title: Early detection of poor outcome in patients with metastatic colorectal cancer: tumor kinetics evaluated by circulating tumor cells.
abstract: BACKGROUND
  Colorectal cancer (CRC) is the third most prevalent cancer worldwide. New prognostic markers are needed to identify patients with poorer prognosis, and circulating tumor cells (CTCs) seem to be promising to accomplish this.
  
  
  METHODS
  A prospective study was conducted by blood collection from patients with metastatic CRC (mCRC), three times, every 2 months in conjunction with image examinations for evaluation of therapeutic response. CTC isolation and counting were performed by Isolation by Size of Epithelial Tumor Cells (ISET).
  
  
  RESULTS
  A total of 54 patients with mCRC with a mean age of 57.3 years (31-82 years) were included. Among all patients, 60% (n=32) were carriers of wild-typeKRAS(WTKRAS) tumors and 90% of them (n=29) were exposed to monoclonal antibodies along with systemic treatment. Evaluating CTC kinetics, when we compared the baseline (pretreatment) CTC level (CTC1) with the level at first follow-up (CTC2), we observed that CTC1-positive patients (CTCs above the median), who became negative (CTCs below the median) had a favorable evolution (n=14), with a median progression-free survival (PFS) of 14.7 months. This was higher than that for patients with an unfavorable evolution (CTC1- that became CTC2+; n=13, 6.9 months;P=0.06). Patients with WTKRASwith favorable kinetics had higher PFS (14.7 months) in comparison to those with WTKRASwith unfavorable kinetics (9.4 months;P=0.02). Moreover, patients whose imaging studies showed radiological progression had an increased quantification of CTCs at CTC2 compared to those without progression (P=0.04).
  
  
  CONCLUSIONS
  This study made possible the presentation of ISET as a feasible tool for evaluating CTC kinetics in patients with mCRC, which can be promising in their clinical evaluation.
authors.affiliation: Department of Clinical Oncology.
authors.forename: Virgílio
authors.initials: V
authors.lastname: Souza E Silva
authors.affiliation: International Research Center.
authors.forename: Ludmilla Thomé Domingos
authors.initials: LT
authors.lastname: Chinen
authors.affiliation: International Research Center.
authors.forename: Emne A
authors.initials: EA
authors.lastname: Abdallah
authors.affiliation: International Research Center.
authors.forename: Aline
authors.initials: A
authors.lastname: Damascena
authors.affiliation: Image Department, A. C. Camargo Cancer Center, São Paulo, Brazil.
authors.forename: Jociana
authors.initials: J
authors.lastname: Paludo
authors.affiliation: Image Department, A. C. Camargo Cancer Center, São Paulo, Brazil.
authors.forename: Rubens
authors.initials: R
authors.lastname: Chojniak
authors.affiliation: Department of Clinical Oncology.
authors.forename: Aldo Lourenço Abbade
authors.initials: AL
authors.lastname: Dettino
authors.affiliation: Department of Clinical Oncology.
authors.forename: Celso Abdon Lopes
authors.initials: CA
authors.lastname: de Mello
authors.affiliation: International Research Center.
authors.forename: Vanessa S
authors.initials: VS
authors.lastname: Alves
authors.affiliation: Department of Clinical Oncology.
authors.forename: Marcello F
authors.initials: MF
authors.lastname: Fanelli
keywords: ISET; circulating tumor cells; kinetics; metastatic colorectal cancer