High-definition imaging of circulating tumor cells and associated cellular events in non-small cell lung cancer patients: a longitudinal analysis

Abstract

Sampling circulating tumor cells from peripheral blood is ideally accomplished using assays that detect high numbers of cells and preserve them for downstream characterization. We sought to evaluate a method using enrichment free fluorescent labeling of CTCs followed by automated digital microscopy in patients with non-small cell lung cancer. Twenty-eight patients with non-small cell lung cancer and hematogenously seeded metastasis were analyzed with multiple blood draws. We detected CTCs in 68% of analyzed samples and found a propensity for increased CTC detection as the disease progressed in individual patients. CTCs were present at a median concentration of 1.6 CTCs per milliliter of analyzed blood in the patient population. Higher numbers of detected CTCs were associated with an unfavorable prognosis.

Clinical utility of circulating tumor cells in patients with non-small-cell lung cancer

“…Nieva and co-workers assessed CTC by three color immunofluorescence imaging in 28 either chemo-naïve or previously treated NSCLC patients who received cytotoxic chemotherapy or EGFR kinase inhibitor (42). A CTC count ≥ 5/mL predicted a HR for death four times higher as compared with lower CTC count (P=0.0084) at univariate analysis.…”

Biophysical technologies for understanding circulating tumor cell biology and metastasis

“…Of a total of 66 blood samples from 28 patients with NSCLC were evaluated, HD-CTCs were detected in 68% of the samples. A significant increase in the risk of death was found in patients with 5 or more CTCs per mL blood, compared to patients who had fewer than 5/mL, with a HR of 4.0 (41). Similarly, PD-L1 expression seems to correlate with worse prognosis in patients with NSCLC.…”

“…HD-CTCs were shown to have nuclei up to five times the average size of surrounding leukocyte nuclei, irregular nuclear contours, large cytoplasmic domain with an eccentric distribution of cytoplasm relative to nucleus, polygonal or elongated cytoplasmic shape, and clusters of two or more HD-CTCs (19). In comparison to CellSearch, the HD-CTC assay found significantly higher numbers of CTCs in significantly more patients with metastatic breast, prostate, and lung cancer (19,41). Furthermore, tumor staging did not seem to make a difference in the detection of CTCs in NSCLC (40).…”

The role of genetic and other biomarkers in NSCLC prognosis

“…Progression-free survival was 6.8 months for patients with detected less than 5 CTCs in blood compared with 2.4 months for patients with more than 5 CTCs detected in blood (p<0.001). Nieva et al [56] also reported that higher numbers of detected CTCs in blood were associated with an unfavorable prognosis for NSCLC patients with metastatic disease. Time to death was shorter for patients with more than 5 detectable CTCs compared with those patients who had 5 or less CTCs (35±59 days vs. 211±207 days, p=0.003).…”