ADC histograms predict response to anti-angiogenic therapy in patients with recurrent high-grade glioma.
BACKGROUND
The purpose of this study is to evaluate apparent diffusion coefficient (ADC) maps to distinguish anti-vascular and anti-tumor effects in the course of anti-angiogenic treatment of recurrent high-grade gliomas (rHGG) as compared to standard magnetic resonance imaging (MRI).


METHODS
This retrospective study analyzed ADC maps from diffusion-weighted MRI in 14 rHGG patients during bevacizumab/irinotecan (B/I) therapy. Applying image segmentation, volumes of contrast-enhanced lesions in T1 sequences and of hyperintense T2 lesions (hT2) were calculated. hT2 were defined as regions of interest (ROI) and registered to corresponding ADC maps (hT2-ADC). Histograms were calculated from hT2-ADC ROIs. Thereafter, histogram asymmetry termed "skewness" was calculated and compared to progression-free survival (PFS) as defined by the Response Assessment Neuro-Oncology (RANO) Working Group criteria.


RESULTS
At 8-12 weeks follow-up, seven (50%) patients showed a partial response, three (21.4%) patients were stable, and four (28.6%) patients progressed according to RANO criteria. hT2-ADC histograms demonstrated statistically significant changes in skewness in relation to PFS at 6 months. Patients with increasing skewness (n = 11) following B/I therapy had significantly shorter PFS than did patients with decreasing or stable skewness values (n = 3, median percentage change in skewness 54% versus -3%, p = 0.04).


CONCLUSIONS
In rHGG patients, the change in ADC histogram skewness may be predictive for treatment response early in the course of anti-angiogenic therapy and more sensitive than treatment assessment based solely on RANO criteria.
Department of Neurology, Innsbruck Medical University, Anichstrasse 35, A-6020, Innsbruck, Austria. Martha.Nowosielski@i-med.ac.at
Martha
M
Nowosielski
Wolfgang
W
Recheis
Georg
G
Goebel
Ozgür
O
Güler
Gerd
G
Tinkhauser
Herwig
H
Kostron
Michael
M
Schocke
Thaddaeus
T
Gotwald
Günther
G
Stockhammer
Markus
M
Hutterer
D000328:Adult; D000368:Aged; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols; D000068258:Bevacizumab; D001932:Brain Neoplasms / Q000188:drug therapy / Q000473:pathology*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D038524:Diffusion Magnetic Resonance Imaging / Q000379:methods*; D005260:Female; D005500:Follow-Up Studies; D005910:Glioma / Q000188:drug therapy / Q000473:pathology*; D006801:Humans; D000077146:Irinotecan; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012008:Recurrence; D012189:Retrospective Studies; D016896:Treatment Outcome
D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000972:Antineoplastic Agents, Phytogenic; D000068258:Bevacizumab; D000077146:Irinotecan; D002166:Camptothecin