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. 2012 Mar;14(3):333-43.
doi: 10.1093/neuonc/nor220. Epub 2012 Jan 22.

Functional diffusion maps (fDMs) evaluated before and after radiochemotherapy predict progression-free and overall survival in newly diagnosed glioblastoma

Benjamin M Ellingson  1 , Timothy F Cloughesy, Taryar Zaw, Albert Lai, Phioanh L Nghiemphu, Robert Harris, Shadi Lalezari, Naveed Wagle, Kourosh M Naeini, Jose Carrillo, Linda M Liau, Whitney B Pope
Affiliations

Functional diffusion maps (fDMs) evaluated before and after radiochemotherapy predict progression-free and overall survival in newly diagnosed glioblastoma

Benjamin M Ellingson et al. Neuro Oncol. 2012 Mar.

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.

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Figures

Fig. 1.
Fig. 1.
Anatomical MRIs and functional diffusion maps (fDMs) for 3 patients with glioblastoma. From left column to right column: pretreatment fluid-attenuated inversion recovery (FLAIR); posttreatment FLAIR; pretreatment, postcontrast T1-weighted images (T1 + C); posttreatment T1 + C; fDMs in pretreatment FLAIR regions of interest (ROIs); fDMs in posttreatment FLAIR ROIs; fDMs in pretreatment T1 + C ROIs; and posttreatment T1 + C ROIs. (A) Patient with a short progression-free survival (PFS) and overall survival (OS), demonstrating a large volume fraction of voxels with decreased ADC (blue) relative to pretreatment ADC maps. (B) Patient with a short PFS but relatively longer OS demonstrates a mixed response of both voxels with a significant increase in ADC (red) and decrease in ADC (blue). (C) Long-term survival patient demonstrating a large volume fraction of tissue with increased ADC (red) and a small volume fraction of tissue with decreased ADC (blue).
Fig. 2.
Fig. 2.
Kaplan-Meier curves for progression-free survival (PFS) using functional diffusion map (fDM) metrics in FLAIR regions of interest (ROIs). (A) Relative volume fraction of tissue within pretreatment FLAIR ROIs exhibiting a significant decrease in ADC [ADC(−)]. (B) Relative volume fraction of tissue within pretreatment FLAIR ROIs exhibiting a significant increase in ADC [ADC(+)]. (C) Relative volume fraction of tissue within pretreatment FLAIR ROIs exhibiting any significant change in ADC [ADC(+/−)]. (D) Relative volume fraction of tissue within posttreatment FLAIR ROIs exhibiting a significant decrease in ADC [ADC(−)]. (E) Relative volume fraction of tissue within posttreatment FLAIR ROIs exhibiting a significant increase in ADC [ADC(+)]. (F) Relative volume fraction of tissue within posttreatment FLAIR ROIs exhibiting any significant change in ADC [ADC(+/−)].
Fig. 3.
Fig. 3.
Kaplan-Meier curves for progression-free survival (PFS) using functional diffusion map (fDM) metrics within T1 + C regions of interest (ROIs). (A) Relative volume fraction of tissue within pretreatment T1 + C ROIs exhibiting a significant decrease in ADC [ADC(−)]. (B) Relative volume fraction of tissue within pretreatment T1 + C ROIs exhibiting a significant increase in ADC [ADC(+)]. (C) Relative volume fraction of tissue within pretreatment T1 + C ROIs exhibiting any significant change in ADC [ADC(+/−)]. (D) Relative volume fraction of tissue within posttreatment T1 + C ROIs exhibiting a significant decrease in ADC [ADC(−)]. (E) Relative volume fraction of tissue within posttreatment T1 + C ROIs exhibiting a significant increase in ADC [ADC(+)]. (F) Relative volume fraction of tissue within posttreatment T1 + C ROIs exhibiting any significant change in ADC [ADC(+/−)].
Fig. 4.
Fig. 4.
Kaplan-Meier curves for overall survival (OS) using functional diffusion map (fDM) metrics within FLAIR regions of interest (ROIs). (A) Relative volume fraction of tissue within pretreatment FLAIR ROIs exhibiting a significant decrease in ADC [ADC(−)]. (B) Relative volume fraction of tissue within pretreatment FLAIR ROIs exhibiting a significant increase in ADC [ADC(+)]. (C) Relative volume fraction of tissue within pretreatment FLAIR ROIs exhibiting any significant change in ADC [ADC(+/−)]. (D) Relative volume fraction of tissue within posttreatment FLAIR ROIs exhibiting a significant decrease in ADC [ADC(−)]. (E) Relative volume fraction of tissue within posttreatment FLAIR ROIs exhibiting a significant increase in ADC [ADC(+)]. (F) Relative volume fraction of tissue within posttreatment FLAIR ROIs exhibiting any significant change in ADC [ADC(+/−)].
Fig. 5.
Fig. 5.
Kaplan-Meier curves for overall survival (OS) using functional diffusion map (fDM) metrics within T1 + C regions of interest (ROIs). (A) Relative volume fraction of tissue within pretreatment T1 + C ROIs exhibiting a significant decrease in ADC [ADC(−)]. (B) Relative volume fraction of tissue within pretreatment T1 + C ROIs exhibiting a significant increase in ADC [ADC(+)]. (C) Relative volume fraction of tissue within pretreatment T1 + C ROIs exhibiting any significant change in ADC [ADC(+/−)]. (D) Relative volume fraction of tissue within posttreatment T1 + C ROIs exhibiting a significant decrease in ADC [ADC(−)]. (E) Relative volume fraction of tissue within posttreatment T1 + C ROIs exhibiting a significant increase in ADC [ADC(+)]. (F) Relative volume fraction of tissue within posttreatment T1 + C ROIs exhibiting any significant change in ADC [ADC(+/−)].
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