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

ABSTRACT: Purpose: Fluorine-18 fluorodeoxyglucose positron emission tomography with CT attenuation correction (18F-FDG PET/CT) is useful in the detection and enumeration of focal lesions and in semiquantitative 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 progression-free survival (PFS) and overall survival (OS), and whether they improve risk assessments such as International Staging System (ISS) stage and GEP70 risk.Experimental Design: 192 patients underwent whole body PET/CT in the Total Therapy 3A (TT3A) trial and were evaluated using three-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 > 620 g and MTV > 210 cm3 remained a significant factor of poor PFS and OS after adjusting for baseline myeloma variables. Combined with the GEP70 risk score, TLG > 205 g identifies a high-risk-behaving subgroup with poor expected survival. In addition, TLG > 205 g accurately divides ISS stage II patients into two subgroups with similar outcomes to ISS stage I and ISS stage III, respectively.Conclusions: 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. Clin Cancer Res; 23(8); 1981-7. ©2016 AACR.

SUBMITTER: McDonald JE

PROVIDER: S-EPMC5777601 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature

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

McDonald James E JE Kessler Marcus M MM Gardner Michael W MW Buros Amy F AF Ntambi James A JA Waheed Sarah S van Rhee Frits F Zangari Maurizio M Heuck Christoph J CJ Petty Nathan N Schinke Carolina C Thanendrarajan Sharmilan S Mitchell Alan A Hoering Antje A Barlogie Bart B Morgan Gareth J GJ Davies Faith E FE

Clinical cancer research : an official journal of the American Association for Cancer Research 20161003 8

Purpose: Fluorine-18 fluorodeoxyglucose positron emission tomography with CT attenuation correction (18F-FDG PET/CT) is useful in the detection and enumeration of focal lesions and in semiquantitative 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 ...[more]

PMID: 27698001

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Project description:BACKGROUND:Despite the significant upgrading in recent years of the role of 18F-FDG PET/CT in multiple myeloma (MM) diagnostics, there is a still unmet need for myeloma-specific radiotracers. 3'-Deoxy-3'-[18F]fluorothymidine (18F-FLT) is the most studied cellular proliferation PET agent, considered a potentially new myeloma functional imaging tracer. The aim of this pilot study was to evaluate 18F-FLT PET/CT in imaging of MM patients, in the context of its combined use with 18F-FDG PET/CT. RESULTS:Eight patients, four suffering from symptomatic MM and four suffering from smoldering MM (SMM), were enrolled in the study. All patients underwent 18F-FDG PET/CT and 18F-FLT PET/CT imaging by means of static (whole body) and dynamic PET/CT of the lower abdomen and pelvis (dPET/CT) in two consecutive days. The evaluation of PET/CT studies was based on qualitative evaluation, semi-quantitative (SUV) calculation, and quantitative analysis based on two-tissue compartment modeling. 18F-FDG PET/CT demonstrated focal, 18F-FDG avid, MM-indicative bone marrow lesions in five patients. In contrary, 18F-FLT PET/CT showed focal, 18F-FLT avid, myeloma-indicative lesions in only two patients. In total, 48 18F-FDG avid, focal, MM-indicative lesions were detected with 18F-FDG PET/CT, while 17 18F-FLT avid, focal, MM-indicative lesions were detected with 18F-FLT PET/CT. The number of myeloma-indicative lesions was significantly higher for 18F-FDG PET/CT than for 18F-FLT PET/CT. A common finding was a mismatch of focally increased 18F-FDG uptake and reduced 18F-FLT uptake (lower than the surrounding bone marrow). Moreover, 18F-FLT PET/CT was characterized by high background activity in the bone marrow compartment, further complicating the evaluation of bone marrow lesions. Semi-quantitative evaluation revealed that both SUVmean and SUVmax were significantly higher for 18F-FLT than for 18F-FDG in both MM lesions and reference tissue. SUV values were higher in MM lesions than in reference bone marrow for both tracers. CONCLUSIONS:Despite the limited number of patients analyzed in this pilot study, the first results of the trial indicate that 18F-FLT does not seem suitable as a single tracer in MM diagnostics. Further studies with a larger patient population are warranted to generalize the herein presented results.

Project description:BACKGROUND:The International Myeloma Working Group recommends the use of 18-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) for treatment response evaluation, as it is superior to magnetic resonance imaging (MRI). However, at initial staging, the sensitivity of FDG-PET remains inferior to that of MRI. Therefore, there is a need for an imaging technique that could have a sensitivity equal to that of MRI at diagnosis and could serve to evaluate therapy. 18F-choline has shown increased sensitivity when compared with 18-FDG, with about 75% more lesions detected in patients with relapsed or progressive multiple myeloma (MM). OBJECTIVE:Our primary objective is to prospectively compare the detection rate of bone lesions by 18F-choline PET/CT (FCH-PET) and FDG-PET in newly diagnosed MM. Our secondary objectives are to assess the accuracy of both PET modalities for the detection of bone lesions and the diagnosis of diffuse disease, to assess the detection rate of extramedullary lesions. METHODS:We will prospectively include 30 patients in a paired comparative accuracy study. Patients with de novo MM will undergo FCH-PET, FDG-PET, and whole-body MRI (WB-MRI) within a 3-week period. WB-MRI will be composed of conventional sequences on the spine and pelvis and of whole-body diffusion axial sequences. The following 6 skeletal areas will be defined: skull, sternum/costal grid, spine, pelvis, superior limbs, and inferior limbs. The number of focal lesions, their respective localization, and intensity of uptake will be retrieved for each skeletal area. Readings will be performed blinded from other imaging techniques. The reference standard will be WB-MRI. Focal lesions present on PET/CT but not on WB-MRI will require a decision made with a consensus of experts based on clinical and imaging data. The number of bone lesions and number of extramedullary lesions will be compared using the Wilcoxon test. The accuracy of FCH-PET and FDG-PET will be compared using the McNemar test. RESULTS:The study started in September 2019, and enrollment is ongoing. As of June 2020, 8 participants have been included. Data collection is expected to be completed in June 2021, and the results are expected to be available in December 2021. CONCLUSIONS:This study will assess if FCH-PET is superior to FDG-PET for the evaluation of MM tumor burden. This will pave the way for future prospective evaluations of the prognostic value of 18-FCH for treatment response evaluation in MM patients. Additionally, this work may provide new perspectives for better assessment of the risk of smoldering MM progressing to MM. TRIAL REGISTRATION:ClinicalTrials.gov NCT03891914; https://clinicaltrials.gov/ct2/show/NCT03891914. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID):DERR1-10.2196/17850.

Dataset Information

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

Publications

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

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