Circulating endothelial cells and microparticles as diagnostic and prognostic biomarkers in small-cell lung cancer.

OBJECTIVES: It has been proposed that circulating endothelial cells (CECs) and microparticles (MPs) may be useful for the assessment of patients with non-small-cell lung cancer (NSCLC). However, little is known about the potential clinical relevance of these biomarkers in small-cell lung cancer (SCLC). Therefore, we investigated the utility of baseline levels of CECs and MPs in SCLC patients. MATERIALS AND METHODS: An immunomagnetic separation (IMS) technique was used to isolate and quantify CECs in the peripheral blood, while plasma samples were analyzed using flow cytometry for the measurement of circulating MPs. RESULTS: We prospectively collected data from 56 patients and 41 healthy individuals. Forty-three patients presented at initial diagnosis and 13 patients presented at relapse. Baseline levels of CECs and MPs were significantly higher in SCLC patients either at initial diagnosis or at relapse than in healthy subjects (p < 0.0002 and p < 0.007, respectively). However, estimated tumor volume (ETV) was significantly correlated with basal MP values (p < 0.0001) but not with pretreatment CECs (p = 0.57). The amount of baseline CECs and MPs was significantly lower in patients with an objective response (OR, n = 23) than in those with progressive disease (PD, n = 15) after treatment (p = 0.016 and 0.05, respectively). With cut-off values of 110 cells/mL for CECs and 1257 events/µL for MPs according to receiver operating characteristics (ROC) analysis, baseline levels of these biomarkers were not significantly correlated with either progression-free survival (PFS) or overall survival (OS). However, patients with 6-month PFS displayed significantly decreased pretreatment CEC counts (p = 0.042), whereas basal MP values significantly increased in 1-year survivors compared with those in non-survivors (p = 0.05). CONCLUSION: Our results suggest that baseline CECs and MPs may be predictive biomarkers of tumor response and long-term survival in SCLC patients.

Circulating endothelial cells and microparticles for prediction of tumor progression and outcomes in advanced non-small cell lung cancer.

BACKGROUND: Circulating endothelial cells (CECs) and microparticles (MPs) are proposed as useful biosensors for angiogenesis and membrane damage in cancer. OBJECTIVE: We investigated their predictive value for progression disease (PD) and clinical outcomes in advanced non-small cell lung cancer (NSCLC) patients treated with cytotoxic chemotherapy. METHODS: Peripheral blood samples were obtained from 60 patients. Immunomagnetic separation (IMS) and flow cytometry techniques were used to quantify CECs and MPs, respectively. Receiver operating characteristics (ROC) analysis was used to determine the optimal cutoff values for CECs and MPs counts according to their levels in patients with an objective response (OR) and non-responders after treatment. Baseline serum biomarkers levels and their kinetics after chemotherapy were correlated with tumor response and outcomes in advanced NSCLC patients. RESULTS: Forty-seven patients presented an OR after chemotherapy. Of these, 28 patients progressed within three months. Through an increase in their levels during or after chemotherapy, CECs and MPs correctly predicted PD in 57% and 61% of these patients, respectively. Regarding tumor stage, NSCLC patients with stage IV had significantly higher pretreatment CECs and MPs levels than stage III patients (p= 0.037 and 0.018, respectively). Moreover, progression-free survival (PFS) was significantly longer in patients with high baseline CECs levels than those with low pretreatment CECs values (p= 0.05). Moreover, patients with high percentage change in CECs count after chemotherapy had significantly longer time to progression (TTP) duration (p= 0.018). CONCLUSIONS: Our findings suggest the increase in CECs and MPs number during or after chemotherapy as predictive biomarkers of tumor progression in advanced NSCLC patients. An association of basal CECs and MPs values with tumor stage was also shown in advanced NSCLC patients. However, baseline CECs levels and their kinetics after chemotherapy seem to be prognostic factors in advanced NSCLC.

Predictive and prognostic value of circulating endothelial cells in non-small cell lung cancer patients treated with standard chemotherapy.

PURPOSE: Monitoring circulating endothelial cells (CECs) count reflects the tumor vasculature in cancer patients and might be a predictor of response to chemotherapy. We therefore investigated the clinical significance of changes in CECs count after three cycles of platinum-based chemotherapy in patients with advanced non-small cell lung cancer (NSCLC). METHODS: Peripheral blood samples were collected from 89 naive NSCLC patients at diagnosis and after chemotherapy. The CECs were quantified by an immuno-magnetic technique and fluorescent microscopy. After chemotherapy, patients were assessed according to the response evaluation criteria in solid tumors as partial response (PR), stable disease (SD) or progression disease (PD). RESULTS: Baseline CECs levels were significantly higher in PR patients (n = 62) than those in patients with SD/PD (n = 27) (p = 0.0007). Although there was no significant correlation between baseline CECs levels and progression-free survival (PFS) (p = 0.287), patients with high percentage change in CECs count after chemotherapy had significantly longer PFS than those with low percentage change (p = 0.048). Regarding treatment efficacy, CECs count significantly decreased after chemotherapy in comparison with CECs count at baseline in patients with PR (p < 0.0001). By contrast, CECs levels after chemotherapy were significantly higher than those at diagnosis in patients with PD (p = 0.002). Moreover, there was no significant change between pre- and post-treatment CECs amount in patients with SD (p = 0.681). CONCLUSIONS: Baseline CECs levels might be an early predictive biomarker for treatment efficacy in advanced NSCLC patients. Our results suggest the change in CECs count after chemotherapy as a prognostic factor for tumor response and PFS in NSCLC.