Biomedical Engineering Reference
In-Depth Information
Institutes of Health (NIH) consensus classification system, based on
tumor size and mitotic count, is commonly used to assess patient
prognosis after surgical resection (Table 9.1). Large retrospective
cohort studies from several countries indicate that the NIH
classification carries substantial prognostic value. Patients with
high-risk GIST (approximately 44% of all) have substantially poorer
outcome than those with intermediate-risk (24%) or low/very low-
risk GIST (32%), whose survival is not markedly inferior to that of
the general population in some studies. Gastric GISTs are associated
with better outcome and have a lower risk of recurrence than non-
gastric tumors of the same size and mitotic count. Tumor rupture
carries an increased risk. These 2 important risk stratification factors
are not considered in the NIH classification. Patients with certain
non-gastric tumors (2.1-5 cm and > 5 mitoses per 50 high-power
fields or 5.1-10 cm and < or = 5 per 50 high-power fields) and those
with tumor rupture are proposed to be included in the NIH high-
risk category. High-risk patients defined by the proposed modified
system have more than 15% to 20% risk of disease recurrence.
The use of this system may aid in identifying which patients might
potentially benefit from adjuvant therapy.
9.4
Treatment of GIST
Systemic treatment with chemotherapy is generally ineffective in
the treatment of GIST [81-84]. In a multicenter, randomized trial
evaluating the efficacy of imatinib in advanced GIST, Demetri and
colleagues reported that none of the patients previously treated with
chemotherapy demonstrated any objective response to any regimen
[29]. With the introduction of tyrosine kinase inhibitors, the median
survival of patients with advanced GIST has substantially increased
[28].
9.4.1
Imatinib Mesylate
Imatinib is a selective small molecule competitive inhibitor of
KIT, PDGFRA, and other tyrosine kinases downstream signaling
[85-88]. Imatinib was originally approved by the FDA for chronic
myeloid leukemia (CML). It inhibited proliferation of leukemic cells
expressing BCR-ABL, as well as leukemic cells and GIST cells with
