Neuroendocrine Tumours (NETs), Lutetium-177 Octreotate Therapy, Theranotics, Cancer Treatment Singapore

What Is Lutetium-177 Octreotate Therapy?

One of the therapies used to treat neuroendocrine tumours is Lutetium-177 Octreotate Therapy. It is a targeted radioligand therapy that specially targets tumours that express somatostatin receptors (i.e. neuroendocrine tumours). 

Its method of action consists of using peptide molecules such as artificial octreotate – transport – linked to a carrier agent for radioisotopes such as Lu-177 that destroy cancer cells.

Where Are Neuroendocrine Tumours Located?

Neuroendocrine tumours are cancers that arise from very specialised cells in the body (neuroendocrine cells). These cells have similar traits to nerve cells and hormone-producing cells. They are rare tumours and can appear in the lungs, pancreas, appendix, small intestine, and rectum.

Some produce hormones excessively (functional neuroendocrine tumours), while others produce little to no hormones (non-functional neuroendocrine tumours).

How Effective Is Lutetium-177 Octreotate Therapy?

The clinical effect of Lutetium-177 Octreotate Therapy for neuroendocrine tumours has shown improvements in overall survival, progression-free survival, and symptom relief. 

How Is Lutetium-177 Octreotate Therapy Administered? 

This type of therapy can be performed on an outpatient basis in the nuclear medicine department. Before starting, the patient will be asked to consume an average of 1.5L of fluids.

A peripheral intravenous line is placed in the patient to administer the treatment, in conjunction with an antiemetic before the infusion of amino acid compounds.

Administration of amino acids will take place 30 minutes before the drug is accompanied by intravenous fluids. This stage of the procedure takes a couple of hours.

It is then given as a slow, controlled infusion, which will last for approximately 20 minutes. After that, you must wait a couple of hours while the radioactivity decreases.

The entire treatment lasts approximately 4 to 6 hours, ranging from the preparation phase and the time spent waiting for the manifestation of side effects, if any.

What Are the Side Effects of Lutetium-177 Octreotate Therapy?

The infusion process is typically painless, with no acute complications expected. The most common side effects experienced are nausea and vomiting, generalised fatigue following treatment (this may last for a few weeks), and pain at the disease site. There may be potential marrow suppression or renal effect following treatment, depending on the number of treatment cycles, doses, and stage of the cancer. 

What Happens After Lutetium-177 Octreotate Therapy?

You will be monitored regularly by your managing doctor, and regular blood tests and imaging studies will be expected. 

Click here more information on Lutetium-177 Octreotate Therapy and the treatment of neuroendocrine tumours (NETs) through theranostics.

What is Theranostics, Cancer Cells, Theranostics Singapore, Dr Andrew Tan

What Is Theranostics?

Theranostics is a viable method of treating cancer, especially when the cancer cells have spread or are at a more advanced stage and are unable to respond to other treatments.

While there is still a lot of potential to replicate the procedure for other types of cancers, to date, theranostics has shown success mostly in treating liver cancer, metastatic prostate cancer, and neuroendocrine tumours.

Who Invented Theranostics?

The term theranostics was invented in 2002 by John Funkhouser, who was the Chief Executive Officer of PharmaNetics at the time. The term is essentially a combination of the word “therapeutics” and “diagnostics” – a portmanteau describing the PharmaNetics business model for developing diagnostic tests to identify cancer cells and the application of specific therapies.

What Is Theranostics in Nuclear Medicine?

Theranostics in nuclear medicine, or nuclear theranostics, refers to a specific type of cancer treatment.

It targets infection sites by first using diagnostic imaging or a radioactive drug to identify if target receptors are present on cancer cells, followed by a second radioactive drug to deliver therapy to treat the primary tumour and any advanced or metastatic tumours.

Does Nuclear Medicine Have Side Effects?

Only small amounts of radioactive material, known as radiopharmaceuticals or radiotracers, are used in nuclear medicine. These radiopharmaceuticals emit radiation that travels a short and safe distance, which is why very few people experience side effects or allergic reactions from nuclear medicine tests.

Any adverse reactions or side effects are usually mild and need little to no medical treatment. Generally, you should not feel much difference after the radiotracers are administered.

What Is the Theranostic Approach?

The theranostic approach is personalised, using both diagnosis and therapy tools as part of the treatment.

Theranostics in the Treatment of Cancer

Theranostics eliminates the need for multiple procedures to treat cancer, which reduces delays in treatment and improves patient care. In the diagnosis stage, PET scan imaging is used to locate specific targets known as tumour receptors or target receptors present on tumour cells.

As for the therapy stage, once these targets are visible on the scan, a radioactive drug will be injected into the body. This drug is used to treat tumours by selectively targeting the tumour cells and avoiding healthy areas. The radioactive drug that is not utilised or cannot reach the target will be passed out of the body.

What Is Metastatic Prostate Cancer?

Metastatic prostate cancer is an advanced stage of prostate cancer where cancer cells have spread to other parts of the body. It occurs when cells break away from the tumour in the prostate.

During the metastatic stage, these cancer cells usually break away and travel through the lymphatic system in the lymph nodes and the bones or through the bloodstream to other parts of the body.

What Is the Survival Rate for Metastatic Prostate Cancer?

The survival rate of prostate cancer entirely depends on the various stages of cancer. The staging system uses three different aspects of tumour growth – tumour, nodes, and metastasis. Patients whose prostate cancer has spread to other areas like the bones, liver or lymph nodes are in the metastasis stage and may need more advanced treatment.

According to the American Society of Clinical Oncology, about one-third of patients with metastatic prostate cancer will survive for more than five years.

Can Metastatic Prostate Cancer Be Cured?

There are many types of treatment available to slow down the spread of metastatic prostate cancer. Your doctor or oncologist will develop a treatment plan that takes into account your symptoms, stage of cancer, and general health.

What Are the Treatment Options Available For Metastatic Prostate Cancer?

Radiation therapy: External radiation therapy shrinks the tumour in the prostate or kills any new metastasised cancer cells in other areas.

Hormone therapy: This form of therapy lowers the production of male sex hormones, which can help prevent the spread of cancer cells.

Chemotherapy: Chemotherapy prevents cancer cells from multiplying. Patients usually receive chemotherapy once the prostate cancer has stopped responding to hormone therapy.

Immunotherapy: This form of therapy triggers and boosts the immune system to attack cancer cells. Immunotherapy filters immune cells out of the body and stimulates them at a lab to target prostate cancer. These cells are then reinfused back into the patient’s body intravenously (IV).

Bisphosphonate therapy: Patients with prostate cancer that has spread to the bones may undergo bisphosphonate therapy which blocks a bone cell from breaking down other parts of the bone.

How Is Theranostics Used to Treat Metastatic Prostate Cancer?

Radium 223 (Xofigo) is a radioactive drug used in a theranostics procedure to treat castrate-resistant Prostate Cancer, symptomatic Bone Metastases and no known Visceral Metastatic Disease.

The aim of the therapy is to control the bony metastases and to reduce symptoms of bony pain (if present).

Lutetium 177 PSMA is another radioactive drug that is used to treat metastatic castrate resistant prostate cancer, and can target all prostate cancer lesions as long as they express the PSMA ligand on the cell surface.

What Is Hepatocellular Carcinoma (HCC)?

Hepatocellular carcinoma (HCC), also known as primary liver cancer, is a complex heterogeneous cancer. When diagnosing this form of cancer, the choices for treatment will depend heavily on the extent of the cancer and the severity of the underlying chronic liver disease.

What Is the Survival Rate for Hepatocellular Carcinoma?

As Hepatocellular carcinoma is generally diagnosed late in its course, its median survival rate is approximately 6 to 20 months from the time of diagnosis. Globally, it is the 6th most common cancer, and it has become the 2nd most common cause of cancer-related mortality.

Can Hepatocellular Carcinoma Be Cured?

If caught early, it can sometimes be cured with surgery or a transplant. In more advanced cases, it often cannot be cured, but consistent treatment and support can help you live longer, with an improved quality of life.

What Are the Treatment Options Available For Hepatocellular Carcinoma?

There are two types of treatments for Hepatocellular carcinoma; curative and non-curative treatment options.

Curative treatment options include partial liver resection or hepatectomy, local ablation, and liver transplantation, which may provide a high probability of long-term survival.

Non-curative treatment options can be administered when patients are no longer suitable for curative treatment options due to the severity of the disease and condition of the liver or individual’s overall fitness capacity.

Non-curative treatment options that may prolong life are transarterial chemoembolisation (TACE), selective internal radiation therapy (SIRT) with yttrium-90 and systemic therapy. These treatment options are also occasionally used as a neoadjuvant treatment to downstage patients for curative therapy.

How Is Theranostics Used to Treat Hepatocellular Carcinoma?

In theranostics procedures, Yttrium-90 SIRT therapy, a form of Selective Internal Radiation Therapy (SIRT), can be used to treat liver cancer. Yttrium-90 SIRT therapy aims to reduce the size of inoperable tumours that cannot be removed in surgery and/or decrease the number of abnormal cells in the liver. Occasionally, a successful Yttrium-90 SIRT treatment may make it plausible for tumours to be removed surgically.

This form of radiation therapy targets and damages the cancer cells in the liver, reduces the size of the tumours, and prevents the cancer from metastasising further. It is administered via an injection of Yttrium-90 into the main blood vessels in the liver.

What Are Neuroendocrine Tumours (NETs)?

Neuroendocrine tumours (NETs) or neuroendocrine neoplasms (NENs) are rare tumours that develop in cells of the neuroendocrine system.

The World Health Organization (WHO) groups neuroendocrine tumours according to three main categories of tumour grade:

Well-differentiated neuroendocrine tumours, further subdivided into tumours with benign and those with uncertain behaviour
Well-differentiated (low grade) neuroendocrine carcinomas with low-grade malignant behaviour
Poorly differentiated (high grade) neuroendocrine carcinomas, which are the large cell neuroendocrine and small cell carcinomas.

What Is the Survival Rate for Neuroendocrine Tumours?

According to a study conducted on NETs patients from 1973 to 2014, the median survival duration was 41 months. Out of 73,782 NETs patients, the 1-, 3-, 5-, and 10-year overall survival rates were 72.8%, 52.7%, 39.4%, and 18.1%, respectively.

However, general statistics on survival rates must be viewed within the proper context. Your physician should conduct further prognosis depending on your condition.

Can Neuroendocrine Tumours Be Cured?

There are treatments available to prevent the tumours from spreading further. In some cases, neuroendocrine tumours are dormant, small and slow-growing. Studies have shown that slow-growing tumours, when diagnosed early and with proper treatment, can reduce symptoms and limit spreading.

What Are the Treatment Options Available For Neuroendocrine Tumours?

The treatment of neuroendocrine tumours depends on the prognosis and diagnosis of your condition. Treatment options depend on the grade of tumour, which part of the body it originated from, the level of aggressiveness, and how advanced it has spread to distant parts of the body.

How Is Theranostics Used to Treat Neuroendocrine Tumours?

In theranostics procedures to treat neuroendocrine tumours, Lutetium-177 Octreotate therapy (Lu-Octreotate) can be considered a radioactive drug to target radiation on cancer cells without damaging much of the healthy tissue.

Also referred to as Peptide Receptor Radionuclide Therapy (PRRT), Lu-Octreotate therapy combines octreotate, a manufactured form of the naturally produced hormone somatostatin, and lutetium-177, a compound that releases radiation into a tumour.

This theranostic procedure kills abnormal cells, which in turn reduces the size of the NETs tumour from growing further and multiplying. This may mean that the tumour will be relatively dormant for longer periods of time, but it does not mean that NETs can be cured completely.

Neuroendocrine Tumours, NETs, Coping With Neuroendocrine Tumours, Cancer Treatment in Singapore

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 an 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. The most common sites are the lungs, pancreas, appendix, small intestine, and rectum.

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. Common cancer symptoms such as fatigue, weight loss, and loss of appetite may be experienced if you have a neuroendocrine tumour (NET). 

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 signs and symptoms are usually more specific according to the type of NET.

How Are Neuroendocrine Tumours (NETs) Diagnosed?

When diagnosing neuroendocrine tumours, our doctors may order several tests to help them understand your symptoms. 

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.

Biopsy:

When a tumour is localised, a tissue biopsy is performed to help doctors 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 diagnosing neuroendocrine tumours is nuclear medicine imaging tests. We have mentioned octreotide scintigraphy (using a radioactive medium). Others may include PET-Gallium68 octreotide imaging (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. 

Iodine 123/131 MIBG Scans:

Iodine 123/131 MIBG Scans are usually used for neuroendocrine tumours of the paraganglionic type and pheochromocytoma.

Other Imaging Studies:

Other diagnostic means used are endoscopy, ultrasound, computed tomography, and magnetic resonance imaging (MRI).

What Are Some of the Treatment Options & Side Effects of Treatment 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.

  1. 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. 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.
  1. 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.

  1. 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 are fatigue, nausea accompanied by vomiting, hair loss, loss of appetite, and diarrhoea.

  1. 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.

  1. 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.

  1. 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.

The most common side effects of this type of therapy are nausea and vomiting, generalised fatigue, potential renal impairment, and marrow suppression. 

  1. 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. It is typically used to target lesions that might be causing symptoms. 

Side effects depend on the site of radiotherapy and will usually include skin dryness and redness in the treated area.

  1. TREATMENT TARGETING THE LIVER

Treatment targeting the liver can be used for individuals where the NETs have metastasised to the liver. Some examples of targeted treatment include;

Radiofrequency ablation (RFA). This involves inserting a probe into the lesion, which is subsequently destroyed typically by radiofrequency or microwave ablation.  

Chemoembilisation. This treatment involves injecting small particles with a chemotherapy agent into the liver artery and blocking the blood supply to the tumour with the effects of chemotherapy. 

Radioemboilisation. This involves injecting small radioactive particles directly into the liver artery, which causes radioactive damage to the tumours. 

Coping With Neuroendocrine Tumours (NETs) & Seeking Support

Being diagnosed with neuroendocrine tumours (NETs) can be overwhelming and stressful. Patients should find ways to cope with these feelings and seek support where possible. 

Learn about your diagnosis to help you understand and process what you are going through. Speak to our doctors and medical team should you have any questions about your treatment options and prognosis. This information can allow you to feel more confident in making the decisions you need to make during this period. 

Lean on loved ones for support, and do not be afraid to ask for help. Your family and friends can provide a healthy outlet for you to process and deal with your feelings. Let them know how they can help you out during this time, whether it is accompanying you to doctors appointments or helping you run errands. 

Coping & Support

Being diagnosed with a neuroendocrine tumour can be a stressful and overwhelming period. Over time, patients will find methods to cope. Until then, you may find it helpful to:

  • Learn as much as you can about your diagnosis, allowing you to make decisions about your care and treatment. Ask your doctor about your neuroendocrine tumour, including the available treatment options. As you gain a better understanding of the type of neuroendocrine tumour you have, you may become more confident in making decisions regarding your treatment. This can help you to feel more in control of the situation. 
  • Lean on your family and friends for support. While it can be difficult to address your diagnosis, talking about it allows you to share the load with those who love you. Additionally, verbalising your situation can help you think through your decisions regarding your treatment.
  • Connect with others with neuroendocrine tumours. Joining a support group can help you feel less alone. Support groups are also a safe space for you to voice your experience with others experiencing a similar diagnosis.

What Are Some Recommended Changes to My Diet if I Have Neuroendocrine Tumours (NETs)?

Diet & NETs

Eating a balanced diet is essential. However, neuroendocrine tumours (NETs) and their treatment options can result in diet problems. To ease this issue, speak to your dietitian and medical team about any dietary issues that you are facing during treatment. They will be able to give you medication and tips to help you cope with the side effects of neuroendocrine tumours. 

Common Diet Issues

There are many different types of NETs, and each type may have a different effect on your diet and appetite.

Diarrhoea

Diarrhoea is defined as having more than 3 watery or liquid stools within 24 hours. This can be severe, especially if you suffer from carcinoid syndrome, a group of symptoms that happen when a neuroendocrine tumour produces large amounts of hormones. 

During bouts of diarrhoea, you lose a lot of fluid as a result. Therefore, it is important to drink small sips of water frequently throughout the day.

Unfortunately, a high-fibre diet can worsen diarrhoea. You should instead stick to foods such as: 

  • White rice, pasta, and bread
  • Well-cooked eggs

Weight Loss & Loss of Appetite

If you have been diagnosed with neuroendocrine tumours, you may find that you are losing weight even if you are eating normally. Your body may not be effectively absorbing the nutrients from your food. Alternatively, you may be burning calories quicker than normal. 

To keep your body’s weight up, you can try: 

  • Eating smaller meals and snacks every 2 to 3 hours
  • Opting for foods that contain proteins such as meat or meat alternatives (tofu and soya), eggs, beans, or legumes
  • Using whole milk and butter
  • Drinking high-calorie drinks such as full-fat milk or smoothies

Feeling or Being Sick

To help with sickness, try:

  • Eating several small meals and snacks as opposed to 3 large meals
  • Eating light such as plain toast and crackers
  • Avoiding greasy and fatty foods

Difficulty Absorbing Fat (Fat Malabsorption)

Carcinoid syndrome refers to a group of symptoms that can happen when NETs produce excessive amounts of hormones. The most common symptoms of carcinoid syndrome are flushing of the skin, diarrhoea and tummy (abdominal) pain.

For some patients, certain foods and drinks can trigger the symptoms of carcinoid syndrome. Some common triggers are having a large meal and eating fatty or spicy foods. Additionally, foods and beverages containing high levels of amines can also trigger diarrhoea and flushing of the skin. These include:

  • Aged cheese
  • Alcohol and fermented beverages
  • Vinegar
  • Smoked and salted fish and meats
  • Yeast
  • Soybean products

Where Can I Find Support in Singapore if I Have Neuroendocrine Tumours (NETs)?

If you have been diagnosed with neuroendocrine tumours and are looking for support groups in Singapore, here are two options that you may want to consider: 

https://www.carcinoid.org/resources/support-groups/ 

https://www.nccs.com.sg/patient-care/specialties-services/support-groups 

How Can I Help Support a Loved One With Neuroendocrine Tumours (NETs)?

If you are the primary caregiver for someone who has been diagnosed with neuroendocrine tumours, you may be wondering how you can better care for your loved one. 

Understanding the Caregiver Role

As a caregiver, you provide support in various forms. This may include day-to-day activities, medical needs, helping them make important decisions, and tending to their emotional needs. 

The role of a caregiver takes many forms. Understanding what is required of you can better prepare you to carry out your responsibilities in helping your loved one. The extent of help that your loved one needs may vary depending on their stage of diagnosis, age, and overall health. 

There are 5 broad categories of what is needed from a caregiver. They are: 

  1. Physical needs, which includes aiding with daily activities.
  2. Health and medical needs; where you ensure that the patient is taking medicine and attending their medical appointments. 
  3. Emotional needs; in which you show your love and support. 
  4. Spiritual needs; where you are there to help them continue their religious practices and beliefs. 
  5. Financial and legal needs; where you aid them in managing their insurance and assets when they cannot do so and planning for their future. 

Caregiving Is a Team Effort

It is important to talk to your loved ones and include them in the planning and decision-making process if the patient is comfortable with this. It helps to be able to share the load amongst different caregivers. 

For instance, one family member or friend could be handling financial affairs and another providing daily care. Sharing the load can make it easier for you to take care of your loved one. 

Caregiver Support

Taking on the role of a caregiver can come with its own set of stresses and uncertainties. It is important to recognise your own needs and capabilities. This will help you avoid caregiver burnout. Remember, you cannot care for your loved one if you are unwell or burnt out. 

Lutetium-177 Octreotate Therapy, Neuroendocrine Tumours, What to Expect, Patient Journey, Theranostics, Theranostics Singapore, Cancer Treatment, Dr Andrew Tan

What Is Lutetium-177 Octreotate Therapy? 

One of the therapies used to treat neuroendocrine tumours is Lutetium-177 Octreotate Therapy. It is a targeted radioligand therapy that specially targets tumours that express somatostatin receptors (i.e. neuroendocrine tumours). 

Its method of action consists of using peptide molecules such as artificial octreotate – transport – linked to a carrier agent for radioisotopes such as Lu-177 that destroy cancer cells.

What Are Neuroendocrine Tumours (NETs)?

Neuroendocrine tumours are cancers that arise from very specialised cells in the body (neuroendocrine cells). These cells have similar traits to nerve cells and hormone-producing cells. They are rare tumours and can appear in the lungs, pancreas, appendix, small intestine, and rectum.

Some produce hormones excessively (functional neuroendocrine tumours), while others produce little to no hormones (non-functional neuroendocrine tumours).

What to Expect Before Treatment With Lutetium-177 Octreotate Therapy?

If you have been diagnosed with a neuroendocrine tumour, our doctor shall do the pertinent assessment to corroborate the disease and determine the exact stage of the disease.  

Among the laboratory tests, you can expect to require a complete blood count, 24h creatinine clearance, chromogranin A, kidney, and liver function test.

In addition – before starting the treatment – a PET scan with gallium octreotate shall be carried out. This will determine the extent of the disease as well as the somatostatin receptor density on the tumours. 

Then, our doctor will explain the procedure as well as the possible side effects, together with all the recommendations that you should know after applying the treatment.

What to Expect During Treatment With Lutetium-177 Octreotate Therapy?

This type of therapy can be performed on an outpatient basis in the nuclear medicine department. Before starting, the patient will be asked to consume an average of 1.5L of fluids.

A peripheral intravenous line is placed in the patient for the administration of the treatment, in conjunction with an antiemetic before the infusion of amino acid compounds.

Administration of amino acids will be 30 minutes before lutetium-177 octreotate accompanied by intravenous fluids. This stage of the procedure takes a couple of hours.

Lutetium-177 octreotate is then given as a slow, controlled infusion, which will last for approximately 20 minutes. After that, you must wait a couple of hours while the radioactivity decreases.

The entire treatment lasts approximately 4 to 6 hours, ranging from the preparation phase and the time spent waiting for the manifestation of side effects if any.

What to Expect After Treatment With Lutetium-177 Octreotate Therapy?

After the treatment, you may experience a series of varied symptoms, for which you will spend a couple of hours in the nuclear medicine department. The most common immediate side effect is nausea. 

The medical staff will be attentive to any manifestation outside of what is expected and will treat these side effects accordingly. 

Lutetium-177 octreotate therapy has been shown to increase progression-free survival and an increase in overall survival, with excellent safety profiles.

How Long Before I Can Be Discharged After Lutetium-177 Octreotate Therapy? 

Discharge from the nuclear medicine department will be after 6 to 8 hours on average after starting treatment. The reason behind this is to wait for radioactivity levels to decrease and for the side effects to subside.

The patient must go back to the nuclear medicine department for a full body scan and check on the progress of the treatment after 24 hours.

How Will I Feel After Lutetium-177 Octreotate Therapy? 

It is normal to experience several side effects since it is a radioactive treatment. 

Some possible side effects of Lutetium-177 Octreotate Therapy include: 

  • Nausea (usually counteracted with prophylactic treatment)
  • General fatigue and tiredness
  • Marrow suppression, leading to decreased platelet and red cell counts. This is usually transient and mild, but some patients may require a blood transfusion. 
  • Renal impairment 
  • Diarrhoea

Many of these symptoms are transitory. In the face of uncertainty, please consult our doctor.

Radiation Precautions of Lutetium-177 Octreotate Therapy

In general, the patients must follow a series of recommendations that we will mention below to avoid contamination to third parties:

  • The patient must keep well hydrated for two days after treatment. In other words, he must increase his fluid intake.
  • The radiotracer will be expelled in the urine in the next few days, so you must flush the toilet twice.
  • Avoid contact with pregnant women and children under five years of age – at least 6 feet apart – for at least a week after treatment. 
  • Normal activities can be resumed after a complete post-treatment body scan.

What Questions Should I Ask My Doctor?

Most individuals feel many fears when diagnosed with some type of cancer, so it is important to clarify each of your concerns. 

Below is a summary of questions (although there may be more):

  • What are my treatment options if I have a neuroendocrine tumour?
  • How many tests do I need to know if I am a candidate for Lutetium-177 Octreotate Therapy?
  • How long is the total duration of Treatment With Lutetium-117 Octreotate Therapy?
  • Is it really necessary to do a scan 24 hours after the infusion?
  • Will my overall survival increase after therapy?
  • What recommendations should you follow after treatment?
  • How long should I wait to be intimate with my partner?

In case of presenting discomfort or not feeling in a more optimal state of mind, always remember to call or go to our specialist. They will help you mitigate any discomfort through symptomatic treatments if necessary.

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.

Biopsy:

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.