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  • Writer's pictureDoç.Dr.Mutlu Ünver

What is Neuroendocrine Tumor (NETs)? - Assoc. Prof. Dr. Mutlu Unver - Izmir, Turkey

Updated: May 1

Neuroendocrine tumors (NETs) are found at the junction of hormone-secreting cells and nerve cells in the body and are cells that secrete hormones through nerve impulses. Because such cells are found all over the body, NETs can originate in any organ in the body. The most common NETs originate from the digestive tract, pancreas and lung.


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The incidence of NETs has increased approximately 5-fold in the last 30 years. Some of the increase can be attributed to better detection of tumors with methods such as CT, MRI and PET-CT, while others may be due to an actual increase in tumors. Still, NETs are less common than other types of cancer. However, there is an increase in the number of patients with NETs in the population as patients live longer.


A significant proportion of NETs are benign and non-metastasizing. Some may metastasize, but they usually have a very slow course. Unlike classical cancers, the term "carcinoid tumor" is used for NETs, especially those arising from the small intestine, as most of them have a slow course.


However, some NETs can have an aggressive course like classical cancers. Pathologic examination of the biopsy material is of great importance in determining the course of NETs. On pathological examination, NETs are graded as good, moderate or poor based on the grade of the tumor (the degree to which cancer cells differ from normal cells), the rate of cell division (mitosis), the presence of dead tissue (necrosis) and the amount of Ki-67 protein, which indicates the rate of cell division.


Accordingly, NETs with a good grade have the slowest course, while those with a poor grade may have the most aggressive course. Assoc. Prof. Dr. Mutlu Ünver's studies and knowledge on this subject are very important and can make a great contribution to the treatment of patients.



What are the Symptoms of Neuroendocrine Tumors (NETs)?


Most neuroendocrine tumors do not secrete hormones and do not show symptoms. Such tumors are detected incidentally during examinations such as ultrasound, tomography and MRI due to other health problems of the patient and NETs are diagnosed by needle biopsy.


However, NETs may secrete hormones in some patients and cause various symptoms depending on the type of hormone secreted. For example, a NET that secretes insulin in the pancreas (insulinoma) can cause sudden drops in blood sugar and fainting. A NET that secretes the hormone "gastrin", which increases acid secretion in the stomach (Zollinger-Ellison Syndrome), can cause multiple ulcers in the stomach and intestines, resulting in abdominal pain and stomach bleeding.


A NET that releases the hormone serotonin can cause facial flushing, diarrhea, high blood pressure, palpitations and arrhythmia attacks. In patients with such symptoms, examinations such as ultrasound, tomography and MRI are performed and NETs can be diagnosed by needle biopsy of the detected masses.


Biopsy not only diagnoses NETs, but also provides insight into the rate of tumor spread and guides treatment by looking at factors such as grade, mitosis rate, necrosis and Ki-67.


In some cases, NETs may contain areas of both slow progression and aggressive tumors in the same patient or even within the same mass (tumor heterogeneity). In this case, it may be observed that tumors in the patient generally shrink while some tumors grow, or that one part of the same tumor shrinks with treatment while another part grows. In such cases, it may be necessary to re-needle biopsy the growing parts to examine the tumor. This is an important step to evaluate the treatment process and determine appropriate treatment strategies.

 

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Staging of Neuroendocrine Tumors (NETs)


The most useful methods for staging NETs are needle biopsy and imaging findings. Biopsy is used to differentiate between well, moderately and poorly differentiated forms of NETs, while imaging techniques such as tomography, MRI and PET-CT are used to assess the extent of the tumor. NETs can sometimes be located in a single organ (e.g. thyroid, stomach, intestine, pancreas).


However, most NETs, especially poorly differentiated NETs, have spread to distant organs, especially the liver, at the time of diagnosis. The classical methods used to assess tumor extent are CT and MRI.


Classical PET-CT (FDG PET) does not show well well and moderately differentiated NETs; however, it is very successful in showing poorly differentiated NETs with aggressive course. Currently, gallium 68 PET-CT is the most successful method for demonstrating well-moderately differentiated NETs.


In this method, somatostatin receptors on the surface of NET cells are used for both diagnosis and treatment. A protein called Ga-68 DOTATATE binds to these receptors and makes tumors visible on PET-CT. This method can also detect NET metastases that are not visible on CT, MRI and conventional PET-CT.


If a radioisotope called Lutetium 177, which delivers high doses of radiation, is given instead of Gallium 68, it can also bind to receptors on NET cells and destroy them (Lutetium DOTATATE treatment). The information obtained with these methods is crucial in determining the stage of the tumor and in evaluating appropriate treatment options.


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Neuroendocrine Tumors (NETs) Treatment


After assessing the differentiation and extent of NETs by biopsy and imaging methods, treatment is initiated. Rarely, the tumor can be found in a single organ and in this case, the tumor can be removed by surgical operation or percutaneous ablation. Percutaneous ablation may be preferred especially in some patients due to its minimally invasive, reproducible and low risk.


Most patients with NET have metastases to distant organs, especially the liver, at the time of diagnosis. In these patients, drug therapies are initiated first; somatostatin receptor analogs such as ocreotide and lanreotide may be given in moderately-poorly differentiated NETs.


In well-moderately differentiated NETs, Ga-68 PET-CT is first performed to investigate the amount of somatostatin receptors in tumor cells. If there is intense uptake on Ga-68 PET (meaning a high number of receptors), a targeted treatment is applied by giving Lutetium DOTATATE. In this treatment, the Lutetium 177 isotope containing high doses of radiation adheres to somatostatin receptors in NET cells and destroys the tumor cell with radiation.


By applying this treatment directly to the tumor through the artery (intra-arterial lutetium), it is possible to further increase the effectiveness of the treatment. The treatment plans determined by these methods are individualized according to the patient's condition and the characteristics of the tumor and help the patient achieve the best results.


New Therapies for Liver Metastases of Neuroendocrine Tumors - Treatment of Neuroendocrine Tumor Liver Metastases


More than 90% of NET patients develop liver metastases at any stage of the disease. Metastases can occur in the liver alone or in other organs in addition to the liver. In all cases, however, it is important to treat liver metastases more aggressively because the status of liver metastases is one of the most important factors affecting survival.


NET patients with metastases only in the liver or predominantly in the liver are primarily treated with chemotherapy or Lutetium therapy. Administration of lutetium through the hepatic artery may increase the efficacy of treatment. In addition, percutaneous ablation methods such as radiofrequency, microwave and cryoablation may be preferred if metastases are few in number. In some cases, percutaneous ablation can also be applied to primary tumors with metastases.


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New treatments and approaches in this field are constantly being explored. Innovative drugs, immunotherapy and targeted therapies may offer more effective options for the treatment of liver metastases in the future. It is important to determine the most appropriate treatment plan, taking into account the patient's condition, tumor characteristics and extent. A multidisciplinary approach in the treatment process can provide patients with the best results.


Alternative Therapies for Liver Metastases of Neuroendocrine Tumors - Treatment for Neuroendocrine Liver Metastases


Transarterial therapies such as bland embolization, radioembolization and chemoembolization can be used in patients who are not suitable or do not respond adequately to these treatments. Transarterial therapies are highly effective in NET metastases and work as follows:


  • Normal liver tissue and tumor tissue are supplied by separate arteries. The hepatic artery, which is used to supply NETs, supplies 99% of NETs compared to 30% of normal tissue. Therefore, transarterial therapies through the hepatic artery directly target NET cells without causing much damage to normal tissue.

  • NET masses are vascular-rich (hypervascular) and attract the particles injected in transarterial therapies. In this way, the particles travel to NET masses at a higher rate than to other tissues and have a greater effect on tumors.


Chemoembolization is the most commonly used method in liver metastases of NET. In this method, the chemotherapy drug doxorubicin is either loaded into drug eluting beads or mixed with a substance called lipiodol, which is retained by tumor cells, and administered through the hepatic artery into the vessels feeding the tumors. With this method, the tumors are anemic by blocking the feeding vessels and the drug doxorubicin is released into the tumors for days. Both chemoembolization methods have been used successfully in NETs. Plain (drug-free) embolization has also been used in this patient group and some studies have reported that it is as effective as chemoembolization and has minimal side effects, especially when particles smaller than 100 microns are used.


Another effective method for NET liver metastases is radioembolization (TARE or SIRT). In this method, a radioactive isotope called Yttrium 90 is loaded into special particles with a diameter of 50 microns and injected into the vessels feeding the tumor through the hepatic artery. This allows a much higher radiation dose to be delivered to tumors than conventional radiotherapy, while preserving the intact liver and surrounding organs. Radioembolization has been shown to be effective and safe in NET liver metastases in many studies.


While minimally invasive treatments can provide complete cure in some cases, in some cases they can increase the patient's life expectancy and quality of life. In these patients, an experienced team should determine which treatment should be applied at which stage.


Frequently Asked Questions About Neuroendocrine Tumors (NETs)


Neuroendocrine Tumor Survival


Neuroendocrine tumors usually grow slowly and do not spread. Depending on the response to treatment and the type of tumor, most patients can live a normal life. However, this may vary according to individual factors and responses to treatment.


The prognosis of such tumors can usually be improved with early diagnosis and treatment, but in some cases the size and spread of the tumor can affect survival. Therefore, the treatment plan and prognosis should be determined taking into account the patient's specific situation.


Pancreatic Neuroendocrine Tumor Life Expectancy


The survival of pancreatic neuroendocrine tumors depends on a number of factors and often depends on factors such as the type of tumor, its size, the extent of spread and the patient's responses to treatment. With early diagnosis and appropriate treatment, in some cases patients can live a normal life span, while in other cases it may be shorter. Pathological examination plays a critical role in determining whether the tumor is cancerous and is an important step in determining the course of treatment.


However, in general, the survival of such tumors can vary depending on individual factors, the stage of the disease and the response to treatment. Therefore, the treatment plan and prognosis should be evaluated by specialized doctors, taking into account the patient's condition.


Is a Neuroendocrine Tumor Benign or Maligant?


Neuroendocrine tumors can be both benign (benign) and malignant (cancerous or malignant). Some neuroendocrine tumors have benign characteristics and do not tend to spread. Such tumors are usually less aggressive and grow slowly. However, some neuroendocrine tumors can be cancerous and have the potential to spread.


During the diagnosis and treatment process, pathological examination and other medical tests may be required to determine whether the tumor is benign or cancerous. Therefore, whether any neuroendocrine tumor is benign or malignant may vary depending on the specific condition and the characteristics of the tumor.


Is a Neuroendocrine Tumor Cancer?


Neuroendocrine tumors can be both benign (benign) and malignant (cancerous or malignant). Some neuroendocrine tumors show benign characteristics and do not tend to spread. In this case, the tumor is not cancer. However, some neuroendocrine tumors can be cancerous and have the potential to spread throughout the body. Pathological examination and other medical tests are usually required to determine whether the tumor is cancerous. Therefore, whether neuroendocrine tumors are cancerous or not can vary depending on the specific condition, the characteristics of the tumor and the patient's condition.


Where are Neuroendocrine Tumors Most Commonly Located?


Neuroendocrine tumors can be located in various parts of the body, but they are most commonly found in organs such as the pancreas, intestines (especially the small intestine), lungs, stomach, kidneys and hormonal glands. These tumors originate from cells in the endocrine system and can therefore develop in glands or tissues that produce hormones.


However, neuroendocrine tumors can occur in different parts of the body and tend to be located in a particular organ. The location of such tumors can be important for the symptoms and treatment options.


Assoc.Prof.Dr Mutlu Unver Best Cancer Surgeon in Izmir Turkey

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