Clinical Significance of Circulating Tumor Microemboli as a Prognostic Marker in Patients with Pancreatic Ductal Adenocarcinoma

Abstract

BACKGROUND Characterization of circulating tumor cells (CTCs) has been used to provide prognostic, predictive, and pharmacodynamic information in many different cancers. However, the clinical significance of CTCs and circulating tumor microemboli (CTM) in patients with pancreatic ductal adenocarcinoma (PDAC) has yet to be determined. METHODS In this prospective study, CTCs and CTM were enumerated in the peripheral blood of 63 patients with PDAC before treatment using anti-EpCAM (epithelial cell adhesion molecule)–conjugated supported lipid bilayer–coated microfluidic chips. Associations of CTCs and CTM with patients' clinical factors and prognosis were determined. RESULTS CTCs were abundant [mean (SD), 70.2 (107.6)] and present in 81% (51 of 63) of patients with PDAC. CTM were present in 81% (51 of 63) of patients with mean (SD) 29.7 (1101.4). CTM was an independent prognostic factor of overall survival (OS) and progression free survival (PFS). Patients were stratified into unfavorable and favorable CTM groups on the basis of CTM more or less than 30 per 2 mL blood, respectively. Patients with baseline unfavorable CTM, compared with patients with favorable CTM, had shorter PFS (2.7 vs 12.1 months; P < 0.0001) and OS (6.4 vs 19.8 months; P < 0.0001). Differences persisted if we stratified patients into early and advanced diseases. The number of CTM before treatment was an independent predictor of PFS and OS after adjustment for clinically significant factors. CONCLUSIONS The number of CTM, instead of CTCs, before treatment is an independent predictor of PFS and OS in patients with PDAC.

CTC immune escape mediated by PD-L1

“…In order to explore the reason, we observed the CTC and white blood cells. We found CTC are surrounded by many white blood cells, which is the same with CTC clusters, observed by other scientists [2].…”

“…Meanwhile, the high expression of PD-L1 in CTC surface (68.6%) has also been reported [19]. We thought CTC have its own immune environment, throught which CTC interact with immune cell, cytokines to form a cells cluster [2][3]. Including the negative regulation of inhibitory immune cells and cytokines.…”

“…Most breast cancer-related deaths are from CTC (circulating tumor cells) metastasis [2]. CTC is associated with the breast cancer patients' prognosis.…”

Detection of Circulating Tumour Cells in Urothelial Cancers and Clinical Correlations: Comparison of Two Methods

“…Moreover, they were more frequently detected in M + compared to M 0 cases, suggesting higher metastatic potential and possible prognostic role also in metastatic urothelial cancers, as already reported for other tumour types [36, 39–42]. Similar results have been reported by Anantharaman et al [43] who were able to identify by cytokeratin immunostaining CTC clusters in 6/21 (28.6%) metastatic cases and in none of four nonmetastatic bladder tumours.…”

The next step: mechanisms driving adrenocortical carcinoma metastasis

“…CTCs may be isolated or arranged in groups of 3-20 cells (circulating tumor microemboli, CTMs) which are detached together from the primary lesion. CTMs seem to be more prone to metastatize than single CTC and their presence/number is a poor prognostic factor in solid tumors (Hou et al 2012, Chang et al 2016.…”