Predicting Response to Radiotherapy in Cancer-Induced Bone Pain: Cytokines as a Potential Biomarker?

Abstract

Aims: Radiotherapy (XRT) for cancer-induced bone pain (CIBP) has varying levels of efficacy. A biomarker that predicts likely efficacy could stratify XRT to those most likely to benefit. No biomarker is used in clinical practice, but potential candidate cytokines have been identified. The aim of the present study was to examine the relationship between candidate cytokines and analgesic response after XRT.

Materials and methods: An exploratory analysis was undertaken on biobank data from patients who had received single fraction (8 Gy) XRT for CIBP. The biobank data were prospectively collected from multiple centres in the UK as part of a larger clinical trial, which had institutional review board approval and all patients provided written informed consent for the use of their data in future research. Phenotypic data, pain assessments as well as plasma samples were collected at baseline (within the 24 h before the XRT) and at follow-up (4 weeks after XRT). Baseline and follow-up samples were analysed and levels of 16 pre-identified cytokines were compared in patients classified as XRT 'responders' or 'non-responders'.

Results: Data from 60 patients were analysed. Insulin-like growth factor binding protein 9 (NOV/CCN3/IGFBP-9) and interleukin-1ß (IL-1ß) were identified as potential predictors of response to XRT. A significant relationship was shown between the response to XRT and the ratio of the median level of NOV/CCN3/IGFBP-9 at baseline:follow-up (P = 0.024). Furthermore, for the patients up to 64 years of age, the median level of NOV/CCN3/IGFBP-9 was significantly different between responders and non-responders (P = 0.047). For IL-1ß, the median level was significantly different between responders and non-responders in patients with breast cancer (P = 0.006).

Conclusion: Although the present findings do not identify robust biomarkers, this is the first such study to examine the role of cytokines in predicting response to XRT in patients with CIBP, and studies that build on these findings are encouraged.

Keywords: Bone metastases; cancer; cytokines; radiotherapy; response.