Evaluation of dynamic contrast-enhanced MRI biomarkers for stratified cancer medicine: How do permeability and perfusion vary between human tumours?

Publication date: February 2018
Source:Magnetic Resonance Imaging, Volume 46
Author(s): Ross A. Little, Hervé Barjat, Jennifer I. Hare, Mary Jenner, Yvonne Watson, Susan Cheung, Katherine Holliday, Weijuan Zhang, James P.B. O'Connor, Simon T. Barry, Sanyogitta Puri, Geoffrey J.M. Parker, John C. Waterton
BackgroundSolid tumours exhibit enhanced vessel permeability and fenestrated endothelium to varying degree, but it is unknown how this varies in patients between and within tumour types. Dynamic contrast-enhanced (DCE) MRI provides a measure of perfusion and permeability, the transfer constant K^trans, which could be employed for such comparisons in patients.AimTo test the hypothesis that different tumour types exhibit systematically different K^trans.Materials and methodsDCE-MRI data were retrieved from 342 solid tumours in 230 patients. These data were from 18 previous studies, each of which had had a different analysis protocol. All data were reanalysed using a standardised workflow using an extended Tofts model. A model of the posterior density of median K^trans was built assuming a log-normal distribution and fitting a simple Bayesian hierarchical model.Results12 histological tumour types were included. In glioma, median K^trans was 0.016min⁻¹ and for non-glioma tumours, median K^trans ranged from 0.10 (cervical) to 0.21min⁻¹ (prostate metastatic to bone). The geometric mean (95% CI) across all the non-glioma tumours was 0.15 (0.05, 0.45)min⁻¹. There was insufficient separation between the posterior densities to be able to predict the K^trans value of a tumour given the tumour type, except that the median K^trans for gliomas was below 0.05min⁻¹ with 80% probability, and median K^trans measurements for the remaining tumour types were between 0.05 and 0.4min⁻¹ with 80% probability.ConclusionWith the exception of glioma, our hypothesis that different tumour types exhibit different K^trans was not supported. Studies in which tumour permeability is believed to affect outcome should not simply seek tumour types thought to exhibit high permeability. Instead, K^trans is an idiopathic parameter, and, where permeability is important, K^trans should be measured in each tumour to personalise that treatment.



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