title: Heterogeneity of circulating tumor cells (CTCs) in patients with recurrent small cell lung cancer (SCLC) treated with pazopanib.
abstract: To investigate the effect of pazopanib on different CTCs subpopulations in patients with recurrent SCLC and evaluate their clinical relevance.
  
  
  
  Peripheral blood was obtained before the administration of pazopanib (n=56 patients), after the first cycle (n=35 patients) and at disease progression (n=45 patients). CTCs were detected by CellSearch and double immunofluorescent staining using antibodies against the cytokeratins (CK), TTF-1, CD56 and VEGFR2.
  
  
  
  Before treatment, CTCs could be detected in 50% of patients by CellSearch; phenotypic characterization of CTCs demonstrated that 50%, 46.6% and 27.6% of patients had CD45-/TTF1+, CD45-/CD56+and TTF-1+/CD56+CTCs, respectively. Additionally, 59% of CTCs were TTF-1+/VEGFR2+and 53% CK+/VEGFR2+. One pazopanib cycle resulted to a significant decrease of the number of CTCs (CellSearch: p=0.043) and CK+/VEGFR2+cells (p=0.027). At the time of PD, both the total number of CTCs (p=0.027) and the number of the different subpopulations were significantly increased compared to post-1st cycle values; this increased CTCs number was associated with a significant increase of TTF-1+/VEGFR2+(p=0.028) and CK+/VEGFR2+CTCs (p=0.018). In multivariate analysis, only the number of CTCs as assessed by CellSearch after one treatment cycle was significantly associated with OS (HR: 0.21; p=0.005).
  
  
  
  Pazopanib has a significant effect on different subpopulations of CTCs in patients with relapsed SCLC; the detection of VEGFR2+CTCs during treatment could be a surrogate marker associated with resistance to pazopanib.
authors.affiliation: Laboratory of Tumor Cell Biology, School of Medicine, University of Crete, Greece.
authors.forename: I
authors.initials: I
authors.lastname: Messaritakis
authors.affiliation: Laboratory of Tumor Cell Biology, School of Medicine, University of Crete, Greece.
authors.forename: E
authors.initials: E
authors.lastname: Politaki
authors.affiliation: Laboratory of Tumor Cell Biology, School of Medicine, University of Crete, Greece.
authors.forename: M
authors.initials: M
authors.lastname: Plataki
authors.affiliation: Department of Medical Oncology, "Papageorgiou" General Hospital, Thessaloniki, Greece.
authors.forename: V
authors.initials: V
authors.lastname: Karavassilis
authors.affiliation: Department of Medical Oncology, 251 Air Forces General Hospital, Athens, Greece.
authors.forename: N
authors.initials: N
authors.lastname: Kentepozidis
authors.affiliation: Laboratory of Tumor Cell Biology, School of Medicine, University of Crete, Greece; Department of Medical Oncology, University General Hospital of Heraklion, Crete, Greece.
authors.forename: F
authors.initials: F
authors.lastname: Koinis
authors.affiliation: First Department of Medical Oncology, "Agioi Anargyroi" Anticancer Hospital, Athens, Greece.
authors.forename: E
authors.initials: E
authors.lastname: Samantas
authors.affiliation: Laboratory of Tumor Cell Biology, School of Medicine, University of Crete, Greece; Department of Medical Oncology, University General Hospital of Heraklion, Crete, Greece. Electronic address: georgoul@med.uoc.gr.
authors.forename: V
authors.initials: V
authors.lastname: Georgoulias
authors.affiliation: Laboratory of Tumor Cell Biology, School of Medicine, University of Crete, Greece; Department of Medical Oncology, University General Hospital of Heraklion, Crete, Greece.
authors.forename: A
authors.initials: A
authors.lastname: Kotsakis
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D014408:Biomarkers, Tumor / Q000378:metabolism; D019002:CD56 Antigen / Q000276:immunology; D004268:DNA-Binding Proteins / Q000276:immunology; D005260:Female; D006801:Humans; D007191:Indazoles; D017493:Leukocyte Common Antigens / Q000276:immunology; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D009360:Neoplastic Cells, Circulating / Q000187:drug effects* / Q000473:pathology; D065228:Non-Randomized Controlled Trials as Topic; D011743:Pyrimidines / Q000008:administration & dosage / Q000494:pharmacology*; D055752:Small Cell Lung Carcinoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D013449:Sulfonamides / Q000008:administration & dosage / Q000494:pharmacology*; D014157:Transcription Factors; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000276:immunology
chemical_list: D020533:Angiogenesis Inhibitors; D014408:Biomarkers, Tumor; D019002:CD56 Antigen; D004268:DNA-Binding Proteins; D007191:Indazoles; C522918:NCAM1 protein, human; D011743:Pyrimidines; D013449:Sulfonamides; C504003:TTF1 protein, human; D014157:Transcription Factors; C516667:pazopanib; C000588866:KDR protein, human; D040301:Vascular Endothelial Growth Factor Receptor-2; D017493:Leukocyte Common Antigens; C516769:PTPRC protein, human
keywords: CD56; CTCs; CellSearch; Immunofluorescence; Pazopanib; SCLC; TTF-1; VEGFR2