title: Perfusion computed tomography as functional biomarker in randomized run-in study of bevacizumab and everolimus in well-differentiated neuroendocrine tumors.
abstract: OBJECTIVE
  This study aimed to assess the antitumor activity of everolimus and bevacizumab among patients with advanced neuroendocrine tumors and to assess perfusion computed tomography (CT) as a potential functional biomarker.
  
  
  METHODS
  Patients with low- to intermediate-grade neuroendocrine tumors received one 3-week cycle of 15 mg/kg of bevacizumab on day 1 or 10 mg of everolimus daily. Subsequent cycles consisted of the combination of both drugs. Perfusion CTs were performed at baseline and at the end of cycles 1 and 3.
  
  
  RESULTS
  Therapy decreased blood flow (BF) proportional to baseline measurements. Bevacizumab was associated with a 44% decrease in BF (P < 0.0001). After the addition of everolimus, a further 29% decrease (P = 0.02) in BF was observed. Everolimus alone was associated with 13% increase in mean transit time (P = 0.02). Clinical activity was demonstrated, with a confirmed response rate of 21% and a median progression-free survival of 14.6 (95% confidence interval, 13.0-16.1) months. Pretreatment tumor permeability surface (P = 0.009), posttreatment mean transit time (P = 0.003), percent reduction in BF (P = 0.03), and percent reduction in blood volume (P = 0.002) were associated with best percent reduction in tumor diameters.
  
  
  CONCLUSIONS
  Bevacizumab and everolimus demonstrated antitumor activity. Perfusion CT is a promising tool for the development of antiangiogenic strategies and for the selection of patients who are likely to benefit from therapy.
authors.affiliation: From the Departments of *Gastrointestinal Medical Oncology, †Biostatistics, and ‡Diagnostic Radiology, The University of Texas MD Anderson Cancer Center, Houston, TX.
authors.forename: James C
authors.initials: JC
authors.lastname: Yao
authors.forename: Alexandria T
authors.initials: AT
authors.lastname: Phan
authors.forename: Kenneth
authors.initials: K
authors.lastname: Hess
authors.forename: David
authors.initials: D
authors.lastname: Fogelman
authors.forename: Carmen
authors.initials: C
authors.lastname: Jacobs
authors.forename: Cecile
authors.initials: C
authors.lastname: Dagohoy
authors.forename: Colleen
authors.initials: C
authors.lastname: Leary
authors.forename: Keping
authors.initials: K
authors.lastname: Xie
authors.forename: Chaan S
authors.initials: CS
authors.lastname: Ng
mesh_terms: D000328:Adult; D000368:Aged; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D000068258:Bevacizumab / Q000008:administration & dosage; D001783:Blood Flow Velocity / Q000187:drug effects; D002454:Cell Differentiation; D018450:Disease Progression; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D000068338:Everolimus / Q000008:administration & dosage; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D061330:Multidetector Computed Tomography; D018358:Neuroendocrine Tumors / Q000098:blood supply / Q000000981:diagnostic imaging* / Q000188:drug therapy* / Q000473:pathology; D055420:Perfusion Imaging / Q000379:methods*; D011237:Predictive Value of Tests; D013781:Texas; D013997:Time Factors; D016896:Treatment Outcome; D047368:Tumor Burden
chemical_list: D020533:Angiogenesis Inhibitors; D000068258:Bevacizumab; D000068338:Everolimus