Circulating Tumor Microemboli Diagnostics for Patients with Non–Small-Cell Lung Cancer

Abstract

Introduction Circulating Tumor Microemboli (CTM) are potentially important cancer biomarkers, but using them for cancer detection in early stage disease has been assay limited. We examined CTM test performance using a sensitive detection platform to identify stage I Non-Small Cell Lung Cancer (NSCLC) patients undergoing imaging evaluation. Methods First, we prospectively enrolled patients during [18F] FDG PET-CT imaging evaluation for lung cancer that underwent routine phlebotomy where CTM and circulating tumor cells (CTCs) were identified in blood using nuclear (DAPI), cytokeratin (CK), and CD45 immune-fluorescent antibodies followed by morphologic identification. Second, CTM and CTC data were integrated with patient (age, gender, smoking and cancer history) and imaging (tumor diameter, location in lung and maximum standard uptake value [SUVmax]) data to develop and test multiple logistic regression models using a case-control design in a training and test cohort followed by cross-validation in the entire group. Results We examined 104 patients with NSCLC, and the subgroup of 80 with stage I disease, and compared them to 25 patients with benign disease. Clinical and imaging data alone were moderately discriminating for all comers (Area Under the Curve [AUC] = 0.77) and by stage I disease only (AUC = 0.77). However, the presence of CTM combined with clinical and imaging data was significantly discriminating for diagnostic accuracy in all NSCLC patients (AUC = 0.88, p-value = 0.001) and for stage I patients alone (AUC = 0.87, p-value = 0.002). Conclusion CTM may add utility for lung cancer diagnosis during imaging evaluation using a sensitive detection platform.

Prevalence and number of circulating tumour cells and microemboli at diagnosis of advanced NSCLC

“…Detection, enumeration and molecular characterization of circulating tumour cells (CTC) and circulating tumour microemboli (CTM) in the peripheral blood featuring a type of «liquid biopsy» represent an emerging field in lung cancer research (Huang et al 2013;Krebs et al 2012;Wendel et al 2012;Carlsson et al 2014). In particular, it has been hypothesized that CTM might be more capable of metastasizing as compared with single CTC (Bottos and Hynes 2014).…”

Clusters of circulating tumor cells traverse capillary-sized vessels

“…The greater colonization efficiency of CTC clusters may be due to a number of factors including protection against anchorage-dependent apoptosis (5,10), the cooperation of heterogeneous cell phenotypes within CTC clusters (11), and shielding from assault by immune cells (2,12). Beyond their role in metastasis, CTC clusters may also serve as biomarkers for early detection (13), as prognostic markers (5,9), and may have utility for noninvasively tracking changing drug susceptibilities in patients undergoing treatment (14).…”

Biophysical technologies for understanding circulating tumor cell biology and metastasis

“…The heterogeneity of HD-CTC numbers seen in both early and late stage diseases suggest a potential use of HD-CTC to gain insight into individual tumor biology, and use as a noninvasive diagnostic tool (61). Indeed, when circulating tumor microemboli (CTM) were examined in concordance with imaging in patients with NSCLC, it was shown that CTMs in combination with clinical and imaging data was able to significantly discriminate for diagnostic accuracy in all stages as well as stage I disease (62).…”