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

Abstract

Purpose: We investigated the value of O-(2-[ 18 F]fluoroethyl)-L-tyrosine ( 18 F-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 contrastenhanced 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 18 F-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 27patients, 18 F-FET PET was used for the differentiation of treatment-related changes from BM relapse following ICI or TT. In 13 patients, 18 F-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 18 F-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 18 F-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).

EANO–ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up of patients with brain metastasis from solid tumours

“…Perfusion MRI and MRI spectroscopy are increasingly used in this setting, but evidence for their ability to aid in differential diagnosis remains low [84] for correct differentiation are in the range of 80%-90% [87]. Furthermore, amino acid PET using FET is also of value for the diagnosis of treatment-related changes following immunotherapy, using immune checkpoint inhibitors or targeted therapy, with or without RT [EANO III, C; ESMO IV, C] [88].…”

PET Imaging in Neuro-Oncology: An Update and Overview of a Rapidly Growing Area

“…PET imaging is currently being evaluated to assess treatment responses and preliminary results, with amino acid PET to monitor immune checkpoint inhibition and targeted therapy appearing promising [ 97 ].…”

Use of PET Imaging in Neuro-Oncological Surgery

“…A subsequent case report revealed a reduction in metabolic activity on AA-PET in a patient undergoing targeted therapy for non-small-cell lung cancer brain metastases indicating tumor response, while MR findings remained unchanged [ 52 ]. A recent study in a larger series of patients ( n = 40) with more than 100 brain metastases secondary to melanoma or non-small cell lung carcinoma treated with checkpoint inhibitors or targeted therapy combined with radiosurgery reported that 18 F-FET PET provides important diagnostic information in terms of response assessment [ 53 ]. Moreover, in that study, metabolic responders on 18 F-FET PET had a significantly longer progression-free survival in contrast to response determination based on contrast-enhanced MRI.…”