title: Prognostic significance of growth kinetics in newly diagnosed glioblastomas revealed by combining serial imaging with a novel biomathematical model.
abstract: Glioblastomas are the most aggressive primary brain tumors, characterized by their rapid proliferation and diffuse infiltration of the brain tissue. Survival patterns in patients with glioblastoma have been associated with a number of clinicopathologic factors including age and neurologic status, yet a significant quantitative link to in vivo growth kinetics of each glioma has remained elusive. Exploiting a recently developed tool for quantifying glioma net proliferation and invasion rates in individual patients using routinely available magnetic resonance images (MRI), we propose to link these patient-specific kinetic rates of biological aggressiveness to prognostic significance. Using our biologically based mathematical model for glioma growth and invasion, examination of serial pretreatment MRIs of 32 glioblastoma patients allowed quantification of these rates for each patient's tumor. Survival analyses revealed that even when controlling for standard clinical parameters (e.g., age and Karnofsky performance status), these model-defined parameters quantifying biological aggressiveness (net proliferation and invasion rates) were significantly associated with prognosis. One hypothesis generated was that the ratio of the actual survival time after whatever therapies were used to the duration of survival predicted (by the model) without any therapy would provide a therapeutic response index (TRI) of the overall effectiveness of the therapies. The TRI may provide important information, not otherwise available, about the effectiveness of the treatments in individual patients. To our knowledge, this is the first report indicating that dynamic insight from routinely obtained pretreatment imaging may be quantitatively useful in characterizing the survival of individual patients with glioblastoma. Such a hybrid tool bridging mathematical modeling and clinical imaging may allow for stratifying patients for clinical studies relative to their pretreatment biological aggressiveness.
authors.affiliation: Department of Pathology, University of Washington, Seattle, Washington 98195, USA.
authors.forename: Christina H
authors.initials: CH
authors.lastname: Wang
authors.forename: Jason K
authors.initials: JK
authors.lastname: Rockhill
authors.forename: Maciej
authors.initials: M
authors.lastname: Mrugala
authors.forename: Danielle L
authors.initials: DL
authors.lastname: Peacock
authors.forename: Albert
authors.initials: A
authors.lastname: Lai
authors.forename: Katy
authors.initials: K
authors.lastname: Jusenius
authors.forename: Joanna M
authors.initials: JM
authors.lastname: Wardlaw
authors.forename: Timothy
authors.initials: T
authors.lastname: Cloughesy
authors.forename: Alexander M
authors.initials: AM
authors.lastname: Spence
authors.forename: Russ
authors.initials: R
authors.lastname: Rockne
authors.forename: Ellsworth C
authors.initials: EC
authors.lastname: Alvord
authors.forename: Kristin R
authors.initials: KR
authors.lastname: Swanson
mesh_terms: D001932:Brain Neoplasms / Q000473:pathology*; D048708:Cell Growth Processes / Q000502:physiology; D005909:Glioblastoma / Q000473:pathology*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008954:Models, Biological; D009361:Neoplasm Invasiveness; D016016:Proportional Hazards Models; D016019:Survival Analysis