Discriminating survival outcomes in patients with glioblastoma using a simulation-based, patient-specific response metric.
Accurate clinical assessment of a patient's response to treatment for glioblastoma multiforme (GBM), the most malignant type of primary brain tumor, is undermined by the wide patient-to-patient variability in GBM dynamics and responsiveness to therapy. Using computational models that account for the unique geometry and kinetics of individual patients' tumors, we developed a method for assessing treatment response that discriminates progression-free and overall survival following therapy for GBM. Applying these models as untreated virtual controls, we generate a patient-specific "Days Gained" response metric that estimates the number of days a therapy delayed imageable tumor progression. We assessed treatment response in terms of Days Gained scores for 33 patients at the time of their first MRI scan following first-line radiation therapy. Based on Kaplan-Meier analyses, patients with Days Gained scores of 100 or more had improved progression-free survival, and patients with scores of 117 or more had improved overall survival. Our results demonstrate that the Days Gained response metric calculated at the routinely acquired first post-radiation treatment time point provides prognostic information regarding progression and survival outcomes. Applied prospectively, our model-based approach has the potential to improve GBM treatment by accounting for patient-to-patient heterogeneity in GBM dynamics and responses to therapy.
Department of Pathology, University of Washington, Seattle, Washington, United States of America. mneal@uw.edu
Maxwell Lewis
ML
Neal
Andrew D
AD
Trister
Tyler
T
Cloke
Rita
R
Sodt
Sunyoung
S
Ahn
Anne L
AL
Baldock
Carly A
CA
Bridge
Albert
A
Lai
Timothy F
TF
Cloughesy
Maciej M
MM
Mrugala
Jason K
JK
Rockhill
Russell C
RC
Rockne
Kristin R
KR
Swanson
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001932:Brain Neoplasms / Q000175:diagnosis* / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy; D003198:Computer Simulation; D018450:Disease Progression; D005720:Gamma Rays; D005909:Glioblastoma / Q000175:diagnosis* / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy; D006801:Humans; D016013:Likelihood Functions; D008279:Magnetic Resonance Imaging; D008875:Middle Aged; D057285:Precision Medicine / Q000379:methods*; D011379:Prognosis; D016019:Survival Analysis