PURPOSE: To evaluate the time course and association with survival of anatomic 
lesion volumes and diffusion imaging parameters for patients with newly 
diagnosed glioblastoma who were treated with radiation and concurrently with 
either temozolomide and enzastaurin (TMZ+enza cohort) or temozolomide, 
erlotonib, and bevaciumab (TMZ+erl+bev cohort).
MATERIALS AND METHODS: Regions of interest corresponding to the 
contrast-enhancing and hyperintense lesions on T2-weighted images were 
generated. Diffusion-weighted images were processed to provide maps of apparent 
diffusion coefficient, fractional anisotropy, and longitudinal and radial 
eigenvalues. Histograms of diffusion values were generated and summary 
statistics calculated. Cox proportional hazards models were employed to assess 
the association of representative imaging parameters with survival with 
adjustments for age, Karnofsky performance status, and extent of resection.
RESULTS: Although progression-free survival was significantly longer for the 
TMZ+erl+bev cohort (12.8 vs 7.3 months), there was no significant difference in 
overall survival between the two populations (17.0 vs 17.8 months). The median 
contrast-enhancing lesion volumes decreased from 6.3 to 1.9 cm(3) from baseline 
to the postradiotherapy scan for patients in the TMZ+enza cohort and from 2.8 to 
0.9cm(3) for the TMZ+erl+bev cohort. Changes in the T2 lesion volumes were only 
significant for the latter cohort (26.5 to 11.9 cm(3)). The median apparent 
diffusion coefficient and related diffusion parameters were significantly 
increased for the TMZ+enza cohort (1054 to 1225 μm(2)/s). More of the anatomic 
parameters were associated with survival for the TMZ+enza cohort, whereas more 
diffusion parameters were associated with survival for the TMZ+erl+bev cohort.
CONCLUSION: The early changes in anatomic and diffusion imaging parameters and 
their association with survival reflected differences in the mechanisms of 
action of the treatments that were being given. This suggests that integrating 
diffusion metrics and anatomic lesion volumes into the Response Assessment in 
Neuro-Oncology criteria would assist in interpreting treatment-induced changes 
and predicting outcome in patients with newly diagnosed glioblastoma who are 
receiving such combination treatments.