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Background There is substantial variation in the incidence, likelihood of attempted resuscitation and outcomes from out-of-hospital cardiac arrest (OHCA) across Europe. A European, multi-centre study provides the opportunity to uncover differences throughout Europe and may help find explanations for these differences. Results may also have potential to support the development of quality benchmarking between European Emergency Medical Services (EMS). Methods/Design This prospective European study involves 27 different countries. It provides a common Utstein-based dataset, data collection tool and a common data collection period for all participants. Study research questions will address the following: OHCA incidence in different European regions; incidence of cardiopulmonary resuscitation (CPR); initial presenting rhythm in patients where bystanders or EMS start CPR or any other resuscitation intervention; proportion of patients with any return of spontaneous circulation (ROSC); patient status at the end of pre-hospital treatment i.e. ROSC at handover to hospital, ongoing CPR, dead; proportion of patients still alive 30 days after OHCA; proportion of patients discharged alive from hospital. All patients who suffered an OHCA during October 2014 and were attended and/or treated by an EMS and documented in one of the participating registries will be included in the study. Each National Coordinator is responsible for data collection and quality control in his/her country and will transfer unprocessed anonymised data via secure electronic transfer. Descriptive analysis will be performed at European, national and registry level. For endpoints like ROSC, admission or survival, multivariate logistic regression analysis will be performed. Discussion Documenting differences in epidemiology, treatment and outcome in out-of-hospital cardiac arrest throughout Europe is a first step in finding explanations for these differences. Study results might also support the development of quality benchmarking between Emergency Medical Services (EMS) which in turn will facilitate initiatives to improve OHCA outcome in Europe. Trial registration The EuReCa ONE Study is registered by ClinicalTrials.gov National Coordinator T02236819 ).

Inneholder sammendrag

Undifferentiated pleomorphic sarcoma (UPS) and myxofibrosarcoma (MFS) are genetically complex soft tissue sarcomas with distinct morphological features. Treatment typically involves surgery, often combined with neoadjuvant chemo- or radiotherapy. To better understand the immunobiology of these sarcomas and its associations with treatment response and prognosis, we performed transcriptomic and immunophenotypic profiling. RNA sequencing was performed on 13 UPS and 10 MFS, and immunological profiles were compared with soft tissue sarcoma data from The Cancer Genome Atlas ( n  = 206 including 44 UPS and 17 MFS). Immune contextures were further evaluated in 14 UPS and 15 MFS using imaging mass cytometry. Characterization of T cell and macrophage infiltration in tumors was further assessed in 23 UPS and 22 MFS through multispectral immunofluorescence and immunohistochemical analysis. UPS and MFS demonstrated immunogenic features compared to other soft tissue sarcomas, with subsets of UPS and MFS demonstrating high T cell infiltration, while UPS demonstrated a higher infiltration by myeloid cells as compared to MFS. Prognostically, T cells and CD68 + CD163 + macrophages were associated with metastasis-free survival in UPS but not in MFS. Notably, in UPS, neoadjuvant radiotherapy appeared to induce cytotoxic T cell infiltration and depletion of myeloid cells, whereas these effects were not observed in MFS. These findings highlight important differences in the immunobiology of UPS and MFS with therapeutic and prognostic implications. These differences should be taken into account given the growing availability of immunotherapeutic options for treating patients with soft tissue sarcomas.

BackgroundChordomas are rare cancers from the axial skeleton which present a challenging clinical management with limited treatment options due to their anatomical location. In recent years, a few clinical trials demonstrated that chordomas can respond to immunotherapy. However, an in-depth portrayal of chordoma immunity and its association with clinical parameters is still lacking.MethodsWe present a comprehensive characterization of immunological features of 76 chordomas through application of a multimodal approach. Transcriptomic profiling of 20 chordomas was performed to inform on the activity of immune-related genes through the immunologic constant of rejection (ICR) signature. Multidimensional immunophenotyping through imaging mass cytometry was applied to provide insights in the different immune contextures of 32 chordomas. T cell infiltration was further evaluated in all 76 patients by means of multispectral immunofluorescence and then associated with clinical parameters through univariate and multivariate Cox proportional hazard models as well as Kaplan-Meier estimates. Moreover, distinct expression patterns of human leukocyte antigen (HLA) class I were assessed by immunohistochemical staining in all 76 patients. Finally, clonal enrichment of the T cell receptor (TCR) was sought through profiling of the variable region of TCRB locus of 24 patients.ResultsChordomas generally presented an immune “hot” microenvironment in comparison to other sarcomas, as indicated by the ICR transcriptional signature. We identified two distinct groups of chordomas based on T cell infiltration which were independent from clinical parameters. The highly infiltrated group was further characterized by high dendritic cell infiltration and the presence of multicellular immune aggregates in tumors, whereas low T cell infiltration was associated with lower overall cell densities of immune and stromal cells. Interestingly, patients with higher T cell infiltration displayed a more pronounced clonal enrichment of the TCR repertoire compared with those with low T cell counts. Furthermore, we observed that the majority of chordomas maintained HLA class I expression.ConclusionOur findings shed light on the natural immunity against chordomas through the identification of distinct immune contextures. Understanding their immune landscape could guide the development and application of immunotherapies in a tailored manner, ultimately leading to an improved clinical outcome for patients with chordoma.