Prognostic significance of growth kinetics in newly diagnosed glioblastomas revealed by combining serial imaging with a novel biomathematical model

Christina H. Wang, Jason K. Rockhill, Maciej Mrugala, Danielle L. Peacock, Albert Lai, Katy Jusenius, Joanna M. Wardlaw, Timothy Cloughesy, Alexander M. Spence, Russ Rockne, Ellsworth C. Alvord, Kristin R. Swanson

Research output: Contribution to journalArticlepeer-review

149 Scopus citations


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 patientspecific 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.

Original languageEnglish (US)
Pages (from-to)9133-9140
Number of pages8
JournalCancer research
Issue number23
StatePublished - Dec 1 2009

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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