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The prognostic and predictive value of vascular response parameters measured by dynamic contrast-enhanced-CT, -MRI and -US in patients with metastatic renal cell carcinoma receiving sunitinib

  • Oncology
  • Published:
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Abstract

Objectives

To identify dynamic contrast-enhanced (DCE) imaging parameters from MRI, CT and US that are prognostic and predictive in patients with metastatic renal cell cancer (mRCC) receiving sunitinib.

Methods

Thirty-four patients were monitored by DCE imaging on day 0 and 14 of the first course of sunitinib treatment. Additional scans were performed with DCE-US only (day 7 or 28 and 2 weeks after the treatment break). Perfusion parameters that demonstrated a significant correlation (Spearman p < 0.05) with progression-free survival (PFS) and overall survival (OS) were investigated using Cox proportional hazard models/ratios (HR) and Kaplan-Meier survival analysis.

Results

A higher baseline and day 14 value for Ktrans (DCE-MRI) and a lower pre-treatment vascular heterogeneity (DCE-US) were significantly associated with a longer PFS (HR, 0.62, 0.37 and 5.5, respectively). A larger per cent decrease in blood volume on day 14 (DCE-US) predicted a longer OS (HR, 1.45). We did not find significant correlations between any of the DCE-CT parameters and PFS/OS, unless a cut-off analysis was used.

Conclusions

DCE-MRI, -CT and ultrasound produce complementary parameters that reflect the prognosis of patients receiving sunitinib for mRCC. Blood volume measured by DCE-US was the only parameter whose change during early anti-angiogenic therapy predicted for OS and PFS.

Key Points

• DCE-CT, -MRI and ultrasound are complementary modalities for monitoring anti-angiogenic therapy.

• The change in blood volume measured by DCE-US was predictive of OS/PFS.

• Baseline vascular heterogeneity by DCE-US has the strongest prognostic value for PFS.

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Funding

This study has received funding from the Terry Fox Programme of the National Cancer Institute of Canada, the Canadian Institutes of Health Research and an investigator-initiated grant to Georg A. Bjarnason from Pfizer Canada.

Author information

Authors and Affiliations

  1. Department of Medical Biophysics, University of Toronto, 2075 Bayview Ave, Room S6-39, Toronto, ON, M4N 3M5, Canada

    John M. Hudson, Greg Stanisz, Ross Williams & Peter N. Burns

  2. Sunnybrook Research Institute, University of Toronto, Toronto, ON, Canada

    John M. Hudson, Colleen Bailey, Greg Stanisz, Alex Kiss & Peter N. Burns

  3. Department of Medical Imaging, University of Toronto Health Network, Toronto, ON, Canada

    Mostafa Atri

  4. Department of Medical Imaging, Sunnybrook Health Sciences Centre, Toronto, ON, Canada

    Laurent Milot

  5. Department of Health Policy, Management and Evaluation, University of Toronto, Toronto, ON, Canada

    Alex Kiss

  6. Division of Medical Oncology, Sunnybrook Odette Cancer Centre, Sunnybrook Health Sciences Centre, 2075 Bayview Ave., Room T2 049, Toronto, ON, M4N 3M5, Canada

    Georg A. Bjarnason

Authors
  1. John M. Hudson
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  2. Colleen Bailey
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  3. Mostafa Atri
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  4. Greg Stanisz
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  5. Laurent Milot
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  6. Ross Williams
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  7. Alex Kiss
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  8. Peter N. Burns
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  9. Georg A. Bjarnason
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Corresponding authors

Correspondence to John M. Hudson or Georg A. Bjarnason.

Ethics declarations

Guarantor

The scientific guarantor of this publication is Georg Bjarnason.

Conflict of interest

The authors of this manuscript declare relationships with the following companies:

Georg A. Bjarnason: Pfizer Canada: grant support for this study, CME presentations and travel support to oncology meetings. The remaining authors have no further conflicts to disclose.

Statistics and biometry

Alex Kiss (author) has significant statistical expertise.

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

A subset of the patient cohort included in this article has been reported in the following journal publications. The referenced articles were reports on technical protocol development (3), a new DCE-US parameter development (2) or describing using DCE-US vascular volume changes during and after sunitinib therapy to justify changes in sunitinib scheduling (1):

1. Bjarnason G A, Khalil B, Hudson JM, Williams R, Milot LM, Atri M, et al. Outcomes in patients with metastatic renal cell cancer treated with individualized sunitinib therapy: Correlation with dynamic microbubble ultrasound data and review of the literature. Urol Oncol. Elsevier; 2013;32(4):1–8.

2. Hudson JM, Williams R, Karshafian R, Milot L, Atri M, Burns PN, et al. Quantifying vascular heterogeneity using microbubble disruption-replenishment kinetics in patients with renal cell cancer. Invest Radiol [Internet]. 2014;49(2):116–23.

3. Williams R, Hudson JJM, Lloyd BBA, Sureshkumar AR, Lueck G, Bjarnason GA, et al. Dynamic microbubble contrast-enhanced US to measure tumor response to targeted therapy: a proposed clinical protocol with results from renal cell carcinoma patients receiving antiangiogenic therapy. Radiology [Internet]. 2011 [cited 2012 Oct 12];260(2):581–90.

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Hudson, J.M., Bailey, C., Atri, M. et al. The prognostic and predictive value of vascular response parameters measured by dynamic contrast-enhanced-CT, -MRI and -US in patients with metastatic renal cell carcinoma receiving sunitinib. Eur Radiol 28, 2281–2290 (2018). https://doi.org/10.1007/s00330-017-5220-2

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  • DOI: https://doi.org/10.1007/s00330-017-5220-2

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