Adjuvant Therapy for High-Risk Gastrointestinal Stromal Tumour

One randomized trial has found that adjuvant treatment with imatinib for gastrointestinal stromal tumour (GIST) 3 cm or larger in diameter prolongs recurrence-free survival, and another trial has reported that 3 years of adjuvant imatinib improves both recurrence-free and overall survival compared with 1 year of imatinib in high-risk GIST. The US National Comprehensive Cancer Network now recommends consideration of adjuvant imatinib for at least 3 years for patients with a high risk of GIST recurrence.

Estimation of the risk of GIST recurrence is mandatory when considering adjuvant therapy. The risk varies greatly from negligible risk (tumours smaller than 1 cm) to 90% or greater risk (large tumours with frequent mitoses). The risk of recurrence can be estimated using one of the three validated risk stratification schemes, the National Institutes of Health (NIH) consensus risk criteria, the Armed Forces Institute of Pathology criteria or the modified NIH criteria, which have roughly similar prognostic accuracy, or with nomograms or prognostic contour maps. Patients with an intermediate risk may pose a problem when considering adjuvant therapy because few research data are available. The decision about whether or not to treat these patients with adjuvant imatinib can be solved using the modified NIH risk stratification criteria, since, with these criteria, patients with intermediate risk have similar outcomes to those with low risk, leaving only patients with high risk for consideration of adjuvant therapy. Analysis of tumour tissue for KIT and PDGFRA mutations is recommended to exclude patients with imatinib-insensitive mutations from adjuvant therapy (notably patients with PDGFRA substitution mutation D842V), and those with neurofibromatosis-1-associated wild-type GIST.