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小细胞肺癌循环肿瘤细胞的纵向评估及预后:一项使用低分子量肝素的RASTEN随机试验的子研究

Longitudinal Assessment of Circulating Tumor Cells and Outcome in Small Cell Lung Cancer: A Sub-Study of RASTEN-A Randomized Trial with Low Molecular Weight Heparin.

作者信息

Bendahl Pär-Ola, Belting Mattias, Gezelius Emelie

机构信息

Department of Clinical Sciences, Lund, Division of Oncology, Lund University, Barngatan 4, SE-221 85 Lund, Sweden.

Department of Hematology, Radiophysics and Oncology, Skåne University Hospital, Lasarettsgatan 23A, SE-221 85 Lund, Sweden.

出版信息

Cancers (Basel). 2023 Jun 13;15(12):3176. doi: 10.3390/cancers15123176.

Abstract

Circulating tumor cells (CTCs) may provide a liquid biopsy approach to disease monitoring in small cell lung cancer (SCLC), a particularly aggressive tumor subtype. Yet, the prognostic role of CTCs during and after treatment in relation to baseline remains ill-defined. Here, we assessed the value of longitudinal CTC analysis and the potential of low-molecular-weight heparin (LMWH) to reduce CTC abundance in SCLC patients from a randomized trial (RASTEN). Blood samples were collected at baseline, before chemotherapy Cycle 3, and at 2-month follow-up from 42 patients in total, and CTCs were quantified using the FDA-approved CellSearch system. We found a gradual decline in CTC count during and after treatment, independently of the addition of LMWH to standard therapy. Detectable CTCs at baseline correlated significantly to reduced survival compared to undetectable CTCs (unadjusted hazard ratio (HR) of 2.75 (95% CI 1.05-7.20; = 0.040)). Furthermore, a persistent CTC count at 2-month follow-up was associated with a HR of 4.22 (95% CI 1.20-14.91; = 0.025). Our findings indicate that persistently detectable CTCs during and after completion of therapy offer further prognostic information in addition to baseline CTC, suggesting a role for CTC in the individualized management of SCLC.

摘要

循环肿瘤细胞(CTCs)可能为小细胞肺癌(SCLC,一种侵袭性特别强的肿瘤亚型)的疾病监测提供一种液体活检方法。然而,治疗期间及治疗后CTCs相对于基线水平的预后作用仍不明确。在此,我们从一项随机试验(RASTEN)评估了小细胞肺癌患者纵向CTCs分析的价值以及低分子量肝素(LMWH)降低CTCs丰度的潜力。总共从42例患者中在基线、化疗第3周期前以及2个月随访时采集血样,并使用FDA批准的CellSearch系统对CTCs进行定量。我们发现治疗期间及治疗后CTCs计数逐渐下降,与在标准治疗中添加LMWH无关。与未检测到CTCs相比,基线时可检测到的CTCs与生存率降低显著相关(未调整风险比(HR)为2.75(95%CI 1.05 - 7.20;P = 0.040))。此外,2个月随访时持续的CTCs计数与HR为4.22相关(95%CI 1.20 - 14.91;P = 0.025)。我们的研究结果表明,治疗期间及治疗完成后持续可检测到的CTCs除了基线CTCs外还提供了进一步的预后信息,提示CTCs在小细胞肺癌个体化管理中的作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/20fb/10295929/8b878ca81a8d/cancers-15-03176-g001.jpg

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