Early diagnosis of neuroendocrine tumors is vital for treatment success.
Neuroendocrine tumors (NETs) are small, slow-growing tumors that are usually found in the gastrointestinal tract and lungs but can also occur elsewhere in the body, such as the pancreas and rectum. Because most of these grow very slowly compared to other cancers, it often takes years before they become measurable or cause symptoms. Answering our questions about the early diagnosis of neuroendocrine cancers and new treatment options, Gazi University Faculty of Medicine, Department of Medical Oncology faculty member Prof. Dr. Mustafa Benekli evaluated the current developments in the treatment of NETs.
What are neuroendocrine tumors (NET), how would you describe it?
prof. Dr. Mustafa Spotted: When neuroendocrine tumors are mentioned, tumors originating from neuroendocrine cells, mostly in the gastrointestinal tract, are understood. They are spread over a wide range, they can originate from anywhere in the body, but the most common place we see is the gastrointestinal tract. We can count the places where it is seen, especially the pancreas, small intestine, stomach. Recent research has focused on this area.
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What are the symptoms of neuroendocrine tumors, how is the diagnosis made?
prof. Dr. Mustafa Spotted: The vast majority of patients are asymptomatic, that is, they may not show any signs or symptoms. Since the majority of these are slow-growing tumors, patients usually present with jaundice in advanced stages, liver metastases, and extremely nonspecific complaints such as abdominal pain. Neuroendocrine tumors; are hormone-secreting tumors, at least in part. They can also give symptoms according to the type of hormones they secrete. For example; The stomach-related hormone-releasing type may present with ulcers.
The type that increases intestinal motility and secretes hormones may come with diarrhea more. And there is something we call carcinoid syndrome. When carcinoid syndrome is mentioned, they come with complaints such as hot flashes, hot flashes, and sweating. It can have a serious effect on the heart. It can cause right heart failure by accelerating the work of the heart, and it can go with frequent diarrhea in the future. But because they are slow-growing tumors, the vast majority of patients do not show any symptoms.
What is the importance of early diagnosis and its effect on treatment in neuroendocrine tumors?
prof. Dr. Mustafa Spotted: Early diagnosis is important in every disease, every cancer, including neuroendocrine tumors. But of course, it also varies according to the type of neuroendocrine tumor. If it is diagnosed very early, which is usually coincidental, then surgery can be performed depending on where this disease is located. If surgery is done, these patients are cured because they are caught in the very early period.
If they are not caught at an early stage, there is no cure for metastatic disease. It is graded as Grade 1, 2, 3. Then they combined grades 2 and 3 as well and badly differentiated. In these, especially the patients of the type we call carcinoid, they can live for many years even if nothing is done. The tumor progresses very slowly, it can last for years even in metastatic disease, but there is no complete cure, it is not possible to destroy the tumor.
Physicians Regarding neuroendocrine tumors How is the awareness level?
prof. Dr. Mustafa Spotted: These are not very well-known tumors. Until now, their classification was already very complicated, new classifications emerged. People’s awareness has increased a little more. If there is no cure for a disease, if you do not see it very often, naturally, you are not aware of it. Pathology is also very important here. Pathologists should make the classification of neuroendocrine tumors clearly and put them in front of you. As oncology, we are a branch that is very dependent on pathology.
That’s why pathology is so important. The awareness of this has increased with new developments, new drugs, and the industry clinging to this job a little more frankly. Their incidence is also increasing, so neuroendocrine tumors, which we used to see much less often, are now much more common. Of course, the incidence is not like a breast cancer or colon cancer, it is much less and the rate in our country is not known exactly.
In our country, it is not known very clearly due to diagnostic problems. Since neuroendocrine tumors are not tumors of a single organ, there are neuroendocrine cancers of the lung, neuroendocrine cancers of the stomach, neuroendocrine cancers of the pancreas. Therefore, it is not possible for us to know the exact incidence of NETs in Turkey for now. I don’t think the world is too clear.
How is the treatment of neuroendocrine tumors, what are the new treatment options?
prof. Dr. Mustafa Spotted: If the tumor is caught early, we can say that surgery is a must, indispensable. Secondly, I am talking about metastatic tumors, they are also treated locally. They mostly occur in the liver, they spread through the blood. Direct local treatments can also be applied to tumors in the liver. Things like radiofrequency ablation can be done or Transarterial Chemoembolization (TAKE) can be applied. It is also the same as angiography is entered through the groin and given directly into the liver with chemotherapy drugs as well as some agents that bind chemotherapy.
In that case, it can go and directly affect the tumor. None of them are 100 percent effective. It stops the tumor, regresses, but it can recur. If it is metastatic, it is not possible to completely get rid of the tumors. Despite these, in advanced tumors, especially low-grade tumors, as I said, if the tumor itself is very aggressive and high-grade, they behave more like small cell cancer of the lung. They spread so fast, we can lose the patient all of a sudden. We apply chemotherapy, the longer the life expectancy with chemotherapy. But patients with low-to-moderate tumors can live for years.
There are a number of emerging, targeted agents. Some of them act by preventing the blood supply of the tumor, they are called antiandrogenic agents. Also called smart molecules, their number has increased in recent years. Their use has also increased in neuroendocrine tumors. Their effects are usually in the form of slowing the growth of the tumor or at least keeping it stable. Sometimes they shrink the tumor, but mostly the disease remains stable. It also prolongs the patient’s life expectancy because it remains stable. These are currently approved in our country, they have been used abroad for a few years, not for a very long time. Since it is approved in our country, we can also use it.
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There’s also a second group of agents, this mTOR inhibitor it is called. There are also pathways that cause cancer formation, and it works by blocking certain enzymes and certain proteins. The efficacy of these two agents is more or less the same, but they are only used in low-grade and moderate-grade neuroendocrine tumors that progress slowly and stop the progression of the disease. They extend the patient’s overall life expectancy by increasing the patient’s time to stay stable without any disease progression, which we call progression-free survival. Of course, other drugs will follow.
By the way, I talked about some hormones, there are some drugs that work by stopping those hormones, hormonal treatments. These Somatostatin Analogs. We said that most of the tumors were asymptomatic, they were the agents used only in symptomatic patients. These are hormones similar to the hormones released from the body. We used them especially in patients with diarrhea complaints to reduce secretions. Thus, the symptoms of the patients regressed and the patients were relieved.
It was later shown that they also have anti-tumor effects. We now use it as somatostatin analogues, whether symptomatic or not. Sometimes chemotherapies can be used when we no longer have a choice. Some chemotherapy is also effective. We want to save chemotherapy predominantly for high-grade tumors that grow much faster.
What is the benefit of the multidisciplinary approach to the diagnosis and treatment process in cancer?
prof. Dr. Mustafa Spotted: A multidisciplinary approach is very important in cancer, not only in neuroendocrine tumors. When a patient comes, all disciplines related to that disease should be involved in this work in some way, like joint councils. When you say multidisciplinary, what are the related disciplines? The first is surgery, the first stage I have already mentioned. If it is caught early, surgery should definitely be done. This is the only curative treatment for this disease, when caught at an early stage. Apart from that, gastroenterologists are very interested. While these patients did not have a proper treatment in the previous periods, local treatments are always at the forefront. Of course, we don’t do this as oncologists. Those who do are usually general surgeons, gastroentorologists, and radiologists. We should be working very closely with these three branches, this is how we work at Gazi University.
Except for recent chemoembolization radioembolization there is such a thing. This is again, like an angio, injecting radioactive substances directly into the liver, again depending on certain molecules. Again, they go and find the tumor, adhere to it and treat it by giving it radiation at the same time. ChemoembolizationIt is said to be a little more effective than the medicine, but it is very expensive, not suitable for every patient, and there may be complications such as radiation to the lungs. We have patients that we apply, but it is not a very common treatment. Therefore, as a discipline, nuclear medicine teachers should be included in this work. A multidisciplinary approach is not unique to neuroendocrine cancers, it should be the same for all cancers. Pathology, another very important discipline, is indispensable for cancer, and pathology is definitely included in it.
What are your thoughts on World NET Day?
prof. Dr. Mustafa Spotted: NETs should be known as awareness, of course, should be in the news. In fact, it is doctors rather than patients who should be aware of it. Because most of the patients can come without any symptoms. That’s why physicians need to be aware, physicians need to be vigilant. Most of them are slow-growing tumors, so our patients should not be afraid, but they should be followed up by an oncologist. Currently, there are NET patients followed by gastroenterologists who still do not see an oncologist. When it comes to cancer, patients must be under the follow-up of an oncologist for all types of cancer.