Diagnostic leukapheresis enables reliable detection of circulating tumor cells of nonmetastatic cancer patients

Abstract

Significance The infrequent detection of circulating tumor cells (CTCs) has hindered their clinical implication and their potential use in the sense of a “liquid biopsy” for cancer diagnosis and therapy. Hypothesizing that the limited blood volume commonly used for CTC analysis (1–10 mL) accounts for variable detection rates, we used leukapheresis to screen large blood volumes for CTCs. This enabled a more reliable detection of CTCs at high frequency even in nonmetastatic cancer patients. Thus, diagnostic leukapheresis may facilitate the routine clinical use of CTCs as biomarkers for personalized medicine. Combined with technologies for single-cell molecular genetics or cell biology, it may significantly improve prediction of therapy response and monitoring, especially in early systemic cancer.

Genomic High-Resolution Profiling of Single CKpos/CD45neg Flow-Sorting Purified Circulating Tumor Cells from Patients with Metastatic Breast Cancer

“…Circulating tumor cells (CTCs) 7 have recently gained much attention because they hold great promise as biomarkers for real-time monitoring of systemic cancer as a "liquid biopsy" for diagnosis and during therapy (1)(2)(3)(4). Moreover, in light of the well-documented genetic and phenotypic differences between primary tumors and metastatic cells (5)(6)(7)(8)(9), CTCs appear to be more suitable surrogate markers for systemic disease than the bulk tissue of the primary tumor.…”

Critical issues in the clinical application of liquid biopsy in non-small cell lung cancer

“…CTCs were detected in more than 90% of non-metastatic breast cancer patients by a CellSearch ® test adapted to DLA, and a correlation was found between CTC numbers and anatomic disease spread. This study also combined DLA to genomic single-cell profiling and suggested their use in order to improve both the prediction of therapy response and the monitoring of early systemic cancer (59).…”

“…At this regard, we described the processing of large volumes of blood to increase CTC detection, in early non-metastatic patients (59) and in metastatic NSCLC (37,38), conditions in which CTCs occur at very low rate. This approach has revealed the potential to greatly improve CTC sensitivity, allowing recovery of higher cell number for downstream molecular analyses (59), and increasing detection rate up to 70% CTC positive patients in lung cancer (38). In addition, the use of high throughput microfluidic-based platforms has greatly improved CTC recovery in the huge amount of contaminating leukocytes [1 CTC against 10 6 -10 7…”

A comparison of CellCollector with CellSearch in patients with neuroendocrine tumours

“…Indeed, a recent study in lung cancer demonstrated both KRAS and EGFR mutations known to be present in the primary tumour, in CTCs derived from the CellCollector using chip-based digital PCR (Gorges et al 2016). Other strategies to increase the volume of blood sampled for CTCs include the use of leukapheresis (Fischer et al 2013). However, the leukapheresis product has a very high rate …”