Effects of Anti-Angiogenesis on Glioblastoma Growth and Migration: Model to Clinical Predictions |
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| Authors: | Elizabeth Scribner Olivier Saut Paula Province Asim Bag Thierry Colin Hassan M Fathallah-Shaykh |
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| Institution: | 1. Department of Mathematics, The University of Alabama at Birmingham, Birmingham, Alabama, United States of America.; 2. Department of Mathematics, University of Bordeaux, Talence, France.; 3. Department of Neurology, The University of Alabama at Birmingham, Birmingham, Alabama, United States of America.; 4. Department of Radiology, The University of Alabama at Birmingham, Birmingham, Alabama, United States of America.; University of Michigan School of Medicine, United States of America, |
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| 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. |
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