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.
Highlights
Kidney cancer is the third most common genitourinary malignancy, with over 400,000 new diagnoses per year, over 175,000 deaths worldwide annually and a rising incidence [1,2,3]
There are no validated imaging biomarkers that predict which patients with Metastatic renal cell carcinoma (mRCC) will benefit from anti-angiogenic therapy [10]
The aim of this study was to investigate if dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI)-based parameters (perfused tumour volume, the transfer constant Ktrans, extracellular volume (ECV) and extracellular mean transit time (MTT)) at 4- and 10-weeks could predict progressive disease (PD) at 6-months after initiation of tyrosine kinase inhibitors (TKI) therapy
Summary
Kidney cancer is the third most common genitourinary malignancy, with over 400,000 new diagnoses per year, over 175,000 deaths worldwide annually and a rising incidence [1,2,3]. Determining whether a patient is continuing to derive benefit from treatment with each cycle can be difficult as traditional imaging assessment criteria, such as Response Evaluation Criteria in Solid Tumours (RECIST), are limited to evaluating size changes that may be slow to occur [7]. Changes in physiology, such as tumour blood flow, precede morphological changes and potentially enables earlier response assessment [8,9]. The aim of this study was to investigate if DCE-MRI-based parameters (perfused tumour volume, the transfer constant Ktrans, extracellular volume (ECV) and extracellular mean transit time (MTT)) at 4- and 10-weeks could predict progressive disease (PD) at 6-months after initiation of TKI therapy
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