Pan-European EHE prospective registry moving forward

INT team

The PROSPHERE study aims to provide a description of the population affected by EHE, giving an insight into the natural history of the disease and its variants, leading to the possible identification of clinical and biochemical prognostic and predictive factors and answering some of the outstanding questions on its management.

Study design

The original plan was to create a stand-alone registry, coordinated and run by the team at INT in Milan. However, personnel in INT quickly realised that the EHE registry would be more sensibly set up within a broader European project named STARTER, developed in the framework of EURACAN, the European Reference Network (ERN) dedicated to rare adult solid cancers, that is also being coordinated by INT.  Dr Annalisa Trama (Department of Research, Evaluative Epidemiology Unit, Fondazione IRCCS Istituto Nazionale Tumori, Milan), the STARTER project PI, explained:

STARTER is a Health Programme funded project, aiming to set-up a clinical registry for EURACAN, the European Reference Network (ERN) dedicated to rare adult solid cancers. The project was launched in April 2020 and will be running for 36 months. It will exploit at a European level, data coming from individual expert health care providers, from national and European registries and it will be interoperable with already existing rare disease registries.

The EURACAN registry will progressively cover all the 10 families of rare adult solid cancers included in EURACAN (sarcomas; rare neoplasms of the female genital organs and placenta; rare genitourinary cancers; rare neuroendocrine tumours; rare digestive cancers; rare endocrine cancers; rare head and neck cancers; rare thoracic cancers; rare skin/eye melanoma and rare brain tumours). However, sarcomas and head and neck cancers have been selected as the two initial target groups to get the project started.

Among the sarcoma domain (coordinated by Prof. Paolo Casali, Medical Oncology, Fondazione IRCCS Istituto Nazionale Tumori, Milan) ultra-rare sarcomas, such as EHE, have been selected as the topic to start with, as the community believe that, given the exceeding rarity of these sarcoma types,  international prospective registries could provide an invaluable contribution, both by allowing a better understanding of the natural history of the different diseases, and in order to provide external control data, potentially useful in the process of drug development and approval.

Dr Anna Maria Frezza explained further:

“Incorporating and operating the PROSPHERE study within and as part of the STARTER project represents an extraordinary opportunity to develop an EHE prospective registry that will be broader, larger and more cost effective than if PROSPHERE was run as a standalone study”.

Incorporating the PROSPHERE study within STARTER  will deliver the following benefits:

  1. The establishment of a full registry in EHE, which with appropriate funding can be maintained on an ongoing basis with no pre-defined duration over time.
  2. The use of the existing free web-based application for database management (RedCap). The INT, using RedCap, will set up a case report form (CRF) dedicated to EHE that includes data quality checks based on the experience gathered in the development of the head and neck EURACAN registry.
  3. A simplification in terms of administrative, legal and ethical issues implicit in the project as the STARTER project team has already addressed, through huge regulatory analysis over the last two years, and is compliant with very complex ethical and administrative issues such as current GDPR requirements.
  4. The supervision of a dedicated coordination team of data manager, CRF developers and statisticians.
  5. The potential enrolment of a large number of patients through the contribution of multiple sarcoma reference centers, within and outside EURACAN.

Currently, the EURACAN sarcoma domain includes more than 50 sarcoma reference centres across Europe. Originally, three centres in the UK were also part of the domain (Royal Marsden Hospital, London; University College of London Hospital, London; and Oxford University Hospital, Oxford), but these centres formally left EURACAN as a consequence of Brexit. However, given their expertise in the disease and valuable contributions, they are still working closely with the ERN as expert guests. The PROSPHERE registry will initially start with approximately 10 centres across the European Union and the UK, and by joining STARTER, the PROSPHERE registry will then be able to progressively include many more sarcoma reference centres.

This prospective registry will include all consecutive patients with a histological diagnosis of EHE and treated at participating sarcoma reference centres. For every patient included, a confirmation of the histological diagnosis performed by the expert sarcoma pathologist of each contributing institution (centralization at a national level) will be performed, and molecular testing for WWTR1-CAMTA1 and/or YAP-TFE3 will be required.

Clinical data (demographic, symptoms, disease clinical and pathological features, treatment, outcome) will be prospectively collected through an electronic CRF which will be put in place and shared with all contributing institutions. Data quality check will be performed by a dedicated study coordinator.

The initial plan is to include a minimum of approximately 100 patients (range: 80-120), in 36 months, followed by a follow up time of at least 3 years.