Christie NHS Foundation Trust, Wilmslow Road, Withington, Manchester, M20 4BX, UK.
The Clatterbridge Cancer Centre NHS Foundation Trust, Wirral, UK.
BMC Cancer. 2021 Apr 1;21(1):354. doi: 10.1186/s12885-021-08097-9.
Patients with metastatic colorectal cancer are treated with cytotoxic chemotherapy supplemented by molecularly targeted therapies. There is a critical need to define biomarkers that can optimise the use of these therapies to maximise efficacy and avoid unnecessary toxicity. However, it is important to first define the changes in potential biomarkers following cytotoxic chemotherapy alone. This study reports the impact of standard cytotoxic chemotherapy across a range of circulating and imaging biomarkers.
A single-centre, prospective, biomarker-driven study. Eligible patients included those diagnosed with colorectal cancer with liver metastases that were planned to receive first line oxaliplatin plus 5-fluorouracil or capecitabine. Patients underwent paired blood sampling and magnetic resonance imaging (MRI), and biomarkers were associated with progression-free survival (PFS) and overall survival (OS).
Twenty patients were recruited to the study. Data showed that chemotherapy significantly reduced the number of circulating tumour cells as well as the circulating concentrations of Ang1, Ang2, VEGF-A, VEGF-C and VEGF-D from pre-treatment to cycle 2 day 2. The changes in circulating concentrations were not associated with PFS or OS. On average, the MRI perfusion/permeability parameter, K, increased in response to cytotoxic chemotherapy from pre-treatment to cycle 2 day 2 and this increase was associated with worse OS (HR 1.099, 95%CI 1.01-1.20, p = 0.025).
In patients diagnosed with colorectal cancer with liver metastases, treatment with standard chemotherapy changes cell- and protein-based biomarkers, although these changes are not associated with survival outcomes. In contrast, the imaging biomarker, K, offers promise to direct molecularly targeted therapies such as anti-angiogenic agents.
转移性结直肠癌患者接受细胞毒性化疗，并辅以分子靶向治疗。迫切需要定义生物标志物，以优化这些治疗方法的使用，最大限度地提高疗效，避免不必要的毒性。然而，首先定义单独使用细胞毒性化疗后潜在生物标志物的变化是很重要的。本研究报告了一系列循环和影像学生物标志物在标准细胞毒性化疗中的作用。
这是一项单中心、前瞻性、以生物标志物为驱动的研究。符合条件的患者包括那些被诊断为结直肠癌伴肝转移的患者，这些患者计划接受一线奥沙利铂加 5-氟尿嘧啶或卡培他滨治疗。患者接受了配对的血液采样和磁共振成像（MRI），并将生物标志物与无进展生存期（PFS）和总生存期（OS）相关联。
本研究共招募了 20 名患者。数据显示，与治疗前相比，化疗在第 2 周期第 2 天显著减少了循环肿瘤细胞的数量以及循环中的 Ang1、Ang2、VEGF-A、VEGF-C 和 VEGF-D 的浓度。循环浓度的变化与 PFS 或 OS 无关。平均而言，MRI 灌注/渗透性参数 K 在接受细胞毒性化疗后从治疗前到第 2 周期第 2 天增加，这种增加与较差的 OS 相关（HR 1.099，95%CI 1.01-1.20，p=0.025）。
在被诊断为结直肠癌伴肝转移的患者中，标准化疗改变了基于细胞和蛋白的生物标志物，尽管这些变化与生存结果无关。相比之下，成像生物标志物 K 有望指导分子靶向治疗，如抗血管生成药物。
