Urinary cytokines/chemokines after magnetic resonance-guided high intensity focused ultrasound for palliative treatment of painful bone metastases

Ahmad Bushehri, Gregory Czarnota, Liying Zhang, Kullervo Hynynen, Yuexi Huang, Michael Chan, William Chu, Kristopher Dennis, Charles Mougenot, Jennifer Coccagna, Arjun Sahgal, Edward Chow, Carlo DeAngelis


Background: Pain is experienced by 50–75% of patients with bone metastases, representing a major source of morbidity amongst cancer patients. Magnetic resonance-guided high intensity focused ultrasound (MRgHIFU) is a new, non-invasive, outpatient treatment modality for painful bone metastases. The aim of this study was to analyze urinary cytokines/chemokines pattern after MRgHIFU for palliative treatment of painful bone metastases. The findings were compared to the cytokines/chemokines pattern post single 8 Gy fraction radiation from our previous study.
Methods: Urine samples were collected from patients with painful bone metastases 3 days before and 2 days after treatment with MRgHIFU. Each urine sample was tested for pro-inflammatory cytokines and anti-inflammatory cytokines. Patients received teaching on how to collect urine samples on their own. The Millipore Milliplex 42-Plex Cytokine/Chemokine Kit™ was used to measure urinary levels of a panel of cytokines/chemokines.
Results: Ten patients were enrolled for the study. The following 15 cytokines were above the level of detection (LOD) in at least 50% of patients at both pre MRgHIFU and post MRgHIFU: EGF, eotaxin, Fit-3 ligand, fractalkine, G-CSF, GRO, IFNα2, IL-1ra, IL-8, IP-10, MCP-1, PDGF-AA, RANTES, sIL-2Rα, and VEGF. Nine urinary cytokines significantly decreased post MRgHIFU, namely, eotaxin, GRO, IL-8, IL-13, IP-10, MCP-1, MIP-1β, RANTES, and sIL-2Rα. In addition, there were significant differences between post MRgHIFU and post-8 Gy fraction radiation in most urinary cytokines.
Conclusions: Nine urinary cytokines significantly reduced post-MRgHIFU in patients with painful bone metastases. The significance of cytokines/chemokines pattern for palliative treatment of painful bone metastases is still unknown.