Clinical applications and prospects of PET imaging in patients with IDH-mutant gliomas.

PET imaging using radiolabeled amino acids in addition to MRI has become a valuable diagnostic tool in the clinical management of patients with brain tumors. This review provides a comprehensive overview of PET studies in glioma patients with a mutation in the isocitrate dehydrogenase gene (IDH). A considerable fraction of these tumors typically show no contrast enhancement on MRI, especially when classified as grade 2 according to the World Health Organization classification of Central Nervous System tumors. Major diagnostic challenges in this situation are differential diagnosis, target definition for diagnostic biopsies, delineation of glioma extent for treatment planning, differentiation of treatment-related changes from tumor progression, and the evaluation of response to alkylating agents. The main focus of this review is the role of amino acid PET in this setting. Furthermore, in light of clinical trials using IDH inhibitors targeting the mutated IDH enzyme for treating patients with IDH-mutant gliomas, we also aim to give an outlook on PET probes specifically targeting the IDH mutation, which appear potentially helpful for response assessment.

Efficacy and tolerability of regorafenib in pretreated patients with progressive CNS grade 3 or 4 gliomas.

BACKGROUND: The phase 2 REGOMA trial suggested an encouraging overall survival benefit in glioblastoma patients at first relapse treated with the multikinase inhibitor regorafenib. Here, we evaluated the efficacy and side effects of regorafenib in a real-life setting. METHODS: From 2018 to 2021, 30 patients with progressive WHO CNS grade 3 or 4 gliomas treated with regorafenib (160 mg/day; first 3 weeks of each 4-week cycle) with individual dose adjustment depending on toxicity were retrospectively identified. Side effects were evaluated according to the Common Terminology Criteria for Adverse Events (version 5.0). MRI was obtained at baseline and after every second cycle. Tumor progression was assessed according to RANO criteria. After regorafenib initiation, the median PFS and OS were calculated. RESULTS: The median number of treatment lines before regorafenib was 2 (range 1-4). Most patients (73%) had two or more pretreatment lines. At first relapse, 27% of patients received regorafenib. A total of 94 regorafenib cycles were administered (median 2 cycles; range 1-9 cycles). Grade 3 and 4 side effects were observed in 47% and 7% of patients, respectively, and were not significantly increased in patients with two or more pretreatments (P > 0.05). The most frequent grade 3 or 4 side effects were laboratory abnormalities (62%). PFS was 2.6 months (range 0.8-8.2 months), and the OS was 6.2 months (range 0.9-24 months). CONCLUSIONS: In patients with progressive WHO grade 3 or 4 gliomas, predominantly with two pretreatment lines or more, regorafenib seems to be effective despite considerable grade 3 or 4 side effects.

Current Landscape and Emerging Fields of PET Imaging in Patients with Brain Tumors.

The number of positron-emission tomography (PET) tracers used to evaluate patients with brain tumors has increased substantially over the last years. For the management of patients with brain tumors, the most important indications are the delineation of tumor extent (e.g., for planning of resection or radiotherapy), the assessment of treatment response to systemic treatment options such as alkylating chemotherapy, and the differentiation of treatment-related changes (e.g., pseudoprogression or radiation necrosis) from tumor progression. Furthermore, newer PET imaging approaches aim to address the need for noninvasive assessment of tumoral immune cell infiltration and response to immunotherapies (e.g., T-cell imaging). This review summarizes the clinical value of the landscape of tracers that have been used in recent years for the above-mentioned indications and also provides an overview of promising newer tracers for this group of patients.

FET PET reveals considerable spatial differences in tumour burden compared to conventional MRI in newly diagnosed glioblastoma.

PURPOSE: Areas of contrast enhancement (CE) on MRI are usually the target for resection or radiotherapy target volume definition in glioblastomas. However, the solid tumour mass may extend beyond areas of CE. Amino acid PET can detect parts of the tumour that show no CE. We systematically investigated tumour volumes delineated by amino acid PET and MRI in patients with newly diagnosed, untreated glioblastoma. METHODS: Preoperatively, 50 patients with neuropathologically confirmed glioblastoma underwent O-(2-[18F]-fluoroethyl)-L-tyrosine (FET) PET, and fluid-attenuated inversion recovery (FLAIR) and contrast-enhanced MRI. Areas of CE were manually segmented. FET PET tumour volumes were segmented using a tumour-to-brain ratio of ≥1.6. The percentage overlap volumes, and Dice and Jaccard spatial similarity coefficients (DSC, JSC) were calculated. FLAIR images were evaluated visually. RESULTS: In 43 patients (86%), the FET tumour volume was significantly larger than the CE volume (21.5 ± 14.3 mL vs. 9.4 ± 11.3 mL; P < 0.001). Forty patients (80%) showed both increased uptake of FET and CE. In these 40 patients, the spatial similarity between FET uptake and CE was low (mean DSC 0.39 ± 0.21, mean JSC 0.26 ± 0.16). Ten patients (20%) showed no CE, and one of these patients showed no FET uptake. In five patients (10%), increased FET uptake was present outside areas of FLAIR hyperintensity. CONCLUSION: Our results show that the metabolically active tumour volume delineated by FET PET is significantly larger than tumour volume delineated by CE. Furthermore, the results strongly suggest that the information derived from both imaging modalities should be integrated into the management of patients with newly diagnosed glioblastoma.

Differentiation of treatment-related changes from tumour progression: a direct comparison between dynamic FET PET and ADC values obtained from DWI MRI.

BACKGROUND: Following brain cancer treatment, the capacity of anatomical MRI to differentiate neoplastic tissue from treatment-related changes (e.g., pseudoprogression) is limited. This study compared apparent diffusion coefficients (ADC) obtained by diffusion-weighted MRI (DWI) with static and dynamic parameters of O-(2-[18F]fluoroethyl)-L-tyrosine (FET) PET for the differentiation of treatment-related changes from tumour progression. PATIENTS AND METHODS: Forty-eight pretreated high-grade glioma patients with anatomical MRI findings suspicious for progression (median time elapsed since last treatment was 16 weeks) were investigated using DWI and dynamic FET PET. Maximum and mean tumour-to-brain ratios (TBRmax, TBRmean) as well as dynamic parameters (time-to-peak and slope values) of FET uptake were calculated. For mean ADC calculation, regions-of-interest analyses were performed on ADC maps calculated from DWI coregistered with the contrast-enhanced MR image. Diagnoses were confirmed neuropathologically (21%) or clinicoradiologically. Diagnostic performance was evaluated using receiver-operating-characteristic analyses or Fisher's exact test for a combinational approach. RESULTS: Ten of 48 patients had treatment-related changes (21%). The diagnostic performance of FET PET was significantly higher (threshold for both TBRmax and TBRmean, 1.95; accuracy, 83%; AUC, 0.89 ± 0.05; P < 0.001) than that of ADC values (threshold ADC, 1.09 × 10-3 mm2/s; accuracy, 69%; AUC, 0.73 ± 0.09; P = 0.13). The addition of static FET PET parameters to ADC values increased the latter's accuracy to 89%. The highest accuracy was achieved by combining static and dynamic FET PET parameters (93%). Moreover, in contrast to ADC values, TBRs <1.95 at suspected progression predicted a significantly longer survival (P = 0.01). CONCLUSIONS: Data suggest that static and dynamic FET PET provide valuable information concerning the differentiation of early treatment-related changes from tumour progression and outperform ADC measurement for this highly relevant clinical question.

Dabrafenib Treatment in a Patient with an Epithelioid Glioblastoma and BRAF V600E Mutation.

Novel therapeutic targets in malignant glioma patients are urgently needed. Point mutations of the v-Raf murine sarcoma viral oncogene homolog B (BRAF) gene occur predominantly in melanoma patients, but may also occur in gliomas. Thus, this is a target of great interest for this group of patients. In a nine-year-old male patient, an anaplastic astrocytoma in the left temporoparietal region was diagnosed histologically. After first- and second-line treatment, a malignant progression to a secondary glioblastoma was observed ten years after the initial diagnosis. Within the following seven years, all other conventional treatment options were exhausted. At this time point, recurrent tumor histology revealed an epithelioid glioblastoma, without a mutation in the isocitrate dehydrogenase gene (IDH wild-type). In order to identify a potential target for an experimental salvage therapy, mutational tumor analysis showed a BRAF V600E mutation. Consecutively, dabrafenib treatment was initiated. The patient remained clinically stable, and follow-up magnetic resonance images (MRI) were consistent with "Stable Disease" according to the Response Assessment in Neuro-Oncology Working Group (RANO) criteria for the following ten months until tumor progression was detected. The patient died 16 months after dabrafenib treatment initiation. Particularly in younger glioma patients as well as in patients with an epithelioid glioblastoma, screening for a V600E BRAF mutation is promising since, in these cases, targeted therapy with BRAF inhibitors seems to be a useful salvage treatment option.

PET imaging of gliomas: Status quo and quo vadis?

PET imaging, particularly using amino acid tracers, has become a valuable adjunct to anatomical MRI in the clinical management of patients with glioma. Collaborative international efforts have led to the development of clinical and technical guidelines for PET imaging in gliomas. The increasing readiness of statutory health insurance agencies, especially in European countries, to reimburse amino acid PET underscores its growing importance in clinical practice. Integrating artificial intelligence and radiomics in PET imaging of patients with glioma may significantly improve tumor detection, segmentation, and response assessment. Efforts are ongoing to facilitate the clinical translation of these techniques. Considerable progress in computer technology developments (eg quantum computers) may be helpful to accelerate these efforts. Next-generation PET scanners, such as long-axial field-of-view PET/CT scanners, have improved image quality and body coverage and therefore expanded the spectrum of indications for PET imaging in Neuro-Oncology (eg PET imaging of the whole spine). Encouraging results of clinical trials in patients with glioma have prompted the development of PET tracers directing therapeutically relevant targets (eg the mutant isocitrate dehydrogenase) for novel anticancer agents in gliomas to improve response assessment. In addition, the success of theranostics for the treatment of extracranial neoplasms such as neuroendocrine tumors and prostate cancer has currently prompted efforts to translate this approach to patients with glioma. These advancements highlight the evolving role of PET imaging in Neuro-Oncology, offering insights into tumor biology and treatment response, thereby informing personalized patient care. Nevertheless, these innovations warrant further validation in the near future.

MRI and 18F-FET PET for Multimodal Treatment Monitoring in Patients with Brain Metastases: A Cost-Effectiveness Analysis.

PET using the radiolabeled amino acid O-(2-[18F]fluoroethyl)-l-tyrosine (18F-FET) has been shown to be of value for treatment monitoring in patients with brain metastases after multimodal therapy, especially in clinical situations with equivocal MRI findings. As medical procedures must be justified socioeconomically, we determined the effectiveness and cost-effectiveness of 18F-FET PET for treatment monitoring of multimodal therapy, including checkpoint inhibitors, targeted therapies, radiotherapy, and combinations thereof in patients with brain metastases secondary to melanoma or non-small cell lung cancer. Methods: We analyzed already-published clinical data and calculated the associated costs from the German statutory health insurance system perspective. Two clinical scenarios were considered: decision tree model 1 determined the effectiveness of 18F-FET PET alone for identifying treatment-related changes, that is, the probability of correctly identifying patients with treatment-related changes confirmed by neuropathology or clinicoradiographically using the Response Assessment in Neuro-Oncology criteria for immunotherapy. The resulting cost-effectiveness ratio showed the cost for each correctly identified patient with treatment-related changes in whom MRI findings remained inconclusive. Decision tree model 2 calculated the effectiveness of both 18F-FET PET and MRI, that is, the probability of correctly identifying nonresponders to treatment. The incremental cost-effectiveness ratio was calculated to determine cost-effectiveness, that is, the cost for each additionally identified nonresponder by 18F-FET PET who would have remained undetected by MRI. One-way deterministic and probabilistic sensitivity analyses tested the robustness of the results. Results: 18F-FET PET identified 94% of patients with treatment-related changes, resulting in €1,664.23 (€1.00 = $1.08 at time of writing) for each correctly identified patient. Nonresponders were correctly identified in 60% by MRI and in 80% by 18F-FET PET, resulting in €3,292.67 and €3,915.83 for each correctly identified nonresponder by MRI and 18F-FET PET, respectively. The cost to correctly identify 1 additional nonresponder by 18F-FET PET, who would have remained unidentified by MRI, was €5,785.30. Conclusion: Given the considerable annual cost of multimodal therapy, the integration of 18F-FET PET can potentially improve patient care while reducing costs.

Differentiation of a Falcine Meningioma From Cerebral Venous Sinus Thrombosis Using DOTATATE PET.

ABSTRACT: Differentiating brain tumors from nonneoplastic lesions using conventional MRI may be challenging. Clinical symptoms often remain unspecific, and imaging findings from MRI may be inconclusive. We present the case of a 23-year-old woman in whom an MRI suggested a cerebral venous sinus thrombosis. On the other hand, additional atypical MRI findings raised doubts regarding the initial diagnosis. Given the need for a diagnostic procedure with higher sensitivity and specificity for neoplastic tissue, PET with the radiolabeled somatostatin receptor ligand DOTATATE ( 68 Ga-DOTA- d -Phe1-Tyr3-octreotate) was performed. DOTATATE PET facilitated the diagnosis of a falcine meningioma consistent with its value for the differential diagnosis of meningioma.

Prediction of response to lomustine-based chemotherapy in glioma patients at recurrence using MRI and FET PET.

BACKGROUND: We evaluated O-(2-[18F]fluoroethyl)-l-tyrosine (FET) PET and MRI for early response assessment in recurrent glioma patients treated with lomustine-based chemotherapy. METHODS: Thirty-six adult patients with WHO CNS grade 3 or 4 gliomas (glioblastoma, 69%) at recurrence (median number of recurrences, 1; range, 1-3) were retrospectively identified. Besides MRI, serial FET PET scans were performed at baseline and early after chemotherapy initiation (not later than two cycles). Tumor-to-brain ratios (TBR), metabolic tumor volumes (MTV), the occurrence of new distant hotspots with a mean TBR >1.6 at follow-up, and the dynamic parameter time-to-peak were derived from all FET PET scans. PET parameter thresholds were defined using ROC analyses to predict PFS of ≥6 months and OS of ≥12 months. MRI response assessment was based on RANO criteria. The predictive values of FET PET parameters and RANO criteria were subsequently evaluated using univariate and multivariate survival estimates. RESULTS: After treatment initiation, the median follow-up time was 11 months (range, 3-71 months). Relative changes of TBR, MTV, and RANO criteria predicted a significantly longer PFS (all P ≤ .002) and OS (all P ≤ .045). At follow-up, the occurrence of new distant hotspots (n ≥ 1) predicted a worse outcome, with significantly shorter PFS (P = .005) and OS (P < .001). Time-to-peak changes did not predict a significantly longer survival. Multivariate survival analyses revealed that new distant hotspots at follow-up FET PET were most potent in predicting non-response (P < .001; HR, 8.578). CONCLUSIONS: Data suggest that FET PET provides complementary information to RANO criteria for response evaluation of lomustine-based chemotherapy early after treatment initiation.

Advances in PET imaging for meningioma patients.

In patients with meningioma, diagnosis and treatment planning are predominantly based on anatomical imaging using MRI or CT. Constraints of these imaging modalities include precise meningioma delineation-especially at the skull base, in the case of trans-osseus growth, and in tumors with complex geometry-and the differentiation of post-therapeutic reactive changes from meningioma relapse. Advanced metabolic imaging using PET may help to characterize specific metabolic and cellular features providing additional information beyond the information derived from anatomical imaging alone. Accordingly, the use of PET in meningioma patients is steadily increasing. This review summarizes recent advances in PET imaging helpful for improving the clinical management of patients with meningioma.

An updated review on the diagnosis and assessment of post-treatment relapse in brain metastases using PET.

INTRODUCTION: Brain 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 COVERED: The 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 OPINION: Available 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.

Use of advanced neuroimaging and artificial intelligence in meningiomas.

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.

Cost Effectiveness of 18F-FET PET for Early Treatment Response Assessment in Glioma Patients After Adjuvant Temozolomide Chemotherapy.

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 (18F-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 18F-FET PET parameter changes predicted a significantly longer survival already after 2 cycles whereas MRI changes were not significant. Methods: To determine the effectiveness and cost effectiveness of serial 18F-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 18F-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 18F-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, 18F-FET PET increased the rate of correctly identified responders to chemotherapy by 26%; thus, 4 patients needed to be examined by 18F-FET PET to identify 1 additional responder. Considering the respective costs for serial 18F-FET PET and MRI, the ICER resulted in €4,396.83 for each additional correctly identified responder by 18F-FET PET. Sensitivity analyses confirmed the robustness of the results. Conclusion: In contrast to conventional MRI, the model suggests that 18F-FET PET is cost-effective in terms of ICER values. Considering the high cost of temozolomide, the integration of 18F-FET PET has the potential to avoid premature chemotherapy discontinuation at reasonable cost.

Oncologic Outcome and Immune Responses of Radiotherapy with Anti-PD-1 Treatment for Brain Metastases Regarding Timing and Benefiting Subgroups.

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% (non-concurrent; p = 0.008). Univariate Cox regression analysis detected following prognostic factors for OS: neutrophil-to-lymphocyte ratio NLR favoring <3 (low; HR 2.037 (1.184−3.506), p = 0.010), lactate dehydrogenase (LDH) favoring ≤ULN (HR 1.853 (1.059−3.241), p = 0.031), absence of neurological symptoms (HR 2.114 (1.285−3.478), p = 0.003), RT concept favoring SRS (HR 1.985 (1.112−3.543), p = 0.019), RT dose favoring ≥60 Gy (HR 0.519 (0.309−0.871), p = 0.013), and prior anti-CTLA4 treatment (HR 0.498 (0.271−0.914), p = 0.024). Independent prognostic factors for OS were concurrent RT-ICI application (HR 0.539 (0.299−0.971), p = 0.024) with a median OS of 17.61 vs. 6.83 months (non-concurrent), ECOG performance status favoring 0 (HR 7.756 (1.253−6.061), p = 0.012), cancer type favoring melanoma (HR 0.516 (0.288−0.926), p = 0.026), BM volume (PTV) favoring ≤3 cm3 (HR 1.947 (1.007−3.763), p = 0.048). Subgroups with the following factors showed significantly longer OS when being treated concurrently: RT dose <60 Gy (p = 0.014), PTV > 3 cm3 (p = 0.007), other cancer types than melanoma (p = 0.006), anti-CTLA4-naïve patients (p < 0.001), low NLR (p = 0.039), steroid intake ≤4 mg (p = 0.042). Specific immune responses, such as abscopal effects (AbEs), pseudoprogression (PsP), or immune-related adverse events (IrAEs), occurred more frequently with concurrent RT-ICI and resulted in better OS. Other toxicities, including radionecrosis, were not statistically different in both groups. The concurrent application of RT and ICI, the ECOG-PS, cancer type, and PTV had an independently prognostic impact on OS. In concurrently treated patients, treatment response (LC) was delayed and specific immune responses (AbE, PsP, IrAE) occurred more frequently with longer OS rates. Our results suggest that concurrent RT-ICI application is more beneficial than sequential treatment in patients with low pretreatment inflammatory status, more and larger BMs, and with other cancer types than melanoma.

Two Decades of Brain Tumour Imaging with O-(2-[18F]fluoroethyl)-L-tyrosine PET: The Forschungszentrum Jülich Experience.

O-(2-[18F]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 long experience in FET PET. Fifty to seventy per cent rated FET PET as being important for different aspects of the assessment of newly diagnosed gliomas, including differential diagnosis, delineation of tumour extent for biopsy guidance, and treatment planning such as surgery or radiotherapy, 95% for the diagnosis of recurrent glioma, and 68% for the diagnosis of recurrent brain metastases. Approximately 50% of the referring physicians rated FET PET as necessary for treatment monitoring in patients with glioma or brain metastases. All referring physicians stated that the availability of FET PET is essential and that it should be approved for routine use. Although the present analysis is limited by the fact that only physicians who frequently referred patients for FET PET participated in the survey, the results confirm the high relevance of FET PET in the clinical diagnosis of brain tumours and support the need for its approval for routine use.

Case Report: Detection of Symptomatic Treatment-Related Changes in a Patient With Anaplastic Oligodendroglioma Using FET PET.

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-(18F)-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.

Uncovering an Optic Nerve Sheath Meningioma Using 68Ga-DOTATATE PET/CT.

ABSTRACT: 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. 68Ga-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.

Prognostic value of pre-irradiation FET PET in patients with not completely resectable IDH-wildtype glioma and minimal or absent contrast enhancement.

In glioma patients, complete resection of the contrast-enhancing portion is associated with improved survival, which, however, cannot be achieved in a considerable number of patients. Here, we evaluated the prognostic value of O-(2-[18F]-fluoroethyl)-L-tyrosine (FET) PET in not completely resectable glioma patients with minimal or absent contrast enhancement before temozolomide chemoradiation. Dynamic FET PET scans were performed in 18 newly diagnosed patients with partially resected (n = 8) or biopsied (n = 10) IDH-wildtype astrocytic glioma before initiation of temozolomide chemoradiation. Static and dynamic FET PET parameters, as well as contrast-enhancing volumes on MRI, were calculated. Using receiver operating characteristic analyses, threshold values for which the product of paired values for sensitivity and specificity reached a maximum were obtained. Subsequently, the prognostic values of FET PET parameters and contrast-enhancing volumes on MRI were evaluated using univariate Kaplan-Meier and multivariate Cox regression (including the MTV, age, MGMT promoter methylation, and contrast-enhancing volume) survival analyses for progression-free and overall survival (PFS, OS). On MRI, eight patients had no contrast enhancement; the remaining patients had minimal contrast-enhancing volumes (range, 0.2-5.3 mL). Univariate analyses revealed that smaller pre-irradiation FET PET tumor volumes were significantly correlated with a more favorable PFS (7.9 vs. 4.2 months; threshold, 14.8 mL; P = 0.012) and OS (16.6 vs. 9.0 months; threshold, 23.8 mL; P = 0.002). In contrast, mean tumor-to-brain ratios and time-to-peak values were only associated with a longer PFS (P = 0.048 and P = 0.045, respectively). Furthermore, the pre-irradiation FET PET tumor volume remained significant in multivariate analyses (P = 0.043), indicating an independent predictor for OS. Our results suggest that pre-irradiation FET PET parameters have a prognostic impact in this subgroup of patients.