title: Patient-specific metrics of invasiveness reveal significant prognostic benefit of resection in a predictable subset of gliomas.
abstract: OBJECTIVE
  Malignant gliomas are incurable, primary brain neoplasms noted for their potential to extensively invade brain parenchyma. Current methods of clinical imaging do not elucidate the full extent of brain invasion, making it difficult to predict which, if any, patients are likely to benefit from gross total resection. Our goal was to apply a mathematical modeling approach to estimate the overall tumor invasiveness on a patient-by-patient basis and determine whether gross total resection would improve survival in patients with relatively less invasive gliomas.
  
  
  METHODS
  In 243 patients presenting with contrast-enhancing gliomas, estimates of the relative invasiveness of each patient's tumor, in terms of the ratio of net proliferation rate of the glioma cells to their net dispersal rate, were derived by applying a patient-specific mathematical model to routine pretreatment MR imaging. The effect of varying degrees of extent of resection on overall survival was assessed for cohorts of patients grouped by tumor invasiveness.
  
  
  RESULTS
  We demonstrate that patients with more diffuse tumors showed no survival benefit (P = 0.532) from gross total resection over subtotal/biopsy, while those with nodular (less diffuse) tumors showed a significant benefit (P = 0.00142) with a striking median survival benefit of over eight months compared to sub-totally resected tumors in the same cohort (an 80% improvement in survival time for GTR only seen for nodular tumors).
  
  
  CONCLUSIONS
  These results suggest that our patient-specific, model-based estimates of tumor invasiveness have clinical utility in surgical decision making. Quantification of relative invasiveness assessed from routinely obtained pre-operative imaging provides a practical predictor of the benefit of gross total resection.
authors.affiliation: Department of Neurological Surgery, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States of America.
authors.forename: Anne L
authors.initials: AL
authors.lastname: Baldock
authors.affiliation: Department of Pathology, University of Washington, Seattle, Washington, United States of America.
authors.forename: Sunyoung
authors.initials: S
authors.lastname: Ahn
authors.affiliation: Department of Neurological Surgery, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States of America.
authors.forename: Russell
authors.initials: R
authors.lastname: Rockne
authors.affiliation: Department of Pathology, University of Washington, Seattle, Washington, United States of America.
authors.forename: Sandra
authors.initials: S
authors.lastname: Johnston
authors.affiliation: Department of Pathology, University of Washington, Seattle, Washington, United States of America.
authors.forename: Maxwell
authors.initials: M
authors.lastname: Neal
authors.affiliation: Department of Neurological Surgery, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States of America.
authors.forename: David
authors.initials: D
authors.lastname: Corwin
authors.affiliation: Department of Neurological Surgery, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States of America.
authors.forename: Kamala
authors.initials: K
authors.lastname: Clark-Swanson
authors.affiliation: Department of Pathology, University of Washington, Seattle, Washington, United States of America.
authors.forename: Greg
authors.initials: G
authors.lastname: Sterin
authors.affiliation: Radiation Oncology, University of Washington, Seattle, Washington, United States of America.
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Trister
authors.affiliation: Department of Neurosurgery, Columbia University, New York, New York, United States of America.
authors.forename: Hani
authors.initials: H
authors.lastname: Malone
authors.affiliation: Department of Neurosurgery, Columbia University, New York, New York, United States of America.
authors.forename: Victoria
authors.initials: V
authors.lastname: Ebiana
authors.affiliation: Department of Neurosurgery, Columbia University, New York, New York, United States of America.
authors.forename: Adam M
authors.initials: AM
authors.lastname: Sonabend
authors.affiliation: Department of Neurology, University of Washington, Seattle, Washington, United States of America.
authors.forename: Maciej
authors.initials: M
authors.lastname: Mrugala
authors.affiliation: Radiation Oncology, University of Washington, Seattle, Washington, United States of America.
authors.forename: Jason K
authors.initials: JK
authors.lastname: Rockhill
authors.affiliation: Department of Neurology, University of Washington, Seattle, Washington, United States of America; Department of Neurological Surgery, University of Washington, Seattle, Washington, United States of America.
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Silbergeld
authors.affiliation: Department of Neurology, University of California Los Angeles, Los Angeles, California, United States of America.
authors.forename: Albert
authors.initials: A
authors.lastname: Lai
authors.affiliation: Department of Neurology, University of California Los Angeles, Los Angeles, California, United States of America.
authors.forename: Timothy
authors.initials: T
authors.lastname: Cloughesy
authors.affiliation: Department of Neurosurgery, Columbia University, New York, New York, United States of America.
authors.forename: Guy M
authors.initials: GM
authors.lastname: McKhann
authors.affiliation: Department of Neurosurgery, Columbia University, New York, New York, United States of America.
authors.forename: Jeffrey N
authors.initials: JN
authors.lastname: Bruce
authors.affiliation: Department of Neurological Surgery, University of Washington, Seattle, Washington, United States of America.
authors.forename: Robert C
authors.initials: RC
authors.lastname: Rostomily
authors.affiliation: Department of Pathology and Cell Biology, Columbia University, New York, New York, United States of America.
authors.forename: Peter
authors.initials: P
authors.lastname: Canoll
authors.affiliation: Department of Neurological Surgery, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States of America; Nancy and Buster Alvord Brain Tumor Center, University of Washington, Seattle, Washington, United States of America; Northwestern Brain Tumor Institute, Robert H. Lurie Comprehensive Cancer Center, Chicago, Illinois, United States of America.
authors.forename: Kristin R
authors.initials: KR
authors.lastname: Swanson
mesh_terms: D000328:Adult; D000368:Aged; D001706:Biopsy; D001921:Brain / Q000473:pathology; D001932:Brain Neoplasms / Q000175:diagnosis / Q000473:pathology*; D049109:Cell Proliferation; D015331:Cohort Studies; D003287:Contrast Media / Q000737:chemistry; D018450:Disease Progression; D005260:Female; D005909:Glioblastoma / Q000175:diagnosis / Q000473:pathology*; D005910:Glioma / Q000175:diagnosis / Q000473:pathology*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D008962:Models, Theoretical; D009361:Neoplasm Invasiveness; D011379:Prognosis
chemical_list: D003287:Contrast Media