title: Vascular biomarkers derived from dynamic contrast-enhanced MRI predict response of vestibular schwannoma to antiangiogenic therapy in type 2 neurofibromatosis.
abstract: BACKGROUND
  Antiangiogenic therapy of vestibular schwannoma (VS) in type 2 neurofibromatosis can produce tumor shrinkage with response rates of 40%-60%. This study examines the predictive value of parameter-derived MRI in this setting.
  
  
  METHODS
  Twelve patients with 20 VSs were recruited. Each had at least one rapidly growing tumor. Patients were treated with bevacizumab, 5 mg/kg every 2 weeks. Patients with stable or reduced VS volume were maintained at 2.5-5 mg every 4 weeks after 6 months. Those who failed treatment had their bevacizumab discontinued. Dynamic contrast-enhanced (DCE) MRI performed prior to treatment using a high temporal resolution technique, and data were analyzed to allow measurement of contrast transfer coefficient (K(trans)), vascular fraction (v(p)), extravascular-extracellular fraction (v(e)). Relaxation rate (R1(N)) was measured using a variable flip angle technique. Apparent diffusional coefficient (ADC) was calculated from diffusion-weighted imaging. The predictive power of microvascular parameters and ADC were examined using logistic regression modeling.
  
  
  RESULTS
  Responding tumors were larger (P < .001), had lower R1(N) (P < .001), and higher K(trans) (P < .05) and ADC (P < .01). They showed increases in R1(N) (P < .01) and reduction of K(trans) (P < .01) and ADC (P < .01). Modeling to predict response demonstrated significant independent predictive power for R1(N) (Β = - 0.327, P < .001), and K(trans) (Β = 0.156, P < .05). Modeling to predict percentage change in tumor volume at 90 days identified baseline tumor volume (Β = 5.503, P < .05), R1(N) (Β = - 5.844, P < .05), and K(trans) (Β = 5.622, P < .05) as independent significant predictors.
  
  
  CONCLUSIONS
  In patients with type 2 neurofibromatosis, biomarkers from DCE-MRI are predictive of VS volume response to inhibition of vascular endothelial growth factor inhibition.
authors: Wolfson Molecular Imaging Centre, The University of Manchester, Manchester, UK (K.-L.L., I.D., X.Z., S.Z., A.J.); Institute of Population Health, The University of Manchester, Manchester, UK (K.-L.L., I.D., A.J.); Genomic Medicine, The University of Manchester, Manchester Academic Health Science Centre, Institute of Human Development, Central Manchester NHS Foundation Trust, Manchester Royal Infirmary, Manchester, UK (S.L., D.G.E.); Centre for Paediatric, Adolescent and Young Adult Cancer, Institute of Cancer Sciences, The University of Manchester, UK (M.M.); The Christie NHS Foundation Trust, Manchester, UK (C.M.).
authors: Ka-Loh
authors: KL
authors: Li
authors: Wolfson Molecular Imaging Centre, The University of Manchester, Manchester, UK (K.-L.L., I.D., X.Z., S.Z., A.J.); Institute of Population Health, The University of Manchester, Manchester, UK (K.-L.L., I.D., A.J.); Genomic Medicine, The University of Manchester, Manchester Academic Health Science Centre, Institute of Human Development, Central Manchester NHS Foundation Trust, Manchester Royal Infirmary, Manchester, UK (S.L., D.G.E.); Centre for Paediatric, Adolescent and Young Adult Cancer, Institute of Cancer Sciences, The University of Manchester, UK (M.M.); The Christie NHS Foundation Trust, Manchester, UK (C.M.).
authors: Ibrahim
authors: I
authors: Djoukhadar
authors: Wolfson Molecular Imaging Centre, The University of Manchester, Manchester, UK (K.-L.L., I.D., X.Z., S.Z., A.J.); Institute of Population Health, The University of Manchester, Manchester, UK (K.-L.L., I.D., A.J.); Genomic Medicine, The University of Manchester, Manchester Academic Health Science Centre, Institute of Human Development, Central Manchester NHS Foundation Trust, Manchester Royal Infirmary, Manchester, UK (S.L., D.G.E.); Centre for Paediatric, Adolescent and Young Adult Cancer, Institute of Cancer Sciences, The University of Manchester, UK (M.M.); The Christie NHS Foundation Trust, Manchester, UK (C.M.).
authors: Xiaoping
authors: X
authors: Zhu
authors: Wolfson Molecular Imaging Centre, The University of Manchester, Manchester, UK (K.-L.L., I.D., X.Z., S.Z., A.J.); Institute of Population Health, The University of Manchester, Manchester, UK (K.-L.L., I.D., A.J.); Genomic Medicine, The University of Manchester, Manchester Academic Health Science Centre, Institute of Human Development, Central Manchester NHS Foundation Trust, Manchester Royal Infirmary, Manchester, UK (S.L., D.G.E.); Centre for Paediatric, Adolescent and Young Adult Cancer, Institute of Cancer Sciences, The University of Manchester, UK (M.M.); The Christie NHS Foundation Trust, Manchester, UK (C.M.).
authors: Sha
authors: S
authors: Zhao
authors: Wolfson Molecular Imaging Centre, The University of Manchester, Manchester, UK (K.-L.L., I.D., X.Z., S.Z., A.J.); Institute of Population Health, The University of Manchester, Manchester, UK (K.-L.L., I.D., A.J.); Genomic Medicine, The University of Manchester, Manchester Academic Health Science Centre, Institute of Human Development, Central Manchester NHS Foundation Trust, Manchester Royal Infirmary, Manchester, UK (S.L., D.G.E.); Centre for Paediatric, Adolescent and Young Adult Cancer, Institute of Cancer Sciences, The University of Manchester, UK (M.M.); The Christie NHS Foundation Trust, Manchester, UK (C.M.).
authors: Simon
authors: S
authors: Lloyd
authors: Wolfson Molecular Imaging Centre, The University of Manchester, Manchester, UK (K.-L.L., I.D., X.Z., S.Z., A.J.); Institute of Population Health, The University of Manchester, Manchester, UK (K.-L.L., I.D., A.J.); Genomic Medicine, The University of Manchester, Manchester Academic Health Science Centre, Institute of Human Development, Central Manchester NHS Foundation Trust, Manchester Royal Infirmary, Manchester, UK (S.L., D.G.E.); Centre for Paediatric, Adolescent and Young Adult Cancer, Institute of Cancer Sciences, The University of Manchester, UK (M.M.); The Christie NHS Foundation Trust, Manchester, UK (C.M.).
authors: Martin
authors: M
authors: McCabe
authors: Wolfson Molecular Imaging Centre, The University of Manchester, Manchester, UK (K.-L.L., I.D., X.Z., S.Z., A.J.); Institute of Population Health, The University of Manchester, Manchester, UK (K.-L.L., I.D., A.J.); Genomic Medicine, The University of Manchester, Manchester Academic Health Science Centre, Institute of Human Development, Central Manchester NHS Foundation Trust, Manchester Royal Infirmary, Manchester, UK (S.L., D.G.E.); Centre for Paediatric, Adolescent and Young Adult Cancer, Institute of Cancer Sciences, The University of Manchester, UK (M.M.); The Christie NHS Foundation Trust, Manchester, UK (C.M.).
authors: Catherine
authors: C
authors: McBain
authors: Wolfson Molecular Imaging Centre, The University of Manchester, Manchester, UK (K.-L.L., I.D., X.Z., S.Z., A.J.); Institute of Population Health, The University of Manchester, Manchester, UK (K.-L.L., I.D., A.J.); Genomic Medicine, The University of Manchester, Manchester Academic Health Science Centre, Institute of Human Development, Central Manchester NHS Foundation Trust, Manchester Royal Infirmary, Manchester, UK (S.L., D.G.E.); Centre for Paediatric, Adolescent and Young Adult Cancer, Institute of Cancer Sciences, The University of Manchester, UK (M.M.); The Christie NHS Foundation Trust, Manchester, UK (C.M.).
authors: D Gareth
authors: DG
authors: Evans
authors: Wolfson Molecular Imaging Centre, The University of Manchester, Manchester, UK (K.-L.L., I.D., X.Z., S.Z., A.J.); Institute of Population Health, The University of Manchester, Manchester, UK (K.-L.L., I.D., A.J.); Genomic Medicine, The University of Manchester, Manchester Academic Health Science Centre, Institute of Human Development, Central Manchester NHS Foundation Trust, Manchester Royal Infirmary, Manchester, UK (S.L., D.G.E.); Centre for Paediatric, Adolescent and Young Adult Cancer, Institute of Cancer Sciences, The University of Manchester, UK (M.M.); The Christie NHS Foundation Trust, Manchester, UK (C.M.).
authors: Alan
authors: A
authors: Jackson
mesh_terms: D000293:Adolescent; D000328:Adult; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000068258:Bevacizumab / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D003287:Contrast Media; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D016518:Neurofibromatosis 2 / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D009464:Neuroma, Acoustic / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D011379:Prognosis; D015996:Survival Rate; D047368:Tumor Burden; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D055815:Young Adult
chemical_list: D020533:Angiogenesis Inhibitors; D014408:Biomarkers, Tumor; D003287:Contrast Media; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab
keywords: DCE-MRI; bevacizumab; neurofibromatosis type 2; prediction; treatment response