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Van den Abbeele AID , Gatsonis C , De Vries DJ , Melenevsky Y , Szot-Barnes A , Yap JT , Godwin AK , Rink L , Huang M , Blevins M , Sicks J , Eisenberg B , Siegel BA
ACRIN 6665/RTOG 0132 Phase II Trial of Neoadjuvant Imatinib Mesylate for Operable Malignant Gastrointestinal Stromal Tumor: Monitoring with F-18-FDG PET and Correlation with Genotype and GLUT4 Expression
Journal of Nuclear Medicine. 2012 Apr;53(4) :567-574
PMID: WOS:000302377300038   
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We investigated the correlation between metabolic response by F-18-MG PET and objective response, glucose transporter type 4 (GLUT4) expression, and KIT/PDGFRA mutation status in patients with gastrointestinal stromal tumor undergoing neoadjuvant imatinib rnesylate therapy. Methods: F-18-FDG PET was performed at baseline, 1-7 d, and 4 or 8 wk after imatinib mesylate initiation. Best objective response was defined by version 1.0 of the Response Evaluation Criteria in Solid Tumors (RECIST). Mutational analysis and tumor GLUT4 expression by immunohistochemistry were done on tissue obtained at baseline or surgery. Results: F-18-FDG PET showed high baseline tumor glycolytic activity (mean SUVmax, 14.2; range, 1.3-53.2), decreasing after 1 wk of imatinib mesylate (mean, 5.5; range, -0.5-47.7, P < 0.001, n = 44), and again before surgery (mean, 3.0; range, -0.5-36.1, P < 0.001, n = 40). At week 1, there were 3 patients with complete metabolic response (CMR), 33 with partial metabolic response (PMR), 6 with stable metabolic disease (SMD), and 2 with progressive metabolic disease (PMD). Before surgery, there were 3 with CMR, 33 with PMR, 4 with SMD, and none with PMD. The best response according to RECIST was 2 with partial response, 36 with stable disease, and 1 with progressive disease (n = 39). Of the patients with a posttreatment decrease in GLUT4 expression, 1 had CMR, 15 had PMR, 2 had SMD, and 1 had PMD at week 1, whereas before surgery 1 patient had CMR, 16 had PMR, 2 had SMD, and none had PMD. Among 27 patients with KIT exon 11 mutations, 1 had CMR, 22 had PMR, 3 had SMD, and 1 had PMD at week 1, whereas 1 had CMR, 22 had PMR, 2 had SMD, and 2 were unknown before surgery; among 4 patients with a wild-type genotype, 2 had PMR and 2 SMD at week 1, whereas 1 had CMR, 2 had PMR, and 1 had SMD before surgery. Conclusion: After imatinib mesylate initiation, metabolic response by F-18-FDG PET was documented earlier (1-7 d) and was of much greater magnitude (36/44) than that documented by RECIST (2/39). Immunohistochemistry data suggest that GLUT4 may play a role in F-18-FDG uptake in gastrointestinal stromal tumor, GLUT4 levels decrease after imatinib mesylate therapy in most patients with PMR, and the biologic action of imatinib mesylate interacts with glycolysis and GLUT4 expression. A greater than 85% metabolic response was observed as early as days 1-7 in patients with exon 11 mutations.
Van den Abbeele, Annick D. Gatsonis, Constantine de Vries, Daniel J. Melenevsky, Yulia Szot-Barnes, Agnieszka Yap, Jeffrey T. Godwin, Andrew K. Rink, Lori Huang, Min Blevins, Meridith Sicks, JoRean Eisenberg, Burton Siegel, Barry A. Department of Health and Human Services; National Cancer Institute[U01 CA079778, U01 CA080098, R01 CA106588] We thank all the patients who generously volunteered to participate in this study, the study team staffs at the participating institutions, and ACRIN. We acknowledge the contributions of Ramsey Badawi, and we recognize the pioneering work of George Demetri and his team in bringing novel therapies to patients with GISTs. This project was funded in part by the Department of Health and Human Services and the National Cancer Institute through grants U01 CA079778, U01 CA080098, and R01 CA106588. The contents of this publication do not necessarily reflect the views or policies of the Department of Health and Human Services, nor is endorsement by the U.S. government implied. This study was presented in part at the 2008 annual meeting of the American College of Radiology Imaging Network and at the 2009 annual meeting of the American Society of Clinical Oncology. No other potential conflict of interest relevant to this article was reported. 38 Soc nuclear medicine inc Reston 920bv