Dathathri E, Nanou A, Bidard F-C, Renault S, Pierga J-Y, de Bono J, Terstappen L, Coumans F A W
Department of Medical Cell Biophysics, TechMed Center, Faculty of Science and Technology, University of Twente, Enschede, The Netherlands.
Department of Medical Oncology, Institut Curie, PSL Research University, Paris, France; Circulating Tumor Biomarkers Laboratory, Siric, Institut Curie, PSL Research University, Paris, France; UVSQ, Paris-Saclay University, Paris, France.
ESMO Open. 2025 Jun 17;10(7):105302. doi: 10.1016/j.esmoop.2025.105302.
The load of circulating tumor cells (CTC) and tumor-derived extracellular vesicles (tdEV) strongly correlates with poor clinical outcomes and can be used to evaluate treatment response and the presence of treatment targets. However, the frequency of CTC is low, making an accurate assessment impossible in most patients. Here, we introduce blood tumor load (BTL), in which CTC and tdEV are combined into one value ranging from 0 (low) to 1 (high) to simplify result interpretation and increase the percentage of patients from which a reliable assessment can be made.
The CTC and tdEV counts were obtained from the ACCEPT analysis of the CellSearch image datasets of 98 metastatic breast cancer patients (mBC) and 157 castration-resistant prostate cancer patients (CRPC). The BTL generated using these counts was used in human epidermal growth factor receptor 2 (HER2) expression assessment in mBC patients. The BTL scores of CRPC patients at baseline and first follow-up time points were evaluated, and a change in BTL, indicating response to therapy, was measured in the patients.
Using 10 CTCs as a threshold, the HER2 positivity could be determined in 34/98 (35%) breast cancer patients, whereas with BTL, the positivity increased to 76/98 (78%). The BTL showed an improved Cox hazard ratio for overall survival in 157 CRPC patients before and at first follow-up points compared with CTC and tdEV alone. A decrease in BTL indicating response to therapy was seen in 45% of CRPC patients, and an increase in BTL was seen in 9%, indicating progression on treatment. The remaining 46% of patients showed no change.
In this study, we demonstrated the applications of BTL in improving the reliability of measuring response to therapy and increasing the proportion of patients from which the presence of a treatment target can be assessed.
循环肿瘤细胞（CTC）和肿瘤来源的细胞外囊泡（tdEV）的负荷与不良临床结局密切相关，可用于评估治疗反应和治疗靶点的存在情况。然而，CTC的频率较低，使得大多数患者无法进行准确评估。在此，我们引入血液肿瘤负荷（BTL），将CTC和tdEV合并为一个从0（低）到1（高）的数值，以简化结果解读并增加可进行可靠评估的患者比例。
从98例转移性乳腺癌患者（mBC）和157例去势抵抗性前列腺癌患者（CRPC）的CellSearch图像数据集的ACCEPT分析中获取CTC和tdEV计数。使用这些计数生成的BTL用于mBC患者的人表皮生长因子受体2（HER2）表达评估。评估了CRPC患者在基线和首次随访时间点的BTL评分，并测量了患者中表明对治疗有反应的BTL变化。
以10个CTC为阈值，可在34/98（35%）的乳腺癌患者中确定HER2阳性，而使用BTL时，阳性率增至76/98（78%）。与单独的CTC和tdEV相比，BTL在157例CRPC患者的基线和首次随访时显示出总体生存的Cox风险比有所改善。45%的CRPC患者出现BTL下降表明对治疗有反应，9%的患者BTL升高表明治疗进展。其余46%的患者无变化。
在本研究中，我们证明了BTL在提高测量治疗反应可靠性和增加可评估治疗靶点存在的患者比例方面的应用。
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