title: Suspected recurrence of brain metastases after focused high dose radiotherapy: can [18F]FET- PET overcome diagnostic uncertainties?
abstract: 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 (TBRmaxand 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.
  
  
  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 (TBRmax2.9 vs. 2.0, p < 0.001; TBRmean2.2 vs. 1.7, p < 0.001). Receiver-operating-characteristic (ROC) curve analysis revealed optimal cut-off values of 2.15 for TBRmaxand 1.95 for TBRmean(sensitivity 86 %, specificity 79 %). Increasing TACs and long TTPminwere 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.
authors: Department of Neurosurgery, Ludwig-Maximilians-University of Munich, Munich, Germany.
authors: Alexander
authors: A
authors: Romagna
authors: Department of Nuclear Medicine, Ludwig-Maximilians-University of Munich, Marchioninistr. 15, 81377, Munich, Germany.
authors: Marcus
authors: M
authors: Unterrainer
authors: Institute of Clinical Radiology, Ludwig-Maximilians-University of Munich, Munich, Germany.
authors: Christine
authors: C
authors: Schmid-Tannwald
authors: Department of Nuclear Medicine, Ludwig-Maximilians-University of Munich, Marchioninistr. 15, 81377, Munich, Germany.
authors: Matthias
authors: M
authors: Brendel
authors: Department of Neurosurgery, Ludwig-Maximilians-University of Munich, Munich, Germany.
authors: Jörg-Christian
authors: JC
authors: Tonn
authors: Department of Radiation Oncology, Hospital of the University of Munich, Campus Grosshadern, Ludwig-Maximilians-University of Munich, Munich, Germany.
authors: Silke Birgit
authors: SB
authors: Nachbichler
authors: European CyberKnife Center Munich, Munich, Germany.
authors: Alexander
authors: A
authors: Muacevic
authors: Department of Nuclear Medicine, Ludwig-Maximilians-University of Munich, Marchioninistr. 15, 81377, Munich, Germany.
authors: Peter
authors: P
authors: Bartenstein
authors: Department of Neurosurgery, Ludwig-Maximilians-University of Munich, Munich, Germany.
authors: Friedrich-Wilhelm
authors: FW
authors: Kreth
authors: Department of Nuclear Medicine, Ludwig-Maximilians-University of Munich, Marchioninistr. 15, 81377, Munich, Germany. Nathalie.Albert@med.uni-muenchen.de.
authors: Nathalie Lisa
authors: NL
authors: Albert
mesh_terms: D001918:Brachytherapy; D001932:Brain Neoplasms / Q000000981:diagnostic imaging* / Q000532:radiotherapy* / Q000556:secondary; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000000981:diagnostic imaging*; D049268:Positron-Emission Tomography; D012372:ROC Curve; D016634:Radiosurgery; D014443:Tyrosine / Q000031:analogs & derivatives
chemical_list: C117289:O-(2-fluoroethyl)tyrosine; D014443:Tyrosine
keywords: 18F-FET PET; Brain metastases; Kinetic analysis; Radionecrosis; Radiosurgery