Prognostic significance of 18F-sodium fluoride in newly diagnosed multiple myeloma patients

Mahdi Zirakchian Zadeh, Siavash Mehdizadeh Seraj, Brian Østergaard, Stephanie Mimms, William Y Raynor, Mahmoud Aly, Austin J Borja, Leila S Arani, Oke Gerke, Thomas J Werner, Hongming Zhuang, Mona-Elisabeth Revheim, Niels Abildgaard, Poul Flemming Høilund-Carlsen, Abass Alavi, Mahdi Zirakchian Zadeh, Siavash Mehdizadeh Seraj, Brian Østergaard, Stephanie Mimms, William Y Raynor, Mahmoud Aly, Austin J Borja, Leila S Arani, Oke Gerke, Thomas J Werner, Hongming Zhuang, Mona-Elisabeth Revheim, Niels Abildgaard, Poul Flemming Høilund-Carlsen, Abass Alavi

Abstract

Focal bone lesions and fractures due to weakened bone are associated with higher morbidity and mortality of multiple myeloma (MM) patients. 18F-sodium fluoride (18F-NaF) is a sensitive PET radiotracer for detection of abnormal bone metabolism and, therefore, is particularly suited to assess the degree of bone involvement in MM patients. We aimed to investigate the prognostic significance of metabolic active volume (MAV) of 18F-NaF-avid lesions in MM patients. In addition to MAV, conventional methods of PET quantification, namely SUVmean and SUVmax, were measured in each patient for the purpose of comparison. Thirty-seven newly diagnosed MM patients were included. PET imaging was performed after intravenous administration of 200 MBq NaF. Active bone lesions and fractures on whole-body 18F-NaF-PET/CT scans were identified. An adaptive thresholding algorithm automatically calculated the total MAV, SUVmean and SUVmax for each patient (ROVER, ABX, Radeberg, Germany). The patients were followed for a median of 39.8 months after treatment (range: 17.8-55.4). The overall survival (OS) of patients with 18F-NaF-MAV value > 38.65 (36.36% [N of Events/Total N: 4/11]) was significantly shorter than that of patients with 18F-NaF-MAV value < 38.65 (3.85% [1/26]; P = 0.002). In multivariate forward stepwise (conditional LR) Cox regression analysis of prognostic factors of OS (including 18F-NaF-MAV (> 38.65 or < 38.65), age, gender, beta-2 microglobulin, and revised international staging system), 18F-NaF-MAV remained the only significant factor (HR: 14.39, P = 0.02). The results for PFS were not significant. Moreover, Kaplan-Meier analyses of conventional methods of PET quantification did not reveal any statistically significant log-rank p-values. MM patients with high 18F-NaF-MAV had shorter overall survival, compared to those with low 18F-NaF-MAV levels (NCT02187731).

Keywords: 18F-sodium fluoride; PET/CT; fracture; metabolic active volume; multiple myeloma; myeloma bone disease; osteolytic lesion; survival.