Prognostic Relevance of Circulating Tumor Cells and Circulating Cell-Free DNA Association in Metastatic Non-Small Cell Lung Cancer Treated with Nivolumab
Prognostic Relevance of Circulating Tumor Cells and Circulating Cell-Free DNA Association in Metastatic Non-Small Cell Lung Cancer Treated with Nivolumab
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DOI：
10.3390/jcm8071011
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发表时间：
2019-07-01
影响因子：
3.9
通讯作者：
Grossi, Francesco
中科院分区：
文献类型：
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作者：
Alama, Angela;Coco, Simona;Grossi, Francesco
晚期非小细胞肺癌（NSCLC）的治疗已经被免疫检查点抑制剂（ICI）彻底改变。ICIs治疗患者的预后和预测因素的识别目前具有挑战性。在89名接受纳武单抗的既往治疗过的NSCLC患者中评价了循环肿瘤细胞（CTC）和无细胞DNA（cfDNA）。在治疗前以及第一次和第二次放射学缓解评估时采集血样。通过基于过滤的方法分离CTC。从血浆中提取cfDNA并通过定量PCR进行估计。基线CTC数量和cfDNA低于其中位数值的患者（3 mL血液和血浆中分别为2 ng和836.5 ng）的存活时间显著长于具有较高值的患者（分别为p = 0.05和p = 0.04）。然后将这两种生物标志物分别和联合用作回归模型中的时间依赖性协变量，证实其预后作用。此外，观察到两种循环生物标志物均高于中值的亚组的死亡风险为4倍（p < 0.001）。在循环生物标志物和最佳缓解之间未发现显著差异。然而，伴随较低CTC和cfDNA的进展患者在临床上表现良好（p = 0.007），表明联合CTC和cfDNA可能有助于区分低风险人群，其可能受益于进展后的持续ICI。
The treatment of advanced non-small cell lung cancer (NSCLC) has been revolutionized by immune checkpoint inhibitors (ICIs). The identification of prognostic and predictive factors in ICIs-treated patients is presently challenging. Circulating tumor cells (CTCs) and cell-free DNA (cfDNA) were evaluated in 89 previously treated NSCLC patients receiving nivolumab. Blood samples were collected before therapy and at the first and second radiological response assessments. CTCs were isolated by a filtration-based method. cfDNA was extracted from plasma and estimated by quantitative PCR. Patients with baseline CTC number and cfDNA below their median values (2 and 836.5 ng from 3 mL of blood and plasma, respectively) survived significantly longer than those with higher values (p = 0.05 and p = 0.04, respectively). The two biomarkers were then used separately and jointly as time-dependent covariates in a regression model confirming their prognostic role. Additionally, a four-fold risk of death for the subgroup presenting both circulating biomarkers above the median values was observed (p < 0.001). No significant differences were found between circulating biomarkers and best response. However, progressing patients with concomitant lower CTCs and cfDNA performed clinically well (p = 0.007), suggesting that jointed CTCs and cfDNA might help discriminate a low-risk population which might benefit from continuing ICIs beyond progression.