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

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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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Acknowledgments

The present work was partly supported by a Research Grant (Number 08010901/09 to M. Danova) from the Fondazione IRCCS Policlinico S. Matteo—Pavia. We wish to thank all the volunteers and patients for taking part in the study, as well as the nursing and the medical staff of each involved Clinical Institution for their support in the acquisition of clinical samples. A special thanks to Laurene Kelly for revision of the English.

Conflict of interest

The authors declare that they have no direct or indirect financial or personal relationship with other people or organizations that could bias their work. No benefits in any form have been received from a commercial party related directly or indirectly to the subject of this article.

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Authors and Affiliations

  1. S.C. Oncologia, Fondazione IRCCS Policlinico S. Matteo, Piazzale C. Golgi 19, I-27100, Pavia, Italy

    Mariangela Manzoni, Sara Mariucci, Sara Delfanti, Bianca Rovati, Silvia Brugnatelli & Marco Danova

  2. Oncologia Medica, Istituto Scientifico S. Raffaele, Milan, Italy

    Monica Ronzoni & Eugenio Villa

  3. Dipartimento di Oncologia, dei Trapianti e delle Nuove Tecnologie in Medicina, Oncologia 2 Universitaria, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy

    Fotios Loupakis & Alfredo Falcone

  4. Unità di Epidemiologia Clinica e Biometria, Fondazione IRCCS Policlinico S. Matteo, Pavia, Italy

    Carmine Tinelli

Authors
  1. Mariangela Manzoni
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  2. Sara Mariucci
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  3. Sara Delfanti
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  4. Bianca Rovati
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  5. Monica Ronzoni
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  6. Fotios Loupakis
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  7. Silvia Brugnatelli
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  8. Carmine Tinelli
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  9. Eugenio Villa
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  10. Alfredo Falcone
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  11. Marco Danova
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Correspondence to Mariangela Manzoni.

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Manzoni, M., Mariucci, S., Delfanti, S. et al. Circulating endothelial cells and their apoptotic fraction are mutually independent predictive biomarkers in Bevacizumab-based treatment for advanced colorectal cancer. J Cancer Res Clin Oncol 138, 1187–1196 (2012). https://doi.org/10.1007/s00432-012-1190-6

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  • DOI: https://doi.org/10.1007/s00432-012-1190-6

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