Title Slide

1
fDM Approach and Rationale
Generation of Functional Diffusion Maps (fDM)
Patients underwent a pretreatment diffusion MRI
and a second scan 3 weeks into treatment.
Diffusion MRI data then underwent image analysis
with co-registration of images. Data were used to
generate a three-color overlay representing
regions in which tumor apparent diffusion
coefficient (ADC) values are unchanged (green
voxels), significantly increased (red voxels), or
significantly decreased (blue voxels). This data
can also be presented in a scatter plot and
percentages assigned to the three defined ADC
regions allowing quantitative assessment of
overall changes in tumor ADC values.(Figure from
Moffat et al (2005) Proc Natl Acad Sci U S A 102,
5524-5529.)
2
PD
VR 2.8 VB 3.2 VT 6.0
Representative patient with GBM who had
progressive disease 10 weeks after start of
treatment and the corresponding fDM parameters.
The scatter plot represents pre-treatment ADC on
the x-axis and post-treatment ADC on the y-axis.
3
SD
VR 2.5 VB 16.5 VT 19.0
Representative patient with GBM who had stable
disease 10 weeks after start of treatment and the
corresponding fDM parameters.
4
VR 22.0 VB 0 VT 22.0
PR
Representative patient with GBM who had a partial
response 10 weeks after start of treatment and
the corresponding fDM parameters.
5
fDM Percentages for Grade III/IV Gliomas
p0.04
p0.01
VR
VB
VT
p0.005
Twenty-nine patients were utilized to compare
radiographic response at 10 weeks to fDM at 3
weeks. Fifteen patients had progressive disease
(PD) and 14 patients had either stable disease or
a partial response (SD/PR). Values depicted for
fDM are the mean 95 CI. Based upon these
results all patients were stratified as having
progressive disease if VT was LOW (lt6.57) and as
non-progressive if VT was HIGH (6.57 or
greater). These stratifications were then
utilized to evaluate the ability of fDM to
predict for overall survival and time to
progression
6
fDM Stratification Overall Survival
Median OS (months) Low fDM 7.4 High fDM
18.4 p0.008 HR 3.0 (95 CI 1.5 to 11.1)
7
fDM Stratification Progression Free Survival
Median TTP (months) Low fDM 4.3 High fDM
7.3 p0.038 HR2.2 (95 CI 1.1 to 6.7)
8
Multivariate Analysis

• Multivariate models were constructed for both OS
  and TTP incorporating
• fDM (VT 6.57 vs. gt6.57)
• Pathologic Grade (III vs. IV)
• Age (50 vs. gt50)
• Surgical Resection (Resection vs. Biopsy)
• Tumor Location (Frontal/Parietal vs. Temporal vs.
  Thalamic)
• Only fDM was predictive of OS (plt0.02)
• Both pathologic grade (plt0.03) and fDM (plt0.05)
  were predictive of TTP.