Medical Oncology Unit, Campus Salvatore Venuta, Department of Experimental and Clinical Medicine, Magna Graecia University and Tommaso Campanella Cancer Center, Catanzaro, Italy.
Cancer Biol Ther. 2013 Jun;14(6):469-75. doi: 10.4161/cbt.24425.
Bevacizumab is a humanized anti-VEGF monoclonal antibody able to produce clinical benefit in advanced non-squamous non-small-cell lung cancer (NSCLC) patients when combined to chemotherapy. At present, while there is a rising attention to bevacizumab-related adverse events and costs, no clinical or biological markers have been identified and validated for baseline patient selection. Preclinical findings suggest an important role for myeloid-derived inflammatory cells, such as neutrophils and monocytes, in the development of VEGF-independent angiogenesis. We conducted a retrospective analysis to investigate the role of peripheral blood cells count and of an inflammatory index, the neutrophil-to-lymphocyte ratio (NLR), as predictors of clinical outcome in NSCLC patients treated with bevacizumab plus chemotherapy. One hundred and twelve NSCLC patients treated with chemotherapy ± bevacizumab were retrospectively evaluated for the predictive value of clinical or laboratory parameters correlated with inflammatory status. Univariate analysis revealed that a high number of circulating neutrophils and monocytes as well as a high NLR were associated with shorter progression-free survival (PFS) and overall survival (OS) in bevacizumab-treated patients only. We have thus developed a model based on the absence or the presence of at least one of the above-mentioned inflammatory parameters. We found that the absence of all variables strongly correlated with longer PFS and OS (9.0 vs. 7.0 mo, HR: 0.39, p = 0.002; and 20.0 vs. 12.0 mo, HR: 0.29, p < 0.001 respectively) only in NSCLC patients treated with bevacizumab plus chemotherapy. Our results suggest that a baseline systemic inflammatory status is marker of resistance to bevacizumab treatment in NSCLC patients.
贝伐珠单抗是一种人源化抗 VEGF 单克隆抗体，当与化疗联合用于晚期非鳞状非小细胞肺癌（NSCLC）患者时，能产生临床获益。目前，尽管人们越来越关注贝伐珠单抗相关的不良反应和费用，但尚未确定和验证用于基线患者选择的临床或生物学标志物。临床前研究结果表明，髓系来源的炎性细胞（如中性粒细胞和单核细胞）在 VEGF 非依赖性血管生成的发展中起着重要作用。我们进行了一项回顾性分析，以研究外周血细胞计数和炎症指标，中性粒细胞与淋巴细胞比值（NLR），作为接受贝伐珠单抗联合化疗的 NSCLC 患者临床结局的预测因子。对 112 例接受化疗±贝伐珠单抗治疗的 NSCLC 患者进行了回顾性评估，以研究与炎症状态相关的临床或实验室参数的预测价值。单因素分析显示，循环中性粒细胞和单核细胞数量增加以及 NLR 升高与贝伐珠单抗治疗患者的无进展生存期（PFS）和总生存期（OS）缩短相关。因此，我们基于上述炎症参数中的一种或多种是否存在建立了一个模型。我们发现，至少有一种上述炎症参数不存在与较长的 PFS 和 OS 强烈相关（9.0 个月对 7.0 个月，HR：0.39，p = 0.002；20.0 个月对 12.0 个月，HR：0.29，p < 0.001），仅在接受贝伐珠单抗联合化疗的 NSCLC 患者中如此。我们的结果表明，基线系统性炎症状态是 NSCLC 患者对贝伐珠单抗治疗耐药的标志物。
