ACRIN 6665/RTOG 0132 phase II trial of neoadjuvant imatinib mesylate for operable malignant gastrointestinal stromal tumor: Monitoring with 18F-FDG PET and correlation with genotype and GLUT4 expression

Annick D. Van Den Abbeele, Constantine Gatsonis, Daniel J. De Vries, Yulia V Melenevsky, Agnieszka Szot-Barnes, Jeffrey T. Yap, Andrew K. Godwin, Lori Rink, Min Huang, Meridith Blevins, Jo Rean Sicks, Burton Eisenberg, Barry A. Siegel

Research output: Contribution to journalArticle

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Abstract

We investigated the correlation between metabolic response by 18F-FDG PET and objective response, glucose transporter type 4 (GLUT4) expression, and KIT/PDGFRA mutation status in patients with gastrointestinal stromal tumor undergoing neoadjuvant imatinib mesylate therapy. Methods: 18F-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: 18F-FDG PET showed high baseline tumor glycolytic activity (mean SUV max, 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 5 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 18F-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 18F-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.

Original languageEnglish (US)
Pages (from-to)567-574
Number of pages8
JournalJournal of Nuclear Medicine
Volume53
Issue number4
DOIs
StatePublished - Apr 1 2012

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Glucose Transporter Type 4
Gastrointestinal Stromal Tumors
Metabolic Diseases
Fluorodeoxyglucose F18
Genotype
Imatinib Mesylate
Mutation
Exons
Immunohistochemistry
Glycolysis

Keywords

  • FDG-PET
  • GIST
  • GLUT4
  • Genotype
  • Therapeutic response

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

Cite this

ACRIN 6665/RTOG 0132 phase II trial of neoadjuvant imatinib mesylate for operable malignant gastrointestinal stromal tumor : Monitoring with 18F-FDG PET and correlation with genotype and GLUT4 expression. / Van Den Abbeele, Annick D.; Gatsonis, Constantine; De Vries, Daniel J.; Melenevsky, Yulia V; Szot-Barnes, Agnieszka; Yap, Jeffrey T.; Godwin, Andrew K.; Rink, Lori; Huang, Min; Blevins, Meridith; Sicks, Jo Rean; Eisenberg, Burton; Siegel, Barry A.

In: Journal of Nuclear Medicine, Vol. 53, No. 4, 01.04.2012, p. 567-574.

Research output: Contribution to journalArticle

Van Den Abbeele, AD, Gatsonis, C, De Vries, DJ, Melenevsky, YV, Szot-Barnes, A, Yap, JT, Godwin, AK, Rink, L, Huang, M, Blevins, M, Sicks, JR, Eisenberg, B & Siegel, BA 2012, 'ACRIN 6665/RTOG 0132 phase II trial of neoadjuvant imatinib mesylate for operable malignant gastrointestinal stromal tumor: Monitoring with 18F-FDG PET and correlation with genotype and GLUT4 expression', Journal of Nuclear Medicine, vol. 53, no. 4, pp. 567-574. https://doi.org/10.2967/jnumed.111.094425
Van Den Abbeele, Annick D. ; Gatsonis, Constantine ; De Vries, Daniel J. ; Melenevsky, Yulia V ; Szot-Barnes, Agnieszka ; Yap, Jeffrey T. ; Godwin, Andrew K. ; Rink, Lori ; Huang, Min ; Blevins, Meridith ; Sicks, Jo Rean ; Eisenberg, Burton ; Siegel, Barry A. / ACRIN 6665/RTOG 0132 phase II trial of neoadjuvant imatinib mesylate for operable malignant gastrointestinal stromal tumor : Monitoring with 18F-FDG PET and correlation with genotype and GLUT4 expression. In: Journal of Nuclear Medicine. 2012 ; Vol. 53, No. 4. pp. 567-574.
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abstract = "We investigated the correlation between metabolic response by 18F-FDG PET and objective response, glucose transporter type 4 (GLUT4) expression, and KIT/PDGFRA mutation status in patients with gastrointestinal stromal tumor undergoing neoadjuvant imatinib mesylate therapy. Methods: 18F-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: 18F-FDG PET showed high baseline tumor glycolytic activity (mean SUV max, 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 5 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 18F-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 18F-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.",
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author = "{Van Den Abbeele}, {Annick D.} and Constantine Gatsonis and {De Vries}, {Daniel J.} and Melenevsky, {Yulia V} and Agnieszka Szot-Barnes and Yap, {Jeffrey T.} and Godwin, {Andrew K.} and Lori Rink and Min Huang and Meridith Blevins and Sicks, {Jo Rean} and Burton Eisenberg and Siegel, {Barry A.}",
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TY - JOUR

T1 - ACRIN 6665/RTOG 0132 phase II trial of neoadjuvant imatinib mesylate for operable malignant gastrointestinal stromal tumor

T2 - Monitoring with 18F-FDG PET and correlation with genotype and GLUT4 expression

AU - Van Den Abbeele, Annick D.

AU - Gatsonis, Constantine

AU - De Vries, Daniel J.

AU - Melenevsky, Yulia V

AU - Szot-Barnes, Agnieszka

AU - Yap, Jeffrey T.

AU - Godwin, Andrew K.

AU - Rink, Lori

AU - Huang, Min

AU - Blevins, Meridith

AU - Sicks, Jo Rean

AU - Eisenberg, Burton

AU - Siegel, Barry A.

PY - 2012/4/1

Y1 - 2012/4/1

N2 - We investigated the correlation between metabolic response by 18F-FDG PET and objective response, glucose transporter type 4 (GLUT4) expression, and KIT/PDGFRA mutation status in patients with gastrointestinal stromal tumor undergoing neoadjuvant imatinib mesylate therapy. Methods: 18F-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: 18F-FDG PET showed high baseline tumor glycolytic activity (mean SUV max, 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 5 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 18F-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 18F-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.

AB - We investigated the correlation between metabolic response by 18F-FDG PET and objective response, glucose transporter type 4 (GLUT4) expression, and KIT/PDGFRA mutation status in patients with gastrointestinal stromal tumor undergoing neoadjuvant imatinib mesylate therapy. Methods: 18F-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: 18F-FDG PET showed high baseline tumor glycolytic activity (mean SUV max, 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 5 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 18F-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 18F-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.

KW - FDG-PET

KW - GIST

KW - GLUT4

KW - Genotype

KW - Therapeutic response

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