18F-FDG PET/CT Metabolic Tumor Volume and Intratumoral Heterogeneity in Pancreatic Adenocarcinomas: Impact of Dual-Time Point and Segmentation Methods

Abstract

Objectives: We aimed to determine the consistency of quantitative PET measurements of metabolic tumor volume (MTV) and intratumoral heterogeneity index for primary untreated pancreatic adenocarcinomas, when using dual-time point F-FDG PET/CT imaging.

Methods: This is an institutional review board-approved, retrospective study including 71 patients with pancreatic adenocarcinoma, who underwent dual-time point F-FDG PET/CT imaging, at approximately 1 hour (early) and 2 hours (delayed), after injection. Automated gradient-based and 50% SUVmax-threshold segmentation methods were used to assess the primary tumor MTV and metabolic intratumoral heterogeneity index, calculated as the area under cumulative SUV-volume histograms (AUC-CSH), with lower AUC-CHS indexes corresponding to higher degrees of tumor heterogeneity. We defined that more than a ±10% change in MTV or AUC-CSH, compared with baseline, as clinically significant.

Results: Seventy-one FDG-avid pancreatic tumors were identified, with an average tumor diameter of 3.4 ± 0.9 cm (range, 1.5-6.4 cm). Metabolic tumor volume values remained consistent between early and delayed imaging when using the gradient PET segmentation method (P = 0.086), whereas statistically significant change was seen when using 50% SUVmax-threshold segmentation (P < 0.001). A decrease in more than 10% change in MTV (% ΔMTV) was observed in 70.4% (50/71) tumors, and 7.0% (5/71) of the tumors showed an increase more than 10 % ΔMTV, when using the 50% SUVmax-threshold segmentation. AUC-CSH indexes showed statistically significant differences between early and delayed time points (P < 0.001), when using the gradient segmentation. AUC-CSH index decreased by 10% or greater in 40.8% (29/71) of the tumors. AUC-CSH index remained stable between early and delayed when using the 50% SUVmax-threshold segmentation (P = 0.148) with percentage of change of less than 10% for all tumors.

Conclusions: Metabolic tumor volume was relatively stable between early and delayed time points when PET gradient segmentation was used but changed greater than 10% in 77.4% of the tumors at delayed time point when threshold segmentation was used. The tumor heterogeneity index (AUC-CSH) changed greater than 10% in 40.8% of tumors at delayed imaging, when gradient segmentation was used but remained stable when threshold segmentation was used. It is important to standardize uptake time and segmentation methods to use FDG PET MTV and heterogeneity index as imaging biomarkers.

Figure 1

PET images at early and delayed time points in axial, sagittal, and coronal projections, illustrating the pancreatic metabolic tumor volume (MTV) using gradient-based PET (in yellow) and 50% SUV_max-threshold (in blue) segmentations. When using gradient segmentation, MTV remains stable between early (44.7 ml) and delayed (43.3 ml) time points, whereas MTV decreased when using 50% SUV_max-threshold from 24.6 ml to 12.1 ml.

Figure 2

Early and delayed fused PET/CT (1) and PET (2) images in axial (A1, A2), sagittal (B1, B2) and coronal (C1, C2) projections demonstrated a large 3.6 × 3.9 × 4.2 cm FDG-avid pancreatic tumor within the body of the pancreas. Early images (at ~ 1h p.i.) shows a metabolic tumor uptake with SUV_max of 9.2, metabolic tumor volume (MTV) of 56.24 ml (by gradient-based PET segmentation – in blue) and 5.8 ml (by 50% SUV_max-threshold segmentation – in yellow), and a heterogeneity index (AUC-CSH) of 0.356 (by gradient-based) and 0.621 (by 50% SUV_max-threshold). On delayed (at ~ 2 h p.i.) images, SUV_max increases to 15.6; MTV remains stable with gradient-based delineation (57.4 ml) and decreased with 50% SUV_max-threshold (1.7 ml). AUC-CSH indexes remained stable with 50% SUV_max-threshold (0.597) and decreased with gradient-based segmentation (0.291).