Gastrointestinal Stromal Tumors Treatment (PDQ®): Treatment - Health Professional Information [NCI] - General Information About Gastrointestinal Stromal Tumors Treatment
Approximately 85% of GIST contain oncogenic mutations in one of two receptor tyrosine kinases: KIT or PDGFRA (platelet-derived growth factor receptor alpha).[2,10] Constitutive activation of either of these receptor tyrosine kinases plays a central role in the pathogenesis of GIST.[15,19] Wild-type tumors, with no detectable KIT or PDGFRA mutations, account for 12% to 15% of all GIST. Fewer than 5% of GIST occur in the setting of syndromic diseases, such as neurofibromatosis type 1 (NF1), Carney triad syndrome, and other familial diseases.[2,20,21,22] The correct identification of GIST is very important because of the availability of specific, molecular-targeted therapy with KIT/PDGFRA tyrosine kinase inhibitors (TKI) such as imatinib mesylate or, in the case of imatinib-resistant GIST, sunitinib malate.[1,10,17]
Risk Assessment and Prognosis
At the time of clinical presentation, the prognosis appears to be influenced by genetic events other than kinase mutations, although a particular kinase mutation may help to define the initial clinical course of a GIST. Based on retrospective studies from time periods that predated the clinical use of kinase inhibitors, current recommendations for assessing the risk of progression for a newly diagnosed primary GIST rely on three parameters (see Table 1):[2,23,24,25,26]
- Mitotic index (mitoses per 50 high-power fields).
- Tumor size.
- Tumor location.
Table 1. Risk Stratification of Primary GIST by Mitotic Index, Tumor Size, and Tumor Locationa
|GIST = gastrointestinal stromal tumors; hpf = high-power field, assessed from an area that on initial screen appears to have the highest mitotic activity.|
|a Annual review of pathology by ANNUAL REVIEWS, INC. Reproduced with permission of ANNUAL REVIEWS, INC., in the format Internet posting via Copyright Clearance Center.|
|b Small numbers of cases.|
|Mitotic Index, hpf||Size, cm||Site and Risk of Progressive Disease (%)|
| || ||Gastric||Duodenum||Jejunum/Ileum||Rectum|
|≤5 per 50||≤2||None (0)||None (0)||None (0)||None (0)|
|>2 ≤5||Very low (1.9)||Low (4.3)||Low (8.3)||Low (8.5)|
|>5 ≤10||Low (3.6)||Moderate (24)||(Insufficient data)||(Insufficient data)|
|>10||Moderate (10)||High (52)||High (34)||High (57)|
|>5 per 50||≤2||None||Highb||(Insufficient data)||High (54)|
|>2 ≤5||Moderate (16)||High (73)||High (50)||High (52)|
|>5 ≤10||High (55)||High (85)||(Insufficient data)||(Insufficient data)|
|>10||High (86)||High (90)||High (86)||High (7)|
Compared to other intra-abdominal sarcomas, survival in GIST patients after surgery alone is favorable. In a retrospective study involving 200 patients that predated the use of TKI, the 5-year disease-specific survival rate for GIST patients with primary disease who underwent complete resection of gross disease (N = 80) was 54%, with survival predicted by tumor size; the overall disease-specific survival was 35% at 5 years. Other studies, which also predated TKI, reported 5-year survival rates of 40% to 63% for patients undergoing complete resections of GIST.