Department of Medical Oncology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, PR China.
Department of Lung Cancer and Immunology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, PR China.
Clin Lung Cancer. 2019 Mar;20(2):124-133.e2. doi: 10.1016/j.cllc.2018.11.014. Epub 2018 Dec 4.
There is an urgent need to develop a convenient and less invasive technique to monitor the efficacy of epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) in patients with EGFR-mutated non-small-cell lung cancer (NSCLC). We proposed folate receptor-based assay to count circulating tumor cells (CTCs) to predict and dynamically monitor the therapeutic response to first-line EGFR-TKIs in patients with EGFR-mutated NSCLC.
Eligible patients were enrolled, and 3 mL of blood was obtained before initial treatment, 1 month after treatment, and every 2 months thereafter. CTCs were isolated on the basis of negative enrichment by immunomagnetic beads and detected by a ligand-targeted PCR method.
A total of 232 patients with EGFR-mutated NSCLC and treated with first-line EGFR-TKIs were included. Patients with low baseline CTC count had a markedly longer progression-free survival (hazard ratio = 0.48; P < .001) and overall survival (hazard ratio = 0.52; P = .002) than those with high count. This difference remained significant in multivariate analysis. Dynamic change of CTC count was significantly associated with partial response (P = .042) and stable disease/progressive disease (P = .032). Notably, dynamic monitoring of CTC provided evidence of resistance to EGFR-TKIs before computed tomographic scanning with a median lead time of 113 days (range, 45-169 days).
The current evidence suggests that folate receptor-positive CTC counts can be used for both the dynamic monitoring and prediction of outcome in EGFR-mutated NSCLC patients treated with EGFR-TKIs, which could serve as an alternative or supplement to computed tomographic scanning.
迫切需要开发一种方便且微创的技术来监测表皮生长因子受体（EGFR）-酪氨酸激酶抑制剂（TKI）在 EGFR 突变型非小细胞肺癌（NSCLC）患者中的疗效。我们提出基于叶酸受体的检测方法来计数循环肿瘤细胞（CTC），以预测和动态监测 EGFR 突变型 NSCLC 患者一线 EGFR-TKI 治疗的应答反应。
纳入符合条件的患者，在初始治疗前、治疗后 1 个月以及此后每 2 个月采集 3 mL 血液。CTC 基于免疫磁珠的阴性富集进行分离，并通过配体靶向 PCR 方法进行检测。
共纳入 232 例接受一线 EGFR-TKI 治疗的 EGFR 突变型 NSCLC 患者。基线 CTC 计数低的患者无进展生存期（风险比=0.48；P<0.001）和总生存期（风险比=0.52；P=0.002）明显长于基线 CTC 计数高的患者。多变量分析结果仍具有显著意义。CTC 计数的动态变化与部分缓解（P=0.042）和疾病稳定/进展（P=0.032）显著相关。值得注意的是，EGFR-TKI 治疗前通过动态监测 CTC 提供了对 EGFR-TKI 耐药的证据，中位领先时间为 113 天（范围，45-169 天）。
目前的证据表明，叶酸受体阳性 CTC 计数可用于动态监测和预测 EGFR-TKI 治疗的 EGFR 突变型 NSCLC 患者的结局，可作为 CT 扫描的替代或补充。
