Selection of an early biomarker for vascular normalization using dynamic contrast-enhanced ultrasonography to predict outcomes of metastatic patients treated with bevacizumab

N. Lassau (1, 2) , B. Coiffier (1, 2) , M. Kind (3) , V. Vilgrain (4) , J. Lacroix (5) , M. Cuinet (6) , S. Taieb (7) , R. Aziza (8) , A. Sarran (9) , C. Labbe-Devilliers (10) , B. Gallix (11) , O. Lucidarme (12) , Y. Ptak (13) , L. Rocher (14) , L.M. Caquot (15) , S. Chagnon (16) , D. Marion (17) , A. Luciani (18) , S. Feutray (19) , J. Uzan-Augui (20) , B. Benatsou (1, 2) , J. Bonastre (21, 22) , S. Koscielny (21, 22)

1 Département d'imagerie médicale [Gustave Roussy]
2 IR4M - Imagerie par Résonance Magnétique Médicale et Multi-Modalités
3 Institut Bergonié [Bordeaux]
4 Hôpital Beaujon
5 UNICANCER/CRLC - Centre Régional de Lutte contre le Cancer François Baclesse [Caen]
6 Centre Léon Bérard [Lyon]
7 UNICANCER/Lille - Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille]
8 Institut Claudius Regaud
9 IPC - Institut Paoli-Calmettes
10 CRLCC René Gauducheau
11 CHRU Montpellier - Centre Hospitalier Régional Universitaire [Montpellier]
12 CHU Pitié-Salpêtrière [AP-HP]
13 UNICANCER/CJP - Centre Jean Perrin [Clermont-Ferrand]
14 Hôpital Bicêtre
15 CRLCC Jean Godinot
16 Hôpital Ambroise Paré [AP-HP]
17 HCL - Hospices Civils de Lyon
18 Hôpital Henri Mondor
19 Service de radiologie [Centre Georges-François Leclerc]
20 Hôpital Cochin [AP-HP]
21 SBE - Service de biostatistique et d'épidémiologie
22 CESP - Centre de recherche en épidémiologie et santé des populations

BACKGROUND: Dynamic contrast-enhanced ultrasonography (DCE-US) has been used for evaluation of tumor response to antiangiogenic treatments. The objective of this study was to assess the link between DCE-US data obtained during the first week of treatment and subsequent tumor progression. PATIENTS AND METHODS: Patients treated with antiangiogenic therapies were included in a multicentric prospective study from 2007 to 2010. DCE-US examinations were available at baseline and at day 7. For each examination, a 3 min perfusion curve was recorded just after injection of a contrast agent. Each perfusion curve was modeled with seven parameters. We analyzed the correlation between criteria measured up to day 7 on freedom from progression (FFP). The impact was assessed globally, according to tumor localization and to type of treatment. RESULTS: The median follow-up was 20 months. The mean transit time (MTT) evaluated at day 7 was the only criterion significantly associated with FFP (P = 0.002). The cut-off point maximizing the difference between FFP curves was 12 s. Patients with at least a 12 s MTT had a better FFP. The results according to tumor type were significantly heterogeneous: the impact of MTT on FFP was more marked for breast cancer (P = 0.004) and for colon cancer (P = 0.025) than for other tumor types. Similarly, the differences in FFP according to MTT at day 7 were marked (P = 0.004) in patients receiving bevacizumab. CONCLUSION: The MTT evaluated with DCE-US at day 7 is significantly correlated to FFP of patients treated with bevacizumab. This criterion might be linked to vascular normalization. AFSSAPS NO: 2007-A00399-44.

Mots clés: bevacizumab; breast cancer; colon cancer; dynamic contrast-enhanced ultrasonography (DCE-US); early evaluation; imaging biomarker

Domaines: Cancer

N. Lassau, B. Coiffier, M. Kind, V. Vilgrain, J. Lacroix, et al.. Selection of an early biomarker for vascular normalization using dynamic contrast-enhanced ultrasonography to predict outcomes of metastatic patients treated with bevacizumab. Annals of Oncology, 2016, 27 (10), pp.1922 - 1928. ⟨10.1093/annonc/mdw280⟩. ⟨hal-01830001⟩