
An European Platform for Translational Research in Myelodysplastic Syndromes
Myelodysplastic SyndromesRationale Myelodysplastic syndromes (MDS) are rare cancers with unmet medical needs. Study of MDS has been rapidly transformed by genome characterization. The investigators hypothesize that comprehensive analyses of large patient population will allow to correctly estimate the effect of each mutation on clinical outcomes, and that niche factors and immune dysfunctions may influence the development of MDS, clonal evolution and response to treatments Aims 1- Investigate gene mutations, niche factors and immune dysfunctions influencing the development of MDS, and define biomarkers for early identification of individuals at risk; 2- Develop prognostic models for MDS patients through integration of comprehensive genomic/clinical information; 3- Define biomarkers to better stratify the individual probability of response to specific treatments Methods EuroBloodNet, the European Reference Network in rare hematological diseases, will provide a basis for research activities. Study of genomic features of clonal dominance in elderly subjects enrolled in large population-based studies and description of the dynamics of clonal establishment and evolution; study of bone marrow microenvironment to identify immune dysfunctions influencing MDS development. Development of inclusive statistical models to accurately predict clinical outcome at individual level, based on large MDS populations with comprehensive genomic/clinical data. Finally, analysis of mutational screening and immune profiles from patients enrolled in prospective trials, to provide evidence on genetic/immunologic profiles associated with probability of response to specific compounds Expected results To characterize how clonal hematopoiesis relates to the induction of MDS clinical phenotype, and to test the utility of gene sequencing to detect subjects at risk of developing MDS. To define effective prognostic systems and biomarkers to stratify the individual probability of response to treatment

Child's Study of the Impact of PF Lesion on Motor Skills, Language, Cognitive Functioning and Social...
MedulloblastomaChildhood3 moreOne of the major complications of posterior fossa surgery is Posterior Fossa Syndrome (PFS). This syndrome is due to a possible complication of surgical excision of a tumor of the cerebellum (4th ventricle) and is characterized by transient postoperative mutism, dysarthria, behavioral, and affective disorders, as well as motor disorders. PFS is thought to be related to axonal lesions. The long-term consequences on the cognitive and psychosocial sphere of PFS have been widely documented. On the other hand, the literature concerning the consequences of this syndrome on language is much restricted. Beyond the language, the role of cerebellum would be central in cognition, some authors even comparing it to a great "conductor" who would underlie the learning of most motor and cognitive automatisms.

Concordance Between 2 Means of Temperature Measure in Neutropenic Patients Hospitalized in Intensive...
Haematological MalignancyConnected medicine "2.0" is a major challenge that will lead in the near future to profound changes in medical practices. Our study is part of this technological transformation, which is already taking the form of multiple devices available to practitioners: connected pill dispensers, integrated monitoring and surveillance systems (telemedicine), connected sensors, etc. However, a symptom as crucial and simple as body temperature has not been measured by real-time enteric capsule in a context of neutropenia. We therefore wish to study the concordance between the peripheral (tympanic) temperature and that measured by a capsule ingested in a cohort of patients hospitalized in the USIH. If the measurements are clinically reliable and truly allow anticipation of antimicrobial treatments, a medico-economic evaluation will be proposed between the two options in the context of USIH before its possible generalization.

Immune Monitoring in Metastatic Melanoma
Metastatic MelanomaThe mean survival time in the advanced tumor stage in the presence of distant metastases in malignant melanoma was less than 9 months until a few years ago. Intensive research efforts have led to the development of promising new therapeutic strategies and their clinical application. These include on the one hand mutation-specific inhibitors of important for cell division serine-threonine kinase BRAF such as vemurafenib, dabrafenib and encorafenib and inhibitors of the downstream target protein, the mitogen-activated protein kinase kinase (MEK), such as trametinib, binimetinib and cobimetinib. The group of immunotherapeutics is a second new class of drugs, in which great hope for the treatment of metastatic melanoma is placed. Antibody-mediated blockage of surface molecules expressed on immune cells, referred to as immune checkpoints, results in activation of the immune system. As a result, an anti-tumor immune response is triggered, which has led to considerable therapeutic success in metastatic melanoma. To date, three checkpoint inhibitors have been approved for the treatment of metastatic melanoma. Ipilimumab is an antibody that binds cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4); Pembrolizumab and nivolumab cause immune stimulation by binding the Programmed Death Receptor (PD1). However, the impact of the therapy on the immune system as a whole is largely unknown. A comprehensive understanding of these effects is crucial to be able to further develop the therapy and to evaluate useful combination therapies with other immunomodulatory agents. Within the framework of this project changes of the immune response under a systemic therapy of the malignant melanoma are to be characterized. The material for the analysis comes from blood samples collected during routine patient check-ups. The aim of the analyzes is to precisely characterize the effects of the different therapeutics on the function of the immune system. In particular, the study will investigate whether certain therapeutic agents can weaken or activate the immune system and thus, in addition to the direct effect on the tumor cells, mediate indirect therapeutic effects via immune modulation. In the long term, the investigators want to use the knowledge gained to further improve the already existing therapeutic strategies of malignant melanoma by additional modulation of the immune system.

Influence of Minimally Invasive Thymectomy on the Subsequent Clinical Course of Myasthenia Gravis...
Myasthenia GravisThe aim of this study is to investigate whether minimally invasive thymectomy achieves comparable efficacy and safety results compared to open thymectomy in patients with myasthenia gravis. The planned investigation is a multicenter observational study based on retrospective (present patient data) and prospective data (questionable outcome data). Primary hypothesis: Minimally invasive thymectomy is not inferior to open thymectomy in terms of efficacy and safety (non-inferiority study).

The Gene Profiles of Primary and Heterogeneous Metastases of Colorectal Cancer
Metastatic Colorectal CancerThe incidence and mortality of colorectal cancer in China's cancer disease spectrum is on the rise, and it is a common malignant tumor that harms the health of Chinese residents.In patients with synchronous metastatic colorectal cancer, RAS status is highly consistent in primary focus and metastasis, so NCCN guidelines recommend RAS testing of primary or metastatic tissue is feasible .However, there are also some reports that the difference of RAS status between primary and metastatic lesions was up to 22%.In additiont,there are few studies on whether the gene profile of the metastatic lesion is the same as that of the primary lesion in patients with postoperative heterogeneous metastasis in patients with stage III colorectal cancer.

Microbiome Analysis in esoPhageal, PancreatIc and Colorectal CaNcer Patients Undergoing Gastrointestinal...
Gastrointestinal CancerColorectal Cancer9 moreThe MA-PPING is a multicenter prospective observational study that includes patients undergoing surgery for gastrointestinal cancer. The study aims to map the oral and gut microbiome of patients diagnosed with pancreatic, esophageal or colorectal cancer during their surgical patient journey from the moment of diagnosis until full recovery (three months after surgery).

Novel Multimodality Imaging for Navigation in Skull Base Surgery
Vestibular SchwannomaSuccessful neurosurgery to remove tumours around the base of the skull, such as a vestibular schwannoma, depends on achieving maximal tumour removal whilst preserving crucial neurological functions such as facial movement, and maintaining quality of life. Current techniques to direct surgery are based on the surgeon's expertise and knowledge of the relevant anatomy, supplemented by the use of electrical recording and stimulation of the facial nerve. However, it is often very difficult to visualise the nerve during surgery and facial nerve paralysis remains a potentially devastating complication of surgery. Advanced imaging methods may be used to visualise important neural connections in the brain and computer-assisted processing can generate tumour maps from MRI and ultrasound scans. This study aims to utilise these technologies to develop a 3D navigation system for skull base surgery. This study aims to develop a system that will combine MRI and intraoperative ultrasound imaging to enhance the surgeon's view of the tumour, facial nerve and other surrounding critical structures during surgery. This information will be made available in the navigation system in the operating room so that operations are more precise resulting in better tumour removal rates and fewer complications. The system will be assessed during the treatment of 20 patients with vestibular schwannoma at the National Hospital for Neurology and Neurosurgery. This feasibility study will validate the different parts of the new system and help us design a future research study to determine its effectiveness in improving patient care. This project will result in safer and more effective neurosurgery, with potential consequent financial savings for the NHS and the UK, in addition to marked improvements in the quality of life of patients and reduced dependency upon others.

Efficacy and Safety of Use of Platinum Based Doublet Chemotherapy Plus Antiangiogenesis and Immune...
Advanced Non-squamous Non-small Cell Lung CancerThe purpose of this study is to explore the efficacy and safety of Use of Platinum Based Doublet Chemotherapy Plus Antiangiogenesis and Immune Checkpoint Inhibitors in Patients With Advanced Non-squamous Non-small Cell Lung Cancer

Frailty In Thoracic Surgery for Esophageal Cancer
FrailtyBackground: In Demark we se an increasing life expectancy and an increasing incidence of esophageal cancer and gastroesophageal junction (c.esophagus), with an average age of 65 years at diagnosis time. The consequence of this is an increased number of patients in need of esophageal resection. Esophageal cancer is currently treated with chemotherapy, radiotherapy and, whenever possible, esophageal resection. This multimodal treatment has increased survival, but is also associated with significant morbidity, mortality and adverse postoperative quality of life. At present, there is no standardized risk assessment for patients with c.esophagus who have to undergo esophageal resection. This study evaluates the preoperative risk using the frailty score system, CAF (comprehensive assessment of frailty) score, which identify patients being frail or not based on an assessment of the patient's physical condition. Purpose: Investigate how many patients that are frail undergoing esophageal resection. With the assumptions that CAF score can identify frail patients and that frail patients, have an increased risk of postoperative complications. With CAF score, we believe to become better of predicting complications following esophageal resection. Method: Prospective observational study of patients with c.esophagus undergoing esophageal resection. Plan to include 60 patients over one year period. The patients are deemed frail or not with the use of CAF score, which consist of various smaller physical test and questions. Postoperativley a follow-up after 30-days, six month and 12 month. At follow-up times, data are collected on the somatic readmissions / diagnoses and vital status. Afterwards we compare complications, mortality and quality of life in frail versus non-frail patients. Side effects, risks and disadvantages: At present, there is no standardized risk assessment used for preoperative risk assessment for patients with c.esophagus undergoing esophageal resection. The introduction of CAF score, will not expose patients to a risk or side effect, since the course or treatment does not change. Economy: We consider the study to be economically justified, since we hypothesize that this would lead to fewer readmissions, days of intensive care and shorter hospitalization. Acquisition: The patients will be 60 years or older and are undergoing esophageal resection. They will receive verbal- and written information preoperatively. At the first appearance they meet our project assistant who will answer any questions. Subsequently, the patients will be asked to sign a consent form. Publication of test results / research ethics statement: The knowledge and results gained through the research will provide essential scientific information of significans for the future course and treatment of patients undergoing esophageal resection in terms of number of hospital days, intensive days and readmissions.