Quantitative MR Measurements of Mean Diffusivity in Glioblastoma Patients with Tumor Treating Fields Plus Standard Therapy versus Standard Treatment Alone

Abstract

Quantitative MR parameters such as those derived from diffusion imaging may advance knowledge on the biological characteristics of gliomas in both the diagnostic and treatment settings. Tumor Treating Fields (TTFields) are intermediate frequency alternating currents that have been approved in newly diagnosed and recurrent glioblastoma. The 5-year data from the Phase 3 study has shown significant benefits of TTFields in progression free and overall survival. We evaluated the quantitative diffusion differences that could be detected in glioblastoma patients treated with standard therapy plus TTFields versus standard therapy alone. Twelve patients with glioblastoma were subjected to surgical resection, radiotherapy and temozolomide. Six subjects were additionally treated with TTFields. All patients were followed by MRI every two months (range 210-1036 days) using standard imaging and diffusion tensor imaging until tumor progression. Progression-free survival (PFS) was significantly longer in the subgroup treated by TTFields (mean 784 days ± 163 SD) as compared to standard therapy alone (443 days ± 249). No difference was detected between groups in the initial mean diffusivity values measured within the affected white matter near the resection cavity. However, the linear regression slope describing mean diffusivity in this region over serial measurements was higher in the group treated with TTFields than in the group without TTFields (5.43 ± 2.4 versus -3.77 ± 11.8). Furthermore, we detected significant positive correlation between mean diffusivity slope and PFS. Our data demonstrate increasing mean diffusivity in the affected white matter of glioblastoma patients, which is favorable with associated positive correlation to PFS as seen in steeper regression slopes. The patients treated with TTFields showed greater PFS in comparison to those who did not receive TTFields. There was a corresponding increase in mean diffusivity in the affected white matter of these patients. In the group that received standard therapy, the increase was not as apparent and, if present, the slope was not as steep. Changes in mean diffusivity likely reflect changes in tumor density in the white matter.