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

Background: After 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.

Methods: Twenty-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 (TBR_max and TBR_mean) and analysis of time-activity-curves (TAC; increasing vs. decreasing) including minimal time-to-peak (TTP_min). PET parameters were correlated with histological findings and radiological-clinical follow-up evaluation.

Results: Tumor 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 (TBR_max 2.9 vs. 2.0, p < 0.001; TBR_mean 2.2 vs. 1.7, p < 0.001). Receiver-operating-characteristic (ROC) curve analysis revealed optimal cut-off values of 2.15 for TBR_max and 1.95 for TBR_mean (sensitivity 86 %, specificity 79 %). Increasing TACs and long TTP_min 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 %.

Conclusions: In 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.