title: Circulating endothelial cells and their apoptotic fraction are mutually independent predictive biomarkers in Bevacizumab-based treatment for advanced colorectal cancer.
abstract: BACKGROUND
  Bevacizumab has shown consistent clinical efficacy in metastatic colorectal cancer (mCRC), but some patients respond better than others. Thus, it is crucial to identify biomarkers that permit the recognition of potentially responsive subjects and to spare toxicity in those who are unlikely benefit from treatment.
  
  
  METHODS
  In 24 mCRC patients undergoing Bevacizumab-based first-line treatment, we assessed by multiparameter flow cytometry changes in circulating endothelial cell (CEC) number, their apoptotic fraction (APO-CEC) and their mutual relationship. Data were compared with those from a group of 21 healthy subjects.
  
  
  RESULTS
  CECs and APO-CECs were higher in patients versus controls (p = 0.01 and p > 0.05, respectively). The increase in CECs at the 3rd cycle in complete response (CR) patients was statistically significant (p = 0.048). A better progression-free survival was evidenced in patients that showed an increase in CECs at the 6th cycle (p = 0.009). Regarding the changes in CECs and APO-CECs, a strong correlation was evidenced, at baseline, both in the global population (0.002; r: 0.53) and in the CR subgroup (p: 0.02; r: 0.77). In the partial response + stable and progression disease (SD + PD) subgroup, this correlation was highly significant at the 6th cycle (p: 0.001; r: 0.83).
  
  
  CONCLUSIONS
  We confirmed the predictive role of an increase in CECs in mCRC patients treated with Bevacizumab-based therapy and showed that modifications in CECs and APO-CECs are independent factors. This underlines the relevance of a simultaneous quantitative and functional evaluation of these biomarkers in view of their possible diagnostic utility.
authors.affiliation: S.C. Oncologia, Fondazione IRCCS Policlinico S. Matteo, Piazzale C. Golgi 19, I-27100 Pavia, Italy. m.manzoni@smatteo.pv.it
authors.forename: Mariangela
authors.initials: M
authors.lastname: Manzoni
authors.forename: Sara
authors.initials: S
authors.lastname: Mariucci
authors.forename: Sara
authors.initials: S
authors.lastname: Delfanti
authors.forename: Bianca
authors.initials: B
authors.lastname: Rovati
authors.forename: Monica
authors.initials: M
authors.lastname: Ronzoni
authors.forename: Fotios
authors.initials: F
authors.lastname: Loupakis
authors.forename: Silvia
authors.initials: S
authors.lastname: Brugnatelli
authors.forename: Carmine
authors.initials: C
authors.lastname: Tinelli
authors.forename: Eugenio
authors.initials: E
authors.lastname: Villa
authors.forename: Alfredo
authors.initials: A
authors.lastname: Falcone
authors.forename: Marco
authors.initials: M
authors.lastname: Danova
mesh_terms: D000328:Adult; D000368:Aged; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D017209:Apoptosis; D000068258:Bevacizumab; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D042783:Endothelial Cells / Q000473:pathology*; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D008297:Male; D008875:Middle Aged
chemical_list: D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab