Tord Hompland

MRI-guided dynamic risk assessment in cervical cancer based on tumor hypoxia at diagnosis and volume response at brachytherapy

Improvements in treatment outcome for patients with locally advanced cervical cancer (LACC) require a better classification of patients according to their risk of recurrence. We investigated whether an imaging-based approach, combining pretreatment hypoxia and tumor response during therapy, could improve risk classification. Ninety-three LACC patients with T2-weigthed (T2W)-, dynamic contrast enhanced (DCE)- and diffusion weighted (DW)-magnetic resonance (MR) images acquired before treatment, and T2W- and, for 64 patients, DW-MR images, acquired at brachytherapy, were collected. Pretreatment hypoxic fraction (HF HF The combination of pretreatment hypoxia and volume regression at brachytherapy improved patient risk classification. Integration of ADC with volume regression showed promise as a new tumor response parameter.

Incorporating cross-voxel exchange for the analysis of dynamic contrast-enhanced imaging data: pre-clinical results

Abstract Tumours exhibit abnormal interstitial structures and vasculature function often leading to impaired and heterogeneous drug delivery. The disproportionate spatial accumulation of a drug in the interstitium is determined by several microenvironmental properties (blood vessel distribution and permeability, gradients in the interstitial fluid pressure). Predictions of tumour perfusion are key determinants of drug delivery and responsiveness to therapy. Pharmacokinetic models allow for the quantification of tracer perfusion based on contrast enhancement measured with non-invasive imaging techniques. An advanced cross-voxel exchange model (CVXM) was recently developed to provide a comprehensive description of tracer extravasation as well as advection and diffusion based on cross-voxel tracer kinetics (Sinno et al 2021). Transport parameters were derived from DCE-MRI of twenty TS-415 human cervical carcinoma xenografts by using CVXM. Tracer velocity flows were measured at the tumour periphery (mean 1.78–5.82 μm.s−1) pushing the contrast outward towards normal tissue. These elevated velocity measures and extravasation rates explain the heterogeneous distribution of tracer across the tumour and its accumulation at the periphery. Significant values for diffusivity were deduced across the tumours (mean 152–499 μm2.s−1). CVXM resulted in generally smaller values for the extravasation parameter K e x t (mean 0.01–0.04 min−1) and extravascular extracellular volume fraction v e (mean 0.05–0.17) compared to the standard Tofts parameters, suggesting that Toft model underestimates the effects of inter-voxel exchange. The ratio of Tofts’ extravasation parameters over CVXM’s was significantly positively correlated to the cross-voxel diffusivity (P < 0.0001) and velocity (P = 0.0005). Tofts’ increased v e measurements were explained using Sinno et al (2021)’s theoretical work. Finally, a scan time of 15 min renders informative estimations of the transport parameters. However, a duration as low as 7.5 min is acceptable to recognize the spatial variation of transport parameters. The results demonstrate the potential of utilizing CVXM for determining metrics characterizing the exchange of tracer between the vasculature and the tumour tissue. Like for many earlier models, additional work is strongly recommended, in terms of validation, to develop more confidence in the results, motivating future laboratory work in this regard.

Targeted Therapy on the Screen: Do We Hit the Target?

Summary A phase II trial, investigating whether the antidiabetic drug metformin could reduce hypoxia in cervical cancer, used imaging to preselect patients and test the biological hypothesis behind the drug effect. This trial design would be of importance for the implementation of targeted treatment in the clinic. See related article by Han et al., p. 5263