Value of Contrast-Enhanced Ultrasound Quantification Criteria for Identifying Patients not Responding to Bevacizumab-Based Therapy for Colorectal Liver Metastases

IF 3.892International audiencePurpose To evaluate changes in tumor vascularization parameters based on contrast-enhanced ultrasound (CEUS) quantification criteria of at least one visible liver metastasis as an early predictor of non-response to chemotherapy, including bevacizumab for colorectal cancer (CRC) liver metastases. Materials and Methods This multicenter prospective study included patients who received first-line bevacizumab-based chemotherapy. Tumor enhancement measured using CEUS within one liver metastasis and in relation to the surrounding healthy liver was quantified within 8 days before the first infusion of bevacizumab (E0), 24 hours after the end of the first infusion of bevacizumab (E1), in the 24 hours before the 2nd and 3 rd infusion of bevacizumab on day 15 (E2) and day 30 (E3), respectively, and after 2 months of treatment (E4). Endpoints were tumor response using RECIST criteria at 2 months, progression-free survival (PFS) and overall survival (OS). Results Among the 137 patients included in this study, 109 were analyzed. Only CEUS parameters calculated in relation to healthy liver were significant. High wash-in and wash-out rates at baseline were significantly associated with a better tumor response. Increases over time E2-E0 and E3-E0 for peak enhancement were significantly associated with shorter progression-free survival. Increases over time E2-E0 and E3-E0 for peak enhancement and wash-in area under the curve were significantly associated with a shorter overall survival. Conclusion This large study demonstrated that early dynamic changes in the vascularity of liver metastases evaluated by quantified CEUS are associated with outcome in patients receiving first-line bevacizumab-based treatment for metastatic CRC

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

International audienceBACKGROUND: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

Immunohistochemical evaluation of two antibodies against PD-L1 and prognostic significance of PD-L1 expression in epithelioid peritoneal malignant mesothelioma: A RENAPE study

International audienceBACKGROUND:Epithelioid peritoneal malignant mesothelioma (EPMM) is the most common subtype of this aggressive tumor. We compared two antibodies against PD-L1, a recent theranostic biomarker, and evaluated the prognostic value of PD-L1 expression by mesothelial and immune cells in EPMM.METHODS:Immunohistochemistry was performed on 45 EPMM. Clinical and pathological data were extracted from the RENAPE database. Using E1L3N and SP142 clones, inter-observer agreement, PD-L1 expression by mesothelial and immune cells and inter-antibody agreement were evaluated. The prognostic relevance of PD-L1 expression was evaluated in 39 EPMM by univariate and multivariate analysis of overall survival (OS) and progression-free survival (PFS).RESULTS:Inter-observer agreement on E1L3N immunostaining was moderate for mesothelial and immune cells, and fair for mesothelial and poor for immune cells using SP142. Using E1L3N, 31.1% of mesothelial and 15.6% of immune cells expressed PD-L1, and 22.2% of mesothelial and 26.7% of immune cells using SP142. Inter-antibody agreement was moderate. In most positive cases, 1-5% of tumor cells were positive. Using E1L3N, PD-L1 expression by lymphocytes was associated with better OS and PFS by both univariate and multivariate analysis. Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy predicted better prognosis than other treatments. Solid subtype was an independent prognostic factor for worse OS.CONCLUSION:E1L3N appeared easier to use than SP142 to evaluate PD-L1 expression. A minority of EPMM expressed PD-L1, and only a few cells were positive. PD-L1 expression by immune cells evaluated with E1L3N was an independent prognostic factor in EPMM