Longitudinal Volumetric Analysis of FLAIR Hyperintensity Following Radiation Therapy (RT) in Patients with Low-grade Glioma (LGG)
Isabella Sutherland1, Adam Ulano2, Alissa Thomas3
1University of Vermont Larner College of Medicine, 2Radiology, 3Neurology, University of Vermont Medical Center
Objective:

To characterize the changes in MRI FLAIR hyperintensity that occur in LGG patients following RT, to better understand the “pseudoprogression” that occurs in absence of true tumor regrowth.

Background:
With radiation and chemotherapy, patients with IDH-mutant LGG can achieve many years of survival. RT may induce long-term changes within and adjacent to the radiation field, complicating the distinction between post-radiation treatment effects and advancing tumor. Better understanding of volumetric post-radiation FLAIR changes will help with clinical interpretation of disease progression vs treatment effect and guide management decisions.
Design/Methods:
In this IRB-approved retrospective study, serial MRI scans of patients with LGG were reviewed, including pre-RT and for 2.5 years post-RT. Segmentation for volumetric analysis was performed with manual supervision using ITK-SNAP (open-source segmentation software). Descriptive statistics are reported.
Results:

Sixteen patients with histologic grade 2 gliomas were included (4 astrocytoma, 12 oligodendroglioma, 15/16 confirmed IDH mutation).  Time from histologic diagnosis to RT ranged from 2.2 to 235 months (median 6.9 months). 159 MRI scans were segmented using ITK-SNAP (median 9.5 MRIs/patient, range 4-13). Mean pre-RT tumor volume was 31.6 cm3 (std dev 29, range 5-100 cm3). Nine of 16 MRIs showed decreasing FLAIR volume immediately post-RT, while 7/16 showed increasing FLAIR volume.  After the initial post-RT MRI, 12/16 patients had MRIs with an increase in FLAIR volume sometime during the first year (pseudoprogression).  The FLAIR volume stabilized or decreased a median of 18.4 months and mean of 15.0 months post-RT. During the 2.5 year study period, median progression free survival and median overall survival were not reached (14/16 patients alive, 12/16 progression free). 

Conclusions:

FLAIR hyperintensity changes on MRI are highly variable in the first 1.5 years post-RT in low grade glioma, but after 1.5 years, FLAIR volumes stabilize and decrease, likely indicating the inflection point where post-RT pseudoprogression stabilizes.

10.1212/WNL.0000000000204887