Pulmonary venous blood sampling significantly increases the yield of circulating tumor cells in early-stage lung cancer

Reddy, Rishindra M.; Murlidhar, Vasudha; Zhao, Lili; Grabauskiene, Svetlana; Zhang, Zhuo; Ramnath, Nithya; Lin, Jules; Chang, Andrew C.; Carrott, Phillip W.; Lynch, William R.; Orringer, Mark B.; Beer, David G.; Nagrath, Sunitha

doi:10.1016/j.jtcvs.2015.09.126

Cited by 54 publications

(52 citation statements)

References 13 publications

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“…In patients with non–small cell lung cancer or liver cancer, CTC/CTM detection by ISET was shown to be an important tool to predict prognosis [16], [17]. CTM, also known as CTC clusters, have been detected in breast, lung, and colorectal cancer [18], [19], [20]. Although rare in the circulation compared with single CTCs, CTC clusters may possess stronger ability to transfer, greater resistance to anoikis and cytotoxic drugs, and more metastatic potential [18], [21].…”

Section: Introductionmentioning

confidence: 99%

Detection of Circulating Tumor Cells and Circulating Tumor Microemboli in Gastric Cancer

Zheng

Фан

Zhou

et al. 2017

Translational Oncology

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PURPOSE: Gastric cancer studies indicated a potential correlation between circulating tumor cells (CTCs) in peripheral blood and tumor relapse/metastasis. The prevalence and significance of circulating tumor microemboli (CTM) in gastric cancer remain unknown. We investigated the prevalence and prognostic value of CTCs and CTM for progression-free survival (PFS) and overall survival (OS) in gastric cancer patients. METHODS:Eighty-one gastric cancer patients consented to provide 5 ml of peripheral blood before systematic therapy. CTCs and CTM were isolated using isolation by size of epithelial tumor cells and characterized by cytopathologists. For 41 stage IV gastric cancer patients, CTM was investigated as a potential biomarker to predict prognosis. RESULTS:CTCs were detected in 51 patients; the average count was 1.81. In clinical stage I, II, III, and IV patients, the average CTC counts were 1.40, 0.67, 1.24, and 2.71, respectively. CTM were detected in 3 of 33 clinical stage I to IIIb patients, at an average of 0.12 (0-2). CTM were detected in 13 of 53 clinical stage IIIc to IV patients, at an average of 1.26 (0-22). In stage IV patients, CTM positivity correlated with the CA125 level. PFS and OS in CTM-positive patients were significantly lower than in CTM-negative patients (P < .001). CTM positivity was an independent factor for determining the PFS (P = .016) and OS (P = .003) of stage IV patients in multivariate analysis. Using markers of the epithelial-mesenchymal transition, single CTCs were divided into three phenotypes including epithelial CTCs, biphenotypic epithelial/mesenchymal CTCs, and mesenchymal CTCs. For CTM, CK−/Vimentin+/CD45− and CK+/Vimentin+/CD45− phenotypes were observed, but the CK+/Vimentin−/CD45− CTM phenotype was not. CA125 was detected in gastric cancer cell lines BGC823 and MGC803. CONCLUSIONS: In stage IV patients, CTM positivity was correlated with serum CA125 level. CTM were an independent predictor of shorter PFS and OS in stage IV patients. Thus, CTM detection may be a useful tool to predict prognosis in stage IV patients.

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Section: Introductionmentioning

confidence: 99%

Detection of Circulating Tumor Cells and Circulating Tumor Microemboli in Gastric Cancer

Zheng

Фан

Zhou

et al. 2017

Translational Oncology

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“…A number of studies have shown that the levels of CTC are usually higher in PV blood samples as compared with peripheral draws, suggesting that CTC might be in part removed by the circulation after shedding from the tumor mass (14)(15)(16)(17). Interestingly, Reddy et al found that PV CTC were more frequently detected in patients who underwent preoperative bronchoscopic biopsy (8/9 cases), compared with patients who underwent CT-guided biopsy (4/12) (16). Although the limited number of patients included in these studies prevents any firm conclusion, these findings confirm the possibility that biopsy of tumor mass might lead to tumor cell dissemination.…”

Section: Detection and Prognostic Value Of Ctc In Early Nsclcmentioning

confidence: 99%

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

Gallo

Luca

Maiello

et al. 2017

Transl. Lung Cancer Res.

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Several different studies have addressed the role of the circulating tumor cells (CTC) in nonsmall-cell lung cancer (NSCLC). In particular, the potential of CTC analysis in the early diagnosis of NSCLC and in the prediction of the outcome of patients with early and advanced NSCLC have been explored. A major limit of these studies is that they used different techniques for CTC isolation and enumeration, they employed different thresholds to discriminate between high-and low-risk patients, and they enrolled heterogeneous and often small cohort of patients. Nevertheless, the results of many studies are concordant in indicating a correlation between high CTC count and poor prognosis in both early and advanced NSCLC. The reduction of CTC number following treatment might also represent an important indicator of sensitivity to therapy in patients with metastatic disease. Preliminary data also suggest the potential for CTC analysis in the early diagnosis of NSCLC in high-risk individuals. However, these findings need to be confirmed in large prospective trials in order to be transferred to the clinical practice.The molecular profiling of single CTC in NSCLC might provide important information on tumor biology and on the mechanisms involved in tumor dissemination and in acquired resistance to targeted therapies. In this respect, xenografts derived from CTC might represent a valuable tool to investigate these phenomena and to develop novel therapeutic strategies.

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“…One study showed that the presence of CTCs in the pulmonary vein indicated a poor prognosis relative to those with an absence of CTCs in the tumor draining vein (17). Also, the pulmonary vein shows a significantly high number of CTCs relative to that obtained through conventional peripheral vein methods (16,18). The higher yields obtained from the PV offers a useful strategy to study CTCs and their role in tumor progression.…”

Section: Introductionmentioning

confidence: 99%

Poor Prognosis Indicated by Venous Circulating Tumor Cell Clusters in Early-Stage Lung Cancers

et al. 2017

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Early detection of metastasis can be aided by circulating tumor cells (CTCs), which also show potential to predict early relapse. Due to the limited CTC numbers in peripheral blood in early stages, we investigated CTCs in pulmonary vein blood accessed during surgical resection of tumors. Pulmonary vein (PV) and peripheral vein (Pe) blood specimens from patients with lung cancer were drawn during the perioperative period and assessed for CTC burden using a microfluidic device. From 108 blood samples analyzed from 36 patients, PV had significantly higher number of CTCs compared to pre-operative Pe (p<0.0001) and intra-operative Pe (p<0.001) blood. CTC clusters with large number of CTCs were observed in 50% of patients, with PV often revealing larger clusters. Long term surveillance indicated that presence of clusters in pre-operative Pe blood predicted a trend toward poor prognosis. Gene expression analysis by RT-qPCR revealed enrichment of p53 signaling and extracellular matrix involvement in PV and Pe samples. Ki67 expression was detected in 62.5% of PV samples and 59.2% of Pe samples, with the majority (72.7%) of patients positive for Ki67 expression in PV having single CTCs as opposed to clusters. Gene ontology analysis revealed enrichment of cell migration and immune-related pathways in CTC clusters, suggesting survival advantage of clusters in circulation. Clusters display characteristics of therapeutic resistance, indicating the aggressive nature of these cells. Thus, CTCs isolated from early stages of lung cancer are predictive of poor prognosis and can be interrogated to determine biomarkers predictive of recurrence.

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Pulmonary venous blood sampling significantly increases the yield of circulating tumor cells in early-stage lung cancer

Abstract: With a single vein draining the entire tumor basin, lung cancers are unique, allowing the high-yield isolation of CTCs from the PV. This method may facilitate future studies to improve the detection and analysis of early-stage lung CTCs.

Cited by 54 publications

References 13 publications

Detection of Circulating Tumor Cells and Circulating Tumor Microemboli in Gastric Cancer

Detection of Circulating Tumor Cells and Circulating Tumor Microemboli in Gastric Cancer

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

Poor Prognosis Indicated by Venous Circulating Tumor Cell Clusters in Early-Stage Lung Cancers

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