Chris James Rose1,2, James P. O'Connor1,2,
Caleb Roberts1,2, Gio A. Buonaccorsi1,2, Yvon Watson1,2,
Sue Cheung1,2, Gordon Jayson3, Geoff J. Parker1,2
1Imaging Science and Biomedical
Engineering, The University of Manchester, Manchester, United Kingdom; 2The
University of Manchester Biomedical Imaging Institute, Manchester, United
Kingdom; 3Cancer Research UK and University of Manchester
Department of Medical Oncology, The Christie Hospital, Manchester, United
Kingdom
DCE-MRI
is of great utility for studying tumor microvasculature, particularly in
early phase clinical trials. Most analysis methods assume homogeneous tumors,
which is often incorrect and a problem when planning trials, because the
magnitude of effect observed using DCE-MRI will be attenuated, for example,
by contributions from necrotic tissue. By simulating maps of Ktransusing a model of
tumor heterogeneity, we present a method to estimate the distribution of
required sample size. We illustrate the methods application using data from
a trial of bevacizumab in CRC metastases and show that by considering
heterogeneity, more powerful studies can be planned.