needs image registration, which complicates treatment planning and poses the problem of the lack of in vivo standard method of validation. The obstacles in the use of MRI alone in treatment planning were evaluated. Neither geometrical distortion linked with the system and the patient nor the lack of information on electronic densities represent stumbling obstacles. Distortion remained low even in edge of large field of view on modern machines. The assignment of electronic densities to bone structures and soft tissues in MR images permitted to obtain equivalent dosimetry to that carried out on the original CT, with a good reproducibility and homogeneous distribution within target volume. The assignment of electronic densities could not be carried out using 20 MV photons and suitable ballistics. The development of Image Guided Radiotherapy could facilitate the use of MRI alone in treatment planning. Target volumes and organ at risk delineation is a time consuming task in radiotherapy planning. We took part in the development and evaluated a method of automatic and semi automatic delineation of volumes of interest from MRI images for prostate cancer radiotherapy. For prostate and organ at risk automatic delineation an organ model-based method and a seeded region growing method were used respectively. Our results are reproducible with minimal repercussion on dosimetry.; La radiothérapie fait partie des traitements à visée curative des tumeurs malignes. Les techniques de radiothérapie ont considérablement évolué ces dernières années avec l' intégration croissante de l'imagerie en radiothérapie conformationnelle. Cette technique permet d'élaborer une balistique complexe se conformant le mieux possible au volume cible en préservant les tissus sains. L'examen utilisé pour la définition des volumes d'intérêt est actuellement la tomodensitométrie ou « scanner » en raison de son exactitude géométrique et de l'information donnée sur les densités électroniques utilisées pour les calculs dosimétriques. L'Imagerie par Résonance Magnétique (IRM) permet cependant une définition plus précise des volumes cibles dans les localisations pelviennes et cérébrales. Dans le cadre des localisations pelviennes, l'utilisation de l'IRM passe à l'heure actuelle par la fusion d'images, ce qui complexifie la phase de préparation du traitement et pose le problème de l'absence de méthode « standard » de validation in vivo de cette fusion d'images. Nous avons évalué les contraintes posées par l'utilisation de l'IRM seule dans la planification dosimétrique. Nos résultats montrent que ni la distorsion liée au système et au patient ni l'absence d'informations sur les densités électroniques ne représentent des obstacles rédhibitoires à l'utilisation de l'IRM seule dans ce contexte. La distorsion reste contenue y compris en bordure de grands champs de vue sur des machines modernes. Nous avons montré que l'assignation de densités aux structures osseuses et aux tissus mous permettait d'obtenir une dosimétrie équivalente à celle réalisée sur le scanner original avec une bonne reproductibilité et une répartition de dose homogène au sein du volume cible. L'assignation de densités électroniques pourrait même ne pas être réalisée avec des photons de 20 MV et une balistique appropriée. Le développement de la radiothérapie guidée par l'image pourrait faciliter l'utilisation de l'IRM seule dans la planification dosimétrique. La délinéation des volumes d'intérêt est une tâche nécessitant de plus en plus de temps. Nous avons participé au développement et évalué une méthode de segmentation automatique et semi automatique des volumes d'intérêt d'après des images IRM pour la radiothérapie du cancer prostatique. La délinéation automatique de la prostate repose sur un modèle d'organe déformable; une méthode par extension de régions a été utilisée pour la délinéation du rectum et de la vessie. Nos résultats sont reproductibles et le retentissement dosimétrique de la délinéation automatique est minime.

During the latest years, numerous methods of multimodal image matching have been developed. Associated with medical imaging, these developments make it possible to match images using intrinsic data, as anatomical data, instead of external referential, as stereotactic frames. Thus, the use of intrinsic registration considerably increases possibilities in medical image analysis. Unfortunately, these techniques mostly remain in the research field and are rarely used in clinical daily practice. In this paper, we present a method for matching projective imaging (2D, radiography, angiography...) and tomographic imaging (3D, Magnetic Resonance Imaging, Computed Tomography). Furthermore, we propose a radiosurgical application for Arteriovenous Malformation (AVM). Radiosurgery planning for the treatment of AVM requires multiple image acquisitions in multimodality to define the irradiation target and to compute the dosimetry. All the planning images are acquired with a stereotactic frame. We describe in this paper the image registration technique that we propose to include diagnostic images in the planning process and the different steps required to validate our approach. In the current state, the results obtained do not enable us to replace the conventional technique due to the accuracy expected, but the analysis of the results shows that improvements of the protocol would make this application finally operational.

Oligometastatic disease represents a clinical and anatomical manifestation between localised and polymetastatic disease. In prostate cancer, as with other cancers, recognition of oligometastatic disease enables focal, metastasis-directed therapies. These therapies potentially shorten or postpone the use of systemic treatment and can delay further metastatic progression, thus increasing overall survival. Metastasis-directed therapies require imaging methods that definitively recognise oligometastatic disease to validate their efficacy and reliably monitor response, particularly so that morbidity associated with inappropriately treating disease subsequently recognised as polymetastatic can be avoided. In this Review, we assess imaging methods used to identify metastatic prostate cancer at first diagnosis, at biochemical recurrence, or at the castration-resistant stage. Standard imaging methods recommended by guidelines have insufficient diagnostic accuracy for reliably diagnosing oligometastatic disease. Modern imaging methods that use PET-CT with tumour-specific radiotracers (choline or prostate-specific membrane antigen ligand), and increasingly whole-body MRI with diffusion-weighted imaging, allow earlier and more precise identification of metastases. The European Organisation for Research and Treatment of Cancer (EORTC) Imaging Group suggests clinical algorithms to integrate modern imaging methods into the care pathway at the various stages of prostate cancer to identify oligometastatic disease. The EORTC proposes clinical trials that use modern imaging methods to evaluate the benefits of metastasis-directed therapies. ispartof: LANCET ONCOLOGY vol:19 issue:10 pages:E534-E545 ispartof: location:England status: published

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