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Congress news 25/04/2019

ECCMID 2019: new guideline on invasive fungal infections

A dedicated working group of the European Society of Clinical Microbiology and Infectious Diseases is developing a new guideline on invasive fungal infections, which could be of particular relevance for the ICU population. Despite the guideline still being in an early phase, prof. Cornelia Lass-Flörl, who is actively involved in this new guideline, was eager to share some details on the background, methodology, contents, usefulness and expected timelines of this guideline. This editorially independent interview has been financially sponsored by Gilead.

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E-learnings 04/03/2019

E-learning: Update on Renal cell carcinoma with prof. Camillo Porta

During a special Speaker Tour meeting prof. Camillo Porta visited the NKI-AVL to discuss challenges and best practices within the changing treatment landscape in (m)RCC. ‘With the development of new therapeutic systemic options for the treatment of mRCC, including immunotherapy, novel TKIs and combination treatment, we find ourselves standing at the verge of a new era of therapeutic possibilities. Our challenge is to find the best possible treatment algorithm for each (m)RCC patient.’ Topics that are discussed in this e-learning are: When are we ready for adjuvant therapy? What is the role of cytoreductive nephrectomy in mRCC? How to choose from the available options for first, second, and third line treatment? What may be the impact of immunotherapy and novel TKIs on the treatment algorithm? Chair and co-discussant: prof. J. Haanen, medical oncologist, NKI-AVL

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Meet the author 10/01/2019

Quarterly Focus on Hematology | CLL

Treating patients with chronic lymphocytic leukemia in an optimal fashion seems to become more complex every day. After all, our knowledge of the underlying biological complexity keeps on growing, creating new subgroups of patiets, and on top of that new potential drug combinations are constantly being developed and presented. In this program, a very international discussion panel will guide you through 2 highly relevant publications, helping you better understan the latest developments in the field of CLL. Guests Prof. Arnon Kater, MD, PhD Hematologist, Amsterdam UMC (AMC), The Netherlands Prof. Stephan Stilgenbauer, MD Hematologist, Saarland University, Homburg & Ulm University, Ulm, Germany Gert Jan Timmers, MD, PhD Hematologist, Amstelland Ziekenhuis, Amstelveen, The Netherlands Prof. Paolo Ghia, MD, PhD Internist, Università Vita-Salute San Raffaele, Milan, Italy Kostas Stamatopoulos, MD, PhD CERTH, Thessaloniki, Greece Publications to be discussed Fixed Duration of Venetoclax-Rituximab in Relapsed/Refractory Chronic Lymphocytic Leukemia Eradicates Minimal Residual Disease and Prolongs Survival: Post-Treatment Follow-Up of the MURANO Phase III Study - Kater et al., JCO, december 2018 Cytogenetic Complexity in Chronic Lymphocytic Leukemia: Definitions, Assiciations and Clinical Impact - Baliakas et al, Blood, January 2019 About our "Quarterly Focus" format Publications in peer-reviewed journals are a major source for keeping up with the latest developments in your field. However, you may not always have sufficient time to study (difficult) publications thoroughly and to determine the impact on your clinical practice. To support you, MEDtalks Hematology has developed a new program format: the Quarterly Focus. This innovative program brings an expert panel and authors of relevant, selected publications together to explain and discuss the new data.

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Congress news 14/11/2018

Euretina 2018: Important developments

This Euretina Highlight brings you news about: * developments after the presentation of the PLACE trial results . * How will eye diseases being diagnosed in the future? * The importance of OCT in CSC. * Neovaslularization and PCV in CSC.

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Congress news 11/12/2018

ASH 2018: ECHELON-2 trial

Prof. Lorenz Trümper about the ECHELON-2 trial.

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Congress news 21/10/2018

ESMO 2018 in depth: Resistance mechanisms to osimertinib in patients with NSCLC and a EGFR T790M mutation

Vassiliki Papadimitrakopoulou, MD, oncologist at the MD Anderson Cancer Centre in Texas, provides information on EGFR mutations associated with resistance to osimertinib in patients with NSCLC and a T790M mutation. These results are from an analysis of the AURA3 study.

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Meet the author 21/11/2018

Quarterly Focus on GU | Bladder Cancer

Publications in peer-reviewed journals are a major source for keeping up with the latest developments in your field. However, you may not always have sufficient time to study (difficult) publications thoroughly and to determine the impact on your clinical practice. To support you, MEDtalks Oncology has developed a new program format: the Quarterly Focus. This innovative program brings an expert panel and authors of relevant, selected publications together to explain and discuss the new data. In this third episode of the Quarterly Focus on Genitourinary Cancer, two pivotal, international publications on Bladder Cancer from the past few months will be clarified by one of the authors and will be thoroughly discussed by an expert panel including the author. The program will give you the possibility to gain more insight into the selected publications. The expert panel consist of: Michiel van der Heijden, MD, PhD - medical oncologist, Netherlands Cancer Institute, Amsterdam Prof. Fred Witjes, MD - urologist, Radboudumc, Nijmegen Sjoukje Oosting, MD, PhD - medical oncologist, UMCG, Groningen Program: Speaker: Prof. Dipen Parekh, MD – urologist at University of Miami Health System in Miami, USA Robot-assisted radical cystectomy versus open radical cystectomy in patients with bladder cancer (RAZOR): an open-label, randomised, phase 3, non-inferiority trial Lancet 391, 2018 Speaker: Michiel van der Heijden, MD, PhD, medical oncologist, Netherlands Cancer Institute, Amsterdam, The Netherlands Atezolizumab versus chemotherapy in patients with platinum-treated locally advanced or metastatic urothelial carcinoma (IMvigor211): a multicentre, open-label, phase 3 randomised controlled trial Lancet 391, 2017

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Congress news 15/10/2018

Multidisciplinary Immuno-Oncology Symposium: Maria Themeli

How can we make CAR T cell therapy more effective and safer? Adoptive cellular immunotherapy with chimeric antigen receptor engineered T (CAR-T) cells is currently achieving impressive clinical results in patients with hematologic malignancies. CARs are prototypic synthetic receptors wherein the extracellular input is a cell surface antigen and the intracellular output a composite T cell activating signal providing functional and metabolic cues to determine T cell fate. CAR therapy relies on engineering of T lymphocytes in order to redirect them to kill tumor cells and is the first paradigm of successful clinical use of cellular engineering with synthetic receptors. When targeting CD19, a cell surface molecule found in most leukemias and lymphomas, CAR T cells have produced remarkable clinical results, validating the synthetic biology approach to cancer immunotherapy and consecutively the potential for application to other hematological malignancies and solid tumors. To attain broader relevance, T cell engineering and CAR therapy in particular must achieve effective tumor targeting and tumor elimination with minimal or tolerable toxicity. While therapeutic efficacy of CAR-T cell therapy has been remarkable, a critical mechanism of disease escape includes lack of uniform expression of the target antigen within the clonal tumor populations or downregulation of antigen expression to evade effector cell mediated killing. CD19 CAR-T cell therapy often fails owing to CD19-negative relapse and first clinical trials of BCMA-CAR-T cells have already reported relapses of BCMA negative/low clonal variants. In addition, persistence of CAR-T cells has been inconsistent with some studies demonstrating a correlation between early extinguishing of the CAR-T cell population and the development of resistance. As such, strategies to broaden CAR-T cell mediated targeting of the tumor population and enhance their activation, expansion and durability is critical to develop this potential paradigm changing therapy. The broader applicability of CAR therapy is also impeded by safety concerns regarding the on-target/off-tumor effect of CAR T cells on normal tissues due to the lack of unique tumor-specific surface targets. Although the B-cell aplasia caused by CD19-CAR T cells is an easily manageable clinical situation, this is likely not the case for the majority of potential CAR targets. In addition, the experience of CD19-CAR T cell clinical trials brought into attention the cytokine release syndrome (CRS), mediated by large numbers of tumor-targeted activated T cells, as another safety issue of CAR therapy. Several strategies have already been proposed to regulate CAR T cell function. These include the use of suicide gene strategies, such as the inducible caspase-9 (iCasp9) enzyme, to terminate T cell activity, bispecific small molecules that transiently bridge antigen and CAR T cells, οr dimerizing agents that transiently link the antigen-binding and signaling domains of a CAR. The above studies allow remote temporal control of CAR T cell activity, but they do not address spatial control of antigen engagement and tumor selectivity. To the latter end, affinity tuning or engaging two antigens rather than one provide an interesting paradigm for achieving greater tumor selectivity.

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