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经动脉化疗栓塞术后循环肿瘤细胞的早期释放阻碍了肝细胞癌患者的治疗反应。

Early release of circulating tumor cells after transarterial chemoembolization hinders therapeutic response in patients with hepatocellular carcinoma.

作者信息

Espejo-Cruz María L, González-Rubio Sandra, Espejo Juan J, Zamora-Olaya Javier M, Prieto-Torre María, Linares Clara I, Ruiz-Ramas Álvaro, Jiménez-Arranz Álvaro, Guerrero-Misas Marta, Barrera-Baena Pilar, Poyato-González Antonio, Montero José L, Sánchez-Frías Marina, Ayllón María D, Rodríguez-Perálvarez Manuel L, de la Mata Manuel, Ferrín Gustavo

机构信息

Maimonides Biomedical Research Institute of Cordoba (IMIBIC), University of Cordoba, Cordoba, Spain.

Biomedical Research Network Center for Liver and Digestive Diseases (CIBERehd), Madrid, Spain.

出版信息

J Transl Med. 2025 Jan 30;23(1):139. doi: 10.1186/s12967-025-06092-3.

DOI:10.1186/s12967-025-06092-3
PMID:39885581
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11783761/
Abstract

BACKGROUND

Transarterial chemoembolization (TACE) is the first-line therapeutic option for patients with intermediate-stage hepatocellular carcinoma (HCC). Tumor neovascularization allows tumor growth and may facilitate the release of circulating tumor cells (CTCs) to the bloodstream after TACE. We investigated the relationship between early release of CTCs and radiological response after TACE.

METHODS

Prospective, single-center study including patients with HCC undergoing a first TACE from January 2019 to June 2023. The IsoFlux® system was used to evaluate EpCAM+ CTC counts before TACE, at day 1 (D1), and at day 30 after TACE. Radiological response to TACE was assessed according to the mRECIST criteria one month after the procedure. Tumor vascularity was assessed by an interventional radiologist.

RESULTS

In all, 48 patients with HCC undergoing TACE were included (age 64.2 ± 7.6 years, 14.6% women). CTC levels increased at D1 (114.0% [IQR 76.5%-178.0%], p = 0.019) and normalized to baseline levels in the first month after TACE (76.5% [IQR 41.3%-131.8%], p = 0.263). Higher CTC counts at baseline (p = 0.009) and at D1 (p = 0.026) were associated with tumor hypervascularity. Larger tumor size [OR: 1.9 (95% CI: 1.1-3.3), p = 0.020] and CTC increase at D1 [OR: 5.3 (95% CI: 1.3-21.0), p = 0.017] were independent predictors of non-response to TACE, especially for those patients with hypervascular lesions.

CONCLUSIONS

A meaningful release of CTCs 24 h after TACE was associated with suboptimal tumor response one month after the procedure. Future studies should evaluate the role of CTC dynamics to select candidates for adjuvant therapy after TACE and to analyze their impact on long-term outcomes.

摘要

背景

经动脉化疗栓塞术(TACE)是中期肝细胞癌(HCC)患者的一线治疗选择。肿瘤新生血管促进肿瘤生长,并可能促使循环肿瘤细胞(CTC)在TACE术后释放进入血流。我们研究了TACE术后早期CTC释放与放射学反应之间的关系。

方法

一项前瞻性单中心研究,纳入2019年1月至2023年6月期间接受首次TACE的HCC患者。使用IsoFlux®系统评估TACE术前、术后第1天(D1)和术后第30天的EpCAM+ CTC计数。根据mRECIST标准在TACE术后1个月评估对TACE的放射学反应。由介入放射科医生评估肿瘤血管情况。

结果

共纳入48例接受TACE的HCC患者(年龄64.2±7.6岁,女性占14.6%)。CTC水平在D1时升高(114.0%[四分位间距76.5%-178.0%],p=0.019),并在TACE术后第一个月恢复至基线水平(76.5%[四分位间距41.3%-131.8%],p=0.263)。基线时(p=0.009)和D1时(p=0.026)较高的CTC计数与肿瘤血管丰富有关。肿瘤较大[比值比:1.9(95%置信区间:1.1-3.3),p=0.020]和D1时CTC升高[比值比:5.3(95%置信区间:1.3-21.0),p=0.017]是TACE无反应的独立预测因素,尤其是对于那些有血管丰富病变的患者。

结论

TACE术后24小时有意义的CTC释放与术后1个月欠佳的肿瘤反应相关。未来研究应评估CTC动态变化在选择TACE术后辅助治疗候选者以及分析其对长期结局影响方面的作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0db/11783761/b7ea85cbc747/12967_2025_6092_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0db/11783761/18c414d49b0f/12967_2025_6092_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0db/11783761/765ef0b3e04d/12967_2025_6092_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0db/11783761/b7ea85cbc747/12967_2025_6092_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0db/11783761/18c414d49b0f/12967_2025_6092_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0db/11783761/765ef0b3e04d/12967_2025_6092_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0db/11783761/b7ea85cbc747/12967_2025_6092_Fig3_HTML.jpg

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