TKIs made significant improvement in treatment of GIST. Underutilization of TKIs in adjuvant treatments might be the consequence of a) patient's charactersitics as several chronic comorbidities at advance age, b) problems with level of health insurance, c) level of income in a country; or others.
It is generally accepted that GIST arises from interstitial cell of Cajal with active mutation of c-KIT, also referred to as CD117. Some of the cases also harbor the active mutation of PDGF receptor-alpha, which is also inhibited by TKI characterized by imatinib as well as mutant c-KIT. However, as you imply, there is some population that neither c-KIT nor PDGF receptor -alpha harbors genetic mutation. Further, cases with point mutation in exon 9 in c-KIT tend to exhibit resistant response to imatinib treatment. Given the heterogeneous biological characteristics of GIST genetics, your clinical trial would be great important!!!