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PANCREATIC Cancer SINGAPORE

The pancreas is a gland located behind the stomach and next to the intestines. It is made of two types of glands. One type of gland tissue produces insulin and other hormones. Although pancreatic cancer is common in the United States and accounts for the third most common cause of cancer death there, pancreatic cancer is not as common in Singapore.

 

They are called by various names, depending on the specific type of cancer cell or by the hormone produced by the cancer. Names include carcinoid tumour, islet cell carcinoma, insulinoma, glucagonoma, and so forth. These are not covered here because of their rarity. The other type of gland tissue produces enzymes which help in digestion of food. These glands drain into ducts which in turn drain into the small intestine. It is the cells of the ducts which can turn into cancer. These are more common pancreas cancers, usually of the type called adenocarcinoma.

Risk factors

Pancreatic cancer is mainly a genetic disease, a cancer caused by damage to the DNA. These mutations can be inherited or acquired as we age.

  • Smoking: increases the risk of pancreatic cancer and is associated with cancer at an early age. It is the leading preventable cause of pancreatic cancer.
     

  • Age: Risk of developing pancreatic cancer increases with age. Over 80% of pancreatic cancers develop between the ages of 60 and 80 years.
     

  • Gender: Cancer of the pancreas is more common in men.
     

  • Chronic pancreatitis: Long-term inflammation of the pancreas (pancreatitis) has been linked to pancreatic cancer.
     

  • Alcohol: Excessive alcohol intake can cause inflammation of the pancreas (pancreatitis) and also linked to increase the risk of pancreatic cancer.
     

  • Diabetes: Diabetes mellitus can be a symptom of pancreatic cancer, and long-standing adult-onset diabetes also increases the risk of pancreatic cancer.
     

  • Obesity: Obesity increases the risk of pancreatic cancer. Studies suggests that a body mass index ≥ 30 have a higher risk.
     

  • Diet: Diets rich in red meats, cholesterol, fried foods and nitrosamines may increase risk, while diets high in fruits and vegetables reduce risk.
     

  • Genes: One is at a higher risk if you have a family history of pancreatic cancer (≥ 2 first-degree relatives with pancreatic cancer. o  Inherited cancer syndromes increase the risk of pancreatic cancer e.g. breast cancer syndrome (BRCA2), Lynch syndrome, Peutz-Jeghers syndrome.
     

  • Environment: Exposure to cancer-causing substances (called carcinogens) such as asbestos, pesticides, dyes, and petrochemicals may be linked to pancreatic cancer.

Signs and symptoms

Signs and symptoms of pancreatic cancer often don't occur until the disease is advanced.

Jaundice

  • Jaundice is yellowing of the eyes and skin; this is often one of the first signs, it is caused by the build-up of bilirubin which the liver excretes as bile.

  • When the bile duct becomes blocked by the cancer, bile can’t reach the intestines and the level of bilirubin in the body builds up.

 

Dark coloured urine

  • Dark urine may be noticed as the first sign.  As bilirubin levels in the blood increase, the urine becomes brown in color

 

Light coloured stools

  • Bile gives stools their brown color. If the bile duct is blocked, stools might be pale or gray.

  • When bile and pancreatic enzymes can’t get to the intestines to digest fats, the stools can become greasy and might float in the toilet.
     

Itchy skin

  • When bilirubin builds up in the skin, it can start to itch as well as turning yellow.

 

Abdominal or Back pain

  • Pain in the abdomen that radiates to the back is common in pancreatic cancer. It can grow and press on other nearby organs or affect nerves, causing pain.

 

Loss of Weight and appetite

  • Unintended weight loss and poor appetite is very common in people with pancreatic cancer.

 

Nausea and vomiting

  • If the cancer presses on the stomach it can block the outlet and this can cause nausea, vomiting, and pain that tend to be worse after eating.

 

Gallbladder or Liver swelling

  • If the cancer blocks the bile duct, the gallbladder can be enlarged and felt as a lump under the right ribcage. o    The liver also can be enlarged if the cancer has spread to the liver.

 

Diabetes

  • Sudden Adult-onset Diabetes can be a sign- pancreatic cancers cause diabetes (high blood sugar) because they destroy the insulin-making cells.

Diagnosing pancreatic cancer

The signs and symptoms of the disease are non-specific. If pancreatic cancer is suspected, the initial diagnostic test would be a CT or computerised scan of the abdomen. The CT scan is able to detect any pancreatic mass greater than two centimetres, 95 percent of the time. Smaller cancers are more difficult to detect. Magnetic resonance imaging (MRI) scans can visualise the pancreas and the ducts in the pancreas. This can be particularly useful when planning surgery.

 

Another procedure that is often done is an endoscopic retrograde cholangiopancreaticography (ERCP) which involves using a fibre-optic scope to look into the stomach and small intestine where the ducts of the pancreas drain into. X-ray dye is then injected into the ducts of the pancreas and X-rays taken of the pancreas.

 

Irregularities of the pancreatic ducts can then be visualised. Small pieces of tissue can also be biopsied during this procedure. If a blockage of the ducts is seen, a small plastic tube, called a stent, can be placed during this same procedure to try and bypass the block. Potential complications of this procedure include infection of the pancreas and perforation of the small intestine. A stent which is placed will need to be changed three to four times monthly, because the stent can be blocked by normal secretions from the pancreas.

 

Sometimes, when a biopsy cannot be obtained via ERCP, a percutaneous biopsy of the pancreatic lesion is performed to obtain tumour tissue for diagnosis. This involves inserting a needle through the abdominal wall to the pancreas under CT or ultrasound imaging guidance.

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Treatment

Treatment options and recommendations depend on several factors, including the type and stage of cancer, possible side effects, and the patient’s preferences and overall health. Take time to learn about all of your treatment options and be sure to ask questions about things that are unclear. Talk with your doctor about the goals of each treatment and what you can expect while receiving the treatment. These types of talks are called “shared decision making.” Shared decision making is when you and your doctors work together to choose treatments that fit the goals of your care. Shared decision making is particularly important for pancreatic cancer because there are different treatment options. Learn more about making treatment decisions.

 

When detected at an early stage, pancreatic cancer has a much higher chance of being successfully treated. However, there are also treatments that can help control the disease for patients with later stage pancreatic cancer to help them live longer.

Surgery


Surgery for pancreatic cancer includes removing all or part of the pancreas, depending on the location and size of the tumor in the pancreas. An area of healthy tissue around the tumor is also often removed. This is called a margin. A goal of surgery is to have “clear margins” or “negative margins,” which means that there are no cancer cells in the edges of the healthy tissue removed. A surgical oncologist is a doctor who specializes in treating cancer using surgery. Learn more about the basics of cancer surgery. Only about 20% of people diagnosed with pancreatic cancer are able to have surgery because most pancreatic cancers are found after the disease has already spread. When surgery is a potential treatment option, there are many things to think about before a surgery of this type. It's important to have a thorough discussion with your doctor before deciding on surgical treatment, including talking about the benefits, risks, and recovery time. If surgery is not an option, you and your doctor will talk about other treatment options. Surgery for pancreatic cancer may be combined with systemic therapy and/or radiation therapy (see below). Typically, these additional treatments are given after surgery, which is called adjuvant therapy. However, systemic therapy and/or radiation therapy may sometimes be used before surgery to shrink a tumor. This is called neoadjuvant therapy or pre-operative therapy. After neoadjuvant therapy, the tumor is re-staged before planning surgery. Re-staging is usually done with another CT scan to look at the change in tumor size and what nearby structures and blood vessels it is affecting. Different types of surgery are performed depending on the purpose of the surgery.

  • Laparoscopy. Sometimes, the surgeon may choose to start with a laparoscopy. During a laparoscopy, several small holes are made in the abdomen and a tiny camera is passed into the body while a patient receives anesthesia. Anesthesia is medication to help block the awareness of pain. During this surgery, the surgeon can find out if the cancer has spread to other parts of the abdomen. If it has, surgery to remove the primary tumor is generally not recommended.
  • Surgery to remove the tumor. Different types of surgery are used depending on where the tumor is located in the pancreas. In all of the surgeries discussed below, nearby lymph nodes are removed as part of the operation. More than 1 type of surgeon, as well as other specialists, will usually be involved in your surgery.
    • Whipple procedure. This surgery may be done if the cancer is located only in the head of the pancreas. This is an extensive surgery in which the surgeon removes the head of the pancreas and the part of the small intestine called the duodenum, as well as the bile duct and stomach. Then, the surgeon reconnects the digestive tract and biliary system. A surgeon with experience treating pancreatic cancer should perform this procedure.
    • Distal pancreatectomy. This surgery is commonly done if the cancer is located in the tail of the pancreas. In this surgery, the surgeon removes the tail and body of the pancreas, as well as the spleen.
    • Total pancreatectomy. If the cancer has spread throughout the pancreas or is located in many areas in the pancreas, a total pancreatectomy may be needed. A total pancreatectomy is the removal of the entire pancreas, part of the small intestine, a portion of the stomach, the common bile duct, the gallbladder, and the spleen.




Radiation Theraphy


Radiation therapy is the use of high-energy x-rays or other particles to destroy cancer cells. A doctor who specializes in giving radiation therapy to treat cancer is called a radiation oncologist. The most common type of radiation treatment is called external-beam radiation therapy, which is radiation given from a machine outside the body. Learn more about the basics of radiation therapy. External-beam radiation therapy is the type of radiation therapy used most often for pancreatic cancer. A radiation therapy regimen, or schedule, usually consists of a specific number of treatments given over a set period of time. There are different ways that radiation therapy can be given:

  • Traditional radiation therapy. This is also called conventional or standard fraction radiation therapy. It is made up of daily treatments of lower doses of radiation per fraction or day. It is given over 5 to 6 weeks in total.
  • Stereotactic body radiation (SBRT) or cyberknife. These are shorter treatments of higher doses of radiation therapy given over as few as 5 days. This is a newer type of radiation therapy that can provide more localized treatment in fewer treatment sessions. Whether this approach works as well as traditional radiation therapy is not yet known, and it may not be appropriate for every person. It should only be given in specialized centers with experience and expertise in using this technology for pancreatic cancer and identifying who it will work best for.
  • Proton beam therapy. This is a type of external-beam radiation therapy that uses protons rather than x-rays. At high energy, protons can destroy cancer cells. It also lessens the amount of healthy tissue that receives radiation. Proton beam therapy may be given for a standard amount of time or for a shorter time like SBRT. It is not yet known whether it works better than standard radiation therapy, and it may not be an option for every person. It should be given in treatment centers that have the experience and skills needed to use this treatment for pancreatic cancer, which may only be available through a clinical trial.
Radiation therapy may be helpful for reducing the risk of the pancreatic cancer returning or re-growing in the original location. But there remains much uncertainty as to how much, if at all, it lengthens a person’s life.




Therapies using medication


Systemic therapy is the use of medication to destroy cancer cells. This type of medication is given through the bloodstream to reach cancer cells throughout the body. Systemic therapies are generally prescribed by a medical oncologist, a doctor who specializes in treating cancer with medication. Common ways to give systemic therapies include an intravenous (IV) tube placed into a vein using a needle or in a pill or capsule that is swallowed (orally). Chemotherapy is the main type of systemic therapy used for pancreatic cancer. However, targeted therapy and immunotherapy are occasionally used and are being studied as potential. Each of these types of therapies are discussed below in more detail. A person may receive only 1 type of systemic therapy at a time or a combination of systemic therapies given at the same time. They can also be given as part of a treatment plan that includes surgery and/or radiation therapy. The medications used to treat cancer are continually being evaluated. Talking with your doctor is often the best way to learn about the medications prescribed for you, their purpose, and their potential side effects or interactions with other medications. It is also important to let your doctor know if you are taking any other prescription or over-the-counter medications or supplements. Herbs, supplements, and other drugs can interact with cancer medications. Learn more about your prescriptions by using searchable drug databases.




Chemotheraphy


Chemotherapy is the use of drugs to destroy cancer cells, usually by keeping the cancer cells from growing, dividing, and making more cells. A chemotherapy regimen, or schedule, usually consists of a specific number of cycles given over a set period of time. There is usually a rest period in between cycles. A patient may receive 1 drug at a time or a combination of different drugs given at the same time. The following drugs are approved by the U.S. Food and Drug Administration (FDA) for pancreatic cancer:

  • Capecitabine (Xeloda)
  • Erlotinib (Tarceva), a type of targeted therapy (see below)
  • Fluorouracil (5-FU)
  • Gemcitabine (Gemzar)
  • Irinotecan (Camptosar)
  • Leucovorin (Wellcovorin)
  • Nab-paclitaxel (Abraxane)
  • Nanoliposomal irinotecan (Onivyde)
  • Oxaliplatin (Eloxatin)
There are generally more side effects when 2 or more drugs are used together. Combination treatments are usually best for people who are able to carry out their usual activities of daily living without help. The choice of which combination to use varies depending on the cancer center and often depends on the oncologist’s experience with the drugs, as well as the different side effects and a patient’s overall health. For pancreatic cancer, chemotherapy may be described by when and how it is given:
  • First-line chemotherapy. This is generally the first treatment used for people with either locally advanced or metasatic pancreatic cancer.
  • Second-line chemotherapy. When the first treatment does not work or stops working to control cancer growth, the cancer is called refractory. Sometimes, first-line treatment does not work at all, which is called primary resistance. Or, treatment may work well for a while and then stop being effective later, which is sometimes called secondary or acquired resistance. In these situations, patients may benefit from additional treatment with different drugs if the patient’s overall health is good. There is significant ongoing research focused on developing other new treatments for second-line, as well as third-line, treatment and beyond. Some of these have shown considerable promise.
  • Off-label use. This refers to a drug being given for a condition not listed on its label. This means that it is not being given for the condition(s) that the drug is specifically approved for by the FDA. It can also mean that the drug is being given differently than the instructions on the label. An example of this is if your doctor wants to use a drug only approved for breast cancer to treat pancreatic cancer. Using a drug off-label is only recommended when there is solid evidence that the drug may work for another disease not included on the label. This evidence may include previously published research, promising results from ongoing research, or results from molecular tumor testing that suggest that the drug may work. However, off-label use of drugs may not be covered by your health insurance provider. Exceptions are possible, but it is important that you and/or your health care team talk with your insurance provider before this type of treatment begins.




Targeted therapy


Targeted therapy is a treatment that targets the cancer’s specific genes, proteins, or the tissue environment that contributes to cancer growth and survival. This type of treatment blocks the growth and spread of cancer cells and limits damage to healthy cells. Not all tumors have the same targets. To find the most effective treatment, your doctor may run tests to identify the genes, proteins, and other factors in your tumor. This helps doctors better match each patient with the most effective treatment whenever possible. In addition, research studies continue to find out more about specific molecular targets and new treatments directed at them.

  • Erlotinib (Tarceva) is approved by the FDA for people with advanced pancreatic cancer in combination with the chemotherapy drug gemcitabine. Erlotinib blocks the effect of the epidermal growth factor receptor (EGFR), a protein that can become abnormal and help cancer grow and spread. The side effects include a skin rash similar to acne, diarrhoea, and fatigue.
  • Olaparib (Lynparza) is approved for people with metastatic pancreatic cancer associated with a germline (hereditary) BRCA mutation. It is intended for use as maintenance therapy after a patient has been on platinum-based chemotherapy, such as oxaliplatin or cisplatin, for at least 16 weeks with no evidence of disease progression.
  • Larotrectinib (Vitrakvi) is a tumor-agnostic treatment that can be used for any type of cancer that harbours a specific genetic change called an NTRK fusion. This type of genetic change is found in a range of cancers, including pancreatic cancer, though it is rare. It is approved as a treatment for pancreatic cancer that is metastatic or locally advanced and has not responded to chemotherapy.




Immunotherapy


Immunotherapy, also called biologic therapy, is designed to boost the body's natural defences to fight the cancer. It uses materials made either by the body or in a laboratory to improve, target, or restore immune system function. Immune checkpoint inhibitors, which include anti-PD-1 antibodies such as pembrolizumab (Keytruda), are an option for treating pancreatic cancers that have high microsatellite instability (MSI-H) (see Diagnosis). Approximately 1% to 1.5% of pancreatic cancers are associated with high MSI-H.