title: Evaluation of the functional diffusion map as an early biomarker of time-to-progression and overall survival in high-grade glioma.
abstract: Diffuse malignant gliomas, the most common type of brain tumor, carry a dire prognosis and are poorly responsive to initial treatment. The response to treatment is typically evaluated by measurements obtained from radiographic images several months after the start of treatment; therefore, an early biomarker of tumor response would be useful for making early treatment decisions and for prognostic information. Thirty-four patients with malignant glioma were examined by diffusion MRI before treatment and 3 weeks later. These images were coregistered, and differences in tumor-water diffusion values were calculated as functional diffusion maps (fDM), which were correlated with the radiographic response, time-to-progression (TTP), and overall survival (OS). Changes in fDM at 3 weeks were closely associated with the radiographic response at 10 weeks. The percentage of the tumor undergoing a significant change in the diffusion of water (V(T)) was different between patients with progressive disease (PD) vs. stable disease (SD) (P < 0.001). Patients classified as PD by fDM analysis at 3 weeks were found to have a shorter TTP compared with SD (median TTP, 4.3 vs. 7.3 months; P < 0.04). By using fDM, early patient stratification also was correlated with shorter OS in the PD group compared with SD patients (median survival, 8.0 vs. 18.2 months; P < 0.01). On the basis of fDM, tumor assessment provided an early biomarker for response, TTP, and OS in patients with malignant glioma. Further evaluation of this technique is warranted to determine whether it may be useful in the individualization of treatment or evaluation of the response in clinical protocols.
authors.affiliation: Department of Radiation Oncology, University of Michigan Medical School, Ann Arbor, MI 48109-0648, USA.
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Hamstra
authors.forename: Thomas L
authors.initials: TL
authors.lastname: Chenevert
authors.forename: Bradford A
authors.initials: BA
authors.lastname: Moffat
authors.forename: Timothy D
authors.initials: TD
authors.lastname: Johnson
authors.forename: Charles R
authors.initials: CR
authors.lastname: Meyer
authors.forename: Suresh K
authors.initials: SK
authors.lastname: Mukherji
authors.forename: Douglas J
authors.initials: DJ
authors.lastname: Quint
authors.forename: Stephen S
authors.initials: SS
authors.lastname: Gebarski
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Fan
authors.forename: Christina I
authors.initials: CI
authors.lastname: Tsien
authors.forename: Theodore S
authors.initials: TS
authors.lastname: Lawrence
authors.forename: Larry
authors.initials: L
authors.lastname: Junck
authors.forename: Alnawaz
authors.initials: A
authors.lastname: Rehemtulla
authors.forename: Brian D
authors.initials: BD
authors.lastname: Ross
mesh_terms: D000328:Adult; D000368:Aged; D001932:Brain Neoplasms / Q000473:pathology*; D018450:Disease Progression; D005260:Female; D005910:Glioma / Q000473:pathology*; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008875:Middle Aged; D016019:Survival Analysis