title: Functional diffusion maps (fDMs) evaluated before and after radiochemotherapy predict progression-free and overall survival in newly diagnosed glioblastoma.
abstract: Functional diffusion mapping (fDM) has shown promise as a sensitive imaging biomarker for predicting survival in initial studies consisting of a small number of patients, mixed tumor grades, and before routine use of anti-angiogenic therapy. The current study tested whether fDM performed before and after radiochemotherapy could predict progression-free and overall survival in 143 patients with newly diagnosed glioblastoma from 2007 through 2010, many treated with anti-angiogenic therapy after recurrence. Diffusion and conventional MRI scans were obtained before and 4 weeks after completion of radiotherapy and concurrent temozolomide treatment. FDM was created by coregistering pre- and posttreatment apparent diffusion coefficient (ADC) maps and then performing voxel-wise subtraction. FDMs were categorized according to the degree of change in ADC in pre- and posttreatment fluid-attenuated inversion recovery (FLAIR) and contrast-enhancing regions. The volume fraction of fDM-classified increasing ADC(+), decreasing ADC(-), and change in ADC(+/-) were tested to determine whether they were predictive of survival. Both Bonferroni-corrected univariate log-rank analysis and Cox proportional hazards modeling demonstrated that patients with decreasing ADC in a large volume fraction of pretreatment FLAIR or contrast-enhancing regions were statistically more likely to progress earlier and expire sooner than in patients with a lower volume fraction. The current study supports the hypothesis that fDM is a sensitive imaging biomarker for predicting survival in glioblastoma.
authors.affiliation: Department of Radiological Sciences, David Geffen School of Medicine, University of California Los Angeles, 924 Westwood Blvd, Suite 615, Los Angeles, CA 90024, USA. bellingson@mednet.ucla.edu
authors.forename: Benjamin M
authors.initials: BM
authors.lastname: Ellingson
authors.forename: Timothy F
authors.initials: TF
authors.lastname: Cloughesy
authors.forename: Taryar
authors.initials: T
authors.lastname: Zaw
authors.forename: Albert
authors.initials: A
authors.lastname: Lai
authors.forename: Phioanh L
authors.initials: PL
authors.lastname: Nghiemphu
authors.forename: Robert
authors.initials: R
authors.lastname: Harris
authors.forename: Shadi
authors.initials: S
authors.lastname: Lalezari
authors.forename: Naveed
authors.initials: N
authors.lastname: Wagle
authors.forename: Kourosh M
authors.initials: KM
authors.lastname: Naeini
authors.forename: Jose
authors.initials: J
authors.lastname: Carrillo
authors.forename: Linda M
authors.initials: LM
authors.lastname: Liau
authors.forename: Whitney B
authors.initials: WB
authors.lastname: Pope
mesh_terms: D000368:Aged; D001932:Brain Neoplasms / Q000175:diagnosis / Q000401:mortality* / Q000628:therapy*; D059248:Chemoradiotherapy; D038524:Diffusion Magnetic Resonance Imaging; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D005909:Glioblastoma / Q000175:diagnosis / Q000401:mortality* / Q000628:therapy*; D006801:Humans; D007090:Image Interpretation, Computer-Assisted; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D016896:Treatment Outcome