How are neuroendocrine tumors treated?

​

The type of treatment chosen is determined by the characteristics of the tumor – the type of tumor, its grade, the extent of its spread (stage) – and the extent of the disease, its symptoms and the general condition of the patient.

 

The characteristics of the tumor are determined by microscopic examination of the tumor tissue excised or taken by biopsy. A physician who specializes in pathology assesses whether the tumor cells have high or low differentiation and the rate of differentiation of the tumor according to various indices (KI67 and mitotic index). These characteristics help in adjusting the imaging tests, determining the treatment and planning the follow-up. The stage, determined by the local spread of the tumor and the presence of metastases to lymph nodes and distant sites, is also essential for deciding on the appropriate treatment.

 

Due to the slow progression characteristic of highly differentiated neuroendocrine tumors, leading to vague symptoms, the diagnosis is sometimes made at a stage where there is a scattering of the tumor beyond its initial location. At this stage, surgery is not always possible to effect a cure and systemic treatment (for the whole body) is needed.

 

Surgical treatment

​

The preferred treatment is complete resection of the tumor, if possible. In neuroendocrine tumors, unlike other tumors, even when complete resection of the tumor is not possible, surgery is still a relevant option. This is because reducing the extent of the disease, through surgery, allows for a combination of additional treatment tools and improvement of their effectiveness.

 

In functional neuroendocrine tumors, surgery also plays a role in controlling over-secretion from the tumor, if it is not pharmacologically controlled.

 

Drug therapy

​

There are four groups of drugs for the treatment of neuroendocrine tumors: biotherapeutic drugs (including analogs to somatostatin and interferon alpha), chemotherapeutic drugs (streptozotocin, temozolomide and platinum-containing drugs), small molecule-based drugs (sunitinib, everolimus), and biologic medicines (bevacizumab).

 

The most common type of drug for the treatment of neuroendocrine tumors is based on somatostatin analogs. These are substances that mimic the structure of the hormone somatostatin, and therefore bind to somatostatin receptors across the cell envelope in tumors, blocking them and suppressing their division.

 

Two drugs from this group are given as a first-line treatment to patients with non-dissecting highly differentiated tumors (G1/G2) – octreotide, trade name Sandostatin, and lanreotide, trade name Somatuline. Both drugs, which are usually given once a month by injection, have been shown to reduce the risk of tumor progression, especially in the gastrointestinal tract, and to reduce the symptoms of carcinoid syndrome.

 

PRRT: Directed radioactive therapy

Radioactive peptide-receptor therapy – PRRT – is intended for the treatment of tumors at a medium or high level of differentiation which cannot be removed by surgery.

 

The treatment targets somatostatin receptors. Therefore, expression of the receptors in the tumor should be verified using 68Ga DOTATATE PET/CT. In this treatment, we use DOTATATE again, but this time the radioactive substance (isotope) is of the 177Lutetium type, which damages the tumor cells, in contrast to 68Galium, which marks them.

 

The treatment is given in a new inpatient unit in Sheba. Before treatment, the patient is given an infusion of amino acids for 4 hours to protect the kidneys. Together with the amino acids, some time after starting the treatment, the radioactive substance is given for about 30 minutes.

 

A day after the treatment, body mapping is performed, the purpose of which is to assess the distribution of the substance's absorption in the body. The full treatment is given in four cycles, at intervals of about two months.

 

PRRT treatment is considered highly effective for diffuse neuroendocrine tumors. Studies show that it can stop the progression of the disease, increase the survival rate and improve the quality of life.

 

Interventional radiology

​

Embolization

​

An action that aims to block blood flow to the tumor and thereby reduce liver metastases, reduce hormone secretion and relieve symptoms. This can be done by injecting different drugs during the procedure (chemoembolization) or by injecting radioactive substances (radioembolization), in combination with blocking blood vessels by various means.

 

Ablation

​

Targeted and localized destruction of a tumor using heat energy. Ablation can be performed in several ways, with the use of radio waves being the most common for the treatment of neuroendocrine metastases in the liver.

 

Ablation is a technique suitable for treating small and deep tumors. It can also be used to relieve symptoms when the tumor is not dissected, or when there is a recurrence of the metastases and there is a desire to avoid further surge