Endocrine Abstracts

Neuroendocrine tumours (NETs) tend to be slow growing (although aggressive forms exist) and are often diagnosed when they have already metastasised.

Treatment of NETs is typically multidisciplinary and should be individualised according to the tumour type, burden, and symptoms. Therapeutic tools in NETs include surgery, interventional radiology and medical treatments such as somatostatin analogues, interferon, chemotherapy, new targeted drugs and peptide receptor radionuclide therapy (PRRT) with radiolabelled somatostatin analogues.

Surgery is crucial in many phases, from the eradication of the primary to the debulking of metastatic lesions, especially in a multidisciplinary algorithm. It is also used to control hormonal symptoms.

Interventional radiology techniques (TACE, RFA, and radioembolization) in NETs are frequently used, due to the common spread to the liver with hypervascular metastases.

Medical therapy is used for treating symptoms and/or reducing tumour growth. Traditional chemotherapy is not commonly applied in G1–G2 NETs, since most of them are slow growing. However, schemes based on platinum derivatives and etoposide are considered in poorly differentiated and/or rapidly progressive NETs, but the choice of the regimen is based on the site of the primary, the histopathological differentiation and proliferation index.

NETs usually over-express somatostatin receptors on their cell surface, thus enabling the therapeutic use of somatostatin analogues to reduce signs and symptoms of hormone hypersecretion, to improve quality of life and to slow the tumour growth. α-Interferon has been used in NETs, with similar therapeutic effects.

Recently, the mTOR inhibitor everolimus and the tyrosine kinase inhibitor sunitinib demonstrated an impact on survival parameters in patients with pancreatic NETs and have been introduced in clinical practice. The anti-VEGF monoclonal antibody bevacizumab demonstrated an impact on survival parameters in patient with metastatic carcinoids.

Radiolabelled somatostatin analogues have been experimented in NETs for almost two decades. Several clinical trials have indicated that PRRT with ⁹⁰Y-DOTATOC and ¹⁷⁷Lu-DOTATATE is an efficient tool in the management of NETs. Present knowledge and clinical experience indicate that it is possible to deliver high activities, and therefore high absorbed doses, to tumours expressing sst₂ receptors, with achievement of partial and complete objective therapeutic responses in up to 30% of patients with PFS of 33–36 months and a consistent impact on survival. Side effects, involving the kidney and the bone marrow, are mild if adequate renal protection is used.