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预测癌症骨痛放疗反应:细胞因子是否为潜在的生物标志物?

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

机构信息

Cancer Research UK Edinburgh Centre, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.

Department of Oncology, Mount Vernon Cancer Centre, Mount Vernon Hospital, Northwood, UK.

出版信息

Clin Oncol (R Coll Radiol). 2020 Oct;32(10):e203-e208. doi: 10.1016/j.clon.2020.03.010. Epub 2020 Apr 11.

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.

摘要

目的

癌症骨痛(CIBP)的放射治疗(XRT)疗效不一。预测可能疗效的生物标志物可以将 XRT 分层为最有可能受益的患者。目前在临床实践中没有使用生物标志物,但已确定了潜在的候选细胞因子。本研究旨在探讨 XRT 后候选细胞因子与镇痛反应之间的关系。

材料和方法

对接受单次分割(8 Gy)XRT 治疗 CIBP 的患者的生物库数据进行了探索性分析。生物库数据是从英国多个中心前瞻性收集的,作为更大的临床试验的一部分,该试验获得了机构审查委员会的批准,所有患者均书面同意将其数据用于未来的研究。在 XRT 前 24 小时内采集表型数据、疼痛评估和血浆样本,并在 XRT 后 4 周进行随访。分析了基线(XRT 前 24 小时内)和随访时的样本,并比较了分类为 XRT“应答者”或“非应答者”的患者的 16 种预先确定的细胞因子的水平。

结果

分析了 60 例患者的数据。胰岛素样生长因子结合蛋白 9(NOV/CCN3/IGFBP-9)和白细胞介素 1β(IL-1β)被确定为 XRT 反应的潜在预测因子。XRT 反应与基线:随访时 NOV/CCN3/IGFBP-9 中位数水平的比值之间存在显著关系(P=0.024)。此外,对于年龄在 64 岁以下的患者,应答者和非应答者之间 NOV/CCN3/IGFBP-9 的中位数水平差异有统计学意义(P=0.047)。对于 IL-1β,在乳腺癌患者中,应答者和非应答者之间的中位数水平差异有统计学意义(P=0.006)。

结论

尽管目前的研究结果没有确定可靠的生物标志物,但这是首次研究细胞因子在预测 CIBP 患者 XRT 反应中的作用的研究,鼓励在此基础上开展进一步的研究。

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