循环肿瘤细胞可以反映肿瘤细胞特征的差异，但是通过目前最常用的液体活检方法（CellSearch）从标准的7.5mL血液分离出的循环肿瘤细胞数量太少，而不能可靠地确定肿瘤细胞特征差异，无法真正地反映肿瘤。
2018年9月19日，国际抗癌联盟《国际癌症杂志》在线发表荷兰特文特大学、德国杜塞尔多夫大学、意大利帕多瓦大学、威尼托肿瘤研究所、法国巴黎萨克雷大学、古斯塔夫·鲁西研究所、英国伦敦大学癌症研究院、皇家马斯登医院的研究报告，验证并优化了可以对数升血液进行筛查的诊断性白细胞分离法。
该研究通过欧盟（EU）第七科技框架计划（FP7）循环肿瘤细胞治疗性分离法（CTCTrap）项目的四个不同参与机构，将CellSearch处理7.5mL血液作为参考“金标准”，对34例转移癌（22例转移性前列腺和12例转移性乳腺癌）患者进行诊断性白细胞分离法的验证和优化，整个过程未见任何明显副作用。通过诊断性白细胞分离法进行CellSearch，与处理7.5mL血液相比，可使循环肿瘤细胞的产出量增加0～32倍。7例患者其中4例通过7.5mL血液未检出循环肿瘤细胞，而通过诊断性白细胞分离法检出1～4个循环肿瘤细胞。通过诊断性白细胞分离法获得的循环肿瘤细胞，肿瘤的分子特征更有代表性。不过，仍然需要对循环肿瘤细胞富集技术进行改进，对诊断性白细胞分离法得到的所有循环肿瘤细胞进行分离。
因此，利用诊断性白细胞分离法可以筛查数升血液，循环肿瘤细胞的产出量显著增加，肿瘤的分子特征更有代表性，有必要进一步研究将白细胞分离法作为乳腺癌患者的“液体活检”。
Int J Cancer. 2018 Sep 19. [Epub ahead of print]
Towards a real liquid biopsy in metastatic breast and prostate cancer: Diagnostic LeukApheresis increases CTC yields in a European prospective multi-center study (CTCTrap).
Andree KC, Mentink A, Zeune LL, Terstappen LWMM, Stoecklein NH, Neves RP, Driemel C, Lampignano R, Yang L, Neubauer H, Fehm T, Fischer JC, Rossi E, Manicone M, Basso U, Marson P, Zamarchi R, Loriot Y, Lapierre V, Faugeroux V, Oulhen M, Farace F, Fowler G, Sousa Fontes M, Ebbs B, Lambros M, Crespo M, Flohr P, de Bono JS.
University of Twente, Enschede, the Netherlands; Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany; IOV-IRCC, Padova, Italy; University of Padova, Padova, Italy; University Hospital of Padova, Padova, Italy; Gustave Roussy, Université Paris-Saclay, Villejuif, France; Institute of Cancer Research, Sutton, UK; The Royal Marsden NHS Foundation Trust, Sutton, UK.
Circulating tumor cells (CTC) can mirror tumor heterogeneity but a standard blood sample (7.5 mL) is too small to truly represent the tumor. To increase the yield of CTC, the authors used Diagnostic LeukApheresis in which liters of blood are screened for the presence of CTC in metastatic cancer patients. They report a significant increase in CTC yield and consequently, a better molecular characterization of the tumor, encouraging further research into the use of leukapheresis as "liquid biopsy" in cancer patients.
Frequently, the number of circulating tumor cells (CTC) isolated in 7.5 mL of blood is too small to reliably determine tumor heterogeneity and to be representative as a 'liquid biopsy'. In the EU FP7 program CTCTrap, we aimed to validate and optimize the recently introduced Diagnostic LeukApheresis (DLA) to screen liters of blood. Here we present the results obtained from 34 metastatic cancer patients subjected to DLA in the participating institutions. 7.5 mL blood processed with CellSearch was used as 'gold standard' reference. DLAs were obtained from 22 metastatic prostate and 12 metastatic breast cancer patients at four different institutions without any noticeable side effects. DLA samples were prepared and processed with different analysis techniques. Processing DLA using CellSearch resulted in a 0-32 fold increase in CTC yield compared to processing 7.5 mL blood. Filtration of DLA through 5um pores microsieves was accompanied by large CTC losses. Leukocyte depletion of 18mL followed by CellSearch yielded an increase of the number of CTC but a relative decrease in yield (37%) versus CellSearch DLA. In 4 out of 7 patients with 0 CTC detected in 7.5 mL of blood, CTC were detected in DLA (range 1-4 CTC). The CTC obtained through DLA enables molecular characterization of the tumor. CTC enrichment technologies however still need to be improved to isolate all the CTC present in the DLA.
PMID: 30006930
DOI: 10.1002/ijc.31752
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