Expanding the toolKIT for predicting GIST outcomes.

Gastrointestinal stromal tumors (GIST) have long been recognized to be associated with mutations of KIT and PDGFA, resulting in constitutive tyrosine kinase (TK) activity. This paved the way for breakthrough successes in the molecular era with the use of imatinib (TK inhibitor). Ten-year results of the SWOG S0033 study, which was designed to compare two doses of imatinib, were published this month in JAMA Onc with a focus on long-term outcomes based on mutation status. Re-analysis of path specimens employing next gen sequencing increased the rate of identifiable mutations from 85% -> 97.5%. A remarkable 23% of all enrolled patients remained alive at 10 years, with half of these treated with imatinib alone. Factors associated with better survival included max debulking, KIT exon 11 mutations, and KIT/PDGFA wild-type tumors (which may do better regardless of treatment). These promising results should hammer home the message that genetic analysis is standard of care for GIST.