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

Abstract

Background: Solid 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.

Aim: To test the hypothesis that different tumour types exhibit systematically different K^trans.

Materials and methods: DCE-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.

Results: 12 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.

Conclusion: With 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.

Keywords: Drug delivery; Dynamic contrast-enhanced MRI; Enhanced permeability and retention; Imaging biomarkers; Personalised medicine; Solid tumours.