Quantitative T2 mapping of recurrent glioblastoma under bevacizumab improves monitoring for non-enhancing tumor progression and predicts overall survival.
BACKGROUND
Anti-angiogenic treatment in recurrent glioblastoma patients suppresses contrast enhancement and reduces vasogenic edema while non-enhancing tumor progression is common. Thus, the importance of T2-weighted imaging is increasing. We therefore quantified T2 relaxation times, which are the basis for the image contrast on T2-weighted images.


METHODS
Conventional and quantitative MRI procedures were performed on 18 patients with recurrent glioblastoma before treatment with bevacizumab and every 8 weeks thereafter until further tumor progression. We segmented the tumor on conventional MRI into 3 subvolumes: enhancing tumor, non-enhancing tumor, and edema. Using coregistered quantitative maps, we followed changes in T2 relaxation time in each subvolume. Moreover, we generated differential T2 maps by a voxelwise subtraction using the first T2 map under bevacizumab as reference.


RESULTS
Visually segmented areas of tumor and edema did not differ in T2 relaxation times. Non-enhancing tumor volume did not decrease after commencement of bevacizumab treatment but strikingly increased at progression. Differential T2 maps clearly showed non-enhancing tumor progression in previously normal brain. T2 relaxation times decreased under bevacizumab without re-increasing at tumor progression. A decrease of <26 ms in the enhancing tumor following exposure to bevacizumab was associated with longer overall survival.


CONCLUSIONS
Combining quantitative MRI and tumor segmentation improves monitoring of glioblastoma patients under bevacizumab. The degree of change in T2 relaxation time under bevacizumab may be an early response parameter predictive of overall survival. The sustained decrease in T2 relaxation times toward values of healthy tissue masks progressive tumor on conventional T2-weighted images. Therefore, quantitative T2 relaxation times may detect non-enhancing progression better than conventional T2-weighted imaging.
Corresponding Author: Elke Hattingen, MD, Goethe-University Hospital Frankfurt, Schleusenweg 2-16, 60528, Frankfurt, Germany. elke.hattingen@kgu.de.
Elke
E
Hattingen
Alina
A
Jurcoane
Keivan
K
Daneshvar
Ulrich
U
Pilatus
Michel
M
Mittelbronn
Joachim P
JP
Steinbach
Oliver
O
Bähr
D000328:Adult; D000368:Aged; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D000068258:Bevacizumab; D001929:Brain Edema / Q000188:drug therapy / Q000401:mortality / Q000473:pathology; D001931:Brain Mapping; D001932:Brain Neoplasms / Q000188:drug therapy / Q000401:mortality / Q000473:pathology; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D005909:Glioblastoma / Q000188:drug therapy / Q000401:mortality* / Q000473:pathology*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy / Q000401:mortality / Q000473:pathology; D009367:Neoplasm Staging; D011379:Prognosis; D011446:Prospective Studies; D015996:Survival Rate
D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab
T2 relaxation time; bevacizumab; non-enhancing tumor; quantitative MRI