GIST

Incidence of GIST?

1% of all GI neoplasms. MC mesenchymal derived tumor of the intestinal tract.

What are the three predictive factors of recurrence of localized GIST following resection

1- mitotic rate, 2- tumor size, 3- tumor location

What is the median time to recurrence of GIST?

18-24 months. Recurrence typically occurs in the abdomen (peritoneum, liver)

Mean age of presentation for GIST?

60 yrs of age with a slight male predominance.

What % of GIST patients demonstrate response to imatinib mesylate?

80%. Median survival is now 5 years.

What is the most common IHC marker for GIST?

CD117 or the product of the KIT proto-oncogene.

What are the options for pre-op assessment and staging of a GIST?

CT scan of the abdomen and pelvis with a chest radiograph.

How are GIST's diagnosed?

CT scan- hypervascular lesion associated with the GI tract. Upper endoscopy- submucosal mass. Also biopsy for tissue diagnosis.

What is the most common location of the KIT proto-oncogene mutation?

Exon 11 (70%). Exon 9 (10%), Exon 13 or 17 (1-2%). The KIT proto-oncogene is found on chromosome 4. A small percentage of GIST (5%) harbor a mutation in the PDGFR.

What are the follow-up guidelines after resection of a primary GIST?

Follow up CT scan of the abdomen and pelvis every 6 months for 5 years and annually thereafter.

What are the mutations found in GIST

Gain of function mutation in the KIT (CD117) proto-oncogene.

What is a mainstay medical treatment for GIST?

Imatinib mesylate (gleevac). A tyrosine kinase inhibitor of the BCR-ABL, KIT and PDGFR.

What is the initial approach to GIST recurrence?

Imatinib therapy and assess tumor response. 80% of patients will exhibit a partial response or stable response to gleevac.

What happens when patients develop multifocal resistance or with metastatic disease unresponsive to imatinib?

Increasing the dose of imatinib or changing to sunitinib (selective inhibitor of KIT and PDGFR).

MC sites of initial mets for GIST?

LIver and peritoneum

What are the indications for adjuvant therapy for GIST?

Resection of GIST tumors 3cm or larger. SE of imatinib are diarrhea, dermatitis, abdominal discomfort (3D's) and peripheral edema.

Where are GIST predominately located?

Stomach (60%), SI (30%), esophagus or rectum (10%).

What happens when there is a partial response to gleevac or focal resistance to gleevac in recurrent or metastatic GIST?

Surgical resection or RFA or Hepatic artery embolization for the liver.

What does the KIT proto-oncogene encode for?

codes for a transmembrane tyrosine kinase receptor. GIST's harbor a gain of function mutation in the KIT proto-oncogene leading to constitutive activation of the receptor.

Indications for neodadjuvant imatinib therapy?

large GIST's, those near the GEJ, low rectal GIST's, duodenal GIST's.

Are lymph node dissections required for GIST?

no because of the low incidence of modal metastasis with GIST.

Clinical symptoms of GIST?

vague abdominal pain, 1/4 of patients present with GI bleeding. Obstruction is uncommon because GIST (like other sarcomas) do not invade adjacent tissue.