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 Melenevsky; Agnieszka Szot-Barnes; Jeffrey T. Yap; Andrew K. Godwin; Lori Rink; Min Huang; Meridith Blevins; JoRean Sicks; Burton Eisenberg; Barry A. Siegel

doi:10.2967/jnumed.111.094425

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FIGURE 1.
(A) ¹⁸F-FDG PET before therapy, 1 and 8 wk after imatinib mesylate initiation. Intense ¹⁸F-FDG uptake in seen at baseline within primary perigastric GIST, followed by complete resolution at 1 and 8 wk after therapy. Mild uptake seen in the left supraclavicular region is related to inflammatory changes around the site of the pacemaker. The remainder of ¹⁸F-FDG biodistribution is physiologic. (B) Axial CT, PET, and fused PET/CT slices through the right-upper-quadrant mass before and 1 and 8 wk after imatinib mesylate initiation. Intense ¹⁸F-FDG uptake is seen within the primary perigastric GIST at baseline, followed by marked decrease at 1 wk and complete resolution at 8 wk after therapy.
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FIGURE 2.
Percentage change in SUV_max from baseline to week 1 (A) and before surgery (B). CMR = complete metabolic response; PMR = partial metabolic response; SMD = stable metabolic disease; PMD = progressive metabolic disease. Percentage change in SUV_max from baseline to week 1 (C) and before surgery (D) by RECIST best response. PR = partial response; SD = stable disease; PD = progressive disease.
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FIGURE 3.
GLUT4 immunohistochemical (A) and ¹⁸F-FDG PET (B) studies of patient with primary gastric GIST before and 8 wk after imatinib mesylate therapy. GLUT4 intense brown staining at baseline is no longer apparent on week 8 surgical specimen. ¹⁸F-FDG PET images show intense ¹⁸F-FDG uptake in the gastric mass before treatment and resolution at week 8.

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TABLE 1.

Distribution of Background-Corrected SUV_max, Percentage Change in SUV_max, and GLUT4 Fold Decrease

Measurement	Timing	Category	Number of participants	Number missing	Minimum	Median	Mean	Maximum	P
Background-corrected SUV_max
	Baseline		44	0	1.3	10.1	14.2	53.2
	Week 1		44	0	−0.5	2.7	5.5	47.7	<0.0001^*
	Presurgery		40	4	−0.5	1.4	3.0	36.1	<0.0001^*
Change in SUV_max from baseline (%)
	Week 1		44	0	−100.0	−72.0	−59.4	81.4	<0.0001^†
	Presurgery		40	4	−100.0	−89.6	−76.4	13.4	<0.0001^†
GLUT4 fold decrease
	Week 1	CMR	1	2	4.3	4.3	4.3	4.3
		PMR	17	16	1.0	2.3	9.1	100.0
		SMD	3	3	1.0	2.0	2.5	4.5
		PMD	1	1	1.7	1.7	1.7	1.7
	Presurgery	CMR	1	2	3.0	3.0	3.0	3.0
		PMR	19	14	1.0	2.1	8.4	100.0
		SMD	2	2	1.7	3.1	3.1	4.5
		PMD	0	0

↵* Wilcoxon signed-rank test comparing week 1 (presurgery) absolute SUVmax against baseline.
↵† Wilcoxon signed-rank test comparing week 1 (presurgery) percentage change in SUVmax from baseline.