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IntroductionBrain metastases in patients with extracranial cancer are typically associated with increased morbidity and mortality. Stereotactic radiotherapy and immunotherapy using checkpoint inhibitors currently are essential in brain metastases treatment. Since conventional contrast-enhanced MRI alone cannot reliably differentiate between treatment-induced changes and brain metastasis relapse, several studies investigated the role of PET imaging and, more recently, radiomics, based on routinely acquired PET images, to overcome this clinically relevant challenge.Areas coveredThe current literature on PET imaging, including radiomics, in patients with brain metastases, focusing on the diagnosis and assessment of post-treatment relapse, is summarized.Expert opinionAvailable data suggest that imaging parameters, including radiomics features, mainly derived from amino acid PET, are helpful for diagnosis and assessment of post-treatment relapse in patients with brain metastases.

Simple Summary PET using radiolabelled amino acids has become an essential tool for diagnosing brain tumours in addition to MRI. O-(2-[F-18]fluoroethyl)-L-tyrosine (FET) is one of the most successful tracers in the field. We analysed our database of 6534 FET PET examinations regarding the diagnostic needs and preferences of the referring physicians for FET PET in the clinical decision-making process. The demand for FET PET increased considerably in the last decade, especially for differentiating tumour progress from treatment-related changes in gliomas. Accordingly, referring physicians rated the diagnostics of recurrent glioma and recurrent brain metastases as the most relevant indication for FET PET. The analysis and survey results confirm the high relevance of FET PET in the clinical diagnosis of brain tumours and support the need for approval for routine use. O-(2-[F-18]fluoroethyl)-L-tyrosine (FET) is a widely used amino acid tracer for positron emission tomography (PET) imaging of brain tumours. This retrospective study and survey aimed to analyse our extensive database regarding the development of FET PET investigations, indications, and the referring physicians' rating concerning the role of FET PET in the clinical decision-making process. Between 2006 and 2019, we performed 6534 FET PET scans on 3928 different patients against a backdrop of growing demand for FET PET. In 2019, indications for the use of FET PET were as follows: suspected recurrent glioma (46%), unclear brain lesions (20%), treatment monitoring (19%), and suspected recurrent brain metastasis (13%). The referring physicians were neurosurgeons (60%), neurologists (19%), radiation oncologists (11%), general oncologists (3%), and other physicians (7%). Most patients travelled 50 to 75 km, but 9% travelled more than 200 km. The role of FET PET in decision-making in clinical practice was evaluated by a questionnaire consisting of 30 questions, which was filled out by 23 referring physicians with l

Anatomical cross-sectional imaging methods such as contrast-enhanced MRI and CT are the standard for the delineation, treatment planning, and follow-up of patients with meningioma. Besides, advanced neuroimaging is increasingly used to non-invasively provide detailed insights into the molecular and metabolic features of meningiomas. These techniques are usually based on MRI, e.g., perfusion-weighted imaging, diffusion-weighted imaging, MR spectroscopy, and positron emission tomography. Furthermore, artificial intelligence methods such as radiomics offer the potential to extract quantitative imaging features from routinely acquired anatomical MRI and CT scans and advanced imaging techniques. This allows the linking of imaging phenotypes to meningioma characteristics, e.g., the molecular-genetic profile. Here, we review several diagnostic applications and future directions of these advanced neuroimaging techniques, including radiomics in preclinical models and patients with meningioma.

In light of increasing health-care costs, higher medical expenses should be justified socioeconomically. Therefore, we calculated the effectiveness and cost effectiveness of PET using the radiolabeled amino acid O-(2-18F-fluoroethyl)-L-tyrosine (F-18-FET) compared with conventional MRI for early identification of responders to adjuvant temozolomide chemotherapy. A recently published study in isocitrate dehydrogenase wild-type glioma patients suggested that F-18-FET PET parameter changes predicted a significantly longer survival already after 2 cycles whereasMRI changes were not significant. Methods: To determine the effectiveness and cost effectiveness of serial F-18-FET PET imaging, we analyzed published clinical data and calculated the associated costs from the perspective of the German Statutory Health Insurance system. Based on a decision-tree model, the effectiveness of F-18-FET PET and MRI was calculated-that is, the probability to correctly identify a responder as defined by an overall survival of at least 15 mo. To determine the cost effectiveness, the incremental cost effectiveness ratio (ICER) was calculated-that is, the cost for each additionally identified responder by F-18-FET PET who would have remained undetected by MRI. The robustness of the results was tested by deterministic and probabilistic Monte Carlo sensitivity analyses. Results: Compared with MRI, F-18-FET PET increased the rate of correctly identified responders to chemotherapy by 26%; thus, 4 patients needed to be examined by F-18-FET PET to identify 1 additional responder. Considering the respective costs for serial F-18-FET PET and MRI, the ICER resulted in (sic)4,396.83 for each additional correctly identified responder by F-18-FET PET. Sensitivity analyses confirmed the robustness of the results. Conclusion: In contrast to conventional MRI, the model suggests that F-18-FET PET is cost-effective in terms of ICER values. Considering the high cost of temozolomide, the integration of F-18-F

Simple Summary Immune checkpoint inhibitors (ICIs) and radiotherapy (RT) are widely used for patients with brain metastasis (BM). To evaluate markers for treatment response and find a treatment concept which has the best outcome effects, we analyzed data of 93 patients with BM from different cancer types. Predictive markers for survival were good performance status, melanoma as cancer type, low metastasis volume, normal inflammatory blood parameters, and a stereotactic radiotherapy concept with high doses. We found that the best survival outcome can be achieved with the concurrent use of RT and ICI. Concurrent treatment was particularly beneficial in patients with low inflammatory status and more and larger metastases, and when high doses cannot be administered. In concurrently treated patients, therapeutic response was often delayed compared to sequential treatment. Specific immune responses such as pseudoprogression and abscopal effects were induced by concurrent treatment and associated with prolonged survival. Abstract While immune checkpoint inhibitors (ICIs) in combination with radiotherapy (RT) are widely used for patients with brain metastasis (BM), markers that predict treatment response for combined RT and ICI (RT-ICI) and their optimal dosing and sequence for the best immunogenic effects are still under investigation. The aim of this study was to evaluate prognostic factors for therapeutic outcome and to compare effects of concurrent and non-concurrent RT-ICI. We retrospectively analyzed data of 93 patients with 319 BMs of different cancer types who received PD-1 inhibitors and RT at the University Hospital Cologne between September/2014 and November/2020. Primary study endpoints were overall survival (OS), progression-free survival (PFS), and local control (LC). We included 66.7% melanoma, 22.8% lung, and 5.5% other cancer types with a mean follow-up time of 23.8 months. Median OS time was 12.19 months. LC at 6 months was 95.3% (concurrent) vs. 69.2% (no

We investigated the value of O-(2-F-18-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 metastasis (BM) since contrast-enhanced MRI often remains inconclusive. Methods: We retrospectively identified 40 patients with 107 BMs secondary to melanoma (n = 29 with 75 BMs) or non-small cell lung cancer (n = 11 with 32 BMs) treated with ICI or TT who had F-18-FET PET (n = 60 scans) for treatment monitoring from 2015 to 2019. Most patients (n = 37; 92.5%) had radiotherapy during the course of the disease. In 27 patients, 18 FFET PET was used to differentiate treatment-related changes from BM relapse after ICI or TT. In 13 patients, F-18-FET PET was performed for response assessment to ICI or TT using baseline and follow-up scans (median time between scans, 4.2 mo). In all lesions, static and dynamic F-18-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 neuropathologic findings as a 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 F-18-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 in metabolic responders increased significantly (P = 0.019). Conclusion: F-18-FET PET may add valuable information for treatment monitoring in BM patients treated with ICI or TT.

Purpose The CeTeG/NOA-09 phase III trial demonstrated a significant survival benefit of lomustine-temozolomide chemoradiation in patients with newly diagnosed glioblastoma with methylated O-6-methylguanine-DNA methyltransferase (MGMT) promoter. Following lomustine-temozolomide chemoradiation, late and prolonged pseudoprogression may occur. We here evaluated the value of amino acid PET using O-(2[F-18]fluoroethyl)-L-tyrosine (FET) for differentiating pseudoprogression from tumor progression. Experimental Design: We retrospectively identified patients (i) who were treated off-study according to the CeTeG/NOA-09 protocol, (ii) had equivocal MRI findings after radiotherapy, and (iii) underwent additional FET-PET imaging for diagnostic evaluation (number of scans, 1-3). Maximum and mean tumor-to-brain ratios (TBRmax, TBRmean) and dynamic FET uptake parameters mean, (e.g., time-to-peak) were calculated. In patients with more than one FET-PET scan, relative changes of TBR values were evaluated, that is, an increase or decrease of >10% compared with the reference scan was considered as tumor progression or pseudoprogression. Diagnostic performances were evaluated using ROC curve analyses and Fisher exact test. Diagnoses were confirmed histologically or clinicoradiologically. Results: We identified 23 patients with 32 FET-PET scans. Within 5-25 weeks after radiotherapy (median time, 9 weeks), pseudoprogression occurred in 11 patients (48%). The parameter TBRmean calculated from the FET-PET performed 10 +/- 7 days after the equivocal MRI showed the highest accuracy (87%) to identify pseudoprogression (threshold, <1.95; P = 0.029). The integration of relative changes of TBRmean further improved the accuracy (91%; P < 0.001). Moreover, the combination of static and dynamic parameters increased the specificity to 100% (P = 0.005). Conclusions: The data suggest that FET-PET parameters are of significant clinical value to diagnose pseudoprogression related to lomustine-temozolomid

A 56-year-old woman was initially diagnosed with optic neuritis. However, several red flags were present: older age at presentation, no multiple sclerosis suspicious findings on MRI, and negative oligoclonal bands. Ga-68-DOTATATE PET/CT confirmed the differential diagnosis of an optic sheath meningioma. Our case stresses the value of the somatostatin receptor ligand PET/CT in patients with suspected optic neuritis if the diagnostic workup does not support immune-mediated pathogenesis.

Background: The goal of this study was to compare the value of contrast-enhanced MRI and O-(2-[F-18]fluoroethyl)-L-tyrosine (F-18-FET) PET for response assessment in gliomapatients after adjuvant temozolomide chemotherapy (TMZ). Methods: After biopsy or resection and completion of radiotherapywith concomitant TMZ, 41 newly diagnosed andhistomolecularlycharacterizedgliomapatients (glioblastoma, 90%; age range, 20-79 y) were subsequently treated with adjuvant TMZ. MR and F-18-FETPET imagingwereperformedatbaseline andafter the second cycle of adjuvant TMZ. We obtained F-18-FETmetabolic tumor volumes (MTVs) as well as mean and maximum tumor-to-brain ratios (TBRmean and TBRmax, respectively). Threshold values of F-18-FET PET parameters to predict outcome were established by receiver-operating-characteristic analyses using a median progression-free survival (PFS) of >= 9 mo and overall survival (OS) of >= 15 mo as reference. MRI response assessment was based on the Response Assessment in Neuro-Oncology (RANO) working group criteria. The predictive value of changes of F-18-FET PET andMRI parameters on survival was evaluated subsequently using univariate andmultivariate survival estimates. Results: After 2 cycles of adjuvant TMZ chemotherapy, a treatmentinduced reduction of MTV and TBRmax predicted a significantly longer PFS and OS (both P <= 0.03; univariate survival analyses) whereas RANO criteria were not significant (P = 0.05). Multivariate survival analysis revealed that TBRmax changes predicted a prolonged PFS (P > 0.012) and changes of MTV a prolonged OS (P > 0.005) independent of O-6-methylguanine-DNA-methyltransferase promoter methylation and other strong prognostic factors. Conclusion: Changes of F-18-FET PET parameters appear to be helpful for identifying responders to adjuvant TMZ early after treatment initiation.

Following local and systemic treatment of gliomas, the differentiation between glioma relapse and treatment-related changes such as pseudoprogression or radiation necrosis using conventional MRI is limited. To overcome this limitation, various amino acid PET tracers such as O-[2-(F-18)-fluoroethyl]-L-tyrosine (FET) are increasingly used and provide valuable additional clinical information. We here report neuroimaging findings in a clincally symptomatic 53-year-old woman with a recurrent anaplastic oligodendroglioma with MRI findings highly suspicious for tumor progression. In contrast, FET PET imaging suggested treatment-related changes considerably earlier than the regression of contrast enhancement on MRI. In patients with oligodendroglioma, the phenomenon of symptomatic treatment-related changes is not well described, making these imaging findings unique and important for clinical decision-making.