Department of Oncology, University of Oxford, Oxford, UK.
Centre for Trials Research, Cardiff, UK.
Br J Cancer. 2021 Feb;124(3):581-586. doi: 10.1038/s41416-020-01120-z. Epub 2020 Oct 26.
The Phase 2 SCALOP trial compared gemcitabine with capecitabine-based consolidation chemoradiotherapy (CRT) in locally advanced pancreatic cancer (LAPC).
Thirty-five systematically identified circulating biomarkers were analysed in plasma samples from 60 patients enroled in SCALOP. Each was measured in triplicate at baseline (prior to three cycles of gemcitabine-capecitabine induction chemotherapy) and, for a subset, prior to CRT. Association with overall survival (OS) was determined using univariable Cox regression and optimal thresholds delineating low to high values identified using time-dependent ROC curves. Independence from known prognostic factors was assessed using Spearman correlation and the Wilcoxon rank sum test prior to multivariable Cox regression modelling including independent biomarkers and known prognostic factors.
Baseline circulating levels of C-C motif chemokine ligand 5 (CCL5) were significantly associated with OS, independent of other clinicopathological characteristics. Patients with low circulating CCL5 (CCL5) had a median OS of 18.5 (95% CI 11.76-21.32) months compared to 11.3 (95% CI 9.86-15.51) months in CCL5; hazard ratio 1.95 (95% CI 1.04-8.65; p = 0.037).
CCL5 is an independent prognostic biomarker in LAPC. Given the known role of CCL5 in tumour invasion, metastasis and the induction of an immunosuppressive micro-environment, targeting of CCL5-mediated pathways may offer therapeutic potential in pancreatic cancer.
The SCALOP trial was registered with ISRCTN, number 96169987 (registered 29 May 2008).
SCALOP 二期试验比较了吉西他滨与卡培他滨为基础的巩固放化疗（CRT）在局部晚期胰腺癌（LAPC）中的疗效。
在 SCALOP 试验中，对 60 名患者的血浆样本进行了 35 种系统性鉴定的循环生物标志物分析。每个标志物在基线时（吉西他滨-卡培他滨诱导化疗前三个周期）进行了三次重复测量，对于亚组患者，在 CRT 前也进行了测量。使用单变量 Cox 回归分析和时间依赖性 ROC 曲线确定的最佳阈值来确定与总生存期（OS）的相关性。在多变量 Cox 回归模型中，使用 Spearman 相关性和 Wilcoxon 秩和检验评估与已知预后因素的独立性，该模型包括独立的生物标志物和已知的预后因素。
基线时循环 C-C 基序趋化因子配体 5（CCL5）的水平与 OS 显著相关，独立于其他临床病理特征。循环 CCL5 低（CCL5）的患者中位 OS 为 18.5 个月（95%CI 11.76-21.32），而 CCL5 高的患者中位 OS 为 11.3 个月（95%CI 9.86-15.51）；危险比 1.95（95%CI 1.04-8.65；p=0.037）。
CCL5 是 LAPC 的独立预后生物标志物。鉴于 CCL5 在肿瘤侵袭、转移和诱导免疫抑制微环境中的已知作用，靶向 CCL5 介导的途径可能为胰腺癌提供治疗潜力。
SCALOP 试验在 ISRCTN 注册，编号为 96169987（2008 年 5 月 29 日注册）。
