GIST 2017-05-27T08:19:27+00:00

Gastrointestinal Stromal Tumors

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasms of the gastrointestinal tract. GISTs arise in the smooth muscle pacemaker interstitial cell of Cajal, or similar cells. They are defined as tumors whose behavior is driven by mutations in the KIT gene (85%), PDGFRA gene (10%), or BRAF kinase (rare). 95% of GISTs stain positively for KIT (CD117). Most (66%) occur in the stomach and gastric GISTs have a lower malignant potential than tumors found elsewhere in the GI tract.

EPIDEMIOLOGY

GISTs occur in 10-20 per one million people. The true incidence might be higher, as novel laboratory methods are much more sensitive in diagnosing GISTs.The estimated incidence of GIST in the United States is approximately 5000 cases annually. This makes GIST the most common form of sarcoma, which constitutes more than 70 types of cancer.

The majority of GISTs present at ages 50–70 years. Across most of the age spectrum, the incidence of GIST is similar in men and women.

Adult GISTs are rare before age 40. Pediatric GISTs are considered to be biologically distinct. Unlike GISTs at other ages, pediatric GISTs are more common in girls and young women. They appear to lack oncogenic activating tyrosine kinase mutations in both KIT and PDGFRA. Pediatric GISTs are treated differently than adult GIST. Although the generally accepted definition of pediatric GIST is a tumor that is diagnosed at the age of 18 years or younger,”pediatric-type” GISTs can be seen in adults, which affects risk assessment, the role of lymph node resection, and choice of therapy.

Gastrointestinal stromal tumors (GISTs Symptoms

People with early stage GIST often do not have any symptoms. So early stage GIST may be found when people are having tests for other medical conditions. Most GISTs are diagnosed in later stages of the disease. The symptoms of advanced GIST are likely to include

  • Pain or discomfort in the tummy (abdomen)
  • A feeling of fullness
  • Being sick
  • Blood in stools or vomit
  • Feeling very tired
  • A low red blood cell count (anaemia)

Other medical conditions apart from GIST can cause these symptoms. If you have these symptoms you should see your doctor. GIST is rare so they are more likely to be caused by something less serious, but it is always best to check.

DIAGNOSIS

  • GISTs are often discovered incidentally by computerised tomography (CT) scan or endoscopy.
  • Endoscopic ultrasound helps to locate the lesions on the wall of the gastrointestinal tract accurately.
  • For large tumours, CT scanning of the chest, abdomen and pelvis is recommended to assess primary tumour extension and to stage for metastases.
  • Positron emission tomography (PET) imaging is helpful in identifying small metastases.
  • Magnetic resonance imaging (MRI) can may help to provide greater anatomical detail in the anorectal region and help surgery planning.
  • Biopsy is only recommended for lesions of indeterminate type or unresectable and/or metastatic tumours. If a GIST is highly suspected in a resectabletumour, biopsy should not be performed before resection because of the risk of tumour spread.
  • Pathological review of all cases should be made by a pathologist experienced in this tumour type. Specific immunohistochemical staining is used to support the diagnosis.

TREATMENT FOR GIST

The most common treatment for GIST is surgery.

Surgery

This alone may cure small tumours. But it is less likely that a surgeon can completely remove a larger tumour. If GIST has spread to other parts of yourbody, your surgeon may be able to remove these secondary tumours too.

Your surgeon removes the tumour and some tissue around it that doesn’t contain any cancer cells. It depends on where your tumour is and how big it is, asto what surgery you’ll need.

Biological therapies

Some types of biological therapy can treat GIST.

Imatinib

This drug is used to treat most patients with GIST at some point. It targets both the KIT protein and the PDGFRA protein, blocking their ability to make tumor cells grow and divide. GIST cells often have too much of these proteins.

Overall, about 2 out of 3 tumors shrink by at least half when treated with imatinib. Some other tumors shrink less or at least stop growing for a time. A small number of tumors are not helped by this treatment

Sunitinib

This drug can be useful in treating GIST when imatinib doesn’t work or when patients can’t take imatinib because of its side effects .Sunitinib targets the KIT and PDGFRA proteins (as well as several other proteins that imatinib does not target).

Regorafenib

Regorafenib is given to patients to treat GIST after imatinib and sunitinib stop working for them. It targets many proteins, including KIT and PDGFRA.

In studies, regorafenib has slowed tumor growth and even shrunk some tumors. So far, though, it’s not clear if it helps patients live longer.