6月27日，中华医学会《中华医学杂志》正式发表军事医学科学院附属医院李健斌和江泽飞、河北医科大学第四医院耿翠芝、河南省肿瘤医院闫敏、山东省肿瘤医院王永胜、湖南省肿瘤医院欧阳取长、江苏省人民医院殷咏梅、北京德路通生物科技武林楠、第二军医大学统计学教研室贺佳的研究报告，利用CellCollector检测平台，验证其检测复发转移性乳腺癌患者循环肿瘤细胞（CTC）的有效性及安全性，并利用捕获的CTC进行后续分析。
循环肿瘤细胞（CTC）是指从恶性肿瘤原发部位脱落，通过血管或淋巴系统进入血液循环的细胞，能够反映肿瘤组织情况，也可以用无创方式补充组织样本进行诊断。随着精准医学的到来，已有大量数据验证CTC及其动态检测在乳腺癌领域的重要作用，同时CTC也能够在分子分型和基因分型上发挥重要作用。，美国食品药品监督管理局（FDA）批准了CellSearch技术应用于临床中。随后在国内经过中国国家食品药品监督管理总局（CFDA）批准，成为捕获CTC的金标准。但该技术捕获CTC数目极少，加上血细胞的干扰，无法达到目前对CTC研究的需求，如何提高捕获效能仍然是一个重要挑战阳。CellCollector技术是将上皮细胞黏附分子（EpCAM）抗体涂抹于金属丝上，随后将金属丝置于肘正中静脉内30分钟，利用血液流经金属丝功能区后，上皮细胞与EpCAM抗体结合并被捕获。其优势在于约1L血液流经功能区，因此可以捕获较多CTC，同时捕获的CTC经定位和分离后，可以进行后续的探索与应用研究。该技术目前已在肺癌等领域获得进展，同时也于取得欧洲安全证书，作为医疗器械Ⅱa类产品在欧盟上市。
该多中心临床观察研究于4～8月从军事医学科学院附属医院、河北省第四医院、河南省肿瘤医院、江苏省肿瘤医院、山东省肿瘤医院、湖南省肿瘤医院入组疾病进展后拟接受新一线治疗的复发转移性乳腺癌患者127例、确诊为确诊为良性肿瘤患者63例，利用CellCollector进行CTC计数及后续研究分析。
结果发现：
转移性乳腺癌患者行新一线治疗前CTC检出率达到74.8%（95/127），良性患者CTC检出率为0。
受试者工作特征（ROC）曲线下面积（AUC）达0.832（95%置信区间：0.784～0.879），CellCollector技术灵敏度74.8%，特异度100%（约登指数0.748）。
治疗3～4周后，转移性乳腺癌组有117例接受二次检测，CTC检出率为44.4%（52/117）。
转移性乳腺癌组的不良反应发生率为66.9%（85/127），重要不良事件发生率为39.8%（53/127），主要与病情及治疗反应相关。
利用CellCollector捕获的CTC可以进行HER2染色及后续基因测序分析。
因此，CellCollector技术可以检测复发转移性乳腺癌患者的CTC，同时还可以利用捕获的肿瘤细胞进行后续研究分析。与其他方法相比，体内CTC分离克服了血容量限制。进一步分子分型和基因分型可能有助于将“液体活检”应用于临床决策。
Zhonghua Yi Xue Za Zhi. Jun 27;97(24):1857-1861.
Circulating tumor cells in patients with breast tumors were detected by a novel device: a multicenter, clinical trial in China.
Li JB, Geng CZ, Yan M, Wang YS, Ouyang QC, Yin YM, Wu LN, He J, Jiang ZF.
Affiliated Hospital of Military Medical Science Academy of the PLA, Beijing China.
OBJECTIVE: Circulating tumor cells (CTC) have become an important part of liquid biopsy, which have underwent a process from simple counting to molecular typing and genotyping. To this end, we used CellCollector to verify the effectiveness and safety of CTC detection in patients with breast tumor, and to conduct the following analysis.
METHODS: One hundred and ninety patients who received treatment in six leading Chinese cancer centers were involved from April to August in . Among which, 127 patients were diagnosed as metastatic breast cancer, and the other 63 patients as benign breast tumors.
RESULTS: In metastatic breast cancer group, 74.8%(95/127) were CTC positive. While in benign tumor group, they were all CTC negative patients. The area under the Receiver Operating Characteristic curve were 0.832 (95%CI: 0.784-0.879). The sensitivity of CellCollector was 74.8%, specificity was 100% (Youden index 0.748). A total of 117 patients in MBC groups received a second detection of CellCollector after 3-4 weeks, among which 44.4% (52/117) were CTC positive patients. The incidence of adverse events and severe adverse events in MBC was 66.9%(85/127) and 39.8% (53/127). Furthermore, we used CellCollector to perform the HER2 testing and gene sequencing.
CONCLUSIONS: In vivo isolation of CTCs overcomes blood volume limitations compared to other approaches. The further application of molecular typing and gene typing might help to implement CTC-based "liquid biopsies" into clinical decision making.
KEYWORDS: Breast tumor; Capture efficiency; Circulating tumor cells; Further application
PMID: 28648008
DOI: 10.3760/cma.j.issn.0376-2491..24.003
