Large-scale Radiomic Profiling of Recurrent Glioblastoma Identifies an Imaging Predictor for Stratifying Anti-Angiogenic Treatment Response.
OBJECTIVE
Antiangiogenic treatment with bevacizumab, a mAb to the VEGF, is the single most widely used therapeutic agent for patients with recurrent glioblastoma. A major challenge is that there are currently no validated biomarkers that can predict treatment outcome. Here we analyze the potential of radiomics, an emerging field of research that aims to utilize the full potential of medical imaging.


METHODS
A total of 4,842 quantitative MRI features were automatically extracted and analyzed from the multiparametric tumor of 172 patients (allocated to a discovery and validation set with a 2:1 ratio) with recurrent glioblastoma prior to bevacizumab treatment. Leveraging a high-throughput approach, radiomic features of patients in the discovery set were subjected to a supervised principal component (superpc) analysis to generate a prediction model for stratifying treatment outcome to antiangiogenic therapy by means of both progression-free and overall survival (PFS and OS).


RESULTS
The superpc predictor stratified patients in the discovery set into a low or high risk group for PFS (HR = 1.60; P = 0.017) and OS (HR = 2.14; P < 0.001) and was successfully validated for patients in the validation set (HR = 1.85, P = 0.030 for PFS; HR = 2.60, P = 0.001 for OS).


CONCLUSIONS
Our radiomic-based superpc signature emerges as a putative imaging biomarker for the identification of patients who may derive the most benefit from antiangiogenic therapy, advances the knowledge in the noninvasive characterization of brain tumors, and stresses the role of radiomics as a novel tool for improving decision support in cancer treatment at low cost. Clin Cancer Res; 22(23); 5765-71. ©2016 AACR.
Department of Neuroradiology, University of Heidelberg Medical Center, Heidelberg, Germany philipp.kickingereder@med.uni-heidelberg.de.
Philipp
P
Kickingereder
Medical Image Computing, Division Medical and Biological Informatics, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Michael
M
Götz
Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
John
J
Muschelli
Neurology Clinic, University of Heidelberg Medical Center, Heidelberg, Germany.
Antje
A
Wick
Department of Neuroradiology, University of Heidelberg Medical Center, Heidelberg, Germany.
Ulf
U
Neuberger
Department of Biostatistics and Epidemiology, Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
Russell T
RT
Shinohara
Division of Biostatistics, DKFZ, Heidelberg, Germany.
Martin
M
Sill
Department of Neurology, The Medical University of Innsbruck, Innsbruck, Austria.
Martha
M
Nowosielski
Department of Radiology, DKFZ, Heidelberg, Germany.
Heinz-Peter
HP
Schlemmer
Department of Neuroradiology, University of Heidelberg Medical Center, Heidelberg, Germany.|Department of Radiology, DKFZ, Heidelberg, Germany.
Alexander
A
Radbruch
Neurology Clinic, University of Heidelberg Medical Center, Heidelberg, Germany.|Clinical Cooperation Unit Neurooncology, German Cancer Consortium (DKTK), DKFZ, Heidelberg, Germany.
Wolfgang
W
Wick
Department of Neuroradiology, University of Heidelberg Medical Center, Heidelberg, Germany.
Martin
M
Bendszus
Medical Image Computing, Division Medical and Biological Informatics, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Klaus H
KH
Maier-Hein
Department of Neuroradiology, University of Heidelberg Medical Center, Heidelberg, Germany.|Department of Radiology, DKFZ, Heidelberg, Germany.
David
D
Bonekamp
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000068258:Bevacizumab / Q000627:therapeutic use; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D018572:Disease-Free Survival; D005260:Female; D005909:Glioblastoma / Q000188:drug therapy* / Q000473:pathology*; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000473:pathology*; D012189:Retrospective Studies; D016896:Treatment Outcome
D020533:Angiogenesis Inhibitors; D000068258:Bevacizumab