RESUMEN
BACKGROUND: Circulating tumor cells (CTCs) allow the real-time monitoring of tumor course and treatment response. This prospective multicenter study evaluates and compares the early predictive value of CTC enumeration with EPISPOT, a functional assay that detects only viable CTCs, and with the CellSearch® system in patients with metastatic colorectal cancer (mCRC). METHODS: Treatment-naive patients with mCRC and measurable disease (RECIST criteria 1.1) received FOLFIRI-bevacizumab until progression or unacceptable toxicity. CTCs in peripheral blood were enumerated at D0, D14, D28, D42, and D56 (EPISPOT assay) and at D0 and D28 (CellSearch® system). Progression-free survival (PFS) and overall survival (OS) were assessed with the Kaplan-Meier method and log-rank test. RESULTS: With the EPISPOT assay, at least 1 viable CTC was detected in 21% (D0), 15% (D14), 12% (D28), 10% (D42), and 12% (D56) of 155 patients. PFS and OS were shorter in patients who remained positive, with viable CTCs between D0 and D28 compared with the other patients (PFS = 7.36 vs. 9.43 months, p = 0.0161 and OS = 25.99 vs. 13.83 months, p = 0.0178). The prognostic and predictive values of ≥3 CTCs (CellSearch® system) were confirmed. CONCLUSIONS: CTC detection at D28 and the D0-D28 CTC dynamics evaluated with the EPISPOT assay were associated with outcomes and may predict response to treatment.
RESUMEN
Identification and characterization of circulating tumor cells (CTCs) in peripheral blood can provide information on the direction and the efficacy of treatments. Current techniques such as CellSearch® are limited in differentiating between apoptotic and viable CTCs. In contrast, the fluorescent EPISPOT assay allows for the identification of viable cells by detecting proteins secreted/released/shed by functional single epithelial cancer cells. In addition, as CTCs are rare events, it is required to combine the EPISPOT assay with an enrichment step. In this article, the EPISPOT assay, as well as two technologies for enrichment of viable CTCs, RosetteSep™ and Parsortix™ techniques, will be presented and discussed in detail.
Asunto(s)
Separación Celular/métodos , Diseño de Equipo , Técnicas Analíticas Microfluídicas/instrumentación , Neoplasias/diagnóstico , Células Neoplásicas Circulantes/patología , Anticuerpos Monoclonales/química , Anticuerpos Monoclonales/metabolismo , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/inmunología , Biomarcadores de Tumor/metabolismo , Recuento de Células , Línea Celular Tumoral , Separación Celular/instrumentación , Supervivencia Celular , Centrifugación por Gradiente de Densidad/métodos , Molécula de Adhesión Celular Epitelial , Receptores ErbB/genética , Receptores ErbB/inmunología , Receptores ErbB/metabolismo , Ficoll/química , Colorantes Fluorescentes/química , Humanos , Inmunoensayo , Queratina-19/genética , Queratina-19/inmunología , Queratina-19/metabolismo , Neoplasias/sangre , Neoplasias/inmunología , Neoplasias/patología , Células Neoplásicas Circulantes/inmunología , Células Neoplásicas Circulantes/metabolismo , Unión Proteica , Receptor ErbB-2/genética , Receptor ErbB-2/inmunología , Receptor ErbB-2/metabolismo , Factor A de Crecimiento Endotelial Vascular/genética , Factor A de Crecimiento Endotelial Vascular/inmunología , Factor A de Crecimiento Endotelial Vascular/metabolismoRESUMEN
Circulating tumor cells (CTCs) in the blood of cancer patients have received increasing attention as new diagnostic tool enabling 'liquid biopsies'. In contrast to the wealth of descriptive studies demonstrating the clinical relevance of CTCs as biomarkers, the extremely low concentration of CTCs in the peripheral blood of most cancer patients challenges further functional studies. This article discusses the current possibilities to enrich and, in particular, detect viable CTCs with emphasis on the EPithelial ImmunoSPOT technology. This functional assay detects viable CTCs at the single-cell level and has been used on hundreds of patients with different tumor types including epithelial tumors (breast, prostate and colon cancer) and melanomas. Moreover, the article summarizes recent advances in the in vitro and in vivo expansion of CTCs from cancer patients. These functional analyses will contribute to identifying the biological properties of metastatic cells and reveal new therapeutic targets against disseminating cancer cells.
