Evaluation of the Diagnostic Performance of F18-Fluorodeoxyglucose-Positron Emission Tomography, Dynamic Susceptibility Contrast Perfusion, and Apparent Diffusion Coefficient in Differentiation between Recurrence of a High-grade Glioma and Radiation Necrosis
Authors: Peer Sameer , Gopinath R. , Saini Jitender , Kumar Pardeep , Srinivas Dwarkanath , Nagaraj Chandana 
Published: June 2023

Background:
Differentiation between recurrence of brain tumor and radiation necrosis remains a challenge in current neuro-oncology practice despite recent advances in both radiological and nuclear medicine techniques.

Purpose:
The purpose of this study was to compare the diagnostic performance of dynamic susceptibility contrast (DSC) perfusion magnetic resonance imaging (MRI), apparent diffusion coefficient (ADC) derived from diffusion-weighted imaging, and F18-fluorodeoxyglucose-positron emission tomography (F18-FDG-PET) in the differentiation between the recurrence of a high-grade glioma and radiation necrosis.

Materials and Methods:
Patients with a diagnosis of high-grade glioma (WHO Grades III and IV) who had undergone surgical resection of the tumor followed by radiotherapy with or without chemotherapy were included in the study. DSC perfusion, diffusion-weighted MRI, and PET scan were acquired on a hybrid PET/MRI scanner. For each lesion, early and delayed tumor-to-brain ratio (TBR), early and delayed maximum standardized uptake value (SUVmax), normalized ADC ratio, and normalized relative cerebral blood volume (rCBV) ratio were calculated and the pattern of lesional enhancement was noted. The diagnosis was finalized with either histopathological examination or the characteristics on follow-up imaging. The statistical analysis using the receiver operator characteristic curves was done to determine the diagnostic performance of DSC perfusion, 18-F FDG-PET, and ADC in differentiation between tumor recurrence and radiation necrosis.

Results:
Fifty patients were included in the final analysis, 32 of them being men (64%). A cutoff value of early TBR >0.8 (sensitivity of 100% and specificity of 80%), delayed TBR >0.93 (sensitivity of 92.3% and specificity of 80%), early SUVmax >10.2 (sensitivity of 76.9% and specificity of 80%), delayed SUVmax >13.2 (sensitivity of 61.54% and specificity of 100%), normalized rCBV ratio >1.21 (sensitivity of 100% and specificity of 60%), normalized ADC ratio >1.66 (sensitivity of 38.5% and specificity of 80%), and Grade 3 enhancement (sensitivity of 100% and specificity of 60%) were found to differentiate recurrence from radiation necrosis. Early TBR had the highest accuracy (94.44%), while ADC ratio had the lowest accuracy (50%). A combination of early TBR (cutoff value of 0.8), late TBR (cutoff value of 0.93), and rCBV ratio (cutoff value of 1.21) showed a sensitivity of 100%, specificity of 92.3%, positive predictive value of 88.9%, negative predictive value of 93.7%, and an accuracy of 96.6% in discrimination between radiation necrosis and recurrence of tumor.

Conclusion:
F18-FDG-PET and DSC perfusion can reliably differentiate tumor recurrence from radiation necrosis, with early TBR showing the highest accuracy. ADC demonstrates a low sensitivity, specificity, and accuracy in differentiating radiation necrosis from recurrence. A combination of early TBR, delayed TBR, and rCBV may be more useful in discrimination between radiation necrosis and recurrence of glioma, with this combination showing a better diagnostic performance than individual parameters or any other combination of parameters.