Unsupervised consensus cluster analysis of [18F]-fluoroethyl-L-tyrosine positron emission tomography identified textural features for the diagnosis of pseudoprogression in high-grade glioma

// Sied Kebir 1, 2, * , Zain Khurshid 3, * , Florian C. Gaertner 3 , Markus Essler 3 , Elke Hattingen 4 , Rolf Fimmers 5 , Björn Scheffler 2, 6 , Ulrich Herrlinger 1 , Ralph A. Bundschuh 3, # , Martin Glas 1, 2, 7, # 1 Division of Clinical Neurooncology, Department of Neurology, University of Bonn Medical Center, Germany 2 Stem Cell Pathologies Group, Institute of Reconstructive Neurobiology, University of Bonn Medical Center, Germany 3 Department of Nuclear Medicine, University of Bonn Medical Center, Germany 4 Neuroradiology, Department of Radiology, University of Bonn Medical Center, Germany 5 Institute of Medical Biometry, Informatics and Epidemiology, University of Bonn Medical Center, Germany 6 DKFZ –Division of Translational Oncology/Neurooncology, German Cancer Consortium (DKTK) & University Hospital Essen, Germany 7 Clinical Cooperation Unit Neurooncology, MediClin Robert Janker Klinik, Bonn, Germany * Shared first authorship # Shared last authorship Correspondence to: Martin Glas, email: Martin.Glas@ukb.uni-bonn.de Keywords: heterogeneity, FET-PET, pseudoprogression, glioblastoma, textural Received: September 30, 2016 Accepted: November 23, 2016 Published: December 24, 2016 ABSTRACT Rationale: Timely detection of pseudoprogression (PSP) is crucial for the management of patients with high-grade glioma (HGG) but remains difficult. Textural features of O-(2-[ 18 F]fluoroethyl)-L-tyrosine positron emission tomography (FET-PET) mirror tumor uptake heterogeneity; some of them may be associated with tumor progression. Methods: Fourteen patients with HGG and suspected of PSP underwent FET-PET imaging. A set of 19 conventional and textural FET-PET features were evaluated and subjected to unsupervised consensus clustering. The final diagnosis of true progression vs. PSP was based on follow-up MRI using RANO criteria. Results: Three robust clusters have been identified based on 10 predominantly textural FET-PET features. None of the patients with PSP fell into cluster 2, which was associated with high values for textural FET-PET markers of uptake heterogeneity. Three out of 4 patients with PSP were assigned to cluster 3 that was largely associated with low values of textural FET-PET features. By comparison, tumor-to-normal brain ratio (TNRmax) at the optimal cutoff 2.1 was less predictive of PSP (negative predictive value 57% for detecting true progression, p=0.07 vs. 75% with cluster 3, p=0.04). Principal Conclusions: Clustering based on textural O-(2-[18F]fluoroethyl)-L-tyrosine PET features may provide valuable information in assessing the elusive phenomenon of pseudoprogression.