Inter-lesional variability of DCE-MRI response and changes in cardiac output following infusion of the vascular disruptive agent Combretastatin-A4-Phosphate (CA4P)
Andrew Gaya1, N. Jane Taylor2, Tarun Mittal3, J James Stirling2, James d'Arcy4, D Koh4, Gordon Rustin1, Tim Meyer5, Paul Nathan1, David Collins4, Anwar Padhani2
1Mount Vernon Hospital, Northwood, Middlesex, UK, 2Paul Strickland Scanner Centre, Northwood, Middlesex, UK, 3Dept. Imaging, Harefield Hospital, Harefield, Middlesex, UK, 4CR-UK Imaging Group, Institute of Cancer Research, Sutton, Surrey, UK, 5Dept Medical Oncology, Royal Free Hospital, London,, UK
Aim
To confirm there are no significant reductions in cardiac output 4h following CA4P, and document variability of inter-lesional responses on T1-weighted DCE-MRI.
Background
It is suggested that tumour vascular shutdown seen on DCE-MRI is partly due to decreases in cardiac output(CO). DCE-MRI is a validated pharmacodynamic biomarker for assessing antivascular effects of VDAs and antiangiogenics. Intra- and inter-lesional heterogeneity in DCE-MRI responses are documented on visual inspection of parametric maps. The assumption of similarity of responses has not been investigated.
Method
Patients were imaged in a Siemens Symphony 1.5T MRI. Patients from 2 phase I studies were examined twice with DCE-MRI before therapy, and 4h following CA4P. Phase contrast sequences were obtained in 12 patients from study 1 to calculate CO.Anatomical images, T1W spoiled 2D(study 1)/3D(study 2) GRE[FLASH] sequences were acquired before and after 0.1mmol/kg Gd-DTPA. ROIs were placed around whole tumours to calculate values of transfer constant (Ktrans) using the methods of Tofts.
Results
11/12 patients completed at least 1 pre- and 1 post CA4P MRI. There were significant increases in CO (p=0.026). Mean net increase was 14.0%(range 6.9-47.3%). 9 patients (7 study 1 and 2 study 2) with >1 lesion (31 total; median 3, range 2-5) were evaluated. For 6/9 patients, lesion changes were in the same order of magnitude and direction. In 3/9, significant differences were seen.
Conclusions
No systematic decrease in CO occurred, excluding a central effect for the reduced Ktrans seen. Inter-lesional variability was small for most patients but quite marked for some.
