A Higher Increase In Fdg Uptake In Whole Bone Marrow Of Multiple Myeloma Patients From Early To Delayed Pre-Treatment Scans Is Associated With Poor Response To Treatment And Inferior Survival

21 Objectives: Despite promising results of dual time point imaging (DTPI) studies, the current methods of quantification that have been used for this approach, such as SUVmean and SUVmax, often suffer from lack of reproducibility. According to the International Myeloma Working Group (IMWG), the main drawback of FDG PET/CT is the lack of standardized imaging criteria, resulting in poor inter-observer reliability for interpreting PET images in multiple myeloma (MM). In this study, we aimed to apply a novel method of PET/CT quantification to assess the difference in whole bone marrow (WBM) uptake of FDG between early (1h) and delayed (3h) scans of MM patients. We hypothesized that a significant increase between the two-time points would indicate more aggressive disease associated with poor response to treatment and inferior survival. Furthermore, we expected to observe a high level of inter-observer agreement for this global assessment approach. Methods: Pre-treatment FDG-PET/CT scans of 38 MM patients (28 males, 10 females; median age 66 years, range: 50-87) were acquired 1h and 3h after radiotracer injection [Clinical trial number: NCT02187731].A threshold algorithm based on the bone Hounsfield scale from the CT scans was applied to segment and quantify the WBM FDG uptake (OsiriX software, Pixmeo SARL, Bernex, Switzerland). The percentage of change in FDG uptake in different treatment response groups was evaluated and the correlations with overall survival (OS) and progression-free survival (PFS) were determined. All measurements were replicated by two independent observers. Results: WBM FDG uptake increased significantly from 1h to 3h in the patients who had poorer responses to treatment [partial response patients: from 1.1± 0.2 to 1.9± 0.6; p= 0.001 and very good partial response patients: from 1.3± 0.3 to 1.9± 0.5; p= 0.005], while the increase was insignificant in stringent complete response and complete response patients. In Kaplan-Meier analysis, a higher positive change between the time points was associated with inferior PFS (log-rank p< 0.001). In a multivariate Cox regression analysis, a higher positive change was a significant prognostic factor for both PFS and OS (HR: 4.50; p= 0.014 and HR: 89.94; p= 0.010, respectively). Substantial strength of agreement was observed in Lin9s concordance analysis (concordance correlation coefficient (ρc) = 0.969). Conclusions: Through a reproducible semi-automated method of PET/CT quantification, we evaluated the uptake of FDG in the WBM of MM patients between 1h and 3h scans. A higher increase in WBM FDG uptake was associated with poor response to treatment and inferior survival.