title: Circulating biomarkers in advanced colorectal cancer patients randomly assigned to three bevacizumab-based regimens.
abstract: The need to identify biomarkers for bevacizumab-based treatment in advanced colorectal cancer is imperative. The aim of this study was to investigate the prognostic role of circulating VEGF, PDGF, SDF-1, osteopontin and CEA in patients randomly assigned to three bevacizumab-based regimens. Plasma samples from 50 patients treated at a single Institution were analysed using the multiplex assay BioPlex™ 2200 (Bio-Rad Laboratories, Inc, Berkeley, CA, USA) at baseline, before first three cycles and subsequently every three cycles until disease progression. Prognostic analyses of baseline values were performed using multivariable Cox models, including disease extension >10 cm or ≤10 cm (measured as the sum of the diameters for all target lesions) as adjustment factor. The association between progression-free and overall survival and biomarkers modulation during treatment was studied using multivariable Cox models, which included summary statistics synthesizing during-treatment modulation together with disease extension. The biomarkers significantly associated with disease extension were baseline CEA (p = 0.012) and SDF-1 (p = 0.030). High values of VEGF and SDF-1 tended to be associated with worse prognosis, especially in terms of overall survival. The negative prognostic trend was more marked for baseline CEA as compared to other biomarkers; increasing values during treatment was significantly related to worse prognosis independently of disease extension (p = 0.007 and 0.016 for progression-free and overall survival, respectively). VEGF is related to bevacizumab pharmacodynamics and is associated to other angiogenic cytokines; some of the proposed biomarkers such as SDF-1 and CEA should be further validated for prognosis assessment and monitoring of bevacizumab-based treatment of advanced colorectal cancer.
authors.affiliation: Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Via G. Venezian, Milan 1-20133, Italy. antonia.martinetti@istitutotumori.mi.it.
authors.forename: Antonia
authors.initials: A
authors.lastname: Martinetti
authors.affiliation: Medical Statistics, Biometry and Bioinformatics Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Via G. Venezian, Milan 1-20133, Italy. rosalba.miceli@istitutotumori.mi.it.
authors.forename: Rosalba
authors.initials: R
authors.lastname: Miceli
authors.affiliation: Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Via G. Venezian, Milan 1-20133, Italy. elisa.sottotetti@istitutotumori.mi.it.
authors.forename: Elisa
authors.initials: E
authors.lastname: Sottotetti
authors.affiliation: Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Via G. Venezian, Milan 1-20133, Italy. maria.dibartolomeo@istitutotumori.mi.it.
authors.forename: Maria
authors.initials: M
authors.lastname: Di Bartolomeo
authors.affiliation: Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Via G. Venezian, Milan 1-20133, Italy. filippo.debraud@istitutotumori.mi.it.
authors.forename: Filippo
authors.initials: F
authors.lastname: de Braud
authors.affiliation: Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Via G. Venezian, Milan 1-20133, Italy. arpine.gevorgyan@istitutotumori.mi.it.
authors.forename: Arpine
authors.initials: A
authors.lastname: Gevorgyan
authors.affiliation: Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Via G. Venezian, Milan 1-20133, Italy. katia.dotti@istitutotumori.mi.it.
authors.forename: Katia Fiorella
authors.initials: KF
authors.lastname: Dotti
authors.affiliation: Medical Oncology Unit, IDO Policlinico di Monza, Via Amati, Monza 111-20900, Italy. emilio.bajetta@policlinicodimonza.it.
authors.forename: Emilio
authors.initials: E
authors.lastname: Bajetta
authors.affiliation: Department of Experimental Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Via G. Venezian, Milan 1-20133, Italy. manuela.campiglio@istitutotumori.mi.it.
authors.forename: Manuela
authors.initials: M
authors.lastname: Campiglio
authors.affiliation: Department of Experimental Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Via G. Venezian, Milan 1-20133, Italy. francesca.bianchi@istitutotumori.mi.it.
authors.forename: Francesca
authors.initials: F
authors.lastname: Bianchi
authors.affiliation: Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Via G. Venezian, Milan 1-20133, Italy. giacomo.bregni@gmail.com.
authors.forename: Giacomo
authors.initials: G
authors.lastname: Bregni
authors.affiliation: Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Via G. Venezian, Milan 1-20133, Italy. filippo.pietrantonio@istitutotumori.mi.it.
authors.forename: Filippo
authors.initials: F
authors.lastname: Pietrantonio