Abstract
3108
Introduction: Differentiation of true tumor progression (TP) from pseudoprogression (PsP) is a major unmet need in patients with glioblastoma. 18F-Fluciclovine is a synthetic amino acid PET radiotracer that is FDA-approved in biochemical recurrence in prostate cancer. The study aim was to assess the value of 18F-Fluciclovine PET and MRI in differentiation of histologically confirmed (“true”) TP and PsP in post-treatment of glioblastoma.
Methods: 30 patients with glioblastoma with new contrast-enhancing lesions or lesions showing increased enhancement (> 25% increase in the product of perpendicular diameters) on standard MRI after completion of radiation underwent 60-minutes dynamic PET imaging after injection of 185MBq +/-20% of 18F-Fluciclovine. Patients subsequently underwent resection of the enhancing lesion, and the percentage of tumor as well as treatment-related changes comprising the specimen were quantified on histopathology. Patients were considered "true” TP if tumor represented ≥ 50% of the resected specimen, mixed TP-PsP if < 50% and > 10%, and PsP if tumor represented ≤ 10%. Weight-normalized SUVmax, SUVpeak, and 50% threshold SUVmean were used to quantitate uptake of 18F-Fluciclovine. MRI-based lesion metrics included the minimum apparent diffusion coefficient (ADC min) derived from diffusion tensor imaging, maximum (rCBVmax) and mean relative cerebral blood volume derived from dynamic susceptibility contrast (DSC) MRI and maximum and mean plasma volume (Vp), Ktrans, Kev and Ve derived from dynamic contrast-enhanced (DCE) MRI. The least absolute shrinkage and selection operator (LASSO) was used to determine the variables most predictive of tumor percentage. The strength of association between the primary outcome and selected variables was assessed by Pearson's or Point-biserial correlation. A receiver operating characteristic (ROC) curve was used to illustrate the diagnostic ability of a binary classifier system.
Results: 18 patients with “true” TP, 4 with mixed TP-PsP, and 8 with PsP were included. There was a positive correlation between 50% threshold SUV mean measured from PET images acquired 50-60 minutes post-injection and rCBVmax by MRI and tumor percentage by histology (r= 0.56; p= 0.004 and r=0.50; p=0.012 respectively). 40-50 minutes SUVmax (OR=1.78 rpb=0.51) and rCBVmax (OR=1.64, rpb=0.48) were positively correlated with tumor “true” TP/mixed TP group.
Patients who demonstrated “true” TP/mixed TP-PsP had significantly higher 40-50 minutes SUVmax compared to patients with histological PsP (6.71±2.03 vs 3.93±1.63; p=0.012). 40-50 minutes SUVmax cut-off of 4.46 provided 90% sensitivity and 80% specificity for differentiation of “true” TP/mixed TP-PsP from PsP (AUC=0.88). Combining a 40-50 minutes SUVmax cut-off of 4.46 and an rCBVmax cut-off of 3.67 provided 100% sensitivity and 100% specificity for differentiating “true” TP/mixed TP-PsP from PsP (AUC=1). Patients who demonstrated “true” TP had a significantly higher 40-50 minutes SUVmax compared to patients with histological PsP (6.99±2.06 vs 3.93±1.63; p=0.008). A 40-50 minutes SUVmax cut-off of 4.66 provided 94% sensitivity and 80% specificity for differentiation of “true” TP from PsP (AUC=0.89).
Conclusions: Our results indicated that 18F-Fluciclovine PET imaging is positively correlated with tumor quantification on histology and can accurately differentiate “true” TP and mixed TP-PsP from PsP. The combination of 40-50 minutes SUVmax and rCBVmax increased the accuracy to differentiate “true” TP and mixed TP-PsP from PsP. Further independent studies are required to cross-validate these promising early results