Selection of an early biomarker for vascular normalization using dynamic contrast-enhanced ultrasonography to predict outcomes of metastatic patients treated with bevacizumab.

BACKGROUND: Dynamic contrast-enhanced ultrasonography (DCE-US) has been used for evaluation of tumor response to antiangiogenic treatments. The objective of this study was to assess the link between DCE-US data obtained during the first week of treatment and subsequent tumor progression. PATIENTS AND METHODS: Patients treated with antiangiogenic therapies were included in a multicentric prospective study from 2007 to 2010. DCE-US examinations were available at baseline and at day 7. For each examination, a 3 min perfusion curve was recorded just after injection of a contrast agent. Each perfusion curve was modeled with seven parameters. We analyzed the correlation between criteria measured up to day 7 on freedom from progression (FFP). The impact was assessed globally, according to tumor localization and to type of treatment. RESULTS: The median follow-up was 20 months. The mean transit time (MTT) evaluated at day 7 was the only criterion significantly associated with FFP (P = 0.002). The cut-off point maximizing the difference between FFP curves was 12 s. Patients with at least a 12 s MTT had a better FFP. The results according to tumor type were significantly heterogeneous: the impact of MTT on FFP was more marked for breast cancer (P = 0.004) and for colon cancer (P = 0.025) than for other tumor types. Similarly, the differences in FFP according to MTT at day 7 were marked (P = 0.004) in patients receiving bevacizumab. CONCLUSION: The MTT evaluated with DCE-US at day 7 is significantly correlated to FFP of patients treated with bevacizumab. This criterion might be linked to vascular normalization. AFSSAPS NO: 2007-A00399-44.

Epidermal growth factor receptors in breast cancer: comparison of radioligand and immunocytochemical assays.

Epidermal growth factor receptors (EGFR) are part of second generation biological factors that clinicians caring for breast cancer patients wish to evaluate for their prognostic value. This aim requires the standardization of methods: the radioligand assay (RLA) for the quantification of EGF binding sites was performed on membrane pellets from 261 breast cancer samples (ligand binding and hydroxylapatite separation as recommended by the EORTC Receptor Study Group); the immunocytochemical assay (ICA) for the staining of EGFR antigenic sites was performed on fine needle aspiration (FNA) cytology or touch imprints from 97 surgical specimens. The percentage of EGFR positivity by RLA (specific binding higher than 1% of total radioactivity) and the EGFR positive rate by ICA (more than 5% of stained cells) were respectively 43% and 38%. For 61 cases assayed on the same patient both methods revealed a concordance of 85%. Our results show that both methods are complementary and give quantitative data and information on tumor heterogeneity when they are performed in parallel. The next step of this study will be to determine the prognostic value of EGFR in these subpopulations of tumors for the adjustment of adjuvant treatment.