Neuroendocrine Tumours, NETs, Cancer Treatment, Theranostics, Theranostics Singapore, Dr Andrew Tan

What Are Neuroendocrine Tumours (NETs)?

Neuroendocrine Tumours (NETs) are rare tumours that affect specialised cells known as neuroendocrine cells.

The peculiarity of this type of cell resides in that they have traits similar to nerve cells and hormone-producing cells. Neuroendocrine cells are found in all organs of the individual and help control many of their functions.

A tumour can take years to appear. However, others grow rapidly and appear anywhere in the body. Still, the most common sites are the lungs, pancreas, appendix, small intestine, and rectum.

Where Are Neuroendocrine Tumours (NETs) Typically Found?

As mentioned, neuroendocrine tumours can appear in any part of the human body. Although it has a preference for some regions, these include: 

  • Gastrointestinal Tract: This is one of the main areas affected by this type of tumour, the large intestine taking 20% ​​of appearances, the small intestine 19%, and the appendix 4%. These types of tumours used to be called carcinoids.
  • Lung: Approximately 30% of NETs occur in the bronchial system, making it the second most common area of the body for neuroendocrine tumours. They were also formerly known as carcinoid tumours.
  • Pancreas: The pancreas takes 7% of appearances, formerly known as islet cell tumours. These are classified according to the endocrine cell from which they derive as gastrinoma, insulinoma, glucagonoma, among others.
  • In some cases, the primary organ cannot be found (15%). In some cases, it can affect the adrenal glands, such as the thyroid.

What Causes Neuroendocrine Tumours (NETs)?

Although they are rare, neuroendocrine tumours have an incidence of 10 cases per 100,000 inhabitants – and thanks to better diagnostic techniques – it is possible to study this disease statistically.

In general, neuroendocrine tumours are slow-growing ones, but the direct cause that triggers the disease is still unknown.

However, it is known that these tumours begin when neuroendocrine cells develop changes – in other words: mutations – in their DNA, which trigger structural changes.

There are risk factors that can contribute to developing cancer, although they are not the direct cause. It appears more often in adults than in children.

Additionally, hereditary syndromes are another risk factor, and among them, we have multiple endocrine neoplasia types 1 and 2, Von Hippel-Lindau syndrome, neurofibromatosis type-1, and complex tuberous sclerosis.

What Are the Symptoms of Neuroendocrine Tumours (NETs)?

NETs are, in general, asymptomatic in their initial stages. So their discovery is usually fortuitous unless it generates symptoms or pain according to the location that occurs. Common symptoms of cancer such as fatigue, weight loss, and loss of appetite may be experienced. 

The symptoms of the neuroendocrine tumour – if it is localised – are manifested by recurrent pain in the area, reddish, thickened skin, nausea, vomiting, cough or hoarseness, changes in bowel habits, jaundice, unusual bleeding.

Hyperglycemia/hypoglycemia, diarrhoea, skin rash, facial flushing, confusion, anxiety, ulcer disease, dizziness, tremors are other symptoms that an individual may experience. Some symptoms are usually more specific according to the type of NET that is possessed.

How Are Neuroendocrine Tumours (NETs) Diagnosed?

Initial Blood Study & Urinalysis:

Our doctor may request a 24-hour urine test to reveal a serotonin breakdown product (5-HIAA or 5-hydroxy indole acetic acid). Doctors may also order a blood test to measure fasting serum Chromogranin A levels.


When a tumour is localised, a tissue biopsy is performed to determine the presence of cancer cells, staging the cancer, and guide the patient’s treatment.

Nuclear Medicine Imaging Tests:

One of the most accurate methods for the diagnosis of neuroendocrine tumours is nuclear medicine imaging tests. We have mentioned octreotide scintigraphy and positron emission tomography (using a radioactive medium). Others may include PET-Gallium68 (currently the most sensitive test to identify NETs), whose objective is to detect the expression of somatostatin receptors. Another diagnostic method is the PET-FDG (glucose) that detects tumour activity through the consumption of glucose. 

MIBG 131 Scan:

The MBIG 131 Scan is usually used for neuroendocrine tumours of the paraganglionic type and pheochromocytoma.

Other Imaging Studies:

Other diagnostic means that may be used are endoscopy, ultrasound, computed tomography, and magnetic resonance imaging (MRI);

What Are the Treatment Options Available for Neuroendocrine Tumours (NETs)?

Before starting any treatment of neuroendocrine tumours, our doctor must stage or classify the grade of the cancer to find a suitable treatment plan; this is done through imaging studies, laboratory tests, and monitoring the patient’s symptoms.

1) Active Surveillance

Active surveillance is one of the most conservative treatments and is recommended in cases of slow-growing neuroendocrine tumours that do not present symptoms. The therapeutic approach begins after the first symptoms or in the event of a tumour enlargement.

If the patient neglects their routine check-ups, they may risk excessive tumour growth or metastasis.

2) Surgery

Surgery is the standard recommended treatment for neuroendocrine tumours. It consists of the extraction of the tumour that is often localised, together with the respective margin surrounding tissue to avoid the risk of metastasis.

If the entire tumour cannot be removed, debulking is carried out. This is where a part of the tumour is removed to reduce its size.

However, any procedure runs the risk of side effects. This may include:  

  • General risks of anaesthesia
  • General surgical associated risks
  • Carcinoid crisis (treated with a somatostatin analogue) Symptoms of a carcinoid crisis are reddening of the skin, facial lesions, diarrhoea, shortness of breath, and a fast heartbeat.

3) Somatostatin Analogues

These are drugs that have an action similar to the hormone somatostatin. These analogues manage the symptoms caused by NETs. They also slow their growth, although they do not reduce their size.

There are multiple types of somatostatin analogues available, and they are usually divided into the length of action. The long-acting octreotide (Sandostatin) administered intramuscularly can last for months, while medium and short-acting versions mandate an effect of weeks or days. 

The potential side effects of this treatment include hyperglycemia, gallstones, abdominal distention, nausea, sometimes accompanied by vomiting.

4) Chemotherapy

One drug or a combination of several drugs can be used in patients with neuroendocrine tumours. This treatment is typically used in cases where the disease is metastatic. 

Side effects depend on the chemotherapy cycles that the patient undergoes, the type of medications used, the stage of the NETs. The usual symptoms that may occur are fatigue, nausea accompanied by vomiting, hair loss, loss of appetite, and diarrhoea.

5) Targeted Therapy

This type of treatment limits the damage to healthy cells by blocking the growth and spread of cancer cells. This is achieved through tumour genes and proteins.

Among the targeted therapies is Everolimus (Afinitor), which targets gastrointestinal NETs, pancreas, and lungs, reducing accelerated tumour growth. This therapy acts on a molecule called mTOR present in tumour cells that facilitates their survival.

Another targeted therapy is Sunitinib (Sutent), and it targets a protein called VEGF. This protein is essential in the formation of blood vessels that nourish the tumour. Therefore, by attacking these proteins, nutrients are being removed from the tumour, preventing its growth. This therapy is helpful in the treatment of pancreatic NETs.

The side effects for Everolimus are fatigue, mouth lesions, alteration in the blood formula count. For Sunitinib, the side effects range from tiredness, diarrhoea, nausea accompanied by vomiting, and increased blood pressure.

6) Immunotherapy

Immunotherapy works to improve the patient’s immune system. The drug interferon alfa-2b (Intron A) may be used to treat NETs. It functions to reduce some symptoms of the disease, such as diarrhoea and skin redness.

Immunotherapy may often be used in combination with other treatment forms. 

Possible side effects range from fatigue, fever, nausea, vomiting, diarrhoea, skin rashes, and rarely, difficulty breathing.

7) Peptide Receptor Radionuclide Therapy (PRRT)

In 2018, the FDA approved treatment with 177 Lu-dotatate (Lutathera), aimed at gastrointestinal and pancreatic NETs. It binds to the somatostatin in the tumour through a receptor and sends out radioactive particles that kill cancer cells.

This type of therapy’s most common side effects are low potassium, low white blood cell levels, hyperglycemia, vomiting preceded by nausea, and fatigue.

8) Radiotherapy

The type of radiation therapy used for this pathology is an external beam, which directs the X-ray to a precise point on the individual’s body. Its use is to relieve pain caused by NET.

Patients may experience a dry cough, sore throat (when radiation therapy is aimed at the neck), dryness in the treated area, and skin redness. The most common side effects are nausea, vomiting, and tiredness. Difficulty breathing, while rare, is another side effect that patients may experience.

9) Treatment Targeting the Liver

Treatment targeting the liver is recommended for individuals where the NETs have metastasised to the liver. The first type of this treatment is radiofrequency ablation (RFA), which destroys the tumour by electrical heating. This works if the tumour is small.

The second form of treatment is the embolisation of the hepatic artery, which consists of blocking the blood flow to the tumour. 

There are three methods of doing this: soft embolisation (not combined), chemoembolisation (combined with chemotherapy), radioembolisation (combined with radiation therapy). The latter uses a radioactive material called Yttrium-90.

Side effects include pain in the abdomen at the level of the liver, fever, and increased liver profile after two days after treatment. However, these side effects tend to disappear quickly.

Who Will Benefit From Treatment With Lutetium-177 Octreotate Therapy?

The individuals who may benefit from this type of therapy are typically those with metastatic NETs with a high uptake of the octreotide tracer, demonstrated on imaging. 

What Are Some Questions I Should Be Asking My Doctor When Considering Treatment Options for Neuroendocrine Tumours (NETs)?

Here are some questions that you can ask your doctor regarding the treatment therapy that you will receive.

  • How many treatment options do I have?
  • Is it possible to combine treatment options?
  • What is the effectiveness rate of the treatment that I will receive?
  • What is the goal of my treatment? Relieve the pain? Heal my condition?
  • If the surgery fails, do I have other treatment options?
  • What do I do if the side effects of my treatment persist?
  • Is there treatment for the side effects I may experience?
  • How will the treatment I receive affect my life and current routine?
  • Will the treatment affect my sex life?
  • Will I still be able to conceive children after the treatment?

These are just some questions to ask your doctor before starting treatment.

Radium-223 Therapy, Xofigo, What to Expect, Theranostics, Theranostics Singapore, Cancer Treatment, Patient Information, Dr Andrew Tan

What Is Radium-223 Therapy (Xofigo)? 

Radium-223 Therapy (Xofigo) is a form of targeted radioactive therapy. It is a type of radioactive treatment that targets sclerotic bony metastases.

What Is Prostate Cancer?

Prostate cancer is one of the most common cancers among men. Approximately 1 in 9 men will be diagnosed with prostate cancer in their lifetime, and it is the second leading cause of cancer-related death in men in the United States. 

While most prostate cancers are early stage at diagnosis, a significant portion will have regional or distant metastases.

What to Expect Before Treatment With Radium-223 Therapy (Xofigo)?

Our doctor must confirm that you have prostate cancer through existing studies and tests. Once this is confirmed, our doctor typically requests a series of tests to assess your general health.

You will need a bone scan that demonstrates bony metastases. 

You may also be asked to stop taking calcium before the treatment session. Our doctor will sit down with you to look at your medical history, explain the severity of the disease and everything related to the treatment. Take advantage of this moment to clarify any possible concerns you may have.

What Will My Radium-223 Therapy (Xofigo) Treatment Schedule Look Like?

Our treating doctor will explain the damage to your body caused by prostate cancer and the consequences of not being treated. They will also explain the program you must follow to achieve the best possible treatment outcome with Radium-223 Therapy (Xofigo). 

Other information that will be provided to you will be regarding possible adverse effects and the therapeutic measures that you can take to minimise these effects. 

What happens after treatment and the prevention measures to keep in mind will be explained in detail. 

Finally, you may be advised to stop any other radiotherapy or chemotherapy treatments that you are undergoing before starting Radium-223 Therapy (Xofigo).

What to Expect During Treatment With Radium-223 Therapy (Xofigo)?

The treatment program for Radium-223 Therapy (Xofigo) consists of intravenous administration (peripheral route in one arm) of the drug. 

Treatment typically comprises 4-6 sessions, with a period of 4 weeks between each one.

The drug will be administered directly in the vein, and the procedure is typically fast and painless. 

Before each session, a blood sample will be drawn to evaluate health parameters and haematological conditions.

How Long Does Treatment With Radium-223 (Xofigo) Take?

Radium-223 Therapy (Xofigo) is a relatively quick procedure, which will take no more than half an hour. The application of the intravenous drug takes no more than a minute.

As mentioned, additional time will be required while the nurse places the catheter for the intravenous line and its subsequent removal.

What to Expect After Treatment With Radium-223 Therapy (Xofigo)?

After Radium-223 Therapy (Xofigo) treatment, there will be low-grade radioactivity from the patient. Small amounts of radioactivity may be present in the urine and stools. 

One of the advantages of this type of treatment is that it will not be necessary to avoid contact with family and friends since the radiation levels received is very low. Still, the doctor will give you a card stating that you have received such treatment.

How Long Before I Can Be Discharged After Treatment With Radium-223 (Xofigo) Therapy? 

As it is an outpatient procedure, discharge after intravenous application will be quick – it will not take more than a couple of hours for the first side effects to subside. Generally speaking, within 1-2 hours, you may be on your way home.

How Will I Feel After Treatment With Radium-223 (Xofigo) Therapy? 

Once the treatment is complete, you may feel somewhat dizzy or, in some cases, fatigued. It is normal to have some discomfort since you have received radiation treatment. However, try not to worry as these symptoms should disappear relatively quickly. In case of persistence, consult our doctor.

This type of therapy for prostate cancer is one of the few that generates minimal side effects. Among them, we have:

  • Nausea
  • Diarrhoea
  • Anaemia
  • Oedema in the ankles and wrist 

If you have had a therapy session and you have persistent side effects, feel dizzy, confused, and weaker than normal, or have any other symptoms that are not expected, notify our doctor immediately.

Any prolongation of the symptoms may be a cause for alarm, so you must notify your medical care immediately. Our doctor will take the necessary therapeutic measures to correct any discomfort as your body responds to the treatment.

Radiation Safety Precautions

As mentioned above, there will be small traces of radiation particles in the urine, blood, and faeces. Therefore, you must comply with the following radiological safety conditions:

  • Flush the toilet twice and wash your hands properly.
  • Wash clothes and sheets stained with vomit, blood, urine, and faeces separately. Handle with gloves.
  • Stay well hydrated before and after therapy.
  • Use a condom when having sex to prevent your partner from becoming pregnant (it is dangerous because of the effects of radiation) – this recommendation is valid for six months.
  • Do not expose your partner to pre-seminal fluid and semen, as it may contain radioactive particles.

What Questions Should I Ask My Doctor?

If you are feeling overwhelmed by your diagnosis, here are some questions that you can ask your doctor. 

  • How do I know if I am a candidate for Radium-223 Therapy (Xofigo)?
  • Is it an outpatient procedure? Why?
  • How many therapy sessions with Radium-223 Therapy (Xofigo) do I need?
  • What happens if I don’t follow through with all the Radium-223 Therapy (Xofigo) sessions?
  • Is it mandatory to stop other methods of therapy like chemotherapy?
  • Should I stop taking dietary supplements that contain calcium?
  • Should I take any security measures with my family and partner?
  • Can I have sex?
  • What do I do if I have blood in my urine?
  • Is it mandatory to have blood tests before each session?
  • Could I end up being sterile?