Soft tissue sarcoma

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Gastrointestinal stromal tumours (GISTs)

Gastrointestinal (GI) stromal tumours, or GISTs, start in interstitial cells of Cajal (ICCs). ICCs are specialized cells in the GI tract. They have characteristics of both smooth muscle cells and nerve cells. They receive signals from the brain to make muscles in the stomach, small intestine and large intestine tighten (contract) and relax (expand). The tightening and relaxing of these muscles is called peristalsis. This process moves food and liquid through the digestive system.

GISTs are a common type of soft tissue sarcoma. A GIST can occur anywhere in the GI tract, but they develop most often in the stomach. The small intestine is the second most common location. GISTs can also develop in the esophagus, colon, rectum, omentum and mesentery. The omentum is a fatty fold in the peritoneum (the membrane that lines the walls of the abdomen and pelvis) that covers and supports organs and blood vessels in the abdomen. The mesentery is fatty tissue that contains the blood vessels to the bowel as well as lymph nodes.

GISTs can develop at any age, but they usually occur in people over 50 years of age. Most GISTs have a mutation in the KIT, or c-Kit, gene. This mutation causes the body to make too much of the KIT protein. The second most common mutation in GISTs is in the platelet-derived growth factor receptor alpha (PDGFRA) gene. This mutation causes the body to make too much PDGFRA protein. Both the KIT and PDGFRA proteins are enzymes called tyrosine kinases, which signal cells to grow and can trigger some GISTs to grow in an uncontrolled way.

Risk factors

Almost all GISTs occur sporadically. This means there is no clear reason why they develop. In a small number of people, GIST develops due to a hereditary syndrome. These syndromes include:

  • familial GIST syndrome
  • neurofibromatosis type 1 (von Recklinghausen disease)
  • Carney-Stratakis syndrome
  • Carney’s triad

These syndromes are unavoidable, so there is no way for people who have them to lower their risk of developing GISTs.

Symptoms

GISTs usually don’t cause symptoms in the early stages. Symptoms tend to occur only when the tumour has grown large enough to cause problems. The symptoms of GISTs depend on if they develop in the stomach or small intestine. Signs and symptoms may include:

  • nausea
  • vomiting
  • loss of appetite
  • weight loss
  • a lump in the abdomen
  • abdominal pain or discomfort
  • bleeding from the GI tract, such as vomiting blood or blood in the stool
  • fatigue due to anemia caused by bleeding in the GI tract

GISTs are often discovered when you don’t have any symptoms. They may be found when you have an imaging test for another reason.

Diagnosis

Diagnosing GISTs usually begins with a visit to your family doctor. Your doctor will ask you about any symptoms you have and will do a physical exam. Based on this information, your doctor may refer you to a specialist or order tests to check for GISTs or other health problems. This may include the following:

  • complete blood count (CBC)
  • blood chemistry tests
  • fecal occult blood test (FOBT)
  • computed tomography (CT) scan or magnetic resonance imaging (MRI) of the abdomen and pelvis
  • ultrasound of the abdomen
  • gastroscopy or upper GI endoscopy
  • colonoscopy
  • endoscopic ultrasound
  • biopsy

Your doctor may do a biopsy during an endoscopy. The sample taken during endoscopy may be too small to give a definite diagnosis. Ideally, a tissue biopsy should be taken to confirm the diagnosis of a GIST before a treatment plan is started. This biopsy is usually done at a clinic by doctors with experience treating GISTs. A sarcoma specialist will plan the biopsy, which may be done by a specialized radiologist.

Types of GISTs

GISTs may be non-cancerous, or benign. This means that they usually do not spread, or metastasize, to other parts of the body. They are not usually life-threatening. Smaller tumours that are less than 2 cm in diameter are usually non-cancerous.

GISTs can also be cancerous, or malignant. Cancerous tumours can spread to other parts of the body. GISTs that are larger than 2 cm are more likely to be cancerous. In general, smaller tumours have a better prognosis than larger tumours. Other factors that are important in predicting the behaviour of GISTs are tumour location and grade.

Grading

Grade is the most important factor in planning treatment and predicting outcome for GISTs. To find the grade of a GIST, the pathologist looks at a tissue sample from the tumour under a microscope. The grade that the pathologist gives is based on the mitotic rate, which is how fast the cancer cells are growing and dividing. The grade is described as being either low or high. GISTs with a low mitotic rate have a better prognosis.

Knowing the grade gives your healthcare team an idea of how quickly the cancer may be growing and how likely it is to spread. This helps them plan your treatment. The grade can also help the healthcare team predict how you might respond to treatment.

GradeMitotic rateNumber of mitoses per 50 high-power fields (HPF)

low

low

less than 5

high

high

more than 5

Stages of GISTs

Staging describes or classifies a cancer based on how much cancer there is in the body and where it is when first diagnosed. This is often called the extent of cancer. Information from tests is used to find out the size of the tumour, where the cancer started, whether the cancer has spread from where it first started and where the cancer has spread. Your healthcare team uses the stage to plan treatment and estimate the outcome (your prognosis).

The most common staging system for GISTs is the TNM system. For GISTs there are 4 stages. Often the stages 1 to 4 are written as the Roman numerals I, II, III and IV. Generally, the higher the stage number, the more the cancer has spread. Talk to your doctor if you have questions about staging.

When describing the stage, doctors may use the words localized or metastatic. Localized means that the cancer is only in the organ or close to where it started and has not spread to other parts of the body. Metastatic means in a part of the body farther from where the GIST started.

The stages of GISTs also depend on the mitotic rate, which shows how quickly the cancer cells grow and divide.

Find out more about staging cancer.

Stages for GISTs of the stomach and omentum

Stage 1A – The tumour is 5 cm or smaller with a low mitotic rate.

Stage 1B – The tumour is larger than 5 cm, but not more than 10 cm. It has a low mitotic rate.

Stage 2 – The tumour is 5 cm or smaller with a high mitotic rate. Or the tumour is larger than 10 cm with a low mitotic rate.

Stage 3A – The tumour is larger than 5 cm, but not more than 10 cm. It has a high mitotic rate.

Stage 3B – The tumour is larger than 10 cm with a high mitotic rate.

Stage 4 – The cancer has spread to nearby lymph nodes or to other parts of the body (distant metastasis), such as to the liver or peritoneal cavity. This is also called metastatic cancer. The cancer has a low or high mitotic rate.

Stages for GISTs of the small intestine, esophagus, colon, rectum, mesentery and peritoneum

Stage 1 – The tumour is 5 cm or smaller with a low mitotic rate.

Stage 2 – The tumour is larger than 5 cm, but not more than 10 cm. It has a low mitotic rate.

Stage 3A – The tumour is 2 cm or smaller with a high mitotic rate. Or the tumour is larger than 10 cm with a low mitotic rate.

Stage 3B – The tumour is larger than 2 cm with a high mitotic rate.

Stage 4 – The cancer has spread to nearby lymph nodes or other parts of the body, such as to the liver. This is also called metastatic cancer. The cancer has a low or high mitotic rate.

Recurrent GIST

Recurrent GIST means that the cancer has come back after it has been treated. If it comes back in the same place or close to where the cancer first started, it’s called local recurrence. It can also recur in another part of the body. This is called a metastatic GIST.

Disease progression

GIST cells can spread from the GI tract to other parts of the body and develop into new tumours. The new tumour is called a metastasis or secondary tumour. If more than one tumour develops in another part of the body, they are called metastases.

Understanding how a type of cancer usually grows and spreads helps your healthcare team plan your treatment and future care. If GISTs spread, they are most likely to spread within the abdomen, particularly to the liver or peritoneal cavity (the space in the abdomen that contains the stomach, liver and intestines). GISTs can also spread to the lungs or bones, but this is uncommon.

Treatments

GISTs behave differently than other types of soft tissue sarcoma, so they are treated differently. When deciding which treatments to offer for GISTs, your healthcare team will consider:

  • if the tumour is larger than 2 cm
  • whether or not the tumour is in the stomach
  • if the tumour is cancerous (malignant) or non-cancerous (benign)
  • if it is high or low grade
  • stage
  • your overall health

Surgery

Surgery is usually the main treatment for a GIST that hasn’t spread. The goal of the surgery is to completely remove all of the cancer. Depending on the location of the tumour, the surgeon may also need to remove parts of nearby organs or tissues. Lymph nodes near the tumour are usually not removed because GISTs don’t often spread to the lymph nodes.

GISTs in the stomach

Surgery is the main treatment for GISTs in the stomach. The entire tumour and a margin of healthy tissue around it are removed. The types of surgery used may include:

  • wedge resection
  • partial or total gastrectomy (part or all of the stomach is removed)
  • removal of any nearby organs, such as the spleen, pancreas or diaphragm, that contain cancer

GISTs in the small intestine

Surgery is also the main treatment for GISTs in the small intestine. Different types of surgery may be done depending on where the GIST is in the small intestine. The types of surgery used may include:

  • bowel resection
  • partial removal of the duodenum (the first part of the small intestine) with reconstruction
  • Whipple procedure, or pancreaticoduodenectomy

Biological therapy

Imatinib (Gleevec) is a biological therapy drug used to treat GISTs. Biological therapy uses natural or artificial substances that change the way cells behave. Imatinib is also called a targeted therapy. Targeted therapy uses drugs to target specific molecules (such as proteins) on the surface of cancer cells. These molecules help send signals that tell cells to grow or divide. By targeting these molecules, the drugs stop the growth and spread of cancer cells while limiting harm to normal cells. Imatinib blocks tyrosine kinase, which is an enzyme that the tumour needs to grow. Because it blocks this enzyme, imatinib is called a tyrosine kinase inhibitor.

Imatinib is used to treat GISTs that:

  • can’t be removed with surgery (are unresectable)
  • have come back after treatment, or recurred
  • have spread, or metastasized, to other parts of the body

Imatinib may also be used to shrink a tumour that is borderline resectable. This is done to make it possible to remove the tumour with surgery. It may also be done so the surgeon doesn’t have to completely remove organs that the GIST has grown into. For example, imatinib may be used to shrink GISTs in the rectum that have grown into the bladder or prostate so these organs don’t have to be removed.

Imatinib may be given after surgery when doctors think there is a high risk that the GIST will come back, or recur. Large or high-grade tumours or those that rupture (break open) during removal are usually considered high risk.

Imatinib is taken by mouth, usually every day for up to 3 years. Researchers are still studying this drug to find out how long people should take it for best results. Unfortunately, tumours may no longer respond to the imatinib or may become resistant to it when it is taken for a long time. If imatinib is no longer effective, you may be offered second-line drug therapy.

Second-line drug therapy

Sunitinib (Sutent) is another tyrosine kinase inhibitor. It works by stopping the tumour from creating new blood vessels. The process of making new blood vessels is called angiogenesis. Because sunitinib prevents blood vessels from forming, it is called an anti-angiogenic drug.

Sunitinib may be used when the cancer doesn’t respond to imatinib. It may also be used if you can’t tolerate imatinib. Sunitinib is not as “selective” as imatinib as it inihibits many other growth pathways. Therefore, people often experience a broader range of side effects when using sunitinib.

Radiation therapy

External beam radiation therapy may be offered to relieve symptoms of advanced disease, such as pain or bleeding (palliative radiation therapy).

Recurrent GISTs

Treatment options for GISTs that come back, or recur, after treatment depend on where the cancer comes back and how much cancer is in the body. For most recurrences, imatinib will be used because it offers the best chance of shrinking tumours. If imatinib does not work at first, the doctor may increase the dose or try sunitinib instead. Your healthcare team may also consider surgery to remove recurrent GISTs in certain situations.

For more detailed information on specific drugs, go to sources of drug information.

peritoneal cavity

The space between the parietal peritoneum (the membrane that lines the walls of the abdomen and pelvis) and the visceral peritoneum (the membrane that covers and supports most of the abdominal organs).

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