3'-Deoxy-3'-18F-Fluorothymidine PET-Derived Proliferative Volume Predicts Overall Survival in High-Grade Glioma Patients

A. Idema, A. Hoffmann, H. Boogaarts, E. Troost, P. Wesseling, A. Heerschap, W. van der Graaf, J. Grotenhuis and W. Oyen

Department of Neurosurgery, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
Oct, 2012



3'-deoxy-3'-(18)F-fluorothymidine ((18)F-FLT) is a radiopharmaceutical depicting tumor cell proliferation with PET. In malignancies of the lung, breast, head and neck, digestive tract, brain, and other organs, quantitative assessment of (18)F-FLT targeting has been shown to correlate with the proliferation marker Ki-67 and with clinical outcome measures such as time to progression and overall survival (OS). The aim of this study was to assess various PET segmentation methods to estimate the proliferative volume (PV) and their prognostic value for OS in patients with suspected high-grade glioma. METHODS: Twenty-six consecutive patients underwent preoperative (18)F-FLT PET/CT and T1-weighted MRI of the brain after contrast application. The maximum standardized uptake value (SUV(max)) of all tumors was calculated, and 3 different segmentation methods for estimating the PV were used: the 50\% isocontour of the SUV(max) signal for the PV(50\%), the signal-to-background ratio (SBR) for an adaptive threshold delineation (PV(SBR)) method, and the iterative background-subtracted relative threshold level (RTL) method to estimate the PV(RTL). The prognostic value of the SUV(max) and the different PVs for OS were assessed. RESULTS: Twenty-two patients had glioblastoma multiforme, 2 had anaplastic oligodendroglioma, 1 had anaplastic ependymoma, and 1 had anaplastic astrocytoma. The median OS was 397 d (95\% confidence interval, 204-577); 19 patients died during the follow-up period. The PV(SBR) showed a significantly (P = 0.002) better association with OS than did SUV(max), PV(RTL), and PV(50\%). Receiver-operating-characteristic analysis resulted in a threshold volume for the PV(SBR) of 11.4 cm(3), with a sensitivity and specificity of 70\% and 83\%, respectively, for the prediction of OS. Kaplan-Meier analyses showed a significant discrimination between short and long OS (P = 0.024, log rank) for this threshold. CONCLUSION: The PV as determined by (18)F-FLT PET is associated with OS in high-grade malignant gliomas. The SBR method yielded the best results to predict short and long OS.