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

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 Ktrans 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, Ktrans 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.

Dynamic biomarker and imaging changes from a phase II study of pre‐ and post‐surgical sunitinib

“…However, the significant reduction in K Trans seen in the Neosun after 12 days is in agreement with the reduction observed by Hudson et al [27] after 14 days. Reduction in K Trans has also been observed after 4 and 10 weeks of either sunitinib or pazopanib treatment and change of K Trans between weeks 4 and 10 was associated with the risk of disease progression after 6 months [28].…”

“…[27] after 14 days. Reduction in K Trans has also been observed after 4 and 10 weeks of either sunitinib or pazopanib treatment and change of K Trans between weeks 4 and 10 was associated with the risk of disease progression after 6 months [28].…”

Assessing Tumour Haemodynamic Heterogeneity and Response to Choline Kinase Inhibition Using Clustered Dynamic Contrast Enhanced MRI Parameters in Rodent Models of Glioblastoma

“…The relationship between DCE-MRI parameters (essentially , which reflects the effectiveness of the delivery of oxygen and therapeutic agents between the plasma and interstitial space of the tumour) and clinical outcome following treatment has been evaluated before [ 56 ]. Studies on hepatocellular and renal cancer suggest that both a higher at baseline and an early reduction of are significantly associated with improved outcomes following anti-angiogenic treatment [ 57 , 58 , 59 , 60 , 61 ]. Decrease in permeability has been found to be predominant response of tumour vasculature to bevacizumab therapy in GBMs [ 62 ].…”