BACKGROUND: The aim of this study was to explore circulating tumor cell (CTC) detection in advanced non-small cell lung cancer (NSCLC). CTCs may not only serve as a prognostic marker in selected tumor types, but may also be useful as pharmacodynamic marker in drug development. METHODS: Fourty-six advanced NSCLC patients and fourty-six healthy controls were included in the study and 8.0 ml of peripheral blood was obtained from each of the participants. Immunomagnetic bead enrichment for cells expressing epithelial cell adhesion molecule (EpCAM) was performed, followed by multi-marker quantitative real-time PCR of a panel of marker genes: cytokeratin 7 (CK7), cytokeratin 19 (CK19), human epithelial glycoprotein (EGP) and fibronectin 1 (FN1). Using quadratic discriminant analysis (QDA), expression values were combined into a single score, which indicated CTC-positivity or -negativity. Test characteristics were assessed using receiver operating characteristic (ROC) curve analysis. RESULTS: ROC curve analysis showed capability of discrimination between advanced NSCLC patients and healthy controls (area=0.712; 95% CI 0.606-0.819; P<0.001). A cut-off minimizing overall misclassification for QDA-positivity reached a sensitivity of 46% (95% CI 31-61) and a specificity of 93% (95% CI 82-99). CONCLUSIONS: In this exploratory study, an assay was developed for discriminating CTCs in peripheral blood samples of advanced NSCLC patients from healthy controls. The assay demonstrated an acceptable sensitivity in combination with good specificity. Further validation studies should take place in NSCLC patients and a matched control group.
BACKGROUND: The aim of this study was to explore circulating tumor cell (CTC) detection in advanced non-small cell lung cancer (NSCLC). CTCs may not only serve as a prognostic marker in selected tumor types, but may also be useful as pharmacodynamic marker in drug development. METHODS: Fourty-six advanced NSCLCpatients and fourty-six healthy controls were included in the study and 8.0 ml of peripheral blood was obtained from each of the participants. Immunomagnetic bead enrichment for cells expressing epithelial cell adhesion molecule (EpCAM) was performed, followed by multi-marker quantitative real-time PCR of a panel of marker genes: cytokeratin 7 (CK7), cytokeratin 19 (CK19), humanepithelial glycoprotein (EGP) and fibronectin 1 (FN1). Using quadratic discriminant analysis (QDA), expression values were combined into a single score, which indicated CTC-positivity or -negativity. Test characteristics were assessed using receiver operating characteristic (ROC) curve analysis. RESULTS: ROC curve analysis showed capability of discrimination between advanced NSCLCpatients and healthy controls (area=0.712; 95% CI 0.606-0.819; P<0.001). A cut-off minimizing overall misclassification for QDA-positivity reached a sensitivity of 46% (95% CI 31-61) and a specificity of 93% (95% CI 82-99). CONCLUSIONS: In this exploratory study, an assay was developed for discriminating CTCs in peripheral blood samples of advanced NSCLCpatients from healthy controls. The assay demonstrated an acceptable sensitivity in combination with good specificity. Further validation studies should take place in NSCLCpatients and a matched control group.
Authors: Jay F Dorsey; Gary D Kao; Kelly M MacArthur; Melody Ju; David Steinmetz; E Paul Wileyto; Charles B Simone; Stephen M Hahn Journal: Cancer Date: 2014-09-19 Impact factor: 6.860
Authors: Seung-Min Park; Dawson J Wong; Chin Chun Ooi; David M Kurtz; Ophir Vermesh; Amin Aalipour; Susie Suh; Kelsey L Pian; Jacob J Chabon; Sang Hun Lee; Mehran Jamali; Carmen Say; Justin N Carter; Luke P Lee; Ware G Kuschner; Erich J Schwartz; Joseph B Shrager; Joel W Neal; Heather A Wakelee; Maximilian Diehn; Viswam S Nair; Shan X Wang; Sanjiv S Gambhir Journal: Proc Natl Acad Sci U S A Date: 2016-12-12 Impact factor: 11.205