Urinary cytokines/chemokines pattern in patients with painful bone metastases undergoing external beam radiotherapy experiencing pain flare

Ann Palliat Med. 2016 Apr;5(2):107-15. doi: 10.21037/apm.2016.03.04.

Abstract

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.

Keywords: Bone metastases; external beam radiotherapy (EBRT); inflammatory markers; pain flare; urinary cytokines/chemokines.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Bone Neoplasms / radiotherapy*
  • Bone Neoplasms / secondary
  • Chemokines / urine*
  • Cytokines / urine*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Pain / etiology
  • Pain / physiopathology*
  • Pain / urine*
  • Pain Measurement
  • Radiotherapy / adverse effects
  • Radiotherapy / methods

Substances

  • Chemokines
  • Cytokines