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We herein present a patient initially suspected of multiple lytic skeletal metastasis of unknown primary on anatomical imaging. Metabolic imaging by [18F]-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) detected focal [18F]FDG uptake in the right thyroid nodule, mild [18F]FDG uptake in soft tissue lesion in the left inferior parathyroid region, and multiple nonavid osteolytic skeletal lesions. Fine-needle aspiration cytology of the right thyroid nodule showed papillary thyroid carcinoma (PTC). The patient had raised serum parathyroid hormone and serum calcium levels, suggesting parathyroid disease. [18F]-sodium fluoride (NaF)-PET/CT showed a metabolic superscan pattern of hyperparathyroidism with brown tumors rather than metastatic lytic skeletal lesions. Patient underwent total thyroidectomy and bilateral central compartment clearance, along with soft tissue lesion resection in the left inferior parathyroid region. Finally, histopathology confirmed PTC classical variant with no aggressive histology features (pT1N0) for thyroid nodule and parathyroid adenoma for soft tissue lesion in the left inferior parathyroid region. The findings of the [18F]FDG and [18F]NaF-PET/CT imaging were helpful for making a final diagnosis of synchronous thyroid cancer and parathyroid adenoma, which in turn guided the appropriate treatment strategy. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to determine the organ-specific accuracy of [18F]FDG-PET/CT in identifying immune-related adverse events (irAEs) in patients with high-risk (stage III/IV) surgically resected melanoma treated with an adjuvant immune checkpoint inhibitor (ICI) and determine the incidence of irAEs within the first year after starting treatment. Materials and methods: This registry-based study included individuals who had undergone surgical removal of melanoma and were undergoing adjuvant ICI treatment (either nivolumab or pembrolizumab). The study specifically enrolled patients who had undergone both a baseline and at least one subsequent follow-up [18F]FDG-PET/CT scan. Follow-up scans were performed every third month in the first year after surgery to screen for disease recurrence. We retrospectively compared the follow-up scans with baseline scans to identify irAEs. Clinical information on irAEs was obtained from medical records and served as a reference standard for determining the accuracy of [18F]FDG-PET/CT. Results: A total of 123 patients with 363 [18F]FDG-PET/CT scans were included, and 65 patients (52.8%) developed irAEs. In decreasing order, the organ-specific incidences of irAEs were: skin 26/65 (40%), muscle and joints 21/65 (32.3%), intestines 13/65 (20%), thyroid gland 12/65 (18.5%), lungs 4/65 (6.2%), and heart 2/65 (3.1%). The sensitivities and specificities of [18F]FDG-PET/CT for diagnosing irAEs were: skin 19% (95% CI: 7–39%) and 95% (88–98%), muscles and joints 71% (48–89%) and 83% (75–90%), intestines 100% (75–100%) and 85% (77–91%); thyroid gland 92% (62–99%) and 95% (89–98%), lungs 75% (19–99%) and 90% (83–95%), and heart 50% (13–99%) and 97% (92–99%), respectively. Conclusion: [18F]FDG-PET/CT generally had moderate to high sensitivities (except for skin and heart) and specificities in diagnosing irAEs in patients receiving adjuvant ICI; this could be suggested to be systematically assessed and reported in scan reports. [ABSTRACT FROM AUTHOR]

During the initial staging of certain lymphoma subtypes, 18 F-fluorodeoxyglucose positron emission tomography/computed tomography ([18F]FDG-PET/CT) has become an alternative to bone marrow biopsy (BMB) for detecting bone marrow (BM) involvement. However, whether [18F]FDG-PET/CT can accurately detect BM involvement in angioimmunoblastic T-cell lymphoma (AITL) remains unknown. Our study aimed to assess the diagnostic and prognostic capability of [18F]FDG-PET/CT for detecting BM involvement in AITL. Methods: This retrospective study included 84 individuals newly diagnosed with AITL who underwent baseline BMB and [18F]FDG-PET/CT. "BM involvement" was defined as one or both of the following: 1) angioimmunoblastic T-cells detected in the BM; or 2) initially heightened focal uptake having disappeared on follow-up [18F]FDG-PET/CT. The ability of [18F]FDG-PET/CT to detect BM cancerous lesions was respectively analyzed by BM involvement confirmed by BMB or the aforementioned definition as the reference standard. The patients' clinical characteristics and survival and prognostic outcomes were respectively analyzed. Of the 84 participants, five (6.0%) displayed positive BMB and PET/BM results, 17 (20.2%) had BMB-positive but PET/BM-negative results, eight (9.5%) showed BMB-negative but PET/BM-positive outcomes, and 54 (64.3%) displayed negative BMB and PET/BM outcomes. Using pre-defined BM involvement as the reference standard, [18F]FDG-PET/CT exhibited a specificity of 100%, sensitivity of 40%, negative predictive value (NPV) of 75%, and positive predictive value (PPV) of 100%. In contrast, using BMB-detected BM involvement as reference, [18F]FDG-PET/CT exhibited a sensitivity, specificity, PPV, and NPV of 38.5%, 76.1%, 22.7%, and 87.1%, respectively. Among patients with PET/BM-positive and BMB-negative outcomes, 62.5% (5/8) underwent upstaging from III to IV. In 58.8% (10/17) of patients who were initially diagnosed with stage II/III disease based on the [18F]FDG-PET/CT results, repeat BMB resulted in upstaging to IV. PET/BM-negative patients had a higher 3-year progression-free survival rate (38.3% vs. 22.8%, p = 0.018) and 3-year overall survival rate (64.4% vs. 34.6%, p = 0.011) than PET/BM-positive patients. In AITL patients, PET/BM-positive results may obviate the necessity for repeat BMB to ascertain confirm BM involvement. PET/BM-negative results do not definitively exclude BM involvement. The combined use of [18F]FDG-PET/CT and BMB can increase the diagnostic accuracy of BM involvement for AITL patients. [ABSTRACT FROM AUTHOR]

Background: An accurate preoperative workup of cytologically indeterminate thyroid nodules (ITN) may rule out malignancy and avoid diagnostic surgery for benign nodules. This study assessed the performance of molecular diagnostics (MD) and 2-[18F]fluoro-2-deoxy-d-glucose ([18F]FDG)-positron emission tomography/computed tomography (PET/CT) in ITN, including their combined use, and explored whether molecular alterations drive the differences in [18F]FDG uptake among benign nodules. Methods: Adult, euthyroid patients with a Bethesda III or IV thyroid nodule were prospectively included in this multicenter study. They all underwent MD and an [18F]FDG-PET/CT scan of the neck. MD was performed using custom next-generation sequencing panels for somatic mutations, gene fusions, and copy number alterations and loss of heterozygosity. Sensitivity, specificity, negative and positive predictive value (NPV, PPV), and benign call rate (BCR) were assessed for MD and [18F]FDG-PET/CT separately and for a combined approach using both techniques. Results: In 115 of the 132 (87%) included patients, MD yielded a diagnostic result on cytology. Sensitivity, specificity, NPV, PPV, and BCR were 80%, 69%, 91%, 48%, and 57% for MD, and 93%, 41%, 95%, 36%, and 32% for [18F]FDG-PET/CT, respectively. When combined, sensitivity and specificity were 95% and 44% for a double-negative test (i.e., negative MD plus negative [18F]FDG-PET/CT) and 68% and 86% for a double-positive test, respectively. Concordance was 63% (82/130) between MD and [18F]FDG-PET/CT. There were more MD-positive nodules among the [18F]FDG-positive benign nodules (25/59, 42%, including 11 (44%) isolated RAS mutations) than among the [18F]FDG-negative benign nodules (7/30, 19%, p = 0.02). In oncocytic ITN, the BCR of [18F]FDG-PET/CT was mere 3% and MD was the superior technique. Conclusions: MD and [18F]FDG-PET/CT are both accurate rule-out tests when unresected nodules that remain unchanged on ultrasound follow-up are considered benign. It may vary worldwide which test is considered most suitable, depending on local availability of diagnostics, expertise, and cost-effectiveness considerations. Although complementary, the benefits of their combined use may be confined when therapeutic consequences are considered, and should therefore not routinely be recommended. In nononcocytic ITN, sequential testing may be considered in case of a first-step MD negative test to confirm that withholding diagnostic surgery is oncologically safe. In oncocytic ITN, after further validation studies, MD might be considered. Clinical Trial Registration: This trial is registered with ClinicalTrials.gov: NCT02208544 (August 5, 2014), https://clinicaltrials.gov/ct2/show/NCT02208544. [ABSTRACT FROM AUTHOR]

Abstract Background The main problem of positron emission tomography/computed tomography (PET/CT) for lymph node (LN) staging is the high false positive rate (FPR). Thus, we aimed to explore a clinico-biological-radiomics (CBR) model via machine learning (ML) to reduce FPR and improve the accuracy for predicting the hypermetabolic mediastinal–hilar LNs status in lung cancer than conventional PET/CT. Methods A total of 260 lung cancer patients with hypermetabolic mediastinal–hilar LNs (SUVmax ≥ 2.5) were retrospectively reviewed. Patients were treated with surgery with systematic LN resection and pathologically divided into the LN negative (LN-) and positive (LN +) groups, and randomly assigned into the training (n = 182) and test (n = 78) sets. Preoperative CBR dataset containing 1738 multi-scale features was constructed for all patients. Prediction models for hypermetabolic LNs status were developed using the features selected by the supervised ML algorithms, and evaluated using the classical diagnostic indicators. Then, a nomogram was developed based on the model with the highest area under the curve (AUC) and the lowest FPR, and validated by the calibration plots. Results In total, 109 LN− and 151 LN + patients were enrolled in this study. 6 independent prediction models were developed to differentiate LN− from LN + patients using the selected features from clinico-biological-image dataset, radiomics dataset, and their combined CBR dataset, respectively. The DeLong test showed that the CBR Model containing all-scale features held the highest predictive efficiency and the lowest FPR among all of established models (p

Background: The main problem of positron emission tomography/computed tomography (PET/CT) for lymph node (LN) staging is the high false positive rate (FPR). Thus, we aimed to explore a clinico-biological-radiomics (CBR) model via machine learning (ML) to reduce FPR and improve the accuracy for predicting the hypermetabolic mediastinal–hilar LNs status in lung cancer than conventional PET/CT. Methods: A total of 260 lung cancer patients with hypermetabolic mediastinal–hilar LNs (SUVmax ≥ 2.5) were retrospectively reviewed. Patients were treated with surgery with systematic LN resection and pathologically divided into the LN negative (LN-) and positive (LN +) groups, and randomly assigned into the training (n = 182) and test (n = 78) sets. Preoperative CBR dataset containing 1738 multi-scale features was constructed for all patients. Prediction models for hypermetabolic LNs status were developed using the features selected by the supervised ML algorithms, and evaluated using the classical diagnostic indicators. Then, a nomogram was developed based on the model with the highest area under the curve (AUC) and the lowest FPR, and validated by the calibration plots. Results: In total, 109 LN− and 151 LN + patients were enrolled in this study. 6 independent prediction models were developed to differentiate LN− from LN + patients using the selected features from clinico-biological-image dataset, radiomics dataset, and their combined CBR dataset, respectively. The DeLong test showed that the CBR Model containing all-scale features held the highest predictive efficiency and the lowest FPR among all of established models (p < 0.05) in both the training and test sets (AUCs of 0.90 and 0.89, FPRs of 12.82% and 6.45%, respectively) (p < 0.05). The quantitative nomogram based on CBR Model was validated to have a good consistency with actual observations. Conclusion: This study presents an integrated CBR nomogram that can further reduce the FPR and improve the accuracy of hypermetabolic mediastinal–hilar LNs evaluation than conventional PET/CT in lung cancer, thereby greatly reducing the risk of overestimation and assisting for precision treatment. [ABSTRACT FROM AUTHOR]

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The study aimed to compare the metastatic pattern of breast cancer and the intermodality proportion of agreement between [18F]FDG-PET/CT and CE-CT. Women with metastatic breast cancer (MBC) were enrolled prospectively and underwent a combined [18F]FDG-PET/CT and CE-CT scan to diagnose MBC. Experienced nuclear medicine and radiology physicians evaluated the scans blinded to the opposite scan results. Descriptive statistics were applied, and the intermodality proportion of agreement was used to compare [18F]FDG-PET/CT and CE-CT. In total, 76 women with verified MBC were enrolled in the study. The reported number of site-specific metastases for [18F]FDG-PET/CT vs. CE-CT was 53 (69.7%) vs. 44 (57.9%) for bone lesions, 31 (40.8%) vs. 43 (56.6%) for lung lesions, and 16 (21.1%) vs. 23 (30.3%) for liver lesions, respectively. The proportion of agreement between imaging modalities was 76.3% (95% CI 65.2–85.3) for bone lesions; 82.9% (95% CI 72.5–90.6) for liver lesions; 57.9% (95% CI 46.0–69.1) for lung lesions; and 59.2% (95% CI 47.3–70.4) for lymph nodes. In conclusion, bone and distant lymph node metastases were reported more often by [18F]FDG-PET/CT than CE-CT, while liver and lung metastases were reported more often by CE-CT than [18F]FDG-PET/CT. Agreement between scans was highest for bone and liver lesions and lowest for lymph node metastases. [ABSTRACT FROM AUTHOR]

[18F]FDG-PET/CT is a useful tool for diagnosis and cancer detection in idiopathic inflammatory myopathies (IIMs), especially polymyositis (PM) and dermatomyositis (DM). Data deriving from Europe are lacking. We describe [18F]FDG-PET/CT results in a Belgian cohort with IIMs, focusing on patients with PM and DM. All of the cases of IIMs admitted between December 2010 and January 2023 to the Cliniques Universitaires Saint-Luc (Belgium) were retrospectively reviewed. In total, 44 patients were identified with suspected IIMs; among them, 29 were retained for final analysis. The mean age of the retained patients was 48.7 years; 19 patients were female (65.5%). Twenty-two patients had DM and seven had PM. The mean serum creatinine kinase (CK) and the mean CRP levels were 3125 UI/L and 30.3 mg/L, respectively. [18F]FDG-PET/CT imaging was performed for 27 patients, detecting interstitial lung diseases (ILDs) in 7 patients (25.9%), cancer in 3 patients (11.1%), and abnormal muscle FDG uptake compatible with myositis in 13 patients (48.1%). All of the patients who were detected to have ILDs via PET/CT imaging were confirmed using a low-dose lung CT scan. Among the patients who were detected to have abnormal muscle FDG uptake via PET/CT scans (13/28), the EMG was positive in 12 patients (p = 0.004), while the MRI was positive in 8 patients (p = 0.02). We further observed that there was a significantly higher level of CK in the group with abnormal muscle FDG uptake (p = 0.008). Our study showed that PET/CT is useful for detecting cancer and ILDs. We showed that the detection of abnormal muscle uptake via PET/CT was in accordance with EMG and MRI results, as well as with the mean CK value, and that the presence of dyspnea was significantly associated with the presence of ILDs detected via PET/CT imaging (p = 0.002). [ABSTRACT FROM AUTHOR]

Purpose: The current study explored the association between 2-[18F]fluoro-2-deoxy-D-glucose ([18F]FDG) uptake and the quantitative expression of immunohistochemical markers related to glucose metabolism, hypoxia, and cell proliferation in benign and malignant thyroid nodules of indeterminate cytology. Procedures: Using a case–control design, 24 patients were selected from participants of a randomized controlled multicenter trial (NCT02208544) in which [18F]FDG-PET/CT and thyroid surgery were performed for Bethesda III and IV nodules. Three equally sized groups of [18F]FDG-positive malignant, [18F]FDG-positive benign, and [18F]FDG-negative benign nodules were included. Immunohistochemical staining was performed for glucose transporters (GLUT) 1, 3, and 4; hexokinases (HK) 1 and 2; hypoxia-inducible factor-1 alpha (HIF1α; monocarboxylate transporter 4 (MCT4); carbonic anhydrase IX (CA-IX); vascular endothelial growth factor (VEGF); sodium-iodide symporter (NIS); and Ki-67. Marker expression was scored using an immunoreactive score. Unsupervised cluster analysis was performed. The immunoreactive score was correlated to the maximum and peak standardized uptake values (SUVmax, SUVpeak) and SUVmax ratio (SUVmax of nodule/background SUVmax of contralateral, normal thyroid) of the [18F]FDG-PET/CT using the Spearman's rank correlation coefficient and compared between the three groups using Kruskal–Wallis tests. Results: The expression of GLUT1, GLUT3, HK2, and MCT4 was strongly positively correlated with the SUVmax, SUVpeak, and SUVmax ratio. The expression of GLUT1 (p = 0.009), HK2 (p = 0.02), MCT4 (p = 0.01), and VEGF (p = 0.007) was statistically significantly different between [18F]FDG-positive benign nodules, [18F]FDG-positive thyroid carcinomas, and [18F]FDG-negative benign nodules. In both [18F]FDG-positive benign nodules and [18F]FDG-positive thyroid carcinomas, the expression of GLUT1, HK2, and MCT4 was increased as compared to [18F]FDG-negative benign nodules. VEGF expression was higher in [18F]FDG-positive thyroid carcinomas as compared to [18F]FDG-negative and [18F]FDG-positive benign nodules. Conclusions: Our results suggest that [18F]FDG-positive benign thyroid nodules undergo changes in protein expression similar to those in thyroid carcinomas. To expand the understanding of the metabolic changes in benign and malignant thyroid nodules, further research is required, including correlation with underlying genetic alterations. [ABSTRACT FROM AUTHOR]

Simple Summary: Patients with locally advanced gastric cancer have a five-year survival rate of 36–45% after curatively intended D2-gastrectomy combined with perioperative chemotherapy. This relatively poor survival is mainly due to recurrence of the disease. The aim of this study was to improve detection of peritoneal and distant metastases on [18F]FDG-PET images in patients with advanced gastric cancer using radiomics. Radiomics consists of the extraction of large amounts of quantitative features from medical imaging and the subsequent mining of this dataset for potential information to monitor disease characteristics in clinical practice. Three classification models were developed to determine the added value of radiomics: a model with clinical variables only, a model with radiomic features only, and a clinicoradiomic model, combining clinical variables and radiomic features. [18F]FDG-PET-based radiomics showed no additional value in predicting peritoneal and distant metastases in locally advanced gastric cancer patients. Aim: To improve identification of peritoneal and distant metastases in locally advanced gastric cancer using [18F]FDG-PET radiomics. Methods: [18F]FDG-PET scans of 206 patients acquired in 16 different Dutch hospitals in the prospective multicentre PLASTIC-study were analysed. Tumours were delineated and 105 radiomic features were extracted. Three classification models were developed to identify peritoneal and distant metastases (incidence: 21%): a model with clinical variables, a model with radiomic features, and a clinicoradiomic model, combining clinical variables and radiomic features. A least absolute shrinkage and selection operator (LASSO) regression classifier was trained and evaluated in a 100-times repeated random split, stratified for the presence of peritoneal and distant metastases. To exclude features with high mutual correlations, redundancy filtering of the Pearson correlation matrix was performed (r = 0.9). Model performances were expressed by the area under the receiver operating characteristic curve (AUC). In addition, subgroup analyses based on Lauren classification were performed. Results: None of the models could identify metastases with low AUCs of 0.59, 0.51, and 0.56, for the clinical, radiomic, and clinicoradiomic model, respectively. Subgroup analysis of intestinal and mixed-type tumours resulted in low AUCs of 0.67 and 0.60 for the clinical and radiomic models, and a moderate AUC of 0.71 in the clinicoradiomic model. Subgroup analysis of diffuse-type tumours did not improve the classification performance. Conclusion: Overall, [18F]FDG-PET-based radiomics did not contribute to the preoperative identification of peritoneal and distant metastases in patients with locally advanced gastric carcinoma. In intestinal and mixed-type tumours, the classification performance of the clinical model slightly improved with the addition of radiomic features, but this slight improvement does not outweigh the laborious radiomic analysis. [ABSTRACT FROM AUTHOR]

Several studies have shown a strong predictive value for pretreatment [18F]FDG-PET/CT metabolic parameters in different lymphoma subtypes. However, few publications exist concerning the role of metabolic parameters in mantle cell lymphoma (MCL). We retrospectively investigated the prognostic value of baseline metabolic tumor volume (MTV) and lesion dissemination in untreated MCL. We compared it to currently used prognostic factors such as stage, mantle cell lymphoma international prognostic index (MIPI) and KI-67. We report that a higher baseline MTV is a risk factor for worse overall survival (OS), progression-free survival (PFS), and disease-specific survival (DSS) in univariate analysis. In multivariate analysis, MTV was significantly associated with DSS, but not with OS and PFS. We found no correlation between lesion dissemination and outcome. The MIPI score remains the strongest predictor of outcome. These results show that MTV is an important prognostic tool and can improve patient risk stratification at staging of untreated MCL. [ABSTRACT FROM AUTHOR]

The study aimed to compare the metastatic pattern of breast cancer and the intermodality proportion of agreement between [18F]FDG-PET/CT and CE-CT. Women with metastatic breast cancer (MBC) were enrolled prospectively and underwent a combined [18F]FDG-PET/CT and CE-CT scan to diagnose MBC. Experienced nuclear medicine and radiology physicians evaluated the scans blinded to the opposite scan results. Descriptive statistics were applied, and the intermodality proportion of agreement was used to compare [18F]FDG-PET/CT and CE-CT. In total, 76 women with verified MBC were enrolled in the study. The reported number of site-specific metastases for [18F]FDG-PET/CT vs. CE-CT was 53 (69.7%) vs. 44 (57.9%) for bone lesions, 31 (40.8%) vs. 43 (56.6%) for lung lesions, and 16 (21.1%) vs. 23 (30.3%) for liver lesions, respectively. The proportion of agreement between imaging modalities was 76.3% (95% CI 65.2–85.3) for bone lesions; 82.9% (95% CI 72.5–90.6) for liver lesions; 57.9% (95% CI 46.0–69.1) for lung lesions; and 59.2% (95% CI 47.3–70.4) for lymph nodes. In conclusion, bone and distant lymph node metastases were reported more often by [18F]FDG-PET/CT than CE-CT, while liver and lung metastases were reported more often by CE-CT than [18F]FDG-PET/CT. Agreement between scans was highest for bone and liver lesions and lowest for lymph node metastases.

Bacteremia is the presence of viable bacteria in the bloodstream, a complicated and potentially dangerous systemic medical condition that may range from asymptomatic and clinically relatively indolent cases to more severe bloodstream infection (BSI) and ultimately life-threatening septic shock with fatal outcome. BSI is classified as simple (bacteremia only) or complex (BSI with metastatic spread), and the morbidity is higher in the latter, probably due to insufficient eradication. Treatment of simple BSI is usually short-term antibiotic courses, whereas complex BSI with metastatic foci requires more advanced treatment including long-term antibiotics or invasive drainage to gain infection control. Thus, identifying metastatic infection has an important clinical impact but remains a challenge; only half of the patients progress to complex BSI, and many patients present without relevant signs or symptoms, so imaging is pivotal. This review summarizes the potential role and recommendations of [18F]FDG-PET/CT in BSI, based on the relatively sparse and heterogeneous literature. [18F]FDG-PET/CT should be considered in suspected complex BSI, in patients at high risk of metastatic spread, and in BSI in ICU patients. [18F]FDG-PET/CT has an impact on patient management, treatment strategy, and patient outcome, mainly by directing the diagnostic process toward more specific diagnostics or by modifying treatment regimens resulting in reduced relapse rates and reduced mortality. Finally, a negative scan may obviate the need for further workup.

[18F]fluorodeoxyglucose-positron emission tomography/computed tomography ([18F]FDG-PET/CT) is used to diagnose large vessel vasculitis in giant cell arteritis (GCA). We aimed to define a semi-quantitative threshold for identifying GCA aortitis from aortic atheroma or the control. Contrast enhanced computed tomography (CECT) was used as the reference imaging for aortic evaluation and to define aortitis, aortic atheroma and control aortas. [18F]FDG-PET/CT was performed on 35 GCA patients and in two different control groups (aortic atheroma (n = 70) and normal control (n = 35)). Aortic semi-quantitative features were compared between the three groups. GCA patients without aortitis on CECT were excluded. Of the GCA patients, 19 (54.3%) were not on glucocorticoids (GC) prior to [18F]FDG-PET/CT. The SUVmax, TBRblood and TBRliver aortic values were significantly higher in the GCA aortitis group than in the aortic atheroma and control groups (p < 0.001). Receiver operating characteristic curve analyses brought to light quantitative cut-off values allowing GCA aortitis diagnosis with optimal sensitivity and specificity versus control or aortic atheroma patients for each PET-based feature analyzed. Considering the overall aorta, a SUVmax threshold of 3.25 and a TBRblood threshold of 1.75 had a specificity of 83% and 75%, respectively, a sensitivity of 81% and 81%, respectively, and the area under the ROC curve (AUC) was 0.86 and 0.83, respectively, for aortitis detection compared to control groups in GCA cases with GC. A SUVmax threshold of 3.45 and a TBRblood threshold of 1.97 had a specificity of 90% and 93%, respectively, a sensitivity of 89% and 89%, respectively, with an AUC of 0.89 and 0.96, respectively, for aortitis detection compared to the control in GC-free GCA cases. Discriminative thresholds of SUVmax and TBRblood for the diagnosis of GCA aortitis were established using CECT as the reference imaging. [ABSTRACT FROM AUTHOR]

Objectives: Based on germline and somatic mutation profiles, pheochromocytomas and paragangliomas (PPGLs) can be classified into different clusters. We investigated the use of [18F]FDG-PET/CT radiomics, SUVmax and biochemical profile for the identification of the genetic clusters of PPGLs.Methods: In this single-centre cohort, 40 PPGLs (13 cluster 1, 18 cluster 2, 9 sporadic) were delineated using a 41% adaptive threshold of SUVpeak ([18F]FDG-PET) and manually (low-dose CT; ldCT). Using PyRadiomics, 211 radiomic features were extracted. Stratified 5-fold cross-validation for the identification of the genetic cluster was performed using multinomial logistic regression with dimensionality reduction incorporated per fold. Classification performances of biochemistry, SUVmax and PET(/CT) radiomic models were compared and presented as mean (multiclass) test AUCs over the five folds. Results were validated using a sham experiment, randomly shuffling the outcome labels.Results: The model with biochemistry only could identify the genetic cluster (multiclass AUC 0.60). The three-factor PET model had the best classification performance (multiclass AUC 0.88). A simplified model with only SUVmax performed almost similarly. Addition of ldCT features and biochemistry decreased the classification performances. All sham AUCs were approximately 0.50.Conclusion: PET radiomics achieves a better identification of PPGLs compared to biochemistry, SUVmax, ldCT radiomics and combined approaches, especially for the differentiation of sporadic PPGLs. Nevertheless, a model with SUVmax alone might be preferred clinically, weighing model performances against laborious radiomic analysis. The limited added value of radiomics to the overall classification performance for PPGL should be validated in a larger external cohort.Key Points: • Radiomics derived from [18F]FDG-PET/CT has the potential to improve the identification of the genetic clusters of pheochromocytomas and paragangliomas. • A simplified model with SUVmax only might be preferred clinically, weighing model performances against the laborious radiomic analysis. • Cluster 1 and 2 PPGLs generally present distinctive characteristics that can be captured using [18F]FDG-PET imaging. Sporadic PPGLs appear more heterogeneous, frequently resembling cluster 2 PPGLs and occasionally resembling cluster 1 PPGLs. [ABSTRACT FROM AUTHOR]

Abstract Objectives [18F]FDG-PET/CT is used for diagnosing metastatic infections in Staphylococcus aureus bacteremia (SAB) and guidance of antibiotic treatment. The impact of [18F]FDG-PET/CT on outcomes remains to be determined. The aim of this systematic review was to summarize the effects of [18F]FDG-PET/CT on all-cause mortality and new diagnostic findingsin SAB. Methods We systematically searched PubMed, EMBASE.com, Web of Science, and Wiley’s Cochrane library from inception to 29 January 2021. Eligible studies were randomized controlled trials, clinically controlled trials, prospective and retrospective cohort studies, and case–control studies investigating the effects of [18F]FDG-PET/CT in hospitalized adult patients with SAB. We excluded studies lacking a control group without [18F]FDG-PET/CT. Risk of bias was assessed using the ROBINS-I tool and certainty of evidence using the GRADE approach by two independent reviewers. Results We identified 1956 studies, of which five were included in our qualitative synthesis, including a total of 880 SAB patients. All studies were non-randomized and at moderate or serious risk of bias. Four studies, including a total of 804 patients, reported lower mortality in SAB patients that underwent [18F]FDG-PET/CT. One study including 102 patients reported more detected metastatic foci in the participants in whom [18F]FDG-PET/CT was performed. Discussion We found low certainty of evidence that [18F]FDG-PET/CT reduces mortality in patients with SAB. This effect is possibly explained by a higher frequency of findings guiding optimal antibiotic treatment and source control interventions.

[18F]FDG-PET/CT is a useful tool for diagnosis and cancer detection in idiopathic inflammatory myopathies (IIMs), especially polymyositis (PM) and dermatomyositis (DM). Data deriving from Europe are lacking. We describe [18F]FDG-PET/CT results in a Belgian cohort with IIMs, focusing on patients with PM and DM. All of the cases of IIMs admitted between December 2010 and January 2023 to the Cliniques Universitaires Saint-Luc (Belgium) were retrospectively reviewed. In total, 44 patients were identified with suspected IIMs; among them, 29 were retained for final analysis. The mean age of the retained patients was 48.7 years; 19 patients were female (65.5%). Twenty-two patients had DM and seven had PM. The mean serum creatinine kinase (CK) and the mean CRP levels were 3125 UI/L and 30.3 mg/L, respectively. [18F]FDG-PET/CT imaging was performed for 27 patients, detecting interstitial lung diseases (ILDs) in 7 patients (25.9%), cancer in 3 patients (11.1%), and abnormal muscle FDG uptake compatible with myositis in 13 patients (48.1%). All of the patients who were detected to have ILDs via PET/CT imaging were confirmed using a low-dose lung CT scan. Among the patients who were detected to have abnormal muscle FDG uptake via PET/CT scans (13/28), the EMG was positive in 12 patients (p = 0.004), while the MRI was positive in 8 patients (p = 0.02). We further observed that there was a significantly higher level of CK in the group with abnormal muscle FDG uptake (p = 0.008). Our study showed that PET/CT is useful for detecting cancer and ILDs. We showed that the detection of abnormal muscle uptake via PET/CT was in accordance with EMG and MRI results, as well as with the mean CK value, and that the presence of dyspnea was significantly associated with the presence of ILDs detected via PET/CT imaging (p = 0.002).

Purpose: To evaluate cost-effectiveness of an [18F]FDG-PET/CT-driven diagnostic workup as compared to diagnostic surgery, for thyroid nodules with Bethesda III/IV cytology. [18F]FDG-PET/CT avoids 40% of futile diagnostic surgeries for benign Bethesda III/IV nodules. Methods: Lifelong societal costs and quality-adjusted life years (QALYs) were assessed for 132 patients participating in a randomised controlled multicentre trial comparing [18F]FDG-PET/CT to diagnostic surgery. The observed 1-year trial results were extrapolated using a Markov model. The probability of cost-effectiveness was estimated using cost-effectiveness acceptability curves, taking uncertainty about sampling, imputation, and parameters into account. Results: The observed 1-year cost difference of [18F]FDG-PET/CT as compared to diagnostic surgery was − €1000 (95% CI: − €2100 to €0) for thyroid nodule–related care (p = 0.06). From the broader societal perspective, the 1-year difference in total societal costs was − €4500 (− €9200 to €150) (p = 0.06). Over the modelled lifelong period, the cost difference was − €9900 (− €23,100 to €3200) (p = 0.14). The difference in QALYs was 0.019 (− 0.045 to 0.083) at 1 year (p = 0.57) and 0.402 (− 0.581 to 1.385) over the lifelong period (p = 0.42). For a willingness to pay of €50,000 per QALY, an [18F]FDG-PET/CT-driven work-up was the cost-effective strategy with 84% certainty. Conclusion: Following the observed reduction in diagnostic surgery, an [18F]FDG-PET/CT-driven diagnostic workup reduced the 1-year thyroid nodule–related and societal costs while sustaining quality of life. It is very likely cost-effective as compared to diagnostic surgery for Bethesda III/IV nodules. Trial registration number: This trial is registered with ClinicalTrials.gov: NCT02208544 (5 August 2014), https://clinicaltrials.gov/ct2/show/NCT02208544. [ABSTRACT FROM AUTHOR]

OBJECTIVE: In the hybrid Positron Emission Tomography/Computed Tomography (PET/CT) method, the functional evaluation is integrated with the morphological information provided by co-registered CT, still performed for attenuation correction and lesion localization. However, co-registered CT images could provide additional diagnostic information that PET alone could underestimate. To optimize the diagnostic potential of this hybrid examination, we evaluated the prevalence and the clinical significance of incidental findings detected on co-registered CT images in a cohort of multiple myeloma (MM) patients. PATIENTS AND METHODS: We evaluated 112 MM patients (mean age 65.8 y), who underwent [18F]FDG-PET/CT during their regular workup. All co-registered CT images were retrospectively reviewed by two expert radiologists and each non-myelomatous incidental finding (nM-IF) was collected and clinically graded according to a nMIF Reporting and Data System (nM-RADS). In addition, nM-IFs were classified according to anatomic localization (skull, lung, mediastinum, abdomen, breast, gastrointestinal, genitourinary and cardiovascular system and muscle/soft tissue). RESULTS: 163 nM-IFs were detected in 94/112 patients (83.9%) (mean value: 1.5 IFs per patient). The most interested anatomic districts were the lung (n=33; 20.2%), genitourinary (n=33; 20.2%) and gastrointestinal (n=30; 18.4%) systems. Focusing on the clinically significant findings (nM3+nM4), 92/163 (56.4%) IFs could have been required further investigations, of which 38/163 (23.3%) were potentially important and detected in 33/112 (29.5%) patients. CONCLUSIONS: The high percentage of potentially clinically significant IFs detected in MM patients emphasizes that co-registered CT images hold precious information often missed. Giving more relevance to co-registered CT with tailored acquisition and reconstruction protocols and dedicated reporting could optimize the potentiality of this multimodality imaging method with impact on clinical management. [ABSTRACT FROM AUTHOR]

Abstract Background [18F]-fluorodeoxyglucose-positron emission tomography/computed tomography ([18F]FDG-PET/CT) has been implemented sporadically in hospital settings as the standard of care examination for recurrent breast cancer. We aimed to explore the clinical impact of implementing [18F]FDG-PET/CT for patients with clinically suspected recurrent breast cancer and validate the diagnostic accuracy. Methods Women with suspected distant recurrent breast cancer were prospectively enrolled in the study between September 2017 and August 2019. [18F]FDG-PET/CT was performed, and the appearance of incidental benign and malignant findings was registered. Additional examinations, complications, and the final diagnosis were registered to reflect the clinical consequence of such findings. The diagnostic accuracy of [18F]FDG-PET/CT as a stand-alone examination was analyzed. Biopsy and follow-up were used as a reference standard. Results [18F]FDG-PET/CT reported breast cancer metastases in 72 of 225 women (32.0%), and metastases were verified by biopsy in 52 (52/225, 23.1%). Prior probability and posterior probability of a positive test for suspected metastatic cancer and incidental malignancies were 27%/85% and 4%/20%, respectively. Suspected malignant incidental findings were reported in 46 patients (46/225, 20.4%), leading to further examinations and final detection of nine synchronous cancers (9/225, 4.0%). These cancers originated from the lung, thyroid, skin, pancreas, peritoneum, breast, kidney, one was malignant melanoma, and one was hematological cancer. False-positive incidental malignant findings were examined in 37/225 patients (16.4%), mainly in the colon (n = 12) and thyroid gland (n = 12). Ten incidental findings suspicious for benign disease were suggested by [18F]FDG-PET/CT, and further examinations resulted in the detection of three benign conditions requiring treatment. Sensitivity, specificity, and AUC-ROC for diagnosing distant metastases were 1.00 (0.93–1.0), 0.88 (0.82–0.92), and 0.98 (95% CI 0.97–0.99), respectively. Conclusion [18F]FDG-PET/CT provided a high posterior probability of positive test, and a negative test was able to rule out distant metastases in women with clinically suspected recurrent breast cancer. One-fifth of patients examined for incidental findings detected on [18F]FDG-PET/CT were diagnosed with clinically relevant conditions. Further examinations of false-positive incidental findings in one of six women should be weighed against the high accuracy for diagnosing metastatic breast cancer. Trial registration Clinical.Trials.gov. NCT03358589. Registered 30 November 2017—Retrospectively registered, http://www.ClinicalTrials.gov

Aim: To improve identification of peritoneal and distant metastases in locally advanced gastric cancer using [18F]FDG-PET radiomics. Methods: [18F]FDG-PET scans of 206 patients acquired in 16 different Dutch hospitals in the prospective multicentre PLASTIC-study were analysed. Tumours were delineated and 105 radiomic features were extracted. Three classification models were developed to identify peritoneal and distant metastases (incidence: 21%): a model with clinical variables, a model with radiomic features, and a clinicoradiomic model, combining clinical variables and radiomic features. A least absolute shrinkage and selection operator (LASSO) regression classifier was trained and evaluated in a 100-times repeated random split, stratified for the presence of peritoneal and distant metastases. To exclude features with high mutual correlations, redundancy filtering of the Pearson correlation matrix was performed (r = 0.9). Model performances were expressed by the area under the receiver operating characteristic curve (AUC). In addition, subgroup analyses based on Lauren classification were performed. Results: None of the models could identify metastases with low AUCs of 0.59, 0.51, and 0.56, for the clinical, radiomic, and clinicoradiomic model, respectively. Subgroup analysis of intestinal and mixed-type tumours resulted in low AUCs of 0.67 and 0.60 for the clinical and radiomic models, and a moderate AUC of 0.71 in the clinicoradiomic model. Subgroup analysis of diffuse-type tumours did not improve the classification performance. Conclusion: Overall, [18F]FDG-PET-based radiomics did not contribute to the preoperative identification of peritoneal and distant metastases in patients with locally advanced gastric carcinoma. In intestinal and mixed-type tumours, the classification performance of the clinical model slightly improved with the addition of radiomic features, but this slight improvement does not outweigh the laborious radiomic analysis.

Purpose: To assess the impact of an [18F]FDG-PET/CT-driven diagnostic workup to rule out malignancy, avoid futile diagnostic surgeries, and improve patient outcomes in thyroid nodules with indeterminate cytology. Methods: In this double-blinded, randomised controlled multicentre trial, 132 adult euthyroid patients with scheduled diagnostic surgery for a Bethesda III or IV thyroid nodule underwent [18F]FDG-PET/CT and were randomised to an [18F]FDG-PET/CT-driven or diagnostic surgery group. In the [18F]FDG-PET/CT-driven group, management was based on the [18F]FDG-PET/CT result: when the index nodule was visually [18F]FDG-positive, diagnostic surgery was advised; when [18F]FDG-negative, active surveillance was recommended. The nodule was presumed benign when it remained unchanged on ultrasound surveillance. In the diagnostic surgery group, all patients were advised to proceed to the scheduled surgery, according to current guidelines. The primary outcome was the fraction of unbeneficial patient management in one year, i.e., diagnostic surgery for benign nodules and active surveillance for malignant/borderline nodules. Intention-to-treat analysis was performed. Subgroup analyses were performed for non-Hürthle cell and Hürthle cell nodules. Results: Patient management was unbeneficial in 42% (38/91 [95% confidence interval [CI], 32–53%]) of patients in the [18F]FDG-PET/CT-driven group, as compared to 83% (34/41 [95% CI, 68–93%]) in the diagnostic surgery group (p < 0.001). [18F]FDG-PET/CT-driven management avoided 40% (25/63 [95% CI, 28–53%]) diagnostic surgeries for benign nodules: 48% (23/48 [95% CI, 33–63%]) in non-Hürthle cell and 13% (2/15 [95% CI, 2–40%]) in Hürthle cell nodules (p = 0.02). No malignant or borderline tumours were observed in patients under surveillance. Sensitivity, specificity, negative and positive predictive value, and benign call rate (95% CI) of [18F]FDG-PET/CT were 94.1% (80.3–99.3%), 39.8% (30.0–50.2%), 95.1% (83.5–99.4%), 35.2% (25.4–45.9%), and 31.1% (23.3–39.7%), respectively. Conclusion: An [18F]FDG-PET/CT-driven diagnostic workup of indeterminate thyroid nodules leads to practice changing management, accurately and oncologically safely reducing futile surgeries by 40%. For optimal therapeutic yield, application should be limited to non-Hürthle cell nodules. Trial registration number: This trial is registered with ClinicalTrials.gov: NCT02208544 (5 August 2014), https://clinicaltrials.gov/ct2/show/NCT02208544. [ABSTRACT FROM AUTHOR]

SARS-CoV-2 virus infects organs other than the lung, such as mediastinal lymph nodes, spleen, and liver, but, to date, metabolic imaging studies obtained in short-term follow-ups of patients hospitalized with severe COVID-19 infection are rare. Our objective was to evaluate the usefulness of [18F]FDG-PET/CT in the short-term follow-up of patients admitted for COVID-19 pneumonia and to explore the association of the findings with clinical prognostic markers. The prospective study included 20 patients with COVID-19 pneumonia (November 2020–March 2021). Clinical and laboratory test findings were gathered at admission, 48–72 h post-admission, and 2–3 months post-discharge, when [18F]FDG-PET/CT and respiratory function tests were performed. Lung volumes, spirometry, lung diffusion capacity for carbon monoxide (DLCO), and respiratory muscle strength were measured. Volumetric [18F]FDG-PET/CT results were correlated with laboratory and respiratory parameters. Eleven [18F]FDG-PET/CT (55%) were positive, with hypermetabolic mediastinal lymphadenopathy in 90.9%. Mediastinal lesion's SUVpeak was correlated with white cells' count. Eleven (55%) patients had impaired respiratory function, including reduced DLCO (35%). SUVpeak was correlated with %predicted-DLCO. TLG was negatively correlated with %predicted-DLCO and TLC. In the short-term follow-up of patients hospitalized for COVID-19 pneumonia, [18F]FDG-PET/CT findings revealed significant detectable inflammation in lungs and mediastinal lymph nodes that correlated with pulmonary function impairment in more than half of the patients. [ABSTRACT FROM AUTHOR]

Purpose: [18F]FDG-PET/CT scanning can help detect metastatic infectious foci and reduce mortality in patients with Staphylococcus aureus bacteremia (SAB), but it is unknown if patients with SAB and an indication for prolonged treatment because of possible endovascular, orthopaedic implant, or other metastatic infection still need [18F]FDG-PET/CT. Methods: In a retrospective single-center cohort study, we included all consecutive adult patients with SAB between 2013 and 2020 if an [18F]FDG-PET/CT scan was performed and antibiotic treatment was planned for ≥ 6 weeks prior to [18F]FDG-PET/CT. We aimed to identify patients for whom treatment was adjusted due to the results of [18F]FDG-PET/CT, and assessed concordance of [18F]FDG-PET/CT and clinical diagnosis for infected prosthetic material. Results: Among 132 patients included, the original treatment plan was changed after [18F]FDG-PET/CT in 22 patients (16.7%), in the majority (n = 20) due to diagnosing or rejecting endovascular (graft) infection. Antibiotic treatment modifications were shortening in 2, iv-oral switch in 3, extension in 13, and addition of rifampicin in 4 patients. Ninety additional metastatic foci based on [18F]FDG-PET/CT results were found in 69/132 patients (52.3%). [18F]FDG-PET/CT suggested vascular graft infection in 7/14 patients who lacked clinical signs of infection, but showed no infection of prosthetic joints or osteosynthesis material in eight patients who lacked clinical signs of such an infection. Conclusion: [18F]FDG-PET/CT can help refine treatment for SAB in patients with clinically suspected endovascular infection or vascular grafts, even if 6 weeks treatment is already indicated, but can be safely omitted in other patients who are clinically stable. [ABSTRACT FROM AUTHOR]

Idiopathic inflammatory myopathies (IIM) are considered systemic diseases involving different organs and some subtypes are associated with increased cancer risk. In this review, we provide a comprehensive summary of the current use and potential applications of (semi-)quantitative [18F]FDG-PET/CT indices in patients with IIM focusing on dermatomyositis and polymyositis. Visual interpretation and (semi-)quantitative [18F]FDG-PET indices have a good overall performance to detect muscle activity but objective, robust and standardized interpretation criteria are currently lacking. [18F]FDG-PET/CT is a suitable modality to screen for malignancy in patients with myositis and may be a promising tool to detect inflammatory lung activity and to early identify patients with rapidly progressive lung disease. The latter remains to be determined in large, prospective comparative trials.

In this retrospective study, PET/CT data from 59 patients with suspected giant cell arteritis (GCA) were reviewed using the Deauville criteria to determine an optimal cut-off between PET positivity and negativity. Seventeen standardised vascular regions were analysed per patient by three investigators blinded to clinical information. Statistical analysis included ROC curves with areas under the curve (AUC), Cohen’s and Fleiss’ kappa (κ) to calculate sensitivity, specificity, accuracy, and agreement. According to final clinician’s diagnosis and the revised 2017 ACR criteria GCA was confirmed in 29 of 59 (49.2 %) patients. With a diagnostic cut-off ≥ 4 (highest tracer uptake of a vessel wall exceeds liver uptake) for PET positivity, all investigators achieved high accuracy (range, 89.8–93.2%) and AUC (range, 0.94–0.97). Sensitivity and specificity ranged from 89.7–96.6% and 83.3–96.7%, respectively. Agreement between the three investigators suggested ‘almost perfect agreement’ (Fleiss’ κ = 0.84) A Deauville score of ≥4 as threshold for PET positivity yielded excellent results with high accuracy and almost perfect inter-rater agreement, suggesting a standardized, reproducible, and reliable score in diagnosing GCA. However, the small sample size and reference standard could lead to biases. Therefore, verification in a multicentre study with a larger patient cohort and prospective setting is needed.

Objectives: [18F]FDG-PET/CT is used for diagnosing metastatic infections in Staphylococcus aureus bacteremia (SAB) and guidance of antibiotic treatment. The impact of [18F]FDG-PET/CT on outcomes remains to be determined. The aim of this systematic review was to summarize the effects of [18F]FDG-PET/CT on all-cause mortality and new diagnostic findingsin SAB.Methods: We systematically searched PubMed, EMBASE.com, Web of Science, and Wiley's Cochrane library from inception to 29 January 2021. Eligible studies were randomized controlled trials, clinically controlled trials, prospective and retrospective cohort studies, and case-control studies investigating the effects of [18F]FDG-PET/CT in hospitalized adult patients with SAB. We excluded studies lacking a control group without [18F]FDG-PET/CT. Risk of bias was assessed using the ROBINS-I tool and certainty of evidence using the GRADE approach by two independent reviewers.Results: We identified 1956 studies, of which five were included in our qualitative synthesis, including a total of 880 SAB patients. All studies were non-randomized and at moderate or serious risk of bias. Four studies, including a total of 804 patients, reported lower mortality in SAB patients that underwent [18F]FDG-PET/CT. One study including 102 patients reported more detected metastatic foci in the participants in whom [18F]FDG-PET/CT was performed.Discussion: We found low certainty of evidence that [18F]FDG-PET/CT reduces mortality in patients with SAB. This effect is possibly explained by a higher frequency of findings guiding optimal antibiotic treatment and source control interventions. [ABSTRACT FROM AUTHOR]

Purpose: Septic thrombosis often complicates Staphylococcus aureus bacteremia (SAB) in patients with a central venous catheter. Currently there is no reference standard for diagnosis. We describe the diagnostic value of [18F]FDG-PET/CT imaging in a patient cohort and the potential contribution of quantitative measurements in detecting septic thrombosis. Methods: We selected patients with catheter-related SAB from our institutional database (2013–2020). The contribution of [18F]FDG-PET/CT on clinical diagnosis of septic thrombosis was evaluated. Standardized Uptake Values (SUV) were measured and compared with a composite reference standard (clinical signs, initial [18F]FDG-PET/CT result, Multidisciplinary Team (MDT) meeting outcome) to identify a cut-off value for detecting septic thrombosis. Results: We identified 93 patients with a catheter-related SAB. Quantitative measurements were possible for 43/56 patients in whom a [18F]FDG-PET/CT scan was performed. Septic thrombosis was clinically diagnosed in 30% (13/43) of the cases. In 85% of these cases, significant [18F]FDG-PET/CT uptake at the site of the thrombus was the deciding factor for diagnosis of septic thrombosis during the MDT meeting. All mean SUV’s of thrombotic lesions were higher in patients with clinically proven septic thrombosis compared to patients in whom this diagnosis was rejected (p

[18F]fluorodeoxyglucose-positron emission tomography/computed tomography ([18F]FDG-PET/CT) is used to diagnose large vessel vasculitis in giant cell arteritis (GCA). We aimed to define a semi-quantitative threshold for identifying GCA aortitis from aortic atheroma or the control. Contrast enhanced computed tomography (CECT) was used as the reference imaging for aortic evaluation and to define aortitis, aortic atheroma and control aortas. [18F]FDG-PET/CT was performed on 35 GCA patients and in two different control groups (aortic atheroma (n = 70) and normal control (n = 35)). Aortic semi-quantitative features were compared between the three groups. GCA patients without aortitis on CECT were excluded. Of the GCA patients, 19 (54.3%) were not on glucocorticoids (GC) prior to [18F]FDG-PET/CT. The SUVmax, TBRblood and TBRliver aortic values were significantly higher in the GCA aortitis group than in the aortic atheroma and control groups (p < 0.001). Receiver operating characteristic curve analyses brought to light quantitative cut-off values allowing GCA aortitis diagnosis with optimal sensitivity and specificity versus control or aortic atheroma patients for each PET-based feature analyzed. Considering the overall aorta, a SUVmax threshold of 3.25 and a TBRblood threshold of 1.75 had a specificity of 83% and 75%, respectively, a sensitivity of 81% and 81%, respectively, and the area under the ROC curve (AUC) was 0.86 and 0.83, respectively, for aortitis detection compared to control groups in GCA cases with GC. A SUVmax threshold of 3.45 and a TBRblood threshold of 1.97 had a specificity of 90% and 93%, respectively, a sensitivity of 89% and 89%, respectively, with an AUC of 0.89 and 0.96, respectively, for aortitis detection compared to the control in GC-free GCA cases. Discriminative thresholds of SUVmax and TBRblood for the diagnosis of GCA aortitis were established using CECT as the reference imaging.

Objective: During the initial staging of certain lymphoma subtypes, 18 F-fluorodeoxyglucose positron emission tomography/computed tomography ([ 18 F]FDG-PET/CT) has become an alternative to bone marrow biopsy (BMB) for detecting bone marrow (BM) involvement. However, whether [ 18 F]FDG-PET/CT can accurately detect BM involvement in angioimmunoblastic T-cell lymphoma (AITL) remains unknown. Our study aimed to assess the diagnostic and prognostic capability of [ 18 F]FDG-PET/CT for detecting BM involvement in AITL. Methods: This retrospective study included 84 individuals newly diagnosed with AITL who underwent baseline BMB and [ 18 F]FDG-PET/CT. "BM involvement" was defined as one or both of the following: 1) angioimmunoblastic T-cells detected in the BM; or 2) initially heightened focal uptake having disappeared on follow-up [ 18 F]FDG-PET/CT. The ability of [ 18 F]FDG-PET/CT to detect BM cancerous lesions was respectively analyzed by BM involvement confirmed by BMB or the aforementioned definition as the reference standard. The patients' clinical characteristics and survival and prognostic outcomes were respectively analyzed., Results: Of the 84 participants, five (6.0%) displayed positive BMB and PET/BM results, 17 (20.2%) had BMB-positive but PET/BM-negative results, eight (9.5%) showed BMB-negative but PET/BM-positive outcomes, and 54 (64.3%) displayed negative BMB and PET/BM outcomes. Using pre-defined BM involvement as the reference standard, [ 18 F]FDG-PET/CT exhibited a specificity of 100%, sensitivity of 40%, negative predictive value (NPV) of 75%, and positive predictive value (PPV) of 100%. In contrast, using BMB-detected BM involvement as reference, [ 18 F]FDG-PET/CT exhibited a sensitivity, specificity, PPV, and NPV of 38.5%, 76.1%, 22.7%, and 87.1%, respectively. Among patients with PET/BM-positive and BMB-negative outcomes, 62.5% (5/8) underwent upstaging from III to IV. In 58.8% (10/17) of patients who were initially diagnosed with stage II/III disease based on the [ 18 F]FDG-PET/CT results, repeat BMB resulted in upstaging to IV. PET/BM-negative patients had a higher 3-year progression-free survival rate (38.3% vs. 22.8%, p  = 0.018) and 3-year overall survival rate (64.4% vs. 34.6%, p  = 0.011) than PET/BM-positive patients., Conclusion: In AITL patients, PET/BM-positive results may obviate the necessity for repeat BMB to ascertain confirm BM involvement. PET/BM-negative results do not definitively exclude BM involvement. The combined use of [ 18 F]FDG-PET/CT and BMB can increase the diagnostic accuracy of BM involvement for AITL patients.

Background: [18F]-fluorodeoxyglucose-positron emission tomography/computed tomography ([18F]FDG-PET/CT) has been implemented sporadically in hospital settings as the standard of care examination for recurrent breast cancer. We aimed to explore the clinical impact of implementing [18F]FDG-PET/CT for patients with clinically suspected recurrent breast cancer and validate the diagnostic accuracy. Methods: Women with suspected distant recurrent breast cancer were prospectively enrolled in the study between September 2017 and August 2019. [18F]FDG-PET/CT was performed, and the appearance of incidental benign and malignant findings was registered. Additional examinations, complications, and the final diagnosis were registered to reflect the clinical consequence of such findings. The diagnostic accuracy of [18F]FDG-PET/CT as a stand-alone examination was analyzed. Biopsy and follow-up were used as a reference standard. Results: [18F]FDG-PET/CT reported breast cancer metastases in 72 of 225 women (32.0%), and metastases were verified by biopsy in 52 (52/225, 23.1%). Prior probability and posterior probability of a positive test for suspected metastatic cancer and incidental malignancies were 27%/85% and 4%/20%, respectively. Suspected malignant incidental findings were reported in 46 patients (46/225, 20.4%), leading to further examinations and final detection of nine synchronous cancers (9/225, 4.0%). These cancers originated from the lung, thyroid, skin, pancreas, peritoneum, breast, kidney, one was malignant melanoma, and one was hematological cancer. False-positive incidental malignant findings were examined in 37/225 patients (16.4%), mainly in the colon (n = 12) and thyroid gland (n = 12). Ten incidental findings suspicious for benign disease were suggested by [18F]FDG-PET/CT, and further examinations resulted in the detection of three benign conditions requiring treatment. Sensitivity, specificity, and AUC-ROC for diagnosing distant metastases were 1.00 (0.93–1.0), 0.88 (0.82–0.92), and 0.98 (95% CI 0.97–0.99), respectively. Conclusion: [18F]FDG-PET/CT provided a high posterior probability of positive test, and a negative test was able to rule out distant metastases in women with clinically suspected recurrent breast cancer. One-fifth of patients examined for incidental findings detected on [18F]FDG-PET/CT were diagnosed with clinically relevant conditions. Further examinations of false-positive incidental findings in one of six women should be weighed against the high accuracy for diagnosing metastatic breast cancer. Trial registration Clinical.Trials.gov. NCT03358589. Registered 30 November 2017—Retrospectively registered, http://www.ClinicalTrials.gov [ABSTRACT FROM AUTHOR]

Purpose: This retrospective study aimed to assess the diagnostic performance of preoperative [18F]FDG-PET/CT in predicting the groin and pelvic lymph node (LN) status in a large single-centre series of vulvar cancer patients. Methods: Between January 2013 and October 2018, among all consecutive women with proven vulvar cancer submitted to [18F]FDG-PET/CT, 160 patients were included. LNs were analysed by two qualitative methods assessing PET information (defined as visual assessment) and a combination of PET and low-dose CT information (defined as overall assessment), respectively, as well as semi-quantitative analysis (LN-SUVmax). Sensitivity, specificity, accuracy, positive and negative predictive values (PPV and NPV) in predicting the groin and pelvic LN status were calculated in the overall study population; a subset analysis of groin parameters in clinically/ultrasonography negative patients was also performed. Histopathology was the reference standard. Results: All patients underwent vulvar and inguinofemoral LN surgery, and 35 pelvic LN surgery. Overall, 338 LN sites (296 groins and 42 pelvic sites) were histologically examined with 30.4% prevalence of metastatic groins and 28.6% for metastatic pelvic sites. In the overall study population, sensitivity (95% confidence interval, CI), specificity (95% CI), accuracy (95% CI), PPV (95% CI) and NPV (95% CI) at the groin level were 85.6% (78.3–92.8), 65.5% (59.0–72.0), 71.6% (66.5–76.8), 52.0% (44.0–60.1) and 91.2% (86.7–95.8) for visual assessment; 78.9% (70.5–87.3), 78.2% (72.5–83.8), 78.4% (73.7–83.1), 61.2% (52.3–70.1) and 89.4% (85.0–93.9) for overall assessment; and 73.3% (64.2–82.5), 85.0% (80.1–89.8), 81.4% (77.0–85.8), 68.0% (58.8–77.3) and 87.9% (83.4–92.5) for semi-quantitative analysis (SUVmax cut-off value 1.89 achieved by ROC analysis). Similar results were observed in the pelvis-based analysis. Conclusion: In this large single-centre series of vulvar cancer patients, [18F]FDG-PET/CT showed good values of sensitivity and NPV in discriminating metastatic from non-metastatic LNs. In routine clinical practice, qualitative analysis is a reliable interpretative criterion making unnecessary commonly used semi-quantitative methods such as SUVmax. [ABSTRACT FROM AUTHOR]

Diffuse lymphadenopathy has a long differential diagnosis that includes both malignant and benign causes. As part of the lymphadenopathy work-up, many patients undergo [18F]FDG-PET/CT for purposes of ruling out malignancy. FDG-avid lymph nodes, however, are not specific for malignancy. This review will illustrate the spectrum of nodal findings on FDG-PET/CT with correlation to other cross-sectional imaging and clinical history in patients with representative infectious, inflammatory, and benign lymphoproliferative disorders. These findings are important for the nuclear medicine radiologist to understand, as they can represent common pitfalls in the work-up of lymphadenopathy. While FDG-PET/CT may be limited in ascertaining a definitive diagnosis in a disease process as the cause of lymphadenopathy, it can help to narrow this differential and rule out certain diseases in the correct clinical context. [ABSTRACT FROM AUTHOR]

Purpose/introduction: [18F]FDG-PET/CT is the standard imaging-technique for radiation treatment (RT) planning in locally advanced non-small cell lung cancer (NSCLC). The purpose of this study was to examine the additional value of endobronchial-ultrasound transbronchial needle aspiration (EBUS-TBNA) to standard PET/CT for mediastinal lymph-node (LN) staging and its impact on clinical target volume (CTV). Materials and methods: All consecutive patients with primary stage III NSCLC who underwent [18F]FDG-PET/CT and EBUS-TBNA prior to RT were analyzed from 12/2011 to 06/2018. LN-stations were assessed by an expert-radiologist and a nuclear medicine-physician. CTV was evaluated by two independent radiation oncologists. LNs were grouped with increasing distance along the lymphatic chains from primary tumor into echelon-1 (ipsilateral hilum), echelon-2 (LN-station 7 and ipsilateral 4), and echelon-3 (remaining mediastinum and contralateral hilum). Results: A total of 675 LN-stations of which 291 were positive for tumor-cells, were sampled by EBUS-TBNA in 180 patients. The rate of EBUS-positive LNs was 43% among all sampled LNs. EBUS-positivity in EBUS-probed LNs decreased from 85.8% in echelon-1 LNs to 42.4%/ 9.6% in echelon-2/ -3 LNs, respectively (p < 0.0001, Fisher's exact test). The false discovery rate of PET in comparison with EBUS results rose from 5.3% in echelon-1 to 32.9%/ 69.1% in echelon-2/ -3 LNs, respectively (p < 0.0001, Fisher's exact test). Sensitivity and specificity of FDG-PET/CT ranged from 85 to 99% and 67 to 80% for the different echelons. In 22.2% patients, EBUS-TBNA finding triggered changes of the treated CTV, compared with contouring algorithms based on FDG-avidity as the sole criterion for inclusion. CTV was enlarged in 6.7% patients due to EBUS-positivity in PET-negative LN-station and reduced in 15.5% by exclusion of an EBUS-negative but PET-positive LN-station. Conclusion: The false discovery rate of [18F]FDG-PET/CT increased markedly with distance from the primary tumor. Inclusion of systematic mediastinal LN mapping by EBUS-TBNA in addition to PET/CT has the potential to increase accuracy of target volume definition, particularly in echelon-3 LNs. EBUS-TBNA is recommended as integral part of staging for radiochemotherapy in stage III NSCLC. [ABSTRACT FROM AUTHOR]

Purpose: Several patients experience unexplained persistent symptoms after SARS-CoV-2 recovering. We aimed at evaluating if 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) was able to demonstrate a persistent inflammatory process. Methods: Recovered adult COVID-19 patients, who complained unexplained persisting symptoms for more than 30 days during the follow-up visits, were invited to participate in the study. Patients fulfilling inclusion criteria were imaged by [18F]FDG positron emission tomography/computed tomography ([18F]FDG-PET/CT). Whole-body [18F]FDG-PET/CT, performed according to good clinical practice, was qualitatively (comparison with background/liver) and semi-quantitatively (target-to-blood pool ratio calculated as average SUVmax artery/average SUVmean inferior vena cava) analyzed. Negative follow-up [18F]FDG-PET/CT images of oncologic patients matched for age/sex served as controls. Mann-Whitney test was used to test differences between groups. SPSS version 26 was used for analyses. Results: Ten recovered SARS-CoV-2 patients (seven male and three females, median age 52 years, range 46–80) with persisting symptoms were enrolled in the study. Common findings at visual analysis were increased [18F]FDG uptake in bone marrow and blood vessels (8/10 and 6/10 cases, respectively). [18F]FDG uptake in bone marrow did not differ between cases and controls (p = 0.16). The total vascular score was similar in the two groups (p = 0.95). The target-to-blood pool ratio resulted higher in recovered SARS-CoV-2 patients than in controls. Conclusion: Although the total vascular score was similar in the two groups, the target-to-blood pool ratio was significantly higher in three vascular regions (thoracic aorta, right iliac artery, and femoral arteries) in the recovered COVID-19 cohort than in controls, suggesting that SARS-CoV-2 induces vascular inflammation, which may be responsible for persisting symptoms. [ABSTRACT FROM AUTHOR]

GLO:BVO/01apr21:eji4962-gra-0001.jpg PHOTO (COLOR): . gl Abbrevations CFA Complete Freund's adjuvant dLNs draining lymph nodes DMF Dimethyl fumarate EAE experimental autoimmune encephalomyelitis [ 18 F]FDG 2-deoxy-2-[ 18 F]fluoro-D-glucose iLN inguinal lymph nodes LNs lymph nodes MRI magnetic resonance imaging MS multiple sclerosis PET/CT positron emission tomography/computed tomography pLN popliteal lymph nodes PT Pertussis toxin Dimethyl fumarate (DMF) is a small molecular therapeutic approved for the treatment of inflammatory autoimmune diseases like psoriasis and multiple sclerosis (MS), which are dominated by Th1/Th17 cells. Furthermore, we were able to monitor the anti-inflammatory treatment effect of DMF by determination of the glucose metabolism within the draining pLN by non invasive I in vivo i [ SP 18 sp F]FDG-PET/CT imaging. Our results show that the anti-inflammatory effects of immunotherapeutics like DMF can be assessed non invasively I in vivo i during Th1/Th17 cell-mediated encephalomyelitis (EAE) by [ SP 18 sp F]FDG-PET/CT imaging of the draining lymph nodes. [Extracted from the article]

Abstract Background This study investigated the noninvasive assessment of tumor vascularization with clinical F-18-fluorodeoxyglucose positron emission tomography/computed tomography and contrast-enhanced computed tomography ([18F]FDG-PET/CT and CE-CT) in experimental human xenograft tumors with modifiable vascularization and compared results to histology. Tumor xenografts with modifiable vascularization were established in 71 athymic nude rats by subcutaneous transplantation of human non-small-cell lung cancer (NSCLC) cells. Four different groups were transplanted with two different tumor cell lines (either A549 or H1299) alone or tumors co-transplanted with rat glomerular endothelial (RGE) cells, the latter to increase vascularization. Tumors were assessed noninvasively by [18F]FDG PET/CT and contrast-enhanced CT (CE-CT) using clinical scanners. This was followed by histological examinations evaluating tumor vasculature (CD-31 and intravascular fluorescent beads). Results In both tumor lines (A549 and H1299), co-transplantation of RGE cells resulted in faster growth rates [maximal tumor diameter of 20 mm after 22 (± 1.2) as compared to 45 (± 1.8) days, p

Several patients experience unexplained persistent symptoms after recovering from severe acute respiratory syndrome-related coronavirus disease 2 (SARS-CoV-2) [the so-called long coronavirus disease (COVID)], with a negative impact on their quality of life. We report the evolutionary track of fluorine-18-fluorodeoxyglucose positron emission tomography-computed tomography ([18F]FDG-PET/CT) in two patients incidentally diagnosed with SARS-CoV-2 infection. In both cases, baseline PET/CT showed bilateral pneumonia associated with [18F]FDG vascular uptake. Vascular uptake was more evident in the baseline scan of the asymptomatic patient. Vice versa, it was more marked in the follow-up examinations of the patient who developed long COVID. These findings suggested that vascular inflammation and its duration are responsible for the clinical course of the disease and the development of long COVID.

SARS-CoV-2 virus infects organs other than the lung, such as mediastinal lymph nodes, spleen, and liver, but, to date, metabolic imaging studies obtained in short-term follow-ups of patients hospitalized with severe COVID-19 infection are rare. Our objective was to evaluate the usefulness of [18F]FDG-PET/CT in the short-term follow-up of patients admitted for COVID-19 pneumonia and to explore the association of the findings with clinical prognostic markers. The prospective study included 20 patients with COVID-19 pneumonia (November 2020–March 2021). Clinical and laboratory test findings were gathered at admission, 48–72 h post-admission, and 2–3 months post-discharge, when [18F]FDG-PET/CT and respiratory function tests were performed. Lung volumes, spirometry, lung diffusion capacity for carbon monoxide (DLCO), and respiratory muscle strength were measured. Volumetric [18F]FDG-PET/CT results were correlated with laboratory and respiratory parameters. Eleven [18F]FDG-PET/CT (55%) were positive, with hypermetabolic mediastinal lymphadenopathy in 90.9%. Mediastinal lesion’s SUVpeak was correlated with white cells’ count. Eleven (55%) patients had impaired respiratory function, including reduced DLCO (35%). SUVpeak was correlated with %predicted-DLCO. TLG was negatively correlated with %predicted-DLCO and TLC. In the short-term follow-up of patients hospitalized for COVID-19 pneumonia, [18F]FDG-PET/CT findings revealed significant detectable inflammation in lungs and mediastinal lymph nodes that correlated with pulmonary function impairment in more than half of the patients.

Background: An accurate preoperative workup of cytologically indeterminate thyroid nodules (ITN) may rule out malignancy and avoid diagnostic surgery for benign nodules. This study assessed the performance of molecular diagnostics (MD) and 2-[ 18 F]fluoro-2-deoxy-d-glucose ([ 18 F]FDG)-positron emission tomography/computed tomography (PET/CT) in ITN, including their combined use, and explored whether molecular alterations drive the differences in [ 18 F]FDG uptake among benign nodules. Methods: Adult, euthyroid patients with a Bethesda III or IV thyroid nodule were prospectively included in this multicenter study. They all underwent MD and an [ 18 F]FDG-PET/CT scan of the neck. MD was performed using custom next-generation sequencing panels for somatic mutations, gene fusions, and copy number alterations and loss of heterozygosity. Sensitivity, specificity, negative and positive predictive value (NPV, PPV), and benign call rate (BCR) were assessed for MD and [ 18 F]FDG-PET/CT separately and for a combined approach using both techniques. Results: In 115 of the 132 (87%) included patients, MD yielded a diagnostic result on cytology. Sensitivity, specificity, NPV, PPV, and BCR were 80%, 69%, 91%, 48%, and 57% for MD, and 93%, 41%, 95%, 36%, and 32% for [ 18 F]FDG-PET/CT, respectively. When combined, sensitivity and specificity were 95% and 44% for a double-negative test (i.e., negative MD plus negative [ 18 F]FDG-PET/CT) and 68% and 86% for a double-positive test, respectively. Concordance was 63% (82/130) between MD and [ 18 F]FDG-PET/CT. There were more MD-positive nodules among the [ 18 F]FDG-positive benign nodules (25/59, 42%, including 11 (44%) isolated RAS mutations) than among the [ 18 F]FDG-negative benign nodules (7/30, 19%, p  = 0.02). In oncocytic ITN, the BCR of [ 18 F]FDG-PET/CT was mere 3% and MD was the superior technique. Conclusions: MD and [ 18 F]FDG-PET/CT are both accurate rule-out tests when unresected nodules that remain unchanged on ultrasound follow-up are considered benign. It may vary worldwide which test is considered most suitable, depending on local availability of diagnostics, expertise, and cost-effectiveness considerations. Although complementary, the benefits of their combined use may be confined when therapeutic consequences are considered, and should therefore not routinely be recommended. In nononcocytic ITN, sequential testing may be considered in case of a first-step MD negative test to confirm that withholding diagnostic surgery is oncologically safe. In oncocytic ITN, after further validation studies, MD might be considered. Clinical Trial Registration: This trial is registered with ClinicalTrials.gov: NCT02208544 (August 5, 2014), https://clinicaltrials.gov/ct2/show/NCT02208544.