title: Effects of anti-angiogenesis on glioblastoma growth and migration: model to clinical predictions.
abstract: Glioblastoma multiforme (GBM) causes significant neurological morbidity and short survival times. Brain invasion by GBM is associated with poor prognosis. Recent clinical trials of bevacizumab in newly-diagnosed GBM found no beneficial effects on overall survival times; however, the baseline health-related quality of life and performance status were maintained longer in the bevacizumab group and the glucocorticoid requirement was lower. Here, we construct a clinical-scale model of GBM whose predictions uncover a new pattern of recurrence in 11/70 bevacizumab-treated patients. The findings support an exception to the Folkman hypothesis: GBM grows in the absence of angiogenesis by a cycle of proliferation and brain invasion that expands necrosis. Furthermore, necrosis is positively correlated with brain invasion in 26 newly-diagnosed GBM. The unintuitive results explain the unusual clinical effects of bevacizumab and suggest new hypotheses on the dynamic clinical effects of migration by active transport, a mechanism of hypoxia-driven brain invasion.
authors.affiliation: Department of Mathematics, The University of Alabama at Birmingham, Birmingham, Alabama, United States of America.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Scribner
authors.affiliation: Department of Mathematics, University of Bordeaux, Talence, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Saut
authors.affiliation: Department of Neurology, The University of Alabama at Birmingham, Birmingham, Alabama, United States of America.
authors.forename: Paula
authors.initials: P
authors.lastname: Province
authors.affiliation: Department of Radiology, The University of Alabama at Birmingham, Birmingham, Alabama, United States of America.
authors.forename: Asim
authors.initials: A
authors.lastname: Bag
authors.affiliation: Department of Mathematics, University of Bordeaux, Talence, France.
authors.forename: Thierry
authors.initials: T
authors.lastname: Colin
authors.affiliation: Department of Mathematics, The University of Alabama at Birmingham, Birmingham, Alabama, United States of America; Department of Neurology, The University of Alabama at Birmingham, Birmingham, Alabama, United States of America.
authors.forename: Hassan M
authors.initials: HM
authors.lastname: Fathallah-Shaykh
mesh_terms: D000328:Adult; D000368:Aged; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000068258:Bevacizumab / Q000009:adverse effects / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000503:physiopathology; D015687:Cell Hypoxia; D005260:Female; D005909:Glioblastoma / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009336:Necrosis / Q000139:chemically induced; D009361:Neoplasm Invasiveness / Q000503:physiopathology; D011788:Quality of Life
chemical_list: D020533:Angiogenesis Inhibitors; D000068258:Bevacizumab