title: Validation of dynamic contrast-enhanced ultrasound in predicting outcomes of antiangiogenic therapy for solid tumors: the French multicenter support for innovative and expensive techniques study.
abstract: OBJECTIVE
  Dynamic contrast-enhanced ultrasound (DCE-US) has been used in single-center studies to evaluate tumor response to antiangiogenic treatments: the change of area under the perfusion curve (AUC), a criterion linked to blood volume, was consistently correlated with the Response Evaluation Criteria in Solid Tumors response. The main objective here was to do a multicentric validation of the use of DCE-US to evaluate tumor response in different solid tumor types treated by several antiangiogenic agents. A secondary objective was to evaluate the costs of the procedure.
  
  
  METHODS
  This prospective study included patients from 2007 to 2010 in 19 centers (8 teaching hospitals and 11 comprehensive cancer centers). All patients treated with antiangiogenic therapy were eligible. Dynamic contrast-enhanced ultrasound examinations were performed at baseline as well as on days 7, 15, 30, and 60. For each examination, a perfusion curve was recorded during 3 minutes after injection of a contrast agent. Change from baseline at each time point was estimated for each of 7 fitted criteria. The main end point was freedom from progression (FFP). Criterion/time-point combinations with the strongest correlation with FFP were analyzed further to estimate an optimal cutoff point.
  
  
  RESULTS
  A total of 1968 DCE-US examinations in 539 patients were analyzed. The median follow-up was 1.65 years. Variations from baseline were significant at day 30 for several criteria, with AUC having the most significant association with FFP (P = 0.00002). Patients with a greater than 40% decrease in AUC at day 30 had better FFP (P = 0.005) and overall survival (P = 0.05). The mean cost of each DCE-US was 180&OV0556;, which corresponds to $250 using the current exchange rate.
  
  
  CONCLUSIONS
  Dynamic contrast-enhanced ultrasound is a new functional imaging technique that provides a validated criterion, namely, the change of AUC from baseline to day 30, which is predictive of tumor progression in a large multicenter cohort. Because of its low cost, it should be considered in the routine evaluation of solid tumors treated with antiangiogenic therapy.
authors.affiliation: From the *Integrated Research Cancer Institute, Research Department, Villejuif; †Service Biostatistique et Épidémiologie, Gustave Roussy, Villejuif; ‡Imaging Department, Institut Bergonié, Bordeaux; §Department of Radiology, Assistance Publique-Hôpitaux de Paris, Hôpital Beaujon, Clichy, and Université Paris Diderot, Sorbonne Paris Cité; ∥Department of Radiology, Centre François Baclesse, Caen; ¶Department of Radiology, Centre Léon Bérard, Lyon; #Imaging Department, Centre Oscar Lambret, Lille; **Radiodiagnostics Department, Centre Claudius Regaud, Toulouse; ††Imaging Department, Institut Paoli Calmettes, Marseille; ‡‡Radiodiagnostics Department, Centre R Gauducheau, Institut de Cancérologie de l'Ouest Nantes; §§Department of Abdominal and Digestive Imaging, Hôpital Saint-Éloi, Montpellier; ∥∥Radiology Department, Centre Hospitalier Universitaire La Pitié-Salpêtrière, Paris; ¶¶Radiodiagnostics Department, Centre Jean Perrin, Clermont-Ferrand; ##Radiology Department, Centre Hospitalier Universitaire Bicêtre, Le Kremlin-Bicêtre; ***Radiodiagnostics and Imaging Department, Institut Jean Godinot, Reims; †††Ultrasonography Department, Hôpital Ambroise Paré, Boulogne-Billancourt; ‡‡‡Radiology Department, Centre Hospitalier Universitaire Hôtel-Dieu, Lyon; §§§Radiology Department, Centre Hospitalier Universitaire Henri Mondor, Créteil; ∥∥∥Imaging Department, Centre Georges-François Leclerc, Dijon Cedex; and ¶¶¶Radiology Department, Hôpital Cochin, Paris, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Lassau
authors.forename: Julia
authors.initials: J
authors.lastname: Bonastre
authors.forename: Michèle
authors.initials: M
authors.lastname: Kind
authors.forename: Valérie
authors.initials: V
authors.lastname: Vilgrain
authors.forename: Joëlle
authors.initials: J
authors.lastname: Lacroix
authors.forename: Marie
authors.initials: M
authors.lastname: Cuinet
authors.forename: Sophie
authors.initials: S
authors.lastname: Taieb
authors.forename: Richard
authors.initials: R
authors.lastname: Aziza
authors.forename: Antony
authors.initials: A
authors.lastname: Sarran
authors.forename: Catherine
authors.initials: C
authors.lastname: Labbe-Devilliers
authors.forename: Benoit
authors.initials: B
authors.lastname: Gallix
authors.forename: Olivier
authors.initials: O
authors.lastname: Lucidarme
authors.forename: Yvette
authors.initials: Y
authors.lastname: Ptak
authors.forename: Laurence
authors.initials: L
authors.lastname: Rocher
authors.forename: Louis-Michel
authors.initials: LM
authors.lastname: Caquot
authors.forename: Sophie
authors.initials: S
authors.lastname: Chagnon
authors.forename: Denis
authors.initials: D
authors.lastname: Marion
authors.forename: Alain
authors.initials: A
authors.lastname: Luciani
authors.forename: Sylvaine
authors.initials: S
authors.lastname: Feutray
authors.forename: Joëlle
authors.initials: J
authors.lastname: Uzan-Augui
authors.forename: Benedicte
authors.initials: B
authors.lastname: Coiffier
authors.forename: Baya
authors.initials: B
authors.lastname: Benastou
authors.forename: Serge
authors.initials: S
authors.lastname: Koscielny
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D020533:Angiogenesis Inhibitors / Q000191:economics / Q000627:therapeutic use*; D003287:Contrast Media / Q000191:economics; D005260:Female; D005500:Follow-Up Studies; D005602:France; D006801:Humans; D007089:Image Enhancement / Q000379:methods*; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000000981:diagnostic imaging* / Q000188:drug therapy* / Q000191:economics; D010743:Phospholipids / Q000191:economics; D011446:Prospective Studies; D015203:Reproducibility of Results; D013459:Sulfur Hexafluoride / Q000191:economics; D016019:Survival Analysis; D016896:Treatment Outcome; D014463:Ultrasonography; D055815:Young Adult
chemical_list: D020533:Angiogenesis Inhibitors; D003287:Contrast Media; D010743:Phospholipids; C420843:contrast agent BR1; D013459:Sulfur Hexafluoride