Effect of re-irradiation for painful bone metastases on urinary markers of osteoclast activity (NCIC CTG SC.20U)

Radiother Oncol. 2015 Apr;115(1):141-8. doi: 10.1016/j.radonc.2015.02.025. Epub 2015 Mar 14.

Abstract

Purpose: The NCIC CTG Symptom Control.20 randomized trial (SC.20) confirmed the effectiveness of re-irradiation to painful bone metastases. This companion study correlates urinary markers of osteoclast activity with response to re-irradiation, survival and skeletal related events (SREs).

Methods: Pain response was assessed using the International Consensus Endpoints. Urinary markers of bone turnover-pyridinoline (PYD), deoxypyridinoline (DPD), N-telopeptide (NTX), Alpha and Beta cross-laps of C-telopeptide (CTX)-before and 1month after re-irradiation were correlated to response to re-irradiation and then to both, either or none of the initial and re-irradiation: frequent responders (response to both); eventual responders (response to re-irradiation only); eventual non-responders (response to initial radiation only), and absolute non-responders (no response to both).

Results: Significant differences between 40 responders and 69 non-responders to re-irradiation existed for PYD (p=0.03) and DPD (p=0.04) at baseline. When patients were categorized as frequent responders (N=34), eventual responders (6), eventual non-responders (59) and absolute non-responders (10), the mean values of all markers in the absolute non-responders at baseline and the follow-up were about double those for the other three groups with statistically significant difference for DPD (p=0.03) at baseline. Absolute non-responders had the worst survival. The few occurrences of the SREs did not allow meaningful comparisons among the groups.

Conclusion: There were significant differences between responders and non-responders to re-irradiation for PYD and DPD at baseline. The urinary markers in the absolute non-responders were markedly elevated at both baseline and follow-up with a statistically significant difference for DPD at baseline.

Keywords: Bone metastases; Osteoclast activity; Re-irradiation; Urinary markers.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Amino Acids / urine
  • Biomarkers, Tumor / urine*
  • Bone Neoplasms / radiotherapy*
  • Bone Neoplasms / secondary
  • Collagen Type I / urine
  • Female
  • Follow-Up Studies
  • Humans
  • Male
  • Middle Aged
  • Osteoclasts / radiation effects*
  • Peptides / urine

Substances

  • Amino Acids
  • Biomarkers, Tumor
  • Collagen Type I
  • Peptides
  • collagen type I trimeric cross-linked peptide
  • pyridinoline
  • deoxypyridinoline