Neuroendocrine tumors

Risk factors

In the majority of cases, no cause or contributing factor for the development of NET can be identified. In less than 5% of cases, NET is genetic and is part of an inherited tumor predisposition syndrome.

Symptoms

The discovery of a NET depends mainly on whether it secretes hormones or not. Detection of these tumors can be difficult because their symptoms can vary greatly and are not specific.

Some NETs can progress very slowly and symptoms may not appear for several years. A NET can also be discovered during a medical imaging examination.

Diagnosis

The physician's first objective will be to precisely locate the tumor.

The number of examinations he or she will perform does not mean that a patient's condition is serious, but that the tumor is difficult to identify. The physician will continue the investigations until he or she has gathered all the information needed to propose the most appropriate and effective treatment plan.

What information is the physician looking for?

1. Where exactly is the tumor located?
2. What type of neuroendocrine cells is it made of?
3. Is the tumor functional or not?
4. What is the size of the tumor? The physician will want to know more than just whether the tumor is large or not. He or she wants to get precise measurements, in millimeters, of its height, width and depth.
5. Does the tumor explain the symptoms? In non-functional tumors, the symptoms will be related to the impact of the tumor volume on the surrounding tissues that are compressed by it. In the case of functional tumors, symptoms may be due either to the effects of the molecules secreted by the tumor, or to the volume of the tumor, or both.
6. How fast is it growing? To find out if the tumor is growing fast or not, a sample of the tumor (biopsy) will be taken and examined under a microscope.
7. What is its degree of differentiation? This looks at how much the biopsied cells resemble healthy endocrine cells or not. The more different the cells are from normal cells, the more aggressive they tend to be.
8. How aggressive is it? In other words, is it a benign tumor, local and encapsulated, or a malignant tumor, invasive? In this second case, the tissues that the tumor, in its current stage, has already invaded will be specified: the tissues surrounding it, the lymph nodes close to the tumor, or other distant tissues (metastases of the primary tumor).
9. Is the tumor accessible to surgery? Can it be removed? Factors that are often taken into account include the location of the tumor, which may be difficult for the surgeon to access without causing damage to healthy tissue, or the degree of invasion of tissue around the tumor, such as invasion of the aorta. If the tumor cannot be removed, or if it is too small to warrant surgery, the physician will then consider other treatment modalities.
10. Does the tumor have somatostatin receptors? Fortunately, more than 80% of neuroendocrine tumors do. Medical administration of long-acting somatostatin analogues can have several interesting effects: control of the symptoms caused by the tumor, decrease in the quantity of its secretions, inhibition of the growth of tumor cells in certain cases.
11. Can the symptoms be controlled and how? In addition to the administration of somatostatin and/or its analogues, the knowledge of the messenger molecules responsible for the symptoms (hormones or other molecules) will allow, when available, the administration of inhibitors and the correction of internal imbalances caused by the excess functioning of the tumor cells.
12. What is the most appropriate treatment regimen? There are many treatment options, which are briefly explained in the "Treatments" section.
13. How effective can we expect this treatment regimen to be? The physician will rely on statistics, but the reality will depend on the patient's personal response to the treatment applied.

Again, the physician will be relentless in trying to get a satisfactory answer to all these questions. To do so, he or she will sometimes have to perform multiple tests to find the tumor, because each test has its own detection limits (e.g., the tumor is too small to be visualized) and because each tumor has its own characteristics (e.g., it is non-functional).

Fortunately, there are numerous examinations available to detect a tumor. All these examinations, even if they are sometimes a little unpleasant, are generally not painful.

Examinations

Anatomical imaging techniques aim to give an image of the tumor and its possible metastases. They show the location of the tumor, its volume, its invasive or non-invasive character, its effects on the surrounding tissues, and the possibility of its surgical resection. These techniques include CT scan, magnetic resonance imaging, ultrasound, and digestive or bronchial endoscopy (for endoscopy, the patient is placed under sedation for the duration of the examination).

For functional imaging techniques, the physician injects a small amount of radioactive material. The radioactive material will bind to the tumor and will be quickly eliminated after the examination. Somatostatin receptor scintigraphy is used to determine if the tumor has somatostatin receptors. It can also detect the tumor if other examinations have failed to do so. A small dose of radioactive somatostatin is injected intravenously and binds to the receptors on the tumor. In general, 80% of NETs express somatostatin receptors, but this varies from one tumor to another (94% of metastatic carcinoid tumors but 50% of insulinomas). SPECT and PET scans use other radioactive markers to image the tumor.

Biological assays assess how functional the tumor is and what molecule it produces in the blood or 24-hour urine. It will allow establishing a relationship between the symptoms and the activities related to this messenger molecule.

Finally, a biopsy is essential to perform a histological examination that will establish the growth rate, the dangerousness, and the aggressiveness of the tumor.

Treatments

With all the knowledge acquired about a tumor, the physician can then propose an appropriate and effective treatment plan.

The various treatment modalities have three goals:

1. Control symptoms to improve the patient's overall well-being and quality of life
2. Stabilize the tumor, i.e. stop its growth.
3. Reduce the number of tumor cells as much as possible. Surgery removes them. Chemotherapy, targeted molecular therapies, or radiation therapy aim to kill tumor cells. The goal is to reach a number of residual cells that can be managed again by the immune system. The immune system has not been able to protect the patient, it has been overwhelmed by events. It has to resume its role, because it is the immune system that will eliminate every last tumor cell and guarantee a definitive cure without any possible recurrence.

To reduce the number of tumor cells, surgery is the first choice treatment unless the tumor is very small or inaccessible. The surgeon will remove the entire tumor and some of the surrounding healthy tissue as a precaution. He or she will also remove the lymph nodes that drain the tumor site. Of course, no surgery or anesthesia is free of risk. However, surgery gives very good results, even in the case of metastasized cancer.

Studies show that long-acting somatostatin analogues, injected once every 28 days, can block or reduce hormone production in functional tumors. More interestingly, they can stabilize the tumor in some patients for months to years, and lead to regression of metastases, whether the tumor is functional or not.

Some adverse effects, often transient, occur during treatment. This treatment is obviously only possible if the tumor has somatostatin receptors.

Molecular targeted therapies, which block certain processes necessary for the growth and spread of cancer, are used very regularly. Unlike chemotherapy, these treatments are able to accurately identify cancer cells and therefore cause little damage to healthy cells. Different modalities of molecular targeted therapy exist. They have less severe adverse effects than chemotherapy: skin problems (rash or allergic reactions such as hives or intense itching), high blood pressure, bleeding or clotting problems, and wound healing problems.

Finally, radiation therapy uses high-energy rays to kill tumor cells. These rays are directed at the tumor, but it is impossible to avoid destroying the healthy cells that surround the tumor. Again, this is a treatment managed by a specialist. He or she will determine the type of radiation used, the frequency and the number of sessions. Radiation therapy is completely painless. However, it also has some adverse effects, such as fatigue, mild skin reactions at the site of radiation penetration, gastric disorders, and/or diarrhea.