Caunes Minervois, France

REAL-WORLD DURVALUMAB IN EXTENSIVE-STAGE SMALL CELL LUNG CANCER

Evaluation of the Effect of Nirsevimab on Hospitalizations Due to RSV Infection in Infants Under One Year of Age.

EvoLution of Neoadjuvant TreatMent in 'Triple-negative' or 'HER-2-positive' Breast Cancer Diagnosed in the EaRly Phase

The Epithelioid Hemangioendothelioma Registry of the European Reference Network on Rare Adult Solid Cancers (EURACAN)

Given its incidence of 0.038/100 000/year, EHE is an ultra-rare sarcoma, with distinctive, well-defined pathological, molecular and clinical features. It belongs to the group of vascular sarcomas and is characterized by WWTR1-CAMTA1 (90%) or YAP1-TFE3 (10%) gene fusions, which represents today a hallmark for diagnosis. EHE potentially arises everywhere in the body and shows a high tendency toward metastatic spread, especially in the lung, liver and bone. The onset is characterized by different presentations, including a unifocal lesion (usually in the soft tissues), locoregional metastases (multiple lesions in a single organ or in a single anatomic compartment) and systemic metastases (multi-organ involvement). Also, the biological behavior of the disease is unique in sarcomas and variable, with spontaneous regressions reported, patients with untreated stable disease overtime, slowly progressive variants and highly aggressive and rapidly fatal cases. Today, the relative incidence of the different presentations is undefined, the natural history of the different subtypes is poorly understood, and reliable clinical or biological prognostic factors are lacking. Retrospective data suggest that patients with EHE presenting or developing during their course serosal involvement and / or effusion, systemic associated symptoms and anemia have a worse prognosis, but a prospective validation of this observation is lacking. In terms of management, surgery is the treatment of choice for localized disease, with an excellent outcome (expected cure rate of 70-80%) and no proven role for local or systemic adjuvant therapies. For patients with advanced, asymptomatic disease, active surveillance is often the upfront choice in order to minimize the risk of overtreatment. Systemic therapies are usually considered for patients with progressive or symptomatic disease, although a standard medical approach is currently not established. Unfortunately, conventional chemotherapy, including anthracycline-based regimens widely regarded as the mainstay in the treatment of advanced soft tissue sarcomas, showed marginal activity in EHE. The use of potentially active compounds, such as m-TOR inhibitors which proved the highest activity in EHE and could therefore represent the preferred option, is limited by regulatory constraints as they are not currently labeled in Europe for this indication. Given the degree of uncertainty on EHE management, a global consensus meeting was organized in December 2020 under the umbrella of the European Society for Medical Oncology (ESMO) involving > 80 multidisciplinary, worldwide experts together with a patient representative, with the aim of defining, by consensus, evidence-based best practices for the optimal approach to primary and metastatic EHE. Since the number of patients is inherently low at the hospital level, the only way to increase knowledge about EHE and improve the diagnosis, treatment, and prognosis of this complex and heterogeneous disease is to harmonize and combine real-world data from sarcoma expert centres by leveraging a wide, international, joined effort. In this context, a unique opportunity is provided by the European Reference Networks (ERNs), virtual network established by the EU commission aiming to tackle rare conditions, including cancers. Among the three ERNs dedicated to cancer, EURACAN (https://euracan.eu) is the one focusing on the 10 families of rare adult solid cancers (RACs), including soft tissue sarcomas, bone sarcomas and gastrointestinal stromal tumour. Fostering academic research and promote epidemiological surveillance in rare cancers through setting up of shared registries is recognize as one of ERNs priorities. Within the sarcoma domain, taking into account the challenges described above, priority was given to ultra-rare sarcoma, and thanks to the strong connection, motivation and support provided by EHE Rare Cancer Charity UK, it was decided to start from EHE. We believe that in this context the collection of high-quality data by clinical registries will be crucial to improve the understanding of EHE natural history, validate and identify new prognostic factors, clarify the activity and efficacy of currently available treatment options and eventually provide and external control which might serve as a benchmark for the development of new drugs and support discussion with regulatory authorities. The EURACAN EHE registry is a prospective clinical registry that will collect data from all new patients receiving a pathological and molecularly confirmed diagnosis of EHE starting from the 1st December 2023. To this aim, an EHE-focused clinical record form (CRF) was developed through the Research Electronic Data Capture (REDCap) and designed to capture the specific features of this disease. For each patient, data collection will include: 1. A common baseline, including full details on demographic, comorbidities (special focus on immune-mediated and gynecological diseases), concomitant medications, physical examination, systemic symptoms at presentation, tumour-related pain assessment, blood tests, pathology and molecular features (on the diagnostic specimen), EHE extension at baseline (unifocal disease, loco-regional disease, systemic metastases) 2. Depending on the disease extent, detail on staging modalities, primary site and size, extension of metastatic disease (organs involved, number of lesions), presence and characterization of serosal involvement and effusion, treatment (surgery, radiation therapy, medical therapies, isolated limb perfusion, other locoregional techniques). Although the EHE registry per se does not foresee any collection of pathological samples and / or imaging, the availability for each enrolled patient of pathological samples, massive parallel sequencing data and imaging at the contributing institution will be captured by the CRF, in order to facilitate patients' identification for future dedicated studies which will imply the use of these data. Given the peculiar biological EHE behavior, in absence of any event, a mandatory 6-monthly update will be required at all contributing centers. In the mandatory 6-monthly update, information from the last visit will be recorded regarding: physical examination, time interval of development of systemic symptoms, assessment of tumor-related pain, blood tests, update on ongoing treatment / active surveillance (including modalities and timing of radiological monitoring and radiological response). All events will be recorded at the time of the occurrence (for unifocal disease, local recurrence and metastatic progression; for locoregional and metastatic disease, systemic progression). For every event, information will be recorded on physical examination, time interval of development of systemic symptoms, assessment of tumor-related pain assessment, blood tests (hemoglobin and fibrinogen), radiological modalities detecting progression, extent of progression (by RECIST 1.1 and not), serosal involvement and / or effusion, update on ongoing treatment / active surveillance. Patient status (alive with no evidence of disease, alive with disease, dead) and last follow up will be updated at any data entry. The registry and therefore the electronic CRF have been shaped starting from what have been agreed and reported in the EHE consensus paper from the sarcoma community of experts, published in 2021. A registry kick-off meeting was held in Milan the 15th September 2023, involving the EHE prospective clinical registry coordination team, all the contributing centers and patients' associations (EHE Rare Cancer Charity UK, EHE Italia and EHE US) to present the registry and share common clinical practice guidelines, derived from the consensus paper, to be followed for the patients with EHE included in the registry. The launch of the EHE prospective clinical registry was shared with all the reference institutions belonging as full members or associated partners to EURACAN sarcoma domain (63 institutions across Europe). The project was also opened to EU institutions not belonging to EURACAN and extra-EU institutions. In this case, in order to ensure an adequate degree of expertise in the disease, the institutions interested in joining the registry were asked to provide the number of new EHE cases (molecularly confirmed) seen each year over 3 years (2020-2021-2022) and a threshold of at least 20% of EHE national incident cases was selected for participation. As a result of this process, 21 institutions joined the registry in September 2023, 17 of which belonging to EURACAN, from 10 countries. The registry is federated thus, data are stored by the health care providers contributing to the registry. At the local level, data are pseudonymised. Statistical analyses will be performed based on a study protocol. Queries will be developed, in collaboration with clinical experts, to interrogate the EURACAN EHE registry to generate the descriptive statistics and relevant information needed to plan the analyses envisaged by the study protocol. Data quality checks aim to assess whether data values are present, if they adhere to specific standard and if they are believable in terms of: - Conformance: the data should be recorded in agreement with the correct formats (e.g. range of values, date formats); - Completeness: the data should not have missing values or data records; - Plausibility: the data should be believable (e.g. internal consistency; temporal and atemporal comparison); Quality checks of the data conformance are included in the CRF in the form of predefined alerts and errors running during the data input. Moreover, several additional completeness and plausibility checks (e.g. completeness of variables for each patient, plausibility of temporal intervals between different dates, etc.) are implemented in an external web tool connected to the CRF by use of API key, capable of executing all data quality checks simultaneously. The API key is not transmitted outside the centre, it is used only locally to perform data quality checks. The results of these checks are available locally for each centre and periodically they will be summarized in reports that the registry coordination team (INT) will monitor and discuss with each centre. Legal basis of the registry: In Europe, the processing of personal data for scientific research can be grounded upon several conditions of lawfulness, established in Article 9(2) of the General Data Protection Regulation (GDPR). Among these, the most relevant ones are: - the consent of data subjects (Art. 9(2)lit. a); - the pursuing of a substantial public interest, on the basis of Union or Member State law (Art. 9(2)lit. g); - the pursuing of a scientific research purpose on the basis of Union or Member State law (Art. 9(2)lit. j). The GDPR allows or requires Member States to implement national specifications or derogations from certain rules set out in the GDPR, therefore the legal basis of the federated registry will be based in each participating hospital on the laws and regulations of its country.

Multicentre Prospective Observational Study of Acute Intoxications in Paediatric Age

Multicenter Italian Cohort Study on Tuberculosis in Pediatric Age

In recent decades, Tuberculosis (TB) has been considered, in industrialized countries, as predominantly an infectious disease of the elderly. However, since the 2000s, TB has re-emerged not only in the elderly but also in the young and especially in pediatric populations. Among the factors influencing the increase in the incidence of this pathology are certainly to be considered the rise in immigration from countries with high endemicity, where TB still represents a significant cause of morbidity and mortality, the spread of immunodeficiency caused by HIV infection, the use of immunosuppressive drugs, and the emergence of strains of M. tuberculosis resistant to traditional antibiotic therapy. According to the WHO report of 2021, approximately 10 million new cases were reported in 2020, of which 1 million occurred in the pediatric population. However, epidemiological data available on TB in pediatric age are extremely limited due to diagnostic difficulties in this patient category. In children, in fact, bacteriological examination is negative in 95% of cases, and the diagnosis is made through a combination of clinical criteria and tests that are poorly specific for tuberculous infection and especially not universally accepted. In addition to diagnostic controversies, children are almost never included in national surveillance systems due to the lack of connections between individual pediatricians, pediatric hospitals, and national surveillance programs. It is therefore reasonable to assume that this condition may be significantly underestimated both in Italy and worldwide. Another important aspect to consider is that tuberculous disease, whether active or latent, in a child should be considered a sentinel event that indicates recent transmission of M. tuberculosis within the community. Especially in the pediatric population, in addition to the mandatory reporting of confirmed cases of TB disease, it is important to identify cases of latent TB through historical and diagnostic criteria. Children indeed have a greater likelihood that the disease will progress to the active form compared to adults and that the progression will be towards a more severe form. Children with latent tuberculous infection also become a reservoir for the transmission of the infection, fueling future epidemics.

Prospective and Multicenter Italian Registry of Locally Advanced-Metastatic Urothelial Carcinoma

This is a multicentre, prospective and non-interventional study in which all patients treated according to clinical practice will be included. The registry will include all patients with metastatic urothelial carcinoma or with lymph node involvement defined as unsuitable for surgery. The study involves medical visits and clinical-radiological re-evaluations according to clinical practice. There are no additional procedures. The clinician will establish the number of visits necessary for each patient according to the needs encountered and depending on the treatment chosen. The participating centers were selected in such a way as to adequately represent all the different geographical areas. The duration of the study is 24 months: 12 months of enrollment plus 12 months of further follow-up.

Prospective Observational Study of Localized Angiosarcoma of Any Site: ProStars

The management of localized AS remains a clinical challenge and needs to be better defined and standardized, especially with regards to the role of radiation-therapy and systemic treatment. Several questions about the best treatment approach to some clinical presentations remain open and would need to be answered by clinical studies. Unfortunately, the rarity of this histology among sarcomas makes it challenging to carry out clinical studies in all such presentations. Moreover, prognostic factors are lacking and differences in epidemiological, pathological and clinical aspects between primary AS and secondary AS need to be better characterized. These issues may be addressed with a prospective multi-institutional observational study, through the collection of clinical and pathological data of patients with localized AS. Involving all reference centres for sarcoma in Italy, the Italian Sarcoma Group (ISG) will be the ideal network for this study, with the collaboration of the Italian Rare Cancer Network (RTR), a 7collaborative network among Italian centres focusing on improving the quality of care of patients with rare tumors.

68 Gallium-Fibroblast Activating Protein Inhibitors-46 Positron Emission Tomography - Computerized Tomography for Molecular Assessment of Fibroblast Activation and Risk Assessment in Solid Tumors

The growth and spread of the tumor is determined not only by the tumor cells but also by the non-malignant constituents of the malignant lesion, which contributes to what is commonly referred to as the "tumor microenvironment". In particular, a subpopulation of fibroblasts called cancer-associated fibroblasts are involved in tumor growth, migration and progression. Therefore, these cells represent an attractive target for both diagnosis and anticancer therapy. A distinctive feature of cancer-associated fibroblasts is the expression of the fibroblast activating protein, a type II membrane-bound glycoprotein. Fibroblast Activating Protein plays a role in normal developmental processes during embryogenesis and in tissues modeling. The presence of Fibroblast Activating Protein in cancer-associated fibroblasts in many solid tumors and the fact that overexpression is associated with a worse prognosis in cancer patients has led to the hypothesis that Fibroblast Activating Protein plays a fundamental role in the development of cancer, in the migration of cancer cells, and in the spread of cancer. Therefore, the targeting of this enzyme for imaging and endo-radiotherapy can be seen as a promising strategy for detecting and treating malignant tumors.

Implementing Geriatric Assessment for Dose Optimization of Cyclin-dependent Kinase (CDK) 4/6-inhibitors in Older Breast Cancer Patients