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循环肿瘤细胞(CTCs)/循环肿瘤内皮细胞(CTECs)及其在小细胞肺癌中的亚型:预测反应和预后的标志物。

Circulating tumor cells (CTCs)/circulating tumor endothelial cells (CTECs) and their subtypes in small cell lung cancer: Predictors for response and prognosis.

机构信息

Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.

Department of General Medicine, Beijing Chest Hospital, Capital Medical University & Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, China.

出版信息

Thorac Cancer. 2021 Oct;12(20):2749-2757. doi: 10.1111/1759-7714.14120. Epub 2021 Aug 23.

Abstract

BACKGROUND

The aim of the study was to define the clinical significance of circulating tumor cells (CTCs)/circulating tumor endothelial cells (CTECs) and their subtypes in small cell lung cancer (SCLC) patients.

METHODS

CTCs/CTECs and their subtypes were determined using SE-iFISH technology in 33 SCLC patients before initial treatment (B1), after two cycles of chemotherapy (B2), at the completion of chemotherapy (B3), and disease progression (B4). The correlations with clinical characteristics, progression-free survival (PFS), and overall survival (OS) were analyzed.

RESULTS

CTCs and CTECs were detected in 96.6% and 65.5% of patients, respectively. Patients had higher levels of CTCs compared with CTECs in circulation (p < 0.05). Extensive-stage SCLC patients tended to have higher CTEC counts (p = 0.035), and the detection of CTC-white blood cell (CTC-WBC) clusters was associated with a worse response to treatment (p = 0.030). Patients with CTC-WBC clusters at B1 (17.3 vs. 22.6 months, p = 0.041) and B2 (19.9 vs. 25.2 months, p = 0.018) had significantly shorter OS than those with no detection. Additionally, their presence was revealed as independent predictors for a worse OS in multivariable analyses (B1: HR 9.3, 95% CI: 1.4-48, p = 0.0079; B2: HR 4.4, 95% CI: 1.1-18, p = 0.041). A high CTC level at B4 was an adverse prognostic factor for SCLC patients (PFS: 8.7 vs. 22.5 months, p = 0.0026; OS: 19 months vs. not reached, p = 0.0086). CTC clusters and CTECs also showed prognostic values.

CONCLUSIONS

The presence of CTC-WBC clusters at baseline and after two-cycle chemotherapy and the total CTC counts at the completion of chemotherapy are strong predictors for the prognostic survival of SCLC patients receiving first-line treatment.

摘要

背景

本研究旨在定义循环肿瘤细胞(CTCs)/循环肿瘤内皮细胞(CTECs)及其亚型在小细胞肺癌(SCLC)患者中的临床意义。

方法

采用 SE-iFISH 技术检测 33 例初治患者(B1)、化疗 2 周期后(B2)、化疗结束时(B3)和疾病进展时(B4)的 CTCs/CTECs 及其亚型。分析其与临床特征、无进展生存期(PFS)和总生存期(OS)的相关性。

结果

96.6%的患者检测到 CTCs,65.5%的患者检测到 CTECs。与 CTECs 相比,患者循环中 CTCs 的水平更高(p<0.05)。广泛期 SCLC 患者 CTEC 计数较高(p=0.035),CTCs-白细胞(CTC-WBC)簇的检测与治疗反应较差相关(p=0.030)。B1 时 CTC-WBC 簇存在的患者(17.3 个月 vs. 22.6 个月,p=0.041)和 B2 时 CTC-WBC 簇存在的患者(19.9 个月 vs. 25.2 个月,p=0.018)的 OS 明显短于无检测患者。此外,多变量分析显示,CTC-WBC 簇在 B1 时(HR 9.3,95%CI:1.4-48,p=0.0079)和 B2 时(HR 4.4,95%CI:1.1-18,p=0.041)为 OS 的独立预测因素。B4 时 CTC 水平较高是 SCLC 患者不良预后的因素(PFS:8.7 个月 vs. 22.5 个月,p=0.0026;OS:19 个月 vs. 未达到,p=0.0086)。CTC 簇和 CTECs 也显示出预后价值。

结论

基线和化疗 2 周期后 CTC-WBC 簇的存在以及化疗结束时总 CTC 计数是接受一线治疗的 SCLC 患者预后生存的有力预测因素。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f326/8520806/84a575651e25/TCA-12-2749-g004.jpg

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