title: CT perfusion as an imaging biomarker in monitoring response to neoadjuvant bevacizumab and radiation in soft-tissue sarcomas: comparison with tumor morphology, circulating and tumor biomarkers, and gene expression.
abstract: OBJECTIVE
  The purpose of this study was to evaluate the role of CT perfusion in monitoring response to neoadjuvant antiangiogenic and radiation therapy in resectable soft-tissue sarcomas and correlate the findings with tumor size, circulating and tumor biomarkers, and gene expression.
  
  
  METHODS
  This phase II clinical trial included 20 patients (13 men and 7 women; mean age, 55 years) with soft-tissue sarcomas who were undergoing treatment with the antiangiogenic drug bevacizumab followed by bevacizumab, radiation, and surgical resection. The patients underwent CT perfusion and diagnostic contrast-enhanced CT at baseline, at 2 weeks after bevacizumab therapy, and after completion of bevacizumab and radiation therapy. Multiple CT perfusion parameters (blood flow, blood volume, mean transit time, and permeability) were correlated with tumor size, circulating and tumor biomarkers, and gene expression.
  
  
  RESULTS
  Two weeks after bevacizumab therapy, there was substantial fall in blood volume (31.9% reduction, p = 0.01) with more pronounced reduction in blood flow, blood volume, and permeability after treatment completion (53-64% reduction in blood flow, blood volume, and permeability; p = 0.001), whereas tumor size showed no significant change (p = 0.34). Tumors with higher baseline blood volume and lower baseline tumor size showed superior response to bevacizumab and radiation (p = 0.05). There was also an increase in median plasma vascular endothelial growth factor and placental-derived growth factor concentration after bevacizumab therapy paralleled by a decrease in tumor perfusion depicted by CT perfusion, although this was not statistically significant (p = 0.4). The baseline tumor microvessel density (MVD) correlated with blood flow (p = 0.04). At least 20 different genes were differentially expressed in tumors with higher and lower baseline perfusion.
  
  
  CONCLUSIONS
  CT perfusion is more sensitive than tumor size for monitoring early and late response to bevacizumab and radiation therapy. CT perfusion parameters correlate with MVD, and the gene expression levels of baseline tumors could potentially predict treatment response.
authors.affiliation: 1 Division of Abdominal Imaging and Intervention, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, White 270, 55 Fruit St, Boston, MA 02114.
authors.forename: Avinash
authors.initials: A
authors.lastname: Kambadakone
authors.forename: Sam S
authors.initials: SS
authors.lastname: Yoon
authors.forename: Tae-Min
authors.initials: TM
authors.lastname: Kim
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Karl
authors.forename: Dan G
authors.initials: DG
authors.lastname: Duda
authors.forename: Thomas F
authors.initials: TF
authors.lastname: DeLaney
authors.forename: Dushyant V
authors.initials: DV
authors.lastname: Sahani
mesh_terms: D000328:Adult; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage*; D000970:Antineoplastic Agents / Q000008:administration & dosage; D000068258:Bevacizumab; D014408:Biomarkers, Tumor / Q000378:metabolism*; D059248:Chemoradiotherapy / Q000379:methods*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009360:Neoplastic Cells, Circulating / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000175:diagnosis / Q000188:drug therapy / Q000378:metabolism; D055420:Perfusion Imaging / Q000379:methods*; D012509:Sarcoma / Q000175:diagnosis* / Q000378:metabolism / Q000628:therapy*; D014057:Tomography, X-Ray Computed / Q000379:methods*; D016896:Treatment Outcome
chemical_list: D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D000068258:Bevacizumab
keywords: CT perfusion; bevacizumab; radiation therapy; soft-tissue sarcoma