Restriction Spectrum Imaging Improves Risk Stratification in Patients with Glioblastoma.

BACKGROUND AND PURPOSE: ADC as a marker of tumor cellularity has been promising for evaluating the response to therapy in patients with glioblastoma but does not successfully stratify patients according to outcomes, especially in the upfront setting. Here we investigate whether restriction spectrum imaging, an advanced diffusion imaging model, performed after an operation but before radiation therapy, could improve risk stratification in patients with newly diagnosed glioblastoma relative to ADC. MATERIALS AND METHODS: Pre-radiation therapy diffusion-weighted and structural imaging of 40 patients with glioblastoma were examined retrospectively. Restriction spectrum imaging and ADC-based hypercellularity volume fraction (restriction spectrum imaging-FLAIR volume fraction, restriction spectrum imaging-contrast-enhanced volume fraction, ADC-FLAIR volume fraction, ADC-contrast-enhanced volume fraction) and intensities (restriction spectrum imaging-FLAIR 90th percentile, restriction spectrum imaging-contrast-enhanced 90th percentile, ADC-FLAIR 10th percentile, ADC-contrast-enhanced 10th percentile) within the contrast-enhanced and FLAIR hyperintensity VOIs were calculated. The association of diffusion imaging metrics, contrast-enhanced volume, and FLAIR hyperintensity volume with progression-free survival and overall survival was evaluated by using Cox proportional hazards models. RESULTS: Among the diffusion metrics, restriction spectrum imaging-FLAIR volume fraction was the strongest prognostic metric of progression-free survival (P = .036) and overall survival (P = .007) in a multivariate Cox proportional hazards analysis, with higher values indicating earlier progression and shorter survival. Restriction spectrum imaging-FLAIR 90th percentile was also associated with overall survival (P = .043), with higher intensities, indicating shorter survival. None of the ADC metrics were associated with progression-free survival/overall survival. Contrast-enhanced volume exhibited a trend toward significance for overall survival (P = .063). CONCLUSIONS: Restriction spectrum imaging-derived cellularity in FLAIR hyperintensity regions may be a more robust prognostic marker than ADC and conventional imaging for early progression and poorer survival in patients with glioblastoma. However, future studies with larger samples are needed to explore its predictive ability.

Use of in vitro-in vivo correlation to predict the pharmacokinetics of several products containing a BCS class 1 drug in extended release matrices.

PURPOSE: To determine if an IVIVC model can predict PK profiles of varying formulations of a BCS Class 1 drug that is a salt of a weak base. METHOD: An IVIVC model (Level A) was created by correlating deconvoluted in vivo absorption data obtained from oral administration of 50 mg, 100 mg, and 200 mg fast and slow extended release formulations with in vitro percent dissolved using residual regression analysis. The model was then used to predict the in vivo profile of five test products that varied in formulation characteristics. RESULTS: The model passed internal validation for predicted Cmax and AUC. For external validation, in vitro data of five different test formulations was utilized. The model passed external validation for two test formulations that were different but belonging to the same release mechanism as that of the reference formulation. Three formulations failed external validation because they belonged to either a mixed or different release mechanism. The model and results were further confirmed using GatstroPlus™ simulation software. CONCLUSIONS: These observations indicate that an IVIVC model for a BCS class I drug may be applicable to varying formulations if the principle of the drug release is similar.