Neuroendocrine tumours

Neuroendocrine disorders |
Neuroendocrine tumours (NETs)

Neuroendocrine tumours

Istituto Gentili is committed to the
treatment of neuroendocrine tumours
(NETs), a rare and heterogeneous group
of tumours, which in Italy are diagnosed
in about 2,700 Patients every year.

Characteristics

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Neuroendocrine tumours (NETs) are a rare and heterogeneous category of tumours originating from neuroendocrine cells, which are present throughout our body. NETs can therefore develop in various organs.

In Italy, it is estimated that there are about 25,000 people living with a neuroendocrine tumour, with an incidence of 2,700 new cases a year.

Risk factors

Although we are yet to discover all the risk factors that lead to the development of NETs, there are certain elements that seem to increase the likelihood of occurrence:

family history: in rare cases, NETs can be associated with hereditary disorders, such as multiple endocrine neoplasia type 1 (MEN1),
genetic conditions,
environmental and lifestyle factors.

Symptoms

The symptoms of NETs vary depending on the location of the tumour, the presence of metastases and the tumour cells capacity to secrete hormones (functioning tumours).

Gastrointestinal symptoms

abdominal pain, diarrhoea, vomiting

Pulmonary symptoms

persistent cough, wheezing

Carcinoid syndrome

caused by the secretion of serotonin and other vasoactive substances that cause flushing, diarrhoea and abdominal cramps, bronchospasm, heart disease and pellagra (an illness caused by vitamin B3 deficiency and characterised by diarrhoea, dermatitis, and dementia)

Other symptoms

unexplained weight loss, fatigue

Diagnosis

Diagnosing NETs can be complex and often requires a combination of:

blood tests: measuring levels of specific tumour markers like chromogranin A and hormones in the case of carcinoid syndrome,
imaging procedures: CT, MRI, PET and/or ultrasound scans,
scintigraphy: such as somatostatin receptor scintigraphy,
biopsy: for histological confirmation of the diagnosis.

Identikit

Neuroendocrine tumours are classified according to various criteria, including:

Anatomical origin: NETs can originate from different organs and tissues, including the gastrointestinal tract (60-70%), lungs (20-25%), pancreas, adrenal glands, and other sites.
Degree of cell differentiation:

1. Well-differentiated NETs: tend to grow more slowly and have a better prognosis
2. Poorly-differentiated NETs: grow faster and are generally more aggressive

Level of cell proliferation: the level of cell proliferation is assessed using the marker Ki-67, the cell proliferation index. This classification helps to determine the aggressiveness of a tumour.

Treatment

The therapeutic objectives of treatment for NETs are to:

improve Patients’ quality of life,
control the symptoms associated with the illness,
slow the progression of the tumour,
improve life expectancy.

The treatment of NETs varies depending on various factors, namely:

location,
size of the tumour,
presence of metastases,
degree of differentiation.

The treatment options can include:

Surgery: often the treatment of election for localised and operable tumours.

Pharmacological therapy: drugs can be used to control the symptoms associated with neuroendocrine tumours and slow the progression of the tumour.

Somatostatin analogues (SSAs): that bind with the somatostatin receptors on the surface of neuroendocrine cells. This inhibits the release of hormones (serotonin, vasoactive intestinal peptide [VIP], gastrin and insulin), as well as inhibiting cell growth and angiogenesis.
Peptide Receptor Radionuclide Therapy (PRRT): making it possible to deliver a dose of radiation directly to the tumour cells, while reducing the damage to the adjacent healthy tissues.
Targeted therapies
Chemotherapy
Serotonin synthesis inhibitors

Neuroendocrine tumours constitute a clinical challenge on account of their heterogeneous nature and the variety of their clinical presentations. A multidisciplinary approach is essential for ensuring an optimum management of Patients with NETs.

Ongoing research and the development of new therapies are fundamental for improving the prognosis and quality of life of Patients with this complex set of conditions.

REFERENCES

AIRTUM. ITALIAN CANCER REPORT 2015.
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Faggiano A. Long-acting somatostatin analogs and well differentiated neuroendocrine tumors: a 20-year-old story. J Endocrinol Invest. 2024;47(1):35-46. doi:10.1007/s40618-023-02170-9.
Klöppel G. Neuroendocrine Neoplasms: Dichotomy, Origin and Classifications. Visc Med. 2017;33(5):324-330. doi:10.1159/000481390.
LINEE GUIDA AIOM NEOPLASIE NEUROENDOCRINE Edizione 2021.
Modlin IM et al. The archaic distinction between functioning and nonfunctioning neuroendocrine neoplasms is no longer clinically relevant. Langenbecks Arch Surg. 2011;396(8):1145-1156. doi:10.1007/s00423-011-0794-7.
Pavel M et al. Gastroenteropancreatic neuroendocrine neoplasms: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2020;31(7):844-860. doi:10.1016/j.annonc.2020.03.304.
Pusceddu S et al. Entering the third decade of experience with octreotide LAR in neuroendocrine tumors: A review of current knowledge. Tumori. 2019;105(2):113-120. doi:10.1177/0300891618765362.
Rinke A et al. Placebo-Controlled, Double-Blind, Prospective, Randomized Study on the Effect of Octreotide LAR in the Control of Tumor Growth in Patients with Metastatic Neuroendocrine Midgut Tumors (PROMID): Results of Long-Term Survival. Neuroendocrinology. 2017;104(1):26-32. doi:10.1159/000443612.