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 μm²/ms and ADC_H value of 1.6 μm²/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 = 0.0006). OS was significantly shorter with low ADC_L tumors, showing a median OS of 407 versus 644 days (Cox hazard ratio = 0.31, P = 0.047). 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.