Effects of Anti-Angiogenesis on Glioblastoma Growth and Migration: Model to Clinical Predictions

Elizabeth Scribner, Olivier Saut, Paula Province, Asim Bag, Thierry Colin and Hassan M Fathallah-Shaykh

PLOS ONE, 2014, vol. 9, issue 12, 1-21

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.

Date: 2014
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Persistent link: https://EconPapers.repec.org/RePEc:plo:pone00:0115018

DOI: 10.1371/journal.pone.0115018

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