Diffusion MRI Characteristics After Concurrent Radiochemotherapy Predicts Progression-Free and Overall Survival in Newly Diagnosed Glioblastoma

The standard of care for newly diagnosed glioblastoma (GBM) is surgery first, radiotherapy (RT) with concurrent temozolomide (TMZ) second, and adjuvant TMZ last. We hypothesized patients with low diffusivity measured using apparent diffusion coefficient (ADC) histogram analysis evaluated after RT +/- TMZ and before adjuvant TMZ would have a significantly shorter progression-free survival (PFS) and overall survival (OS). To test this hypothesis, we evaluated 120 patients with newly diagnosed GBM receiving RT +/- TMZ followed by adjuvant TMZ. Magnetic resonance imaging was performed after completing RT +/- TMZ and before initiating adjuvant TMZ. A double Gaussian mixed model was used to describe the ADC histograms within the enhancing tumor, where ADC(L) and ADC(H) were defined as the mean ADC value of the lower and higher Gaussian distribution, respectively. An ADC(L) value of 1.0 mu m(2)/ms and ADC(H) value of 1.6 mu m(2)/ms were used to stratify patients into high-and low-risk categories. Results suggested that patients with a low ADC(L) had a significantly shorter PFS (Cox hazard ratio = 0.12, P = .0006). OS was significantly shorter with low ADC(L) tumors, showing a median OS of 407 versus 644 days (Cox hazard ratio = 0.31, P = .047). ADC(H) did not predict PFS or OS when accounting for age and ADC(L). In summary, after completing RT +/- TMZ, newly diagnosed glioblastoma patients with a low ADC(L) are likely to progress and die earlier than patients with a higher ADC(L). ADC histogram analysis may be useful for patient-risk stratification after completing RT +/- TMZ.