title: Reproducibility and changes in the apparent diffusion coefficients of solid tumours treated with combretastatin A4 phosphate and bevacizumab in a two-centre phase I clinical trial.
abstract: The purpose was to determine the reproducibility of apparent diffusion coefficient (ADC) measurements in a two-centre phase I clinical trial; and to track ADC changes in response to the sequential administration of the vascular disrupting agent, combretastatin A4 phosphate (CA4P), and the anti-angiogenic drug, bevacizumab. Sixteen patients with solid tumours received CA4P and bevacizumab treatment. Echo-planar diffusion-weighted MRI was performed using six b values (b = 0-750 s/mm(2)) before (x2), and at 3 and 72 h after a first dose of CA4P. Bevacizumab was given 4 h after a second dose of CA4P, and imaging performed 3 h post CA4P and 72 h after bevacizumab treatment. The coefficient of repeatability (r) of ADC total (all b values), ADC high (b = 100-750) and ADC low (b = 0-100) was calculated by Bland-Altman analysis. The ADC total and ADC high showed good measurement reproducibility (r% = 13.3, 14.1). There was poor reproducibility of the perfusion-sensitive ADC low (r% = 62.5). Significant increases in the median ADC total and ADC high occurred at 3 h after the second dose of CA4P (p < 0.05). ADC measurements were highly reproducible in a two-centre clinical trial setting and appear promising for evaluating the effects of drugs that target tumour vasculature.
authors: Department of Radiology, Royal Marsden Hospital, Downs Road, SM25PT Sutton, UK. dowmukoh@icr.ac.uk
authors: Dow-Mu
authors: DM
authors: Koh
authors: Matthew
authors: M
authors: Blackledge
authors: David J
authors: DJ
authors: Collins
authors: Anwar R
authors: AR
authors: Padhani
authors: Toni
authors: T
authors: Wallace
authors: Benjamin
authors: B
authors: Wilton
authors: N Jane
authors: NJ
authors: Taylor
authors: J James
authors: JJ
authors: Stirling
authors: Rajesh
authors: R
authors: Sinha
authors: Pat
authors: P
authors: Walicke
authors: Martin O
authors: MO
authors: Leach
authors: Ian
authors: I
authors: Judson
authors: Paul
authors: P
authors: Nathan
mesh_terms: D000328:Adult; D000368:Aged; D020533:Angiogenesis Inhibitors / Q000494:pharmacology; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D038524:Diffusion Magnetic Resonance Imaging / Q000379:methods; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D019047:Phantoms, Imaging; D015203:Reproducibility of Results; D013267:Stilbenes / Q000494:pharmacology*; D013997:Time Factors
chemical_list: D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D013267:Stilbenes; D000068258:Bevacizumab; C058728:fosbretabulin