Pancreatic Neuroendocrine Tumour Metastatic

Pancreatic neuroendocrine tumours that have spread to other parts of the body represent a challenging form of cancer, yet they often grow more slowly than other pancreatic cancers and can be managed for extended periods with appropriate treatment.

Table of contents

• What is a Pancreatic Neuroendocrine Tumour?
• When the Tumour Spreads
• Symptoms
• How It Is Diagnosed
• Treatment Options
• What to Expect

What is a Pancreatic Neuroendocrine Tumour?

A pancreatic neuroendocrine tumour (also called a PNET or pancreatic NET) is a rare type of cancer that starts in the hormone-making cells of the pancreas^[1]. The pancreas is a gland about 6 inches long that sits behind the stomach and in front of the spine. It has two main types of cells: those that make digestive enzymes and those that produce hormones^[2].

Pancreatic neuroendocrine tumours develop from the hormone-producing cells, which are called islet cells. This is why these tumours are sometimes referred to as islet cell tumours or islet cell cancer^[1]. These tumours are much less common than the usual type of pancreatic cancer and tend to have a better outlook^[2].

• Pancreas
• Liver

Some pancreatic neuroendocrine tumours continue to make hormones. These are called functional tumours because they produce extra amounts of hormones such as gastrin, insulin, or glucagon, which cause specific symptoms^[2]. Most pancreatic neuroendocrine tumours, however, do not produce extra hormones and are called nonfunctional tumours. These often do not cause symptoms until they grow large or spread^[2].

When the Tumour Spreads

Pancreatic neuroendocrine tumours are frequently malignant, meaning they are cancerous and can spread to other parts of the body. Between 50 and 80 percent of these tumours are malignant, except for a type called insulinoma, which is usually not cancerous^[6]. When the tumour is metastatic, it means the cancer has spread beyond the pancreas to other organs or distant parts of the body.

The most common place for these tumours to spread is the liver. They may also spread to lymph nodes, bones, and other distant sites^[3][6]. Because nonfunctional tumours do not produce hormones that cause noticeable symptoms, they are often quite large or have already spread by the time they are discovered^[2].

Despite being metastatic, pancreatic neuroendocrine tumours generally grow more slowly than other types of pancreatic cancer. Well-differentiated tumours, where the cancer cells look more like healthy cells, tend to be more slow-growing. Patients with these tumours often live longer, even with advanced disease^[3].

Symptoms

Pancreatic neuroendocrine tumours sometimes do not cause symptoms, especially in the early stages^[1]. When symptoms do appear, they can vary depending on whether the tumour is functional or nonfunctional and where it has spread.

General symptoms that may occur include^[1]:

• Heartburn
• Weakness and fatigue
• Muscle cramps
• Indigestion
• Diarrhea
• Weight loss
• Skin rash
• Constipation
• Pain in the abdomen or back
• Yellowing of the skin and the whites of the eyes
• Dizziness
• Blurred vision
• Headaches
• Increased thirst and hunger

Functional tumours produce specific symptoms based on the type of hormone they make. For example, tumours that make too much gastrin can cause stomach ulcers and severe diarrhea. Tumours that produce too much insulin can cause dangerously low blood sugar levels^[2].

In one reported case, a patient experienced severe digestive problems, including diarrhea and flushing, along with significant weight loss and abdominal pain before being diagnosed with metastatic disease^[3].

How It Is Diagnosed

Diagnosing a pancreatic neuroendocrine tumour and determining whether it has spread involves several types of tests.

Blood and urine tests can show excess hormones or other signs of a pancreatic neuroendocrine tumour. Blood samples can also be checked for genetic changes that may increase the risk of these tumours^[10].

Imaging tests take pictures of the body and can show the location and size of the tumour as well as whether it has spread. Common imaging tests include^[10]:

• Computed tomography (CT) scans
• Magnetic resonance imaging (MRI)
• Positron emission tomography (PET) scans
• Nuclear medicine tests, which involve injecting a radioactive tracer that sticks to neuroendocrine tumour cells

An endoscopic ultrasound may be performed by passing a thin, flexible tube with a camera down the throat and into the stomach and small intestine. The tube has a special ultrasound tool to create detailed pictures of the pancreas from inside the body^[10].

A biopsy involves removing a small sample of tissue to examine under a microscope. This is the only way to confirm the diagnosis and determine the type and grade of the tumour. The biopsy sample can be obtained through the endoscope or by inserting a needle through the skin into the tumour or a metastatic site such as the liver^[10][3].

The tumour tissue is examined for its differentiation and grade. Well-differentiated tumours have cells that look more like normal cells and tend to grow more slowly. The grade is determined by measuring how fast the cancer cells are dividing, often using a marker called Ki67. A Ki67 level of 10 to 15 percent indicates an intermediate-grade tumour^[3].

Treatment Options

The treatment of metastatic pancreatic neuroendocrine tumours is complex and depends on several factors, including the type of tumour, how fast it is growing, where it has spread, and the patient’s overall health. Treatment often involves a team of specialists working together^[6].

Surgery remains the only approach that can potentially cure the disease, even in some cases where the cancer has spread. Surgeons may remove the primary tumour in the pancreas and, in selected patients, also remove metastases from the liver^[6]. However, surgery is not always possible if the tumour has spread too widely.

Medical therapy includes several options^[6]:

• Somatostatin analogues (such as lanreotide and octreotide) are hormone-like drugs that can block the growth of neuroendocrine tumours and help control symptoms caused by functional tumours
• Targeted therapies are newer drugs that specifically target cancer cells. Examples include everolimus and sunitinib
• Chemotherapy uses drugs to kill cancer cells. A combination called CAPTEM (capecitabine and temozolomide) is sometimes used
• Peptide receptor radionuclide therapy (PRRT) is a newer treatment that delivers radiation directly to tumour cells by attaching a radioactive particle to a targeting molecule

One recently approved targeted therapy is cabozantinib, which was shown to significantly slow disease progression in patients with well-differentiated pancreatic neuroendocrine tumours who had received previous treatment^[12].

Liver-directed therapies are treatments aimed specifically at metastases in the liver, since this is the most common site of spread. These may include procedures that block blood flow to the tumours or deliver chemotherapy or radiation directly to the liver^[6].

In very selected cases, liver transplantation may be considered for patients with metastatic neuroendocrine tumours confined to the liver. This option is unique to neuroendocrine tumours among cancers^[6].

In one patient’s experience, treatment included several lines of chemotherapy, somatostatin analogues, and radiotherapy for bone metastases over a period of more than two years^[3].

What to Expect

The outlook for patients with metastatic pancreatic neuroendocrine tumours varies considerably depending on the specific characteristics of the tumour. Well-differentiated, low-grade tumours are generally slow-growing and are described as having a more indolent behavior compared to other cancers^[3][6].

Many patients with metastatic pancreatic neuroendocrine tumours live for years with their disease, especially when it is well-differentiated. The five-year survival rate for metastatic pancreatic neuroendocrine tumours is 23 percent^[12]. This is significantly better than the outlook for the most common type of pancreatic cancer.

However, not all pancreatic neuroendocrine tumours behave the same way. Intermediate-grade tumours have a slightly worse outlook than low-grade tumours^[3]. Poorly differentiated neuroendocrine carcinomas, which are high-grade and fast-growing, behave more aggressively and have a much worse outlook^[3].

Because many patients with metastatic pancreatic neuroendocrine tumours live for extended periods, preserving quality of life and personalizing treatment according to both the tumour’s characteristics and the patient’s individual needs are essential parts of care^[6].