Circulating tumor cells (CTCs)/circulating tumor endothelial cells (CTECs) and their subtypes in small cell lung cancer: Predictors for response and prognosis

Abstract

Background The aim of the study was to define the clinical significance of circulating tumor cells (CTCs)/circulating tumor endothelial cells (CTECs) and their subtypes in small cell lung cancer (SCLC) patients. Methods CTCs/CTECs and their subtypes were determined using SE‐iFISH technology in 33 SCLC patients before initial treatment (B1), after two cycles of chemotherapy (B2), at the completion of chemotherapy (B3), and disease progression (B4). The correlations with clinical characteristics, progression‐free survival (PFS), and overall survival (OS) were analyzed. Results CTCs and CTECs were detected in 96.6% and 65.5% of patients, respectively. Patients had higher levels of CTCs compared with CTECs in circulation (p < 0.05). Extensive‐stage SCLC patients tended to have higher CTEC counts (p = 0.035), and the detection of CTC‐white blood cell (CTC‐WBC) clusters was associated with a worse response to treatment (p = 0.030). Patients with CTC‐WBC clusters at B1 (17.3 vs. 22.6 months, p = 0.041) and B2 (19.9 vs. 25.2 months, p = 0.018) had significantly shorter OS than those with no detection. Additionally, their presence was revealed as independent predictors for a worse OS in multivariable analyses (B1: HR 9.3, 95% CI: 1.4–48, p = 0.0079; B2: HR 4.4, 95% CI: 1.1–18, p = 0.041). A high CTC level at B4 was an adverse prognostic factor for SCLC patients (PFS: 8.7 vs. 22.5 months, p = 0.0026; OS: 19 months vs. not reached, p = 0.0086). CTC clusters and CTECs also showed prognostic values. Conclusions The presence of CTC‐WBC clusters at baseline and after two‐cycle chemotherapy and the total CTC counts at the completion of chemotherapy are strong predictors for the prognostic survival of SCLC patients receiving first‐line treatment.

Circulating Tumor-Derived Endothelial Cells: An Effective Biomarker for Breast Cancer Screening and Prognosis Prediction

“…In addition, our results showed the level of CTECs was higher than the level of CTCs in breast cancer patients. Inversely, other studies reported that CTCs occupied the majority of circulating aneuploid cells in colorectal cancer [ 26 ] and nonsmall cell lung cancer [ 30 ]. A potential mechanism is that epithelial-mesenchymal transition (EMT) and endothelial-to-mesenchymal transition (EndoMT) are generally recognized to be related to cancer cell metastasis, which may proceed diversely in different cancers due to diverse characteristics of the respective blood and lymphatic vessel systems [ 29 ].…”

Comparative characteristics of small cell lung cancer and Ewing’s sarcoma: a narrative review

“…In accordance with the high metastatic capacity, the concentration of CTCs in SCLC exceeds that of solid tumor with exception of inflammatory breast cancer by a wide margin (17). This high number of CTCs in SCLC lends itself to the study of the biology of metastatic seeding, including genomic preconditions and tumor cell heterogeneity (18,19).…”

Liquid biopsy in lung cancer: significance in diagnostics, prediction, and treatment monitoring

“…Using subtraction enrichment-immunofluorescence in situ hybridization (SE-iFISH) quantitative analysis, it was found that counting the total number of CTCs and CTECs may help to identify malignant nodules with high sensitivity, while quantifying tetraploid CTCs and CTECs may help to identify malignant nodules with high specificity [ 83 ]. The results showed that the combined detection of specific subtypes of aneuploid CD31 + CTECs and CD31 − CTCs is helpful in effectively identifying malignant nodules in patients with early NSCLC [ 84 ]. The level of CECs in partial response (PR) patients was found to be significantly higher than that of stable disease (SD) or progression disease (PD) patients.…”