ACRIN 6665/RTOG 0132 phase II trial of neoadjuvant imatinib mesylate (IM) for primary and recurrent operable malignant GIST: Imaging findings and correlation with genotype and GLUT4 expression

Abstract

10552 Background: IM has improved the treatment of GIST patients (pts), but few achieve objective response despite significant clinical benefit. Imaging of tumor metabolism may provide earlier assessment of therapeutic response. In this study, FDG-PET metabolic response (MR) was compared with RECIST, GLUT4 expression, and KIT/PDGFRA mutation status. Methods: FDG-PET was done at baseline, 1–7 days, and 4 or 8 weeks (wk) after IM initiation. Best objective response was defined by RECIST. Immunohistochemical (IHC) tumor GLUT4 expression and mutation analyses were done at baseline and/or surgery. Background-subtracted SUVmax was measured in all lesions and summed; MR based on EORTC criteria was compared to RECIST, GLUT4 expression, and KIT/PDGFRA mutation status. Results: FDG-PET showed high tumor glycolytic activity at baseline (mean SUVmax = 14.2, range: 1.3–53.2), decreasing after 1 wk of IM (5.5, range: 0.5–47.7, p < 0.001, n = 44), and again prior to surgery (3.0, range: 0.5–36.1, p < 0.001, n = 40). FDG-PET response at wk 1 was 3 complete MR (CMR), 33 partial MR (PMR), 6 stable metabolic disease (SMD), and 2 progressive metabolic disease (PMD). Prior to surgery, FDG-PET response was 3 CMR, 33 PMR, 4 SMD, and no PMD. For 39 pts, RECIST best response was 2 PR, 36 SD, and 1 PD. GLUT4 expression decreased in 19 pts with PMR, and 3 with SMD. Among 12 pts with exon 11 mutation, 11 had PMR, 1 SMD; among 5 pts with wild-type genotype, 4 had PMR, and 1 SMD. Conclusions: After IM initiation, MR by FDG-PET was documented earlier (1–7 days), and was of much greater magnitude (36/40) than that documented by RECIST (2/39). IHC data suggest that: (1) GLUT4 plays a role in FDG uptake in GIST; (2) GLUT4 decreases in most pts with PMR; and, (3) the biologic action of IM interacts with glycolysis and GLUT4 expression. No difference in PMR was seen in pts with exon 11 vs. wild type mutations. [Table: see text]