Treatment Monitoring of Immunotherapy and Targeted Therapy using 18F-FET PET in Patients with Melanoma and Lung Cancer Brain Metastases: Initial Experiences.

Purpose: We investigated the value of O-(2-[18F]fluoroethyl)-L-tyrosine (18F-FET) PET for treatment monitoring of immune checkpoint inhibition (ICI) or targeted therapy (TT) alone or in combination with radiotherapy in patients with brain metastases (BM) since contrast-enhanced MRI often remains inconclusive. Methods: We retrospectively identified 40 patients with 107 BM secondary to melanoma (n = 29 with 75 BM) or non-small cell lung cancer (n = 11 with 32 BM) treated with ICI or TT who had 18F-FET PET (n = 60 scans) for treatment monitoring from 2015-2019. The majority of patients (n = 37; 92.5%) had radiotherapy during the course of disease. In 27 patients, 18F-FET PET was used for the differentiation of treatment-related changes from BM relapse following ICI or TT. In 13 patients, 18F-FET PET was performed for response assessement to ICI or TT using baseline and follow-up scans (median time between scans, 4.2 months). In all lesions, static and dynamic 18F-FET PET parameters were obtained (i.e., mean tumor-to-brain ratios (TBR), time-to-peak values). Diagnostic accuracies of PET parameters were evaluated by receiver-operating-characteristic analyses using the clinical follow-up or neuropathological findings as reference. Results: A TBR threshold of 1.95 differentiated BM relapse from treatment-related changes with an accuracy of 85% (P = 0.003). Metabolic responders to ICI or TT on 18F-FET PET had a significantly longer stable follow-up (threshold of TBR reduction relative to baseline, ≥10%; accuracy, 82%; P = 0.004). Furthermore, at follow-up, time-to-peak values in metabolic responders increased significantly (P = 0.019). Conclusion: 18F-FET PET may add valuable information for treatment monitoring in BM patients treated with ICI or TT.