Serial FLT PET imaging to discriminate between true progression and pseudoprogression in patients with newly diagnosed glioblastoma: a long-term follow-up study

Abstract

PurposeResponse evaluation in patients with glioblastoma after chemoradiotherapy is challenging due to progressive, contrast-enhancing lesions on MRI that do not reflect true tumour progression. In this study, we prospectively evaluated the ability of the PET tracer 18F-fluorothymidine (FLT), a tracer reflecting proliferative activity, to discriminate between true progression and pseudoprogression in newly diagnosed glioblastoma patients treated with chemoradiotherapy.MethodsFLT PET and MRI scans were performed before and 4 weeks after chemoradiotherapy. MRI scans were also performed after three cycles of adjuvant temozolomide. Pseudoprogression was defined as progressive disease on MRI after chemoradiotherapy with stabilisation or reduction of contrast-enhanced lesions after three cycles of temozolomide, and was compared with the disease course during long-term follow-up. Changes in maximum standardized uptake value (SUVmax) and tumour-to-normal uptake ratios were calculated for FLT and are presented as the mean SUVmax for multiple lesions.ResultsBetween 2009 and 2012, 30 patients were included. Of 24 evaluable patients, 7 showed pseudoprogression and 7 had true progression as defined by MRI response. FLT PET parameters did not significantly differ between patients with true progression and pseudoprogression defined by MRI. The correlation between change in SUVmax and survival (p = 0.059) almost reached the standard level of statistical significance. Lower baseline FLT PET uptake was significantly correlated with improved survival (p = 0.022).ConclusionBaseline FLT uptake appears to be predictive of overall survival. Furthermore, changes in SUVmax over time showed a tendency to be associated with improved survival. However, further studies are necessary to investigate the ability of FLT PET imaging to discriminate between true progression and pseudoprogression in patients with glioblastoma.

Repeatability of radiomic features in magnetic resonance imaging of glioblastoma: Test–retest and image registration analyses

“…63,64 Although, single imaging studies have found feasible results, several studies have indicated that diagnosis of pseudo-progression could not be achieved by a single imaging technique and suggested that serial imaging will results in improved diagnosis accuracy. 65,66 On the other hand, there are several variations in the clinical definitions of pseudo-progression based on the imaging reports which require higher precision quantitative imaging. 67 Some radiomics studies have shown the feasibility of MR image radiomic features to discriminate between pseudo-progression compared to true progression [68][69][70] and genomic mutation prediction 8-11,71,72 and treatment response assessments.…”

“…Treatment response evaluation in GBM suffers from several uncertainties in differentiation among pseudo‐progression, pseudo‐response, treatment‐related necrosis, and true progression 63,64 . Although, single imaging studies have found feasible results, several studies have indicated that diagnosis of pseudo‐progression could not be achieved by a single imaging technique and suggested that serial imaging will results in improved diagnosis accuracy 65,66 . On the other hand, there are several variations in the clinical definitions of pseudo‐progression based on the imaging reports which require higher precision quantitative imaging 67 .…”

Radiation Necrosis, Pseudoprogression, Pseudoresponse, and Tumor Recurrence: Imaging Challenges for the Evaluation of Treated Gliomas

“…Other PET radiopharmaceuticals that are under investigation to differentiate between progression from pseudoprogression or tumor recurrence include 18 F-fluoromisonidazole (FMISO) PET/MR [48], 4-borono-2-[(18)F]-fluoro-phenylalanine ( 18 F-FBPA) PET [49], [(18)F]-fluoromethyl-dimethyl-2-hydroxyethylammonium ( 18 F-fluoromethylcholine) PET [50], and 3′-deoxy-3′-(18)F-fluorothymidine (FLT) PET [51].…”

In vivo PET Imaging of Gliogenesis After Cerebral Ischemia in Rats

“…[ 18 F]FLT has been extensively used in the field of oncology to characterize tumors and predict the response to personalized therapeutic approaches ( Schelhaas et al, 2017 ). Therefore, the main application of this radiotracer in neurology has been restricted to the diagnosis of glioblastoma ( Nikaki et al, 2017 ; Brahm et al, 2018 ). Nevertheless, few studies have reported the visualization of endogenous neural stem cells in living animals using [ 18 F]FLT after focal cerebral ischemia, that could be used to monitor the effect of drugs aimed at expanding the neural stem cell niche ( Rueger et al, 2010 , 2012 ).…”