Risk stratification models and mutational analysis: Keys to optimising adjuvant therapy in patients with gastrointestinal stromal tumour

Imatinib is a standard of care in the adjuvant treatment of patients with resected gastrointestinal stromal tumour (GIST). Two important trials have shown a reduction in GIST recurrence rates for patients treated with imatinib 400 mg daily for 1 year; one of these trials also demonstrated a significant improvement in overall survival for patients with GIST at high risk of recurrence who were treated for 3 years. However, not all patients will benefit from adjuvant treatment. Considering the patient types in both trials, treatment decisions must take into account a number of factors including risk of recurrence and mutational status. Tumour characteristics including tumour size, location and mitotic index are the main prognostic factors of recurrence-free survival (RFS) after surgical resection of GISTs. Research, much of it in the advanced/metastatic setting, shows that mutational analysis is definitely predictive of treatment efficacy and probably prognostic of RFS. Patients on imatinib whose tumours harbour mutations in exon 11 of the KIT gene tend to have superior RFS compared with patients with exon 9 mutations. In contrast, patients with wild-type GIST often have disease that follows an indolent course and has limited sensitivity to imatinib in most cases. As such, increased use of existing risk-stratification schemes and mutational analysis will be essential for optimising tailored treatment approaches. In this review, the development and prognostic/predictive utility of key risk stratification tools and mutational analysis of GIST are discussed herein with the goal of facilitating adjuvant treatment decisions for patients with GIST.