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不可切除的转移性结直肠癌患者循环肿瘤细胞水平的纵向变化及其与免疫检查点抑制剂治疗获益的关系。

Longitudinal change of circulating tumor cell level and its relationship with immune checkpoint inhibitor-based treatment benefits in unresectable, metastatic colorectal cancer patients.

机构信息

Department of Gastrointestinal Surgery, Yanan University Affilliated Hospital, Yanan, Shanxi, China.

出版信息

Scand J Clin Lab Invest. 2023 Jul;83(4):227-233. doi: 10.1080/00365513.2023.2204404. Epub 2023 May 29.

Abstract

OBJECTIVE

Circulating tumor cell (CTC) exerts diagnostic and prognostic value in colorectal cancer (CRC) patients. This study intended to further investigate the longitudinal change of CTC count, and its correlation with the prognosis of immune checkpoint inhibitor (ICI)-based treatments in unresectable, metastatic CRC patients.

METHODS

Fifty-six unresectable, metastatic CRC patients receiving ICI-based treatments were enrolled. CTC count was assessed by the CellSearch system at baseline and month (M)2 in their peripheral blood samples.

RESULTS

Forty-one (73.2%) and sixteen (28.5%) patients had CTC count ≥1 and ≥5 at baseline, respectively. Meanwhile, CTC count at M2 was decreased versus that at baseline (median (interquartile range): 1.0 (0.0-3.0) versus 3.0 (0.0-5.0)) ( < 0.001). Besides, increased CTC count at baseline ( = 0.009) and M2 ( = 0.006) associated with a reduced overall response rate. Baseline CTC count ≥5 related to worse progression-free survival (PFS) ( = 0.007), but baseline CTC count ≥1 did not; additionally, baseline CTC count ≥1 ( = 0.043) and ≥5 ( = 0.016) linked to shorter overall survival (OS). Furthermore, M2 CTC count ≥1 ( = 0.002) and ≥5 ( < 0.001) both correlated with poor PFS; meanwhile, M2 CTC count ≥1 ( = 0.006) and ≥5 ( < 0.001) also related to worse OS. After adjustment, only CTC count at M2 ≥ 5 independently associated with unsatisfactory PFS (hazard ratio (HR)=3.218,  = 0.011) and OS (HR = 3.229,  = 0.038).

CONCLUSIONS

CTC count is decreased during ICI-based treatments, its reduction represents satisfactory treatment outcomes in unresectable, metastatic CRC patients. Notably, the CTC count at 5 as a cutting threshold after a two-month treatment has an impressive prognostic value.

摘要

目的

循环肿瘤细胞(CTC)在结直肠癌(CRC)患者中具有诊断和预后价值。本研究旨在进一步探讨 CTC 计数的纵向变化,及其与不可切除转移性 CRC 患者接受免疫检查点抑制剂(ICI)治疗的预后的相关性。

方法

共纳入 56 例接受 ICI 治疗的不可切除转移性 CRC 患者。通过 CellSearch 系统在基线和第 2 个月(M)时检测患者外周血样本中的 CTC 计数。

结果

基线时,41(73.2%)例和 16(28.5%)例患者的 CTC 计数≥1 和≥5。同时,M2 时的 CTC 计数较基线时降低(中位数(四分位距):1.0(0.0-3.0)vs. 3.0(0.0-5.0))( < 0.001)。此外,基线( = 0.009)和 M2( = 0.006)时 CTC 计数增加与总缓解率降低相关。基线 CTC 计数≥5 与无进展生存期(PFS)更差相关( = 0.007),但 CTC 计数≥1 与之无关;此外,基线 CTC 计数≥1( = 0.043)和≥5( = 0.016)与总生存期(OS)更短相关。此外,M2 时 CTC 计数≥1( = 0.002)和≥5( < 0.001)均与 PFS 不良相关;同时,M2 时 CTC 计数≥1( = 0.006)和≥5( < 0.001)也与 OS 更差相关。调整后,只有 M2 时 CTC 计数≥5 与不满意的 PFS(风险比(HR)=3.218,  = 0.011)和 OS(HR=3.229,  = 0.038)独立相关。

结论

在接受 ICI 治疗期间,CTC 计数下降,其减少代表不可切除转移性 CRC 患者治疗效果满意。值得注意的是,在接受两个月治疗后,以 5 作为截断值的 CTC 计数具有显著的预后价值。

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