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

Abstract

The standard of care for newly diagnosed glioblastoma (GBM) is surgery, then radiotherapy (RT) with concurrent temozolomide (TMZ), followed by adjuvant TMZ. We hypothesized patients with low diffusivity measured using apparent diffusion coefficient (ADC) histogram analysis evaluated after RT+TMZ, prior to adjuvant TMZ, would have a significantly shorter progression-free (PFS) and overall survival (OS). To test this hypothesis we evaluated 120 patients with newly diagnosed GBM receiving RT+TMZ followed by adjuvant TMZ. MRI was performed after completion of RT+TMZ, prior to initiation of 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 um²/ms and ADC_H value of 1.6 um²/ms were used to stratify patients into high and low risk categories. Results suggest patients with low ADC_L had 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 vs. 644 days (Cox Hazard Ratio = 0.31, P = 0.047). ADC_H was not predictive of PFS or OS when accounting for age and ADC_L. In summary, newly diagnosed glioblastoma patients with low ADC_L after completion of RT+TMZ are likely to progress and die earlier than patients with higher ADC_L. Results suggest ADC histogram analysis may be useful for patient risk stratification following completion of RT+TMZ.