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

  • Oncology
  • Published:
European Radiology Aims and scope Submit manuscript

Abstract

Objectives

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).

Methods

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).

Results

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.

Conclusions

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.

Key Points

• 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.

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Abbreviations

AIFA:

Italian Medicines Agency

AUC:

Area under the curve

A:

Slope of wash-in

B:

Bevacizumab

C:

Chemotherapy

CI:

Confidence interval

CRC:

Colorectal cancer

CT:

Computed tomography

dB:

Decibel

DCE-CT:

Dynamic contrast-enhanced computed tomography

DCE-MRI:

Dynamic contrast-enhanced magnetic resonance imaging

D-CEUS:

Dynamic contrast-enhanced ultrasonography

DPI:

Derived peak intensity

ECOG:

Eastern Cooperative Oncology Group

EFSUMB:

European Federation of Societies for Ultrasound in Medicine and Biology

FOLFOX:

Folinic acid, 5-fluorouracil and oxaliplatin

FOLFIRI:

Folinic acid, 5-fluorouracil and irinotecan

5-FU:

5-Fluorouracil

ITACa:

Italian Trial in Advanced Colorectal Cancer

KRAS:

V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog

LV:

Leucovorin

MI:

Mechanical index

MTT:

Mean transit time

OS:

Overall survival

PD:

Progressive disease

PET:

Positron emission tomography

PFS:

Progression-free survival

PS:

Performance status

rBF:

Relative blood flow

rBV:

Relative blood volume

RECIST:

Response Evaluation Criteria in Solid Tumors

ROC:

Receiver operating characteristic

ROI:

Region of interest

TPI:

Time to peak intensity

V0 :

Initial intensity value

VEGF:

Vascular endothelial growth factor

Vmax :

Maximal intensity value

XELIRI:

Capecitabine and irinotecan

XELOX:

Capecitabine and oxaliplatin

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Acknowledgements

The authors thank the ITACa study investigators and participating patients, and Cristiano Verna for editorial assistance.

Funding

This study was funded by the Italian Medicines Agency (AIFA) [grant number FARM6FJJAY]. The study sponsor was not involved in the study design nor in the collection, analysis, and interpretation of data. The study sponsor did not provide writing support for the report.

Author information

Author notes

  1. Michele Amadori and Domenico Barone contributed equally

Authors and Affiliations

  1. Radiology Unit, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy

    Michele Amadori, Domenico Barone, Devil Oboldi, Elena Amadori, Gianfranco Bandi, Alice Rossi, Fabio Ferroni & Giampaolo Gavelli

  2. Unit of Biostatistics and Clinical Trials, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy

    Emanuela Scarpi & Angela Ragazzini

  3. Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy

    Andrea Casadei Gardini, Giovanni Luca Frassineti & Alessandro Passardi

Authors
  1. Michele Amadori
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  2. Domenico Barone
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Corresponding author

Correspondence to Emanuela Scarpi.

Ethics declarations

Guarantor

The scientific guarantor of this publication is Alessandro Passardi.

Conflict of interest

The authors of this manuscript declare no relationships with any companies whose products or services may be related to the subject matter of the article.

Statistics and biometry

The Corresponding Author, Emanuela Scarpi, is an expert in statistics.

Informed consent

Written informed consent was obtained from all subjects (patients) in this study.

Ethical approval

Institutional Review Board approval was obtained.

Study subjects or cohorts overlap

Some study subjects or cohorts have been previously reported in the ITACa trial paper published in Annals of Oncology in 2015 (Passardi et al, Ann Oncol 2015;26(6):1201-7).

Methodology

• Prospective

• Case-control study/randomized controlled trial

• Performed at one institution

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Amadori, M., Barone, D., Scarpi, E. et al. Dynamic contrast-enhanced ultrasonography (D-CEUS) for the early prediction of bevacizumab efficacy in patients with metastatic colorectal cancer. Eur Radiol 28, 2969–2978 (2018). https://doi.org/10.1007/s00330-017-5254-5

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  • DOI: https://doi.org/10.1007/s00330-017-5254-5

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