Advanced solid tumors treated with cediranib: comparison of dynamic contrast-enhanced MR imaging and CT as markers of vascular activity.
OBJECTIVE
To assess baseline reproducibility and compare performance of dynamic contrast material-enhanced (DCE) magnetic resonance (MR) imaging versus DCE computed tomographic (CT) measures of early vascular response in the same patients treated with cediranib (30 or 45 mg daily).


METHODS
After institutional review board approval, written informed consent was obtained from 29 patients with advanced solid tumors who had lesions 3 cm or larger and in whom simultaneous imaging of an adjacent artery was possible. Two baseline DCE MR acquisitions and two baseline DCE CT acquisitions 7 days or fewer apart (within 14 days of starting treatment) and two posttreatment acquisitions with each modality at day 7 and 28 (±3 days) were obtained. Nonmodeled and modeled parameters were derived (measured arterial input function [AIF] for CT, population-based AIF for MR imaging; temporal sampling rate of 0.5 second for CT, 3-6 seconds for MR imaging). Baseline variability was assessed by using intra- and intersubject analysis of variance and Bland-Altman analysis; a paired t test assessed change from baseline to after treatment.


RESULTS
The most reproducible parameters were DCE MR imaging enhancement fraction (baseline intrapatient coefficient of variation [CV]=8.6%), volume transfer constant (CV=13.9%), and integrated area under the contrast agent uptake curve at 60 seconds (CV=15.5%) and DCE CT positive enhancement integral (CV=16.0%). Blood plasma volume was highly variable and the only parameter with CV greater than 30%. Average reductions (percentage change) from baseline were consistently observed for all DCE MR imaging and DCE CT parameters at day 7 and 28 for both starting-dose groups (45 and 30 mg), except for DCE CT mean transit time. Percentage change from baseline for parameters reflecting blood flow and permeability were comparable, and reductions from baseline at day 7 were maintained at day 28.


CONCLUSIONS
DCE MR imaging and DCE CT can depict vascular response to antiangiogenic agents with response evident at day 7. Improved reproducibility with MR imaging favors its use in trials with small patient numbers.
Cancer Research UK and EPSRC Imaging Centre and Drug Development Unit of Section of Medicine, Institute of Cancer Research and Royal Marsden Hospital, MRI Unit, Downs Road, Sutton, Surrey SM2 5PT, England.
Christina
C
Messiou
Matthew
M
Orton
Joo Ern
JE
Ang
David J
DJ
Collins
Veronica A
VA
Morgan
Dorothy
D
Mears
Isabel
I
Castellano
Dionysis
D
Papadatos-Pastos
Andre
A
Brunetto
Nina
N
Tunariu
Helen
H
Mann
Jean
J
Tessier
Helen
H
Young
Dana
D
Ghiorghiu
Sarah
S
Marley
Stan B
SB
Kaye
Johann S
JS
deBono
Martin O
MO
Leach
Nandita M
NM
deSouza
D000328:Adult; D000368:Aged; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage; D000970:Antineoplastic Agents / Q000008:administration & dosage; D003287:Contrast Media; D004305:Dose-Response Relationship, Drug; D005260:Female; D019786:Gadolinium DTPA; D006801:Humans; D007472:Iohexol; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000150:complications / Q000175:diagnosis* / Q000188:drug therapy*; D009389:Neovascularization, Pathologic / Q000175:diagnosis* / Q000188:drug therapy* / Q000209:etiology; D011799:Quinazolines / Q000008:administration & dosage*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D014057:Tomography, X-Ray Computed / Q000379:methods*; D016896:Treatment Outcome; D007211:Indoles
D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D003287:Contrast Media; D019786:Gadolinium DTPA; D007472:Iohexol; D011799:Quinazolines; C500926:cediranib; D007211:Indoles