Urinary cytokines/chemokines pattern in patients with painful bone metastases undergoing external beam radiotherapy experiencing pain flare.
BACKGROUND
External beam radiotherapy (EBRT) is a mainstay for treatment of painful bone metastases. Transient worsening of pain ("pain flare") occurs in 40% of patients. We investigated the pathophysiology of pain flare through assessment of changes in urinary cytokines/chemokines in patients receiving EBRT for painful bone metastases.


METHODS
Urine samples were collected from patients receiving a single 8 Gy fraction for painful bone metastases preparation, day 1 or 2 and on an additional day between days 3 to 5 post radiation. Patients completed a standardized pain and analgesic use diary daily for 10 days following radiation. Patients were deemed to have pain flare if they had a two-point increase from baseline worst pain on 0-10 scale and no decrease in analgesic intake or a 25% increase in analgesic intake with no decrease in worst pain. The Millipore Milliplex 42-Plex Cyto-kine/Chemokine Kit™ was used to measure urinary levels of a panel of cytokines/chemokines.


RESULTS
Forty-six patients consented to the study of which 28 were evaluable (complete urine and diary data), and 83/84 urine samples were available for analysis. Pain flare was experienced by 11 patients (39%). The following cytokines/chemokines were detectable in at least 50% of the patients: EGF, fractalkine, GRO, IL-4, IL-8, interferon gamma induced protein 10 (IP-10), MCP-1, macrophage derived chemokine (MDC), PDGF-AA, sIL-2Ra, TGF-Alpha, VEGF. Comparing patients with or without pain flare EGF, fractalkine, GRO, IL-8, IP-10, MCP-1, MDC, sIL-2Ra, and TGF-alpha increased following radiation in both groups. Patients with pain flare have significant lower levels on IL-8, IP-10, and MDC over time. No specific time trend was noticed.


CONCLUSIONS
Patients who experience pain flare appear to have a different pattern in urinary cytokine/chemokine levels than patients without pain flare. A larger study is required to confirm the possible role of cytokines/chemokines in predisposition to and/or the cause of pain flare following radiation to painful bone metastases.
Department of Radiation Oncology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, Odette Cancer Centre, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON, Canada.
Ahmad
A
Bushehri
Department of Radiation Oncology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, Odette Cancer Centre, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON, Canada. edward.chow@sunnybrook.ca.
Edward
E
Chow
Department of Radiation Oncology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, Odette Cancer Centre, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON, Canada.
Liying
L
Zhang
Department of Laboratory Medicine and Pathobiology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON, Canada.
Azar
A
Azad
Department of Radiation Oncology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, Odette Cancer Centre, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON, Canada.
Sherlyn
S
Vuong
Department of Pharmacy, Odette Cancer Centre, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON, Canada.
Mark
M
Pasetka
Department of Pharmacy, Odette Cancer Centre, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON, Canada.
Michelle
M
Zhou
Department of Radiation Oncology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, Odette Cancer Centre, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON, Canada.
Amanda
A
Hird
Division of Radiation Oncology, University of Ottawa, Ottawa Hospital Research Institute, Ottawa, Canada.
Kristopher
K
Dennis
Department of Radiation Oncology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, Odette Cancer Centre, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON, Canada.
Rachel
R
McDonald
Department of Pharmacy, Odette Cancer Centre, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON, Canada; Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Canada.
Carlo
C
DeAngelis
D000368:Aged; D000369:Aged, 80 and over; D001859:Bone Neoplasms / Q000532:radiotherapy* / Q000556:secondary; D018925:Chemokines / Q000652:urine*; D016207:Cytokines / Q000652:urine*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010146:Pain / Q000209:etiology / Q000503:physiopathology* / Q000652:urine*; D010147:Pain Measurement; D011878:Radiotherapy / Q000009:adverse effects / Q000379:methods
D018925:Chemokines; D016207:Cytokines
Bone metastases; external beam radiotherapy (EBRT); inflammatory markers; pain flare; urinary cytokines/chemokines