Clinical practice guidelines for the management of non-functioning advanced GEP-NENs: a GRADE approach for evidence evaluation and recommendations by the Italian Association of Medical Oncology (AIOM) in collaboration with the Italian Association for Neuroendocrine Tumors (ITANET)

Abstract

Neuroendocrine neoplasms (NENs) of the gastroenteropancreatic (GEP) tract represent a rare and heterogeneous group of malignancies. They are distinguished into well-differentiated and poorly differentiated neoplasms, with clinical behavior ranging from relatively indolent to fast-growing, respectively. Surgery is the curative option for localized disease, especially in well-differentiated neoplasms, while various systemic therapies are approved and clinically available for advanced disease. However, considering the complexity of these malignancies, the choice of therapeutic strategy must take into account multiple factors, such as histological diagnosis, primary site, extent of disease, evolution features, functional status, patients and treatment characteristics, treatment availability, and safety profile. A multidisciplinary approach dedicated to NENs and conducted by experienced teams is therefore strongly recommended. Since 2013, the Italian Association of Medical Oncology (AIOM), in collaboration with the Italian Association for Neuroendocrine Tumors (ITANET), has produced guidelines using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) approach for assessing the certainty of evidence. This updated version (2024) summarized the main diagnostic and therapeutic decision-making processes on specific topics selected by a panel of experts from the AIOM, ITANET, and other national scientific societies with the aim of guiding clinicians in the diagnosis, treatment, and monitoring of patients with GEP-NENs. The integration of these guidelines into daily clinical practice is expected to improve patient care and drive the evolving landscape of GEP-NEN management.

Keywords: AIOM; GEP-NENs; ITANET; clinical practice guidelines; gastroenteropancreatic neuroendocrine neoplasms.

Figure 1

Diagnostic and therapeutic approach criteria in GEP-NENs. [¹⁸]FDG, [¹⁸F]2-fluoro-2-deoxy-d-glucose; [⁶⁸]Ga, [⁶⁸]-gallium; CT, computed tomography; GEP, gastroenteropancreatic; HB, hepatobiliary; MRI, magnetic resonance imaging; NEN, neuroendocrine neoplasms; PET, positron emission tomography; WHO, World Health Organization.

Figure 2

Therapeutic approach in advanced non-functioning Pan-NET. Cabozantinib, just EMA approved, will be a treatment option in progressive disease after at least one line of therapy beyond the SSA, as soon as it becomes available in Italy. ChT, chemotherapy; EMA, European Medicines Agency; G, grade; NET, neuroendocrine tumor; Pan-NET, pancreatic NET; SRI, somatostatin receptors imaging; 1°L, first line; 2°L, second line; 3°L, third line; SSA, somatostatin analogs. ^aConsidering the lack of a validated sequence of therapies, enrollment in clinical trials is desirable, where available; ^bPreferably with Ki-67 <10%.

Figure 3

Therapeutic approach in advanced non-functioning Si-NET. Cabozantinib, just EMA approved, will be a treatment option in progressive disease after at least one line of therapy beyond the SSA, as soon as it becomes available in Italy. ChT, chemotherapy; EMA, European Medicines Agency; G, grade; NET, neuroendocrine tumor; Si-NET, small intestine NET; SRI, somatostatin receptors imaging; SSA, somatostatin analogs. ^aConsidering the lack of a validated sequence of therapies, enrollment in clinical trials is desirable, where available; ^bPreferably with Ki-67 <10%.