¹⁸F-FDOPA PET for Differentiating Recurrent or Progressive Brain Metastatic Tumors from Late or Delayed Radiation Injury After Radiation Treatment

Abstract

Brain metastases are frequently treated with radiation. It is critical to distinguish recurrent or progressive brain metastases (RPBM) from late or delayed radiation injury (LDRI). The purpose of this study was to examine the diagnostic accuracy as well as the prognostic power of 6-18 F-fluoro-L-dopa ( 18 F-FDOPA) PET for differentiating RPBM from LDRI. Methods: Thirty-two patients who had 83 previously irradiated brain metastases and who underwent 18 F-FDOPA PET because of an MR imaging-based suggestion of RPBM were studied retrospectively. PET studies were analyzed semiquantitatively (lesion-to-striatum and lesion-to-normal brain tissue ratios based on both maximum and mean standardized uptake values) and visually (4-point scale). The diagnostic accuracy of PET was verified by histopathologic analysis (n 5 9) or clinical follow-up (n 5 74) on a lesion-by-lesion basis. Receiver operating characteristic curve analysis was used to identify the best diagnostic indices. The power of 18 F-FDOPA PET to predict disease progression was evaluated with the Kaplan-Meier and Cox regression methods. Results: The best overall accuracy was achieved by visual scoring, with which a score of 2 or more (lesion uptake greater than or equal to striatum uptake) resulted in a sensitivity of 81.3% and a specificity of 84.3%. Semiquantitative 18 F-FDOPA PET uptake indices based on lesion-to-normal brain tissue ratios were significantly higher for RPBM than for LDRI. Among the various predictors tested, 18 F-FDOPA PET was the strongest predictor of tumor progression (hazard ratio, 6.26; P , 0.001), and the lesion-to-normal brain tissue ratio or visual score was the best discriminator. The mean time to progression was 4.6 times longer for lesions with negative 18 F-FDOPA PET results than for lesions with positive 18 F-FDOPA PET results (76.5 vs. 16.7 mo; P , 0.001). 18 F-FDOPA PET findings tended to predict overall survival. Conclusion: Metabolic imaging with 18 F-FDOPA PET was useful for differentiating RPBM from LDRI. Semiquantitative indices, particularly lesionto-normal uptake ratios, could be used. A visual score comparing tumor 18 F-FDOPA uptake and striatum 18 F-FDOPA uptake provided the highest sensitivity and specificity and was predictive of disease progression.

Letter to the Editor: “The role of imaging in the management of progressive glioblastoma. A systematic review and evidence-based clinical practice guideline” [J Neurooncol 2014; 118:435–460]

“…Excellent results with FDOPA PET were also reported regarding the monitoring of antiangiogenic treatement [14] and for the differentiation of recurrent brain metastases from radiation-induced changes [15].…”

PET for Therapy Response Assessment in Glioblastoma

“…Differentiation between RN and recurrent brain tumor presents a diagnostic dilemma as both entities frequently develop at the resection site and often have a similar appearance on conventional MRI (20,21). Both types of lesions can have similar clinical presentations, such as seizures, focal neurologic deficits, and increased intracranial pressure (25). Obviously, a correct diagnosis is important for further patient management.…”

“…Furthermore, amino acid PET was assumed to be superior to both 18 F-FCho PET and 18 F-FDG PET for diagnostic accuracy in distinguishing glioma recurrence from RN (6,49,50,83). Using 18 F-FDOPA PET, a sensitivity and specificity of more than 80% to distinguish recurrent GB or recurrent brain metastasis and radiation-related effects was shown (25,84). However, the lack of physiological 18 F-FET uptake in the basal ganglia when compared with 18 F-FDOPA PET makes 18 F-FET the most promising amino acid tracer for PET imaging in brain tumor patients (31).…”

“…Late vascular changes include vessel wall thickening, with resulting occlusive vasculopathy, perivascular parenchymal coagulative necrosis, and inflammation. Late delayed reactions are reported to occur in 3-24% of patients from 3 months to 13 years after the completion of RT (23)(24)(25)(26). The risk increases with increasing radiation dose, fraction size, irradiated volume, and the (concomitant) administration of chemotherapy (24).…”

18F-fluorodopa positron-emission tomography: an emerging imaging modality for patients with brain metastases

“…The distinction of tumor recurrence or progression from radiation injury is possible with the use of 18 F-FDOPA PET [14,15]. A sensitivity of 81.3% and specificity of 84.3% have been recently reported [15].…”