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

Cyrillo G Brahm,Annemiek M E Walenkamp,Martha W Den Hollander,Mart A A M Heesters,Elisabeth G E De Vries,Jan Pruim,Wilfred F A Den Dunnen,Henk M W Verheul,Michiel Wagemakers,A Millad Solouki,Roelien H Enting,Jan Cees De Groot

doi:10.1007/s00259-018-4090-4

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.

Highlights

Glioblastoma (GBM) is the most common and most aggressive primary brain tumour
Current first-line treatment, consisting of maximal surgical resection followed by postoperative radiation with concomitant and adjuvant temozolomide (TMZ) therapy, has improved 2-year survival from 11% to 27% and 5-year survival from 2% to 10% [2]
Pseudoprogression is defined as progressive gadolinium-enhanced lesions on MRI immediately after the end of concurrent chemoradiotherapy, following stabilisation or spontaneous improvement in the contrast-enhanced lesions without further treatment other than adjuvant TMZ [3, 4]

Summary

Introduction

Glioblastoma (GBM) is the most common and most aggressive primary brain tumour. Pseudoprogression is defined as progressive gadolinium-enhanced lesions on MRI immediately after the end of concurrent chemoradiotherapy, following stabilisation or spontaneous improvement in the contrast-enhanced lesions without further treatment other than adjuvant TMZ [3, 4]. This is observed in 28– 66% of all GBM patients undergoing chemoradiotherapy, and primarily occurs within the first 3 months after completion of chemoradiotherapy [5]. Standard treatment with adjuvant TMZ should be continued, whereas in patients with true tumour progression, other treatment modalities – scarce – or palliative supportive care are more appropriate

Objectives

Methods

Results