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The Inter-Ewing-1 trial is currently implemented in several countries with two randomized questions regarding radiotherapy: (1) dose escalation in definitive radiotherapy and (2) dose optimisation in post-operative radiotherapy. A prospective radiotherapy quality assurance (Quartet RTQA) is an essential part of the trial. Before opening the trial, the French Radiotherapy Group Society organised a delineation workshop to train the participants and evaluate the benefit on the delineation quality. Before the workshop, all the participants were asked to delineate the target volumes of a benchmark case as recommended in the guidelines. During the workshop, the case and delineations were reviewed. A second delineation round was asked after the workshop. Quantitative volume (Dice coefficient (DC)), dimension (Hausdorff distance (HD)), concordance and discordance index comparisons with the reference contours were made for GTVp_Pre, GTVp_Post, CTVp_Pre and CTVp_Post, before and after workshop. Eight centers provided both pre- and post-workshop delineations. Before the workshop, the median [Q25; Q75] DC for CTVp_Pre and CTVp_Post were 0.670 [0.629; 0.723] and 0.552 [0.428. 0.579] respectively versus 0.673 [0.656; 0.752] (Paired T-Test Welch, p=0.06) and 0.686 [0.574. 0.756] (Paired T-Test Welch, p=0.015) after the training. Before the workshop, the median [Q25; Q75] HD for CTVp_Pre and CTVp_Post were 24.4 [19.0; 27.5] and 33.5 [27.1; 49.0] respectively versus 24.7 [19.8; 27.5] (Wilcoxon Signed Rank Test, p=0,830) and 22.8 [20.9; 35.6] (Wilcoxon Signed Rank Test, p=0.110) after the training. The results were similar for the GTVp_Pre and GTVp_Post and will be detailed at the congress. The delineation of target volumes in ES remains difficult despite guidelines. These results confirm that training makes it possible to improve practices but this remains insufficient. This result highlights the importance of developing prospective RTQA to improve the quality of treatments. [ABSTRACT FROM AUTHOR]

Background: Knowledge about the precise effects of radiotherapy on hypothalamo-pituitary functions is limited. Reduction of side effects is a major goal of advanced radiotherapy modalities. We assessed strategies for monitoring and replacement of hormone deficiencies in irradiated patients., Methods: A search strategy was systematically conducted on PubMed ® . Additional articles were retrieved to describe endocrine mechanisms., Results: 45 studies were evaluated from 2000 to 2022. They were predominantly retrospective and highly heterogeneous concerning patient numbers, tumor types, radiotherapy technique and follow-up. Endocrine deficiencies occurred in about 40% of patients within a median follow-up of 5.6 years without a clear difference between radiotherapy modalities. Somatotropic and thyrotropic axes were, respectively, the most and least radiosensitive., Conclusions: Current pituitary gland dose constraints may underestimate radiation-induced endocrine deficiencies, thus impairing quality of life. Little difference might be expected between radiation techniques for PG tumors. For non-PG tumors, dose constraints should be applied more systematically., Competing Interests: The authors declare no conflict of interest. The funder had no role in the study's design; in the collection, analysis, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

Blood flow within the vasculature of the retina has been found to influence the progression of diabetic retinopathy. In this research cell resolved blood flow simulations are used to study the pulsatile flow of whole blood through a segmented retinal microaneurysm. Images were collected using adaptive optics optical coherence tomography of the retina of a patient with diabetic retinopathy, and a sidewall (sacciform) microaneurysm was segmented from the volumetric data. The original microaneurysm neck width was varied to produce two additional aneurysm geometries in order to probe the influence of neck width on the transport of red blood cells and platelets into the aneurysm. Red blood cell membrane stiffness was also increased to resolve the impact of rigid red blood cells, as a result of diabetes, in blood flow. Wall shear stress and wall shear stress gradients were calculated throughout the aneurysm domains, and the quantification of the influence of the red blood cells is presented. Average wall shear stress and wall shear stress gradients increased due to the increase of red blood cell membrane stiffness. Stiffened red blood cells were also found to induce higher local wall shear stress and wall shear stress gradients as they passed through the leading and draining parental vessels. Stiffened red blood cells were found to penetrate the aneurysm sac more than healthy red blood cells, as well as decreasing the margination of platelets to the vessel walls of the parental vessel, which caused a decrease in platelet penetration into the aneurysm sac.

Purpose: Proton therapy (PT) can be a good option to achieve tumor control while reducing the probability of radiation induced toxicities compared to X-ray-based radiotherapy. However, there are still uncertainties about the effects of PT on the organs in direct contact with the irradiated volume. The aim of this prospective series was to report 6-month follow-up of clinical and functional optic neuropathy rates of patients treated by proton therapy using a standardized comprehensive optic examination., Methods and Materials: Standardized ophthalmological examinations were performed to analyze subclinical anomalies in a systematic way before treatment and 6 months after the end of proton therapy with: Automatic visual field, Visual evoked potential (VEP) and optic coherence of tomography (OCT)., Results: From October 2018 to July 2020 we analyzed 81 eyes. No significant differences were found in the analysis of the clinical examination of visual functions by the radiation oncologist. However, considering VEP, the impairment was statistically significant for both fibers explored at 30'angle (p:0.007) and 60'angle (p <0.001). In patients with toxicity, the distance of the target volume from the optical pathways was more important with a p-value for 30'VEP at 0.035 and for 60'VEP at 0.039., Conclusions: These results confirm uncertainties concerning relative biological effectiveness of proton therapy, linear energy transfer appears to be more inhomogeneous especially in areas close to the target volumes. The follow-up of patients after proton therapy is not an easy process to set up but it is necessary to improve our knowledges about the biological effects of proton therapy in real life. Our study which will continue during the coming years, suggests that follow-up with in-depth examinations such as VEP as a biomarker could improve the detection of early abnormalities., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Lecornu, Lesueur, Salleron, Balosso, Stefan, Kao, Plouhinec, Vela, Dutheil, Bouter, Marty, Thariat and Quintyn.)

Introduction: Microinvasive in situ ductal carcinomas of the breast are rare and of good prognosis. They are grouped with early stage invasive carcinomas in the TNM 2017 classification. This study assessed practitioners' treatment decisions and their justifications in comparison to the literature., Materials and Methods: Three clinical cases were evaluated by anonymous forms regarding sentinel node decisions, tumour bed boost irradiation and hormone therapy., Results: Sentinel lymph node was performed by 93.1%, 100% and 44.4% of the practitioners respectively. Radiation boost was a treatment option chosen by 62.1% and 61.1% of practitioners in both clinical cases. Hormone therapy was advocated for 65.5%, 94.7% and 50.0% patients depending on the clinical case., Conclusion: The therapeutic attitude proposed in microinvasive breast carcinomas was heterogeneous in this study, reflecting the absence of specific recommendations. In view of the existing literature, it is not currently possible to propose recommendations for these three therapeutic options. Prospective cohorts and meta-analyses of the microinvasive subgroup could provide answers., (Copyright © 2019 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)

In RNA-World scenarios for the origin of life, replication is catalyzed by polymerase ribozymes. Replicating RNA systems are subject to invasion by non-functional parasitic strands. It is well-known that there are two ways to avoid the destruction of the system by parasites: spatial clustering in models with limited diffusion, or group selection in protocells. Here, we compare computational models of replication in spatial models and protocells as closely as possible in order to determine the relative importance of these mechanisms in the RNA World. For the survival of the polymerases, the replication rate must be greater than a minimum threshold value, k min , and the mutation rate in replication must be less than a maximum value, M max , which is known as the error threshold. For the protocell models, we find that k min is substantially lower and M max is substantially higher than for the equivalent spatial models; thus, the survival of polymerases is much easier in protocells than on surfaces. The results depend on the maximum number of strands permitted in one protocell or one lattice site in the spatial model, and on whether replication is limited by the supply of monomers or the population size of protocells. The substantial advantages that are seen in the protocell models relative to the spatial models are robust to changing these details. Thus, cooperative polymerases with limited accuracy would have found it much easier to operate inside lipid compartments, and this suggests that protocells may have been a very early step in the development of life. We consider cases where parasites have an equal replication rate to polymerases, and cases where parasites multiply twice as fast as polymerases. The advantage of protocell models over spatial models is increased when the parasites multiply faster., Competing Interests: The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, and in the decision to publish the results.