Retrospective observational study on patients with advanced HG GEP-NEN

Level: Level 2

Launch date: 1 March 2023

Principle investigators: Nicola FAZIO

Project description:

Background: Gastroenteropancreatic (GEP) neuroendocrine neoplasms (NEN) are classified based upon morphology and proliferation rate as either well-differentiated low-grade (G1-G2-G3) neuroendocrine tumors (NET) or poorly differentiated high-grade (G3) neuroendocrine carcinoma (NEC) by the WHO 2017 on tumors of the digestive system.

GEP NEC are usually highly aggressive with a propensity for early metastases and a dismal prognosis. Median survival from diagnosis in untreated patients is usually 4-6 months, indicating a rapidly growing tumor. Advanced disease is treated with first-line systemic chemotherapy, more commonly platinum/etoposide. Survival of patients with GEP NET G3 is significantly better than that of patients with GEP NEC.

The new ENETS database (DB) was set up to establish an academic IT platform to promote ENETS research across European NEN-expert centers. The ENETS DB is composed of three levels. Level 1 comprises 100 items, representing the baseline critical characteristics of the patient and the disease. Level 2 comprises 250 items that should cover around 80% of any specialized dataset database. Level 3 (optional) regards additional set focused on specific topics. In 2022 ENETS solicited all Centers of Excellence to propose retrospective studies to validate levels 1 and 2.

In 2021, ENETS streamlined its various scientific activities into two categories: task forces and working groups. Among the others a task force on HG GEP NEN was structured. It is leaded by Anne Couvelard, Nicola Fazio and Halfdan Sorbye.

On this basis we, as leads od the HG GEP NEN task force, would like to conduct a retrospective analysis of patients with advanced HG GEP NEN utilizing the ENETS academic DB to validate levels 1 and 2.

Aim:

• To describe clinical management
• To report relationships between patient/tumor characteristics and clinical outcomes
• To identify potential prognostic and predictive factors to be investigated in future homogeneous prospective studies
• To validate the levels 1 and 2 of the ENETS academic database

Inclusion criteria:

• Age 18+ years
• Histological proven GEP-NEN with a Ki-67 >20%.
• Date of diagnosis > 2 months for NEC and > 6 months for NET G3 according to the ENETS DB definition of retrospective study.
• Unknown primary is allowed when metastases are mainly in the GI tract and clinical/pathological aspects are supposed to be attributable to a GEP NEN
• Distant metastases or unresectable locally-advanced disease
• Written informed consent must be obtained and documented in accordance with the local regulatory requirements.

Publication rules: Every participating institution will have 1 (co)-authorship, further participating persons of the same institution will be listed in the acknowledgement. If the number of co-authors has to be limited to a journals policy, the order will be determined according to the patient numbers recruited.

• The first author is the chairperson or PI of the study group of the study (designer/methodologist of the study).
• The second author is the best recruiter in terms of numbers and quality or the co-main author (if not the PI of the study).
• Subsequent author hierarchy is dependent on quality/quantity of recruitment/methodologist.
• The last author is the second chairperson/PI of the study (if among best recruiter).

The chairperson, Nicola Fazio, and vice-chairperson, Halfdan Sorbye, will be first and last author.