Integration of Translational Research in the European Organization for Research and Treatment of Cancer Research (EORTC) Clinical Trial Cooperative Group Mechanisms

The landscape for cancer research is profoundly different today from that only one decade ago. Basic science is moving rapidly and biotechnological revolutions in molecular targeting and immunology have completely modified the opportunities and concepts for cancer treatment. In contrast to the recent past where cytotoxic molecules were screened in the laboratory and then tested in early clinical studies with toxicity as endpoint instead of the often poorly defined mechanism for its potential anti-tumor effect, we now have entered the age of molecular therapeutics, rationally designed to target "strategic" checkpoints that underlie the malignant phenotype. Translational research in early clinical trials (Phase I and II) is an integral aspect of the development of the new generation of cancer drugs as it is necessary to implement radically different early phase clinical trial design and to validate new biological end-points if the full potential of these new agents is to be realized. The "proof of principle with mechanistic analysis" strategy will allow optimisation of therapy from the beginning, and provide important feedback to pre-clinical drug developers. Translational research is also essential in late (phase III) clinical trials in defining different patient populations that may benefit to differing degrees from new treatments, and thus provide further insight and refine clinical practice in a more and more patient-tailored approach. In this editorial we will discuss the integration of Translational Research in the Organization for Research and Treatment of Cancer (EORTC)

PASSIVE COMPONENT EMBEDDING IN PRINTED CIRCUIT BOARDS FOR SPACE APPLICATIONS

The PCESA project was started in 2014 to investigate the suitability of embedding passive components in printed circuit boards for space applications. After compiling an overview of available technologies for component embedding, a test board was designed and manufactured to evaluate the performance and reliability of direct embedding of passive components in printed circuit boards. In parallel, an existing space PCB was redesigned to use embedded components and act as a functional demonstrator for the project. The main test results, result analysis and recommendations for future use are detailed in this presentation

Diversification of Rice Yellow Mottle Virus and Related Viruses Spans the History of Agriculture from the Neolithic to the Present

The mechanisms of evolution of plant viruses are being unraveled, yet the timescale of their evolution remains an enigma. To address this critical issue, the divergence time of plant viruses at the intra- and inter-specific levels was assessed. The time of the most recent common ancestor (TMRCA) of Rice yellow mottle virus (RYMV; genus Sobemovirus) was calculated by a Bayesian coalescent analysis of the coat protein sequences of 253 isolates collected between 1966 and 2006 from all over Africa. It is inferred that RYMV diversified approximately 200 years ago in Africa, i.e., centuries after rice was domesticated or introduced, and decades before epidemics were reported. The divergence time of sobemoviruses and viruses of related genera was subsequently assessed using the age of RYMV under a relaxed molecular clock for calibration. The divergence time between sobemoviruses and related viruses was estimated to be approximately 9,000 years, that between sobemoviruses and poleroviruses approximately 5,000 years, and that among sobemoviruses approximately 3,000 years. The TMRCA of closely related pairs of sobemoviruses, poleroviruses, and luteoviruses was approximately 500 years, which is a measure of the time associated with plant virus speciation. It is concluded that the diversification of RYMV and related viruses has spanned the history of agriculture, from the Neolithic age to the present

Archives et création : nouvelles perspectives sur l'archivistique. Cahier 1

Ce cahier de recherche fait état des travaux menés au cours de la première étape (2013-2014) du projet « Archives et création : nouvelles perspectives sur l’archivistique ». Il comprend les textes suivants : Yvon Lemay et Anne Klein, « Introduction », p. 4-6; Yvon Lemay, « Archives et création : nouvelles perspectives sur l’archivistique », p. 7-19; Anne-Marie Lacombe, « Exploitation des archives à des fins de création : un aperçu de la littérature », p. 20-59; Simon Côté-Lapointe, « Archives sonores et création : une pratique à la croisée des chemins », p. 60-83; Hélène Brousseau, « Fibres, archives et société », p. 84-104; Annie Lecompte-Chauvin, « Comment les archives entrent dans nos vies par le biais de la littérature », p. 105-120; Aude Bertrand, « Valeurs, usages et usagers des archives », p. 121-150; Laure Guitard, « Indexation, émotions, archives », p. 151-168; Anne Klein, Denis Lessard et Anne-Marie Lacombe, « Archives et mise en archives dans le champ culturel. Synthèse du colloque « Archives et création, regards croisés : tournant archivistique, courant artistique », p. 169-178. De plus, dans le but de situer le projet dans un contexte plus large, le cahier inclut une bibliographie des travaux effectués sur les archives et la création depuis 2007, p. 179-182.Le projet de recherche est financé par le Conseil de recherches en sciences humaines du Canada (Programme Savoir, 2013-2016)

The European Organisation for Research and Treatment of Cancer, State of Science in radiation oncology and priorities for clinical trials meeting report

Background: New technologies and techniques in radiation oncology and imaging offer opportunities to enhance the benefit of loco-regional treatments, expand treatment to new patient populations such as those with oligometastatic disease and decrease normal tissue toxicity. Furthermore, novel agents have become available which may be combined with radiation therapy, and identification of radiation-related biomarkers can be studied to refine treatment prescriptions. Finally, the use of artificial intelligence (AI) capabilities may also improve treatment quality assurance or the ease with which radiation dosing is prescribed. All of these potential advances present both opportunities and challenges for academic clinical researchers. Methods: Recently, the European Organisation for Research and Treatment of Cancer addressed these topics in a meeting of multiple stakeholders from Europe and North America. The following five themes radiobiology-based biomarkers, new technologies - particularly proton beam therapy, combination systemic and radiation therapy, management of oligometastatic disease and AI opportunities in radiation oncology were discussed in a State of Science format to define key controversies, unanswered questions and propose clinical trial priorities for development. Conclusions: Priorities for clinical trials implementing new science and technologies have been defined. Solutions to integrate the multidimensional complexity of data have been explored. New types of platforms and partnerships can support innovative approaches for clinical research in radiation oncology. (C) 2020 The Authors. Published by Elsevier Ltd

MGMT methylation analysis of glioblastoma on the Infinium methylation BeadChip identifies two distinct CpG regions associated with gene silencing and outcome, yielding a prediction model for comparisons across datasets, tumor grades, and CIMP-status

The methylation status of the O6-methylguanine-DNA methyltransferase (MGMT) gene is an important predictive biomarker for benefit from alkylating agent therapy in glioblastoma. Recent studies in anaplastic glioma suggest a prognostic value for MGMT methylation. Investigation of pathogenetic and epigenetic features of this intriguingly distinct behavior requires accurate MGMT classification to assess high throughput molecular databases. Promoter methylation-mediated gene silencing is strongly dependent on the location of the methylated CpGs, complicating classification. Using the HumanMethylation450 (HM-450K) BeadChip interrogating 176 CpGs annotated for the MGMT gene, with 14 located in the promoter, two distinct regions in the CpG island of the promoter were identified with high importance for gene silencing and outcome prediction. A logistic regression model (MGMT-STP27) comprising probes cg1243587 and cg12981137 provided good classification properties and prognostic value (kappa=0.85; log-rank p<0.001) using a training-set of 63 glioblastomas from homogenously treated patients, for whom MGMT methylation was previously shown to be predictive for outcome based on classification by methylation-specific PCR. MGMT-STP27 was successfully validated in an independent cohort of chemo-radiotherapy-treated glioblastoma patients (n=50; kappa=0.88; outcome, log-rank p<0.001). Lower prevalence of MGMT methylation among CpG island methylator phenotype (CIMP) positive tumors was found in glioblastomas from The Cancer Genome Atlas than in low grade and anaplastic glioma cohorts, while in CIMP-negative gliomas MGMT was classified as methylated in approximately 50% regardless of tumor grade. The proposed MGMT-STP27 prediction model allows mining of datasets derived on the HM-450K or HM-27K BeadChip to explore effects of distinct epigenetic context of MGMT methylation suspected to modulate treatment resistance in different tumor type

Actes du 12e Colloque annuel des étudiant-e-s de cycles supérieurs du CRISES

La 12e édition du Colloque annuel des étudiant-e-s de cycles supérieurs du CRISES s’est tenue les 25 et 26 mars 2010 à l’Université Laval. Trente et une (31) communications y ont été présentées sur des thèmes aussi diversifiés que le Vieillissement au travail, les Grappes industrielles, l’Immigration, les Défis de la gouvernance, la Gestion des ressources et les solidarités locales, incluant un atelier spécial sur les Avancées et les limites de l’innovation sociale. Les textes qui nous sont parvenus avant la date limite du 18 mars afin d’être soumis à un processus d’évaluation, ainsi que respectivement le texte et/ou les diapositives PowerPoint des conférenciers d’ouverture et de clôture sont contenus dans ces Actes. Nous tenons ici à remercier chaleureusement nos collègues du comité organisateur : Kamel Béji, Manon Boulianne et Frédéric Hanin et notre assistante : Carole-Anne Gauthier."VIEILLISSEMENT AU TRAVAIL" "APPROCHES DE LA GOUVERNANCE" "GRAPPES INDUSTRIELLES ET DÉVELOPPEMENT LOCAL" "GESTION DES RESSOURCES" "SOLIDARITÉS LOCALES" "IMMIGRATION ET IDENTITÉ" "L'INNOVATION SOCIALE: AVANCÉES ET LIMITES

Defining the role of real-world data in cancer clinical research:The position of the European Organisation for Research and Treatment of Cancer

The emergence of the precision medicine paradigm in oncology has led to increasing interest in the integration of real-world data (RWD) into cancer clinical research. As sources of real-world evidence (RWE), such data could potentially help address the uncertainties that surround the adoption of novel anticancer therapies into the clinic following their investigation in clinical trials. At present, RWE-generating studies which investigate antitumour interventions seem to primarily focus on collecting and analysing observational RWD, typically forgoing the use of randomisation despite its methodological benefits. This is appropriate in situations where randomised controlled trials (RCTs) are not feasible and non-randomised RWD analyses can offer valuable insights. Nevertheless, depending on how they are designed, RCTs have the potential to produce strong and actionable RWE themselves. The choice of which methodology to employ for RWD studies should be guided by the nature of the research question they are intended to answer. Here, we attempt to define some of the questions that do not necessarily require the conduct of RCTs. Moreover, we outline the strategy of the European Organisation for Research and Treatment of Cancer (EORTC) to contribute to the generation of robust and high-quality RWE by prioritising the execution of pragmatic trials and studies set up according to the trials-within-cohorts approach. If treatment allocation cannot be left up to random chance due to practical or ethical concerns, the EORTC will consider undertaking observational RWD research based on the target trial principle. New EORTC-sponsored RCTs may also feature concurrent prospective cohorts composed of off-trial patients

European Organization for Research and Treatment of Cancer (EORTC) open label phase II study on glufosfamide administered as a 60-minute infusion every 3 weeks in recurrent glioblastoma multiforme

BACKGROUND: Glufosfamide is a new alkylating agent in which the active metabolite of isophosphoramide mustard is covalently linked to beta-D-glucose to target the glucose transporter system and increase intracellular uptake in tumor cells. We investigated this drug in a multicenter prospective phase II trial in recurrent glioblastoma multiforme (GBM). PATIENTS AND METHODS: Eligible patients had recurrent GBM following surgery, radiotherapy and no more than one prior line of chemotherapy. Patients were treated with glufosfamide 5000 mg/m(2) administered as a 1-h intravenous infusion. Treatment success was defined as patients with either an objective response according to Macdonald's criteria or 6 months progression-free survival. Toxicity was assessed with the Common Toxicity Criteria (CTC) version 2.0. RESULTS: Thirty-one eligible patients were included. Toxicity was modest, the main clinically relevant toxicities being leukopenia (CTC grade >3 in five patients) and hepatotoxicity (in three patients). No responses were observed; one patient (3%; 95% confidence interval 0 to 17%) was free from progression at 6 months. Pharmacokinetic analysis showed a 15% decrease in area under the curve and glufosfamide clearance in patients treated with enzyme-inducing antiepileptic drugs, but no effect of these drugs on maximum concentration and plasma half-life. CONCLUSION: Glufosfamide did not show significant clinical antitumor activity in patients with recurrent GBM