Dynamic contrast-enhanced ultrasonography (D-CEUS) for the early prediction of bevacizumab efficacy in patients with metastatic colorectal cancer.

Michele Amadori,Domenico Barone,Andrea Casadei Gardini,Alice Rossi,Angela Ragazzini,Elena Amadori,Giovanni Luca Frassineti,Giampaolo Gavelli,Alessandro Passardi,Emanuela Scarpi,Devil Oboldi,Fabio Ferroni,Gianfranco Bandi

doi:10.1007/s00330-017-5254-5

Abstract

To investigate early changes in tumour perfusion parameters by dynamic contrast-enhanced ultrasonography (D-CEUS) and to identify any correlation with survival and tumour response in patients with metastatic colorectal cancer (CRC) treated with bevacizumab (B). Thirty-seven patients randomized to either chemotherapy (C) plus B or C alone were considered for this study. D-CEUS was performed at baseline and after the first treatment cycle (day 15). Four D-CEUS perfusion parameters were considered: derived peak intensity (DPI), area under the curve (AUC), slope of wash-in (A) and time to peak intensity (TPI). In patients treated with C plus B, a ≥22.5 % reduction in DPI, ≥20 % increase in TPI and ≥10 % reduction in AUC were correlated with higher progression-free survival in the C+B arm (p = 0.048, 0.024 and 0.010, respectively) but not in the C arm. None of the evaluated parameter modifications had a correlation with tumour response or overall survival. D-CEUS could be useful for detecting and quantifying dynamic changes in tumour vascularity as early as 15 days after the start of B-based therapy. Although these changes may be predictive of progression-free survival, no correlation with response or overall survival was found. • D-CEUS showed early changes in liver metastasis perfusion in colorectal cancer. • A decrease in tumour perfusion was associated with longer progression-free survival. • The decrease in perfusion was not correlated with higher overall survival.

Highlights

Colorectal cancer (CRC) is the third most common cancer and the fourth most frequent cause of cancer death worldwide [1]
A decrease in tumour vascularization of liver metastases was observed after only one treatment cycle (15 days after the start of treatment in CRC patients treated with B; Fig. 2)
A decrease in perfusion was interpreted as a significant reduction of relative blood volume (rBV) and relative blood flow (rBF) in the median percent change between the value of derived peak intensity (DPI) on day 15 and day 0, a significant decrease in the median percent change between AUC2 and AUC1, and a significant increase in the median percent change between TPI2 and TPI1

Summary

Introduction

Colorectal cancer (CRC) is the third most common cancer and the fourth most frequent cause of cancer death worldwide [1]. About 25 % of CRC patients present with metastatic disease at diagnosis and show a median overall survival (OS) of about 6 months without specific treatments. The combination of a fluoropyrimidine with either oxaliplatin (FOLFOX, XELOX) or irinotecan (FOLFIRI, XELIRI) has been widely accepted as the standard regimen for the first- and second-line treatment of metastatic CRC [2]. The addition of targeted agents has further improved treatment outcomes. Bevacizumab (B), a humanized antivascular endothelial growth factor (VEGF) recombinant monoclonal antibody that inhibits angiogenesis by preventing the binding of VEGF to its cellular receptors, has been shown to improve survival when added to first-line chemotherapy (C) [3,4,5]. B is normally fairly well tolerated, a small number of patients develop severe adverse events and show no survival benefit

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