Assessment of Total Lesion Glycolysis by 18F FDG PET/CT Significantly Improves Prognostic Value of GEP and ISS in Myeloma

Abstract

Introduction Fluorine-18 fluorodexyglucose positron emission tomography with CT attenuation correction (18F-FDG PET/CT) is useful in the detection and enumeration of focal lesions and in semi-quantitative characterization of metabolic activity (glycolytic phenotype) by calculation of glucose uptake. Total lesion glycolysis (TLG) and metabolic tumor volume (MTV) have the potential to improve the value of this approach and enhance the prognostic value of disease burden measures. This study aims to determine whether TLG and MTV are associated with PFS and OS, and whether they improve risk assessments such as ISS stage and GEP70 risk. Materials and Methods 192 patients underwent whole body PET/CT in the TT3A trial and were evaluated using 3 dimensional region of interest analysis with TLG, MTV, and standard measurement parameters derived for all focal lesions with peak SUV above the background red marrow signal. Results In multivariate analysis, baseline TLG >620g and MTV >210cm3 remained a significant factor of poor PFS and OS after adjusting for baseline myeloma variables. Combined with the GEP70 risk score, TLG >205g identifies a high risk-behaving subgroup with poor expected survival. In addition, TLG >205g accurately divides ISS Stage II patients into two subgroups with similar outcomes to ISS Stage I and ISS Stage III, respectively. Conclusion TLG and MTV have significant survival implications at baseline and offer a more precise quantitation of the glycolytic phenotype of active disease. These measures can be assessed more readily than before using FDA approved software and should be standardized and incorporated into clinical trials moving forward.

18F-FDG and 11C-Methionine PET/CT in Newly Diagnosed Multiple Myeloma Patients: Comparison of Volume-Based PET Biomarkers

“…Several studies have suggested a higher sensitivity of 11 C-MET PET/CT over 18 F-FDG PET/CT in the detection of both intra-and extramedullary disease [18,19]. In addition, a better correlation of 11 C-MET uptake with the degree of BM infiltration by malignant PCs has been recently reported [20].…”

“…On top of this, post-therapy imaging studies have demonstrated that PET negativity after induction treatment [6,7] or autologous/allogeneic stem cell transplantation (ASCT) [7][8][9][10] correlates with longer progression-free survival (PFS). Moreover, new parameters measuring tumor burden in 18 F-FDG PET/CT such as metabolic tumor volume (MTV) and total lesion glycolysis (TLG) have also demonstrated an association with survival in MM patients [11,12]. Furthermore, patients with high TLG had poor outcome even in the context of molecularly defined low-risk disease, highlighting the additional value of novel markers in the assessment of MM.…”

“…Nevertheless, 18 F-FDG PET/CT is associated with several shortcomings: (1) the sensitivity is poor in patients with diffuse bone marrow (BM) infiltration; (2) 18 F-FDG avidity may be absent in patients with low hexokinase-2 expression [13] and specificity is not reliable in inflammatory or infectious lesions. For these reasons, alternative tracers such as 11 C-methionine ( 11 C-MET) [14], 11 C-choline [15], or radiolabeled C-X-C chemokine receptor 4 ligands [16,17] have been investigated. Several studies have suggested a higher sensitivity of 11 C-MET PET/CT over 18 F-FDG PET/CT in the detection of both intra-and extramedullary disease [18,19].…”

“…For these reasons, alternative tracers such as 11 C-methionine ( 11 C-MET) [14], 11 C-choline [15], or radiolabeled C-X-C chemokine receptor 4 ligands [16,17] have been investigated. Several studies have suggested a higher sensitivity of 11 C-MET PET/CT over 18 F-FDG PET/CT in the detection of both intra-and extramedullary disease [18,19]. In addition, a better correlation of 11 C-MET uptake with the degree of BM infiltration by malignant PCs has been recently reported [20].…”

Dual‐tracer PET/CT scan after injection of combined [18F]NaF and [18F]FDG outperforms MRI in the detection of myeloma lesions

“…FDG PET/CT provide prognostic information in patients with newly diagnosed MM: The presence of a diffuse pattern with MRI, extramedullary disease, the number of FLs, and/or [ 18 F]FDG-avid lesions are associated with shorter survival. [8][9][10][11][12][13][14][15] Based on its ability to indicate metabolic activity, [ 18 F]FDG is the preferred and widely used tracer for PET/CT 1 ; however, the sensitivity of [ 18…”