Suspected recurrence of brain metastases after focused high dose radiotherapy: can [18F]FET- PET overcome diagnostic uncertainties?

Abstract

BackgroundAfter focused high dose radiotherapy of brain metastases, differentiation between tumor recurrence and radiation-induced lesions by conventional MRI is challenging. This study investigates the usefulness of dynamic O-(2-18F-Fluoroethyl)-L-Tyrosine positron emission tomography (18F-FET PET) in patients with MRI-based suspicion of tumor recurrence after focused high dose radiotherapy of brain metastases.MethodsTwenty-two patients with 34 brain metastases (median age 61.9 years) were included. Due to follow-up scan evaluations after repeated treatment in a subset of patients, a total of 50 lesions with MRI-based suspicion of tumor recurrence after focused high dose radiotherapy could be evaluated. 18F-FET PET analysis included the assessment of maximum and mean tumor-to-background ratio (TBRmax and TBRmean) and analysis of time-activity-curves (TAC; increasing vs. decreasing) including minimal time-to-peak (TTPmin). PET parameters were correlated with histological findings and radiological-clinical follow-up evaluation.ResultsTumor recurrence was found in 21/50 cases (15/21 verified by histology, 6/21 by radiological-clinical follow-up) and radiation-induced changes in 29/50 cases (5/29 verified by histology, 24/29 by radiological-clinical follow-up). Median clinical-radiological follow-up was 28.3 months (range 4.2–99.1 months). 18F-FET uptake was higher in tumor recurrence compared to radiation-induced changes (TBRmax 2.9 vs. 2.0, p < 0.001; TBRmean 2.2 vs. 1.7, p < 0.001). Receiver-operating-characteristic (ROC) curve analysis revealed optimal cut-off values of 2.15 for TBRmax and 1.95 for TBRmean (sensitivity 86 %, specificity 79 %). Increasing TACs and long TTPmin were associated with radiation-induced changes, decreasing TACs with tumor recurrence (p = 0.01). By combination of TBR and TACs, sensitivity and specificity could be increased to 93 and 84 %.ConclusionsIn patients with MRI-suspected tumor recurrence after focused high dose radiotherapy, 18F-FET PET has a high sensitivity and specificity for the differentiation of vital tumor tissue and radiation-induced lesions.

Brain metastases: neuroimaging

“…7.8) (Ceccon et al, 2016). Similar accuracy (sensitivity of 86% and specificity of 79% using tumor-to-brain ratio maximum, with cutoff of 2.15) has been reported in other fairly large studies ( n = 50), which also showed added value of time–activity curves (sensitivity and specificity increased to 93% and 84% respectively) (Romagna et al, 2016). …”

CyberKnife Radiosurgery in Recurrent Brain Metastases: Do the Benefits Outweigh the Risks?

“…For treatment planning, the MRI protocols consisted of T1-weighted ± gadolinium contrast medium, T2-weighted, and fluid-attenuated inversion recovery (FLAIR) sequences, with a slice thickness of 1.0 mm. O-(2-[18 F]fluoroethyl)-1-tyrosine positron emission tomography (FET-PET) was applied with increasing frequency over the course of the treatment, as previously described, but was not part of the standardized management algorithm [9]. Three-dimensional isocentric/conformal noncoplanar treatment planning was routinely chosen to match the tumor volume as previously described.…”

Evaluation of the Performance of 18F-Fluorothymidine Positron Emission Tomography/Computed Tomography (18F-FLT-PET/CT) in Metastatic Brain Lesions

“…Other PET radiopharmaceuticals besides FDG have also been investigated in the setting of brain metastatic disease with promising results. Radiolabeled amino acids are the most common radiopharmaceuticals used for investigating new and recurrent brain metastasis, distinguishing true progression from pseudo progression, visualizing irradiated brain metastatic lesions, and managing patients for long-term treatment [22,23,24,26,27]. Finally, a cost-effectiveness analysis showed that the utilization of 18F-FET, in addition to MRI, for recurrent brain metastasis after radiotherapy may be cost-effective [26].…”