Assessing Response to Imatinib in GIST

In a seminal study that assessed the efficacy of imatinib in patients with gastrointestinal stromal tumor (GIST), those with tumors 3 centimeters or larger were randomized to receive placebo or imatinib. The study showed a significant improvement in recurrence-free survival with imatinib, says Syma Iqbal, MD. However, a large limitation of this study was that it did not take into account the mitotic rate of the tumor.

Another study evaluating imatinib enrolled patients with high-risk features at baseline, explains Anthony P. Conley, MD. These individuals had tumors greater than 10 centimeters, high mitotic rates, or tumor rupture. Results showed a greater survival benefit in the cohort that received 3 years of imatinib compared with those who received 1 year of imatinib. While these findings altered treatment approaches with respect to duration of therapy in patients with high-risk GIST, the optimal length of treatment remains unclear, says Iqbal. Some clinical trials have assessed the use of up to 5 years of imatinib in the adjuvant setting, adds Conley.

Patients who have undergone surgical resection of their GIST should be followed on a regular basis with physical examination and cross-sectional imaging with a CT scan of the abdomen and pelvis, if the tumor is located in the abdomen, and a CT scan of the chest for esophageal GIST, recommends Robert H. I. Andtbacka, MD. These scans should be performed every 3 to 6 months, as per National Comprehensive Cancer Network recommendations.

The scans may reveal solid tumors that have metastasized to the liver or those that have decreased in density and vascularity following surgical resection and adjuvant treatment, says Andtbacka. Individuals who have tumor recurrence typically undergo tumor biopsy to determine the mutational status of the malignancy.

Andtbacka and his colleagues often utilize immunohistochemical analysis and staining to test for c-KIT, DOG1, protein kinase C-theta, and platelet derived growth factor receptor, as well as mutations in exon 9, 11, 13, and 17. How patients respond to treatment depends on these mutations, comments Andtbacka.