title: Toward patient-specific, biologically optimized radiation therapy plans for the treatment of glioblastoma.
abstract: OBJECTIVE
  To demonstrate a method of generating patient-specific, biologically-guided radiotherapy dose plans and compare them to the standard-of-care protocol.
  
  
  METHODS
  We integrated a patient-specific biomathematical model of glioma proliferation, invasion and radiotherapy with a multiobjective evolutionary algorithm for intensity-modulated radiation therapy optimization to construct individualized, biologically-guided plans for 11 glioblastoma patients. Patient-individualized, spherically-symmetric simulations of the standard-of-care and optimized plans were compared in terms of several biological metrics.
  
  
  RESULTS
  The integrated model generated spatially non-uniform doses that, when compared to the standard-of-care protocol, resulted in a 67% to 93% decrease in equivalent uniform dose to normal tissue, while the therapeutic ratio, the ratio of tumor equivalent uniform dose to that of normal tissue, increased between 50% to 265%. Applying a novel metric of treatment response (Days Gained) to the patient-individualized simulation results predicted that the optimized plans would have a significant impact on delaying tumor progression, with increases from 21% to 105% for 9 of 11 patients.
  
  
  CONCLUSIONS
  Patient-individualized simulations using the combination of a biomathematical model with an optimization algorithm for radiation therapy generated biologically-guided doses that decreased normal tissue EUD and increased therapeutic ratio with the potential to improve survival outcomes for treatment of glioblastoma.
authors.affiliation: Department of Neurological Surgery, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, United States of America.
authors.forename: David
authors.initials: D
authors.lastname: Corwin
authors.forename: Clay
authors.initials: C
authors.lastname: Holdsworth
authors.forename: Russell C
authors.initials: RC
authors.lastname: Rockne
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Trister
authors.forename: Maciej M
authors.initials: MM
authors.lastname: Mrugala
authors.forename: Jason K
authors.initials: JK
authors.lastname: Rockhill
authors.forename: Robert D
authors.initials: RD
authors.lastname: Stewart
authors.forename: Mark
authors.initials: M
authors.lastname: Phillips
authors.forename: Kristin R
authors.initials: KR
authors.lastname: Swanson
mesh_terms: D000328:Adult; D000368:Aged; D049109:Cell Proliferation / Q000528:radiation effects; D015331:Cohort Studies; D005260:Female; D005909:Glioblastoma / Q000175:diagnosis / Q000473:pathology / Q000532:radiotherapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D009361:Neoplasm Invasiveness; D057285:Precision Medicine / Q000379:methods*; D011379:Prognosis; D011879:Radiotherapy Dosage; D011880:Radiotherapy Planning, Computer-Assisted / Q000379:methods*; D050397:Radiotherapy, Intensity-Modulated / Q000379:methods*; D016896:Treatment Outcome