Feasibility Study on Using Dynamic Contrast Enhanced MRI to Assess the Effect of Tyrosine Kinase Inhibitor Therapy within the STAR Trial of Metastatic Renal Cell Cancer

Jim Zhong; Ebrahim Palkhi; David L Buckley; Fiona J Collinson; Christy Ralph; Satinder Jagdev; Naveen S Vasudev; Jayne Swain; Janet E Brown; Tze Min Wah

doi:10.3390/diagnostics11071302

Feasibility Study on Using Dynamic Contrast Enhanced MRI to Assess the Effect of Tyrosine Kinase Inhibitor Therapy within the STAR Trial of Metastatic Renal Cell Cancer

Diagnostics (Basel). 2021 Jul 20;11(7):1302. doi: 10.3390/diagnostics11071302.

Authors

Affiliations

¹ Department of Diagnostic and Interventional Radiology, Leeds Teaching Hospitals NHS Trust, Leeds LS9 7TF, UK.
² Biomedical Imaging, School of Medicine, University of Leeds, Leeds LS2 9JT, UK.
³ Department of Medical Oncology, St James's Institute of Oncology, Leeds LS9 7TF, UK.
⁴ Clinical Trials Research Unit, Leeds Institute of Clinical Trials Research, University of Leeds, Leeds LS9 7TF, UK.
⁵ Department of Medical Oncology and Metabolism, University of Sheffield, Sheffield S10 2TN, UK.

Abstract

Objective: To identify dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) parameters predictive of early disease progression in patients with metastatic renal cell cancer (mRCC) treated with anti-angiogenic tyrosine kinase inhibitors (TKI). Methods: The study was linked to a phase II/III randomised control trial. Patients underwent DCE-MRI before, at 4- and 10-weeks after initiation of TKI. DCE-MRI parameters at each time-point were derived from a single-compartment tracer kinetic model, following semi-automated tumour segmentation by two independent readers. Primary endpoint was correlation of DCE-MRI parameters with disease progression at 6-months. Receiver operating characteristic (ROC) curve analysis and area under the curve (AUC) values were calculated for parameters associated with disease progression at 6 months. Inter-observer agreement was assessed using the intraclass correlation coefficient (ICC). Results: 23 tumours in 14 patients were measurable. Three patients had disease progression at 6 months. The percentage (%) change in perfused tumour volume between baseline and 4-week DCE-MRI (p = 0.016), mean transfer constant K^trans change (p = 0.038), and % change in extracellular volume (p = 0.009) between 4- and 10-week MRI, correlated with early disease progression (AUC 0.879 for each parameter). Inter-observer agreement was excellent for perfused tumour volume, K^trans and extracellular volume (ICC: 0.928, 0.949, 0.910 respectively). Conclusions: Early measurement of DCE-MRI biomarkers of tumour perfusion at 4- and 10-weeks predicts disease progression at 6-months following TKI therapy in mRCC.

Keywords: anti-angiogenic therapy; dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI); metastatic renal cell cancer; tyrosine kinase inhibitor.