Circulating endothelial cells and their apoptotic fraction are mutually independent predictive biomarkers in Bevacizumab-based treatment for advanced colorectal cancer

Mariangela Manzoni, Sara Mariucci, Sara Delfanti, Bianca Rovati, Monica Ronzoni, Fotios Loupakis, Silvia Brugnatelli, Carmine Tinelli, Eugenio Villa, Alfredo Falcone, Marco Danova

Research output: Contribution to journalArticle

19 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1187-1196
Number of pages10
JournalJournal of Cancer Research and Clinical Oncology
Volume138
Issue number7
DOIs
Publication statusPublished - Jul 2012

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Colorectal Neoplasms
Endothelial Cells
Biomarkers
Therapeutics
Disease-Free Survival
Disease Progression
Bevacizumab
Healthy Volunteers
Flow Cytometry
Cell Count
Population

Keywords

  • Angiogenesis
  • Apoptosis
  • Biomarkers
  • Circulating endothelial cells
  • Colorectal cancer

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Circulating endothelial cells and their apoptotic fraction are mutually independent predictive biomarkers in Bevacizumab-based treatment for advanced colorectal cancer. / Manzoni, Mariangela; Mariucci, Sara; Delfanti, Sara; Rovati, Bianca; Ronzoni, Monica; Loupakis, Fotios; Brugnatelli, Silvia; Tinelli, Carmine; Villa, Eugenio; Falcone, Alfredo; Danova, Marco.

In: Journal of Cancer Research and Clinical Oncology, Vol. 138, No. 7, 07.2012, p. 1187-1196.

Research output: Contribution to journalArticle

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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.",
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T1 - Circulating endothelial cells and their apoptotic fraction are mutually independent predictive biomarkers in Bevacizumab-based treatment for advanced colorectal cancer

AU - Manzoni, Mariangela

AU - Mariucci, Sara

AU - Delfanti, Sara

AU - Rovati, Bianca

AU - Ronzoni, Monica

AU - Loupakis, Fotios

AU - Brugnatelli, Silvia

AU - Tinelli, Carmine

AU - Villa, Eugenio

AU - Falcone, Alfredo

AU - Danova, Marco

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N2 - 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.

AB - 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.

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KW - Apoptosis

KW - Biomarkers

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KW - Colorectal cancer

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