Recurrent glioblastoma versus late posttreatment changes: diagnostic accuracy of O-(2-[18F]fluoroethyl)-L-tyrosine positron emission tomography (18F-FET PET)

Abstract

Background: Diagnostic accuracy in previous studies of O-(2-[18F]-fluoroethyl)-L-tyrosine (18F-FET) PET in patients with suspected recurrent glioma may be influenced by prolonged dynamic PET acquisitions, heterogeneous populations, different non-standard-of-care therapies, and PET scans performed at different time points post radiotherapy. We investigated the diagnostic accuracy of a 20-minute 18F-FET PET scan in MRI-suspected recurrent glioblastoma 6 months after standard radiotherapy and its ability to prognosticate overall survival (OS).

Methods: In total, 146 glioblastoma patients with 168 18F-FET PET scans were reviewed retrospectively. Patients with MRI responses to bevacizumab or undergoing re-irradiation or immunotherapy after 18F-FET PET were excluded. Maximum and mean tumor-to-background ratios (TBRmax, TBRmean) and biological tumor volume (BTV) were recorded and verified by histopathology or clinical/radiological follow-up. Thresholds of 18F-FET parameters were determined by receiver operating characteristic (ROC) analysis. Prognostic factors were investigated in Cox proportional hazards models.

Results: Surgery was performed after 104 18F-FET PET scans, while clinical/radiological surveillance was used following 64, identifying 152 glioblastoma recurrences and 16 posttreatment changes. ROC analysis yielded thresholds of 2.0 for TBRmax, 1.8 for TBRmean, and 0.55 cm3 for BTV in differentiating recurrent glioblastoma from posttreatment changes with the best performance of TBRmax (sensitivity 99%, specificity 94%; P < 0.0001) followed by BTV (sensitivity 98%, specificity 94%; P < 0.0001). Using these thresholds, 166 18F-FET PET scans were correctly classified. Increasing BTV was associated with shorter OS (P < 0.0001).

Conclusion: A 20-minute 18F-FET PET scan is a powerful tool to distinguish posttreatment changes from recurrent glioblastoma 6-month postradiotherapy, and predicts OS.

Keywords: 18F-FET PET; glioblastoma; posttreatment changes; tumor recurrence.

© The Author(s) 2019. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Figures

Fig. 1

Inclusion and exclusion criteria for patients referred for18F-FET PET in the time period of November 2011 until March 2019.

Fig. 2

Case study: Suspected sampling error. A 62-year-old patient with glioblastoma, treated with subtotal tumor resection (STR) and Stupp. Eight months after radiotherapy, MRI showed a mixed response with regression of the contrast-enhancing necrotic tumor process (shown) and increased T2/FLAIR changes (not shown) in the left-sided frontal lobe, overall suggesting tumor progression.18F-FET PET showed marked uptake in the left orbitofrontal region, indicating tumor recurrence with TBRmax of 2.7 and BTV of 29 cm3. Patient underwent an STR a month later with a histopathology revealing predominantly reactive changes and only insignificant amount of glioblastoma tissue. Patient had an unfavorable outcome with clinical progression only 2 months and death 6.5 months after18F-FET PET. (Left) Preoperative MRI, (middle)18F-FET PET, and (right) postoperative MRI. As brain shift was insignificant, postoperative MRI allowed the resected tissue area to be delineated (red border) and projected to preoperative PET (with previous resection delineated with yellow/orange border) to estimate the volume of active tissue resected, which was below 5%, and might not have been in the tissue specimen at histopathological examination.

Fig. 3

False-negative and false-positive18F-FET PET scans. (A) A 62-year-old patient with a left-sided frontal glioblastoma, treated with gross tumor resection and Stupp. Eleven months after adjuvant TMZ, MRI showed a nonmeasurable solitary contrast enhancement at the anterior part of the surgical cavity, identified by 18F-FET PET with TBRmax of 1.9 and BTV of 0.5 cm3. A suspicion of disease recurrence was raised due to the nodular configuration. Subsequent histopathology showed recurrent glioblastoma (magnification x200). (B) A 48-year-old patient with a left-sided temporal glioblastoma, treated with subtotal tumor resection and Stupp, and re-resection 5 months later with histopathological findings of posttreatment changes. Nine months after radiotherapy, MRI demonstrated progressive contrast-enhancing lesion near the surgical cavity. Two consecutive 18F-FET PET with a 4-week window showed increased uptakes, with TBRmax of 3.1 and 3.5, respectively. Three months later, a spontaneous regression was observed.

Fig. 4

Kaplan–Meier plot of OS. Kaplan–Meier survival analysis plot for prediction of OS, stratified by TBRmax and BTV with thresholds set at 2.0 and 0.55 cm3, respectively.