title: Computational Trials: Unraveling Motility Phenotypes, Progression Patterns, and Treatment Options for Glioblastoma Multiforme.
abstract: Glioblastoma multiforme is a malignant brain tumor with poor prognosis and high morbidity due to its invasiveness. Hypoxia-driven motility and concentration-driven motility are two mechanisms of glioblastoma multiforme invasion in the brain. The use of anti-angiogenic drugs has uncovered new progression patterns of glioblastoma multiforme associated with significant differences in overall survival. Here, we apply a mathematical model of glioblastoma multiforme growth and invasion in humans and design computational trials using agents that target angiogenesis, tumor replication rates, or motility. The findings link highly-dispersive, moderately-dispersive, and hypoxia-driven tumors to the patterns observed in glioblastoma multiforme treated by anti-angiogenesis, consisting of progression by Expanding FLAIR, Expanding FLAIR + Necrosis, and Expanding Necrosis, respectively. Furthermore, replication rate-reducing strategies (e.g. Tumor Treating Fields) appear to be effective in highly-dispersive and moderately-dispersive tumors but not in hypoxia-driven tumors. The latter may respond to motility-reducing agents. In a population computational trial, with all three phenotypes, a correlation was observed between the efficacy of the rate-reducing agent and the prolongation of overall survival times. This research highlights the potential applications of computational trials and supports new hypotheses on glioblastoma multiforme phenotypes and treatment options.
authors.affiliation: The University of Alabama, Birmingham, Department of Biomedical Engineering, Birmingham, Alabama, United States of America.
authors.forename: Fabio
authors.initials: F
authors.lastname: Raman
authors.affiliation: The University of Alabama, Birmingham, Department of Mathematics, Birmingham, Alabama, United States of America.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Scribner
authors.affiliation: The University of Bordeaux, Department of Mathematics, Talence, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Saut
authors.affiliation: Universidade de Lisboa, Faculdade de Ciências da Universidade de Lisboa, Institute of Biophysics and Biomedical Engineering, Lisboa, Portugal.
authors.forename: Cornelia
authors.initials: C
authors.lastname: Wenger
authors.affiliation: The University of Bordeaux, Department of Mathematics, Talence, France.
authors.forename: Thierry
authors.initials: T
authors.lastname: Colin
authors.affiliation: The University of Alabama, Birmingham, Department of Biomedical Engineering, Birmingham, Alabama, United States of America.|The University of Alabama, Birmingham, Department of Mathematics, Birmingham, Alabama, United States of America.|The University of Alabama, Birmingham, Department of Neurology, Birmingham, Alabama, United States of America.
authors.forename: Hassan M
authors.initials: HM
authors.lastname: Fathallah-Shaykh
mesh_terms: D001932:Brain Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D015687:Cell Hypoxia; D002465:Cell Movement; D049109:Cell Proliferation; D002986:Clinical Trials as Topic; D003198:Computer Simulation; D018450:Disease Progression; D005909:Glioblastoma / Q000188:drug therapy* / Q000473:pathology*; D006801:Humans; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy; D009389:Neovascularization, Pathologic / Q000188:drug therapy; D010641:Phenotype; D012008:Recurrence; D015203:Reproducibility of Results; D016019:Survival Analysis