Background

Prediction of early progression in glioblastoma may provide an opportunity to personalize treatment. Simplified intravoxel incoherent motion (IVIM) MRI offers quantitative estimates of diffusion and perfusion metrics. We investigated whether these metrics, during chemoradiation, could predict treatment outcome.

Methods

38 patients with newly diagnosed IDH-wildtype glioblastoma undergoing 6-week/30-fraction chemoradiation had standardized post-operative MRIs at baseline (radiation planning), and at the 10th and 20th fractions. Non-overlapping T1-enhancing (T1C) and non-enhancing T2-FLAIR hyperintense regions were independently segmented. Apparent diffusion coefficient (ADC_T1C, ADC_T2-FLAIR) and perfusion fraction (f_T1C, f_T2-FLAIR) maps were generated with simplified IVIM modelling. Parameters associated with progression before or after 6.9 months (early vs late progression, respectively), overall survival (OS) and progression-free survival (PFS) were investigated.

Results

Higher ADC_T2-FLAIR at baseline [Odds Ratio (OR) = 1.06, 95% CI 1.01-1.15, p = 0.025], lower f_T2-FLAIR at fraction 10 (OR = 2.11, 95% CI 1.04-4.27, p = 0.018), and lack of increase in ADC_T2-FLAIR at fraction 20 compared to baseline (OR = 1.12, 95% CI 1.02-1.22, p = 0.02) were associated with early progression. Combining ADC_T2-FLAIR at baseline, f_T2-FLAIR at fraction 10, ECOG and MGMT promoter methylation status significantly improved AUC to 90.3% compared to a model with only ECOG and MGMT promoter methylation status (p = 0.001). Using multivariable analysis, neither IVIM metrics were associated with OS but higher f_T2-FLAIR at fraction 10 (HR = 0.72, 95% CI 0.56-0.95, p = 0.018) was associated with longer PFS.

Conclusion

ADC_T2-FLAIR at baseline, its lack of increase from baseline to fraction 20, or f_T2-FLAIR at fraction 10 significantly predicted early progression. f_T2-FLAIR at fraction 10 was associated with PFS.

Patients undergoing standard chemoradiation post-resection had MRIs at radiation planning and fractions 10 and 20 of chemoradiation. MRIs were 1.5T and 3D T2-FLAIR, pre- and post-contrast 3D T1-weighted (T1) and echo planar DWI with three b-values (0, 500, and 1000s/mm²) were acquired. T2-FLAIR was coregistered to T1C images. Non-overlapping T1 contrast-enhancing (T1C) and nonenhancing T2-FLAIR hyperintense regions were segmented, with necrotic/cystic regions, the surgical cavity, and large vessels excluded. The simplified IVIM model was used to calculate voxelwise diffusion coefficient (D) and perfusion fraction (f) maps; ADC was calculated using the natural logarithm of b = 1000 over b = 0 images. T1C and T2-FLAIR segmentations were brought into this space, and medians calculated. MGMT promoter methylation status (MGMT_PMS), age at diagnosis, and Eastern Cooperative Oncology Group (ECOG) performance status were extracted from electronic medical records. The data were presented, analyzed, and described in the article, "Intravoxel incoherent motion (IVIM) modeling of diffusion MRI during chemoradiation predicts therapeutic response in IDH wildtype Glioblastoma", published in Radiotherapy and Oncology [1].