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Purpose: This study aimed to determine the organ-specific accuracy of [ 18 F]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 [ 18 F]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 [ 18 F]FDG-PET/CT., Results: A total of 123 patients with 363 [ 18 F]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 [ 18 F]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: [ 18 F]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., (© 2024. The Author(s).)

Background: Diffuse large B-cell lymphoma (DLBCL) is the most common form of lymphoma. European guidelines recommend FDG-PET/CT for staging and end of treatment (EOT) response assessment, mid-treatment response assessment is optional. We compared the Lugano classification and PET Response Criteria In Solid Tumours (PERCIST) for FDG-PET/CT response assessment in DLBCL head-to-head., Methods: We retrospectively included patients with DLBCL who underwent first-line R-CHOP(-like) therapy (2013-2020). Interim and EOT FDG-PET/CT response were reevaluated using the Lugano classification and PERCIST. Response was dichotomized into complete metabolic response (CMR) versus non-CMR (interim and EOT) and responders versus nonresponders (interim only). The cutoff for nonresponse at interim was a Deauville score of 5 (DS5) with the Lugano classification and a partial metabolic response with ≤66% reduction in SUL peak using PERCIST (PERCIST66)., Results: In multivariable Cox regression (N = 170), DS5 at interim, PERCIST66 at interim, non-CMR at EOT with the Lugano classification and non-CMR at EOT with PERCIST were predictive of progression-free survival (PFS). The Lugano classification and PERCIST agreed perfectly at interim and EOT and with 98.4% for the identification of nonresponders at interim. The accuracy for predicting events within 2 years of diagnosis was 84.2% for DS-5 at interim, 87.6% for PERCIST66 at interim, 86% for non-CMR with the Lugano classification at EOT and 83.3% for non-CMR with PERCIST at EOT., Conclusion: The Lugano classification and PERCIST were equally predictive of PFS. Nonresponse at interim and non-CMR at EOT were predictive of poor PFS with comparable accuracy for predicting events within 2 years., (© 2023 The Authors. Clinical Physiology and Functional Imaging published by John Wiley & Sons Ltd on behalf of Scandinavian Society of Clinical Physiology and Nuclear Medicine.)

Purpose: The preferred nuclear medicine method for identification of hyperfunctioning parathyroid glands in hyperparathyroidism (HPT) develops continuously in relation to the technological progress. Diagnostic methods based on PET/CT have during recent years evolved with new tracer possibilities competing with traditional scintigraphic methods. This investigation is a head-to-head comparison of Tc-99m-sestamibi SPECT/CT gamma camera scintigraphy (sestamibi SPECT/CT) and C-11-L-methionin PET/CT imaging (methionine PET/CT) for preoperative identification of hyperfunctioning parathyroid glands., Procedures: The study is a prospective cohort study including 27 patients diagnosed with primary hyperparathyroidism (PHPT). Two nuclear medicine physicians assessed all examinations independently and blinded. All scanning assessments were matched to the final surgical diagnosis as confirmed by histopathology. Biochemical monitoring of the therapeutical effects was performed preoperatively by PTH-measurements and followed postoperatively for up to 12 months. Comparisons were made for differences in sensitivity and positive predictive value (PPV)., Results: Twenty-seven patients (18 females, 9 males; mean age (range): 58.9 years (34.1-79)) were enrolled into the study. The 27 patients had a total of 33 identified sites of lesions of which 28 (85%) turned out to be histopathological verified hyperfunctioning parathyroid glands. The sensitivity and PPV for sestamibi SPECT/CT were 0.71 and 0.95; that of methionine PET/CT was 0.82 and 1, respectively. Both sensitivity and PPV were slightly lower for sestamibi SPECT/CT than for methionine PET PET/CT (-0.11, 95% confidence interval (95% CI): -0.29 to 0.08; -0.05, 95% CI: -0.14 to 0.04, respectively), but not to a statistically significant extent (p=0.38 and p=0.31). The sensitivity and PPV for diagnostic CT were 0.64 (95% CI: 0.44 to 0.81) and 1 (95% CI: 0.81 to 1)., Conclusions: Methionine PET/CT performed comparable to sestamibi SPECT/CT with respect to identification and localization of hyperfunctioning parathyroid glands prior to surgery., (© 2023. The Author(s), under exclusive licence to World Molecular Imaging Society.)

Objectives: HIV affects 36 million people globally with prevalence decreasing due to antiretroviral therapy (ART) and social awareness; transmission occurs during substance use. Cocaine usage independently affects brain activity and may result in reduced ART adherence. This study evaluates brain glucose metabolism measured by 18 F-fluorodeoxyglucose positron emission tomography/computed tomography ( 18 F-FDG PET/CT) in cocaine users with HIV infection., Design: Sixty-three participants were categorized into groups: 36 HIV infected (HIV+) and 27 non-HIV infected (HIV-) individuals. Each group was further split into cocaine users (CO+) and non-cocaine users (CO-). Of the HIV+, half were cocaine users and half were not. Of the HIV-, 14 were cocaine users and 13 were not. 18 F-FDG-PET and low dose CT scans were performed on all participants., Methods: Brain glucose metabolism was evaluated by 18 F-FDG uptake in the whole brain, cortex, basal ganglia, and cerebellum 120 min after injection. ROVER software was used for image analysis and regions of interest masks were applied via an adaptive threshold system. ANOVA tests and t -tests were performed to assess the respective differences between the four groups., Results: Generally, the HIV+/CO+ group (group A) displayed the lowest levels of uptake whereas the HIV-/CO- group (group D) showed the highest; the HIV+/CO- and HIV-/CO+ groups (groups B and C) showed intermediate levels of activity across the whole brain, cortex, basal ganglia, and cerebellum., Conclusion: HIV infection and cocaine usage were independently associated with a decrease in brain glucose uptake as measured by 18 F-FDG PET/CT. When combined, positive HIV status and cocaine patients showed the most decreased 18 F-FDG uptake., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

This study aimed to compare CE-CT and 2-[ 18 F]FDG-PET/CT for response monitoring metastatic breast cancer (MBC). The primary objective was to predict progression-free and disease-specific survival for responders vs. non-responders on CE-CT and 2-[ 18 F]FDG-PET/CT. The secondary objective was to assess agreement between response categorization for the two modalities. Treatment response in women with MBC was monitored prospectively by simultaneous CE-CT and 2-[ 18 F]FDG-PET/CT, allowing participants to serve as their own controls. The standardized response evaluation criteria in solid tumors (RECIST 1.1) and PET response criteria in solid tumors (PERCIST) were used for response categorization. For prediction of progression-free and disease-specific survival, treatment response was dichotomized into responders (partial and complete response) and non-responders (stable and progressive disease) at the first follow-up scan. Progression-free survival was defined as the time from baseline until disease progression or death from any cause. Disease-specific survival was defined as the time from baseline until breast cancer-specific death. Agreement between response categorization for both modalities was analyzed for all response categories and responders vs. non-responders. At the first follow-up, tumor response was reported more often by 2-[ 18 F]FDG-PET/CT than CE-CT, with only fair agreement on response categorization between the two modalities (weighted Kappa 0.28). Two-year progression-free survival for responders vs. non-responders by CE-CT was 54.2% vs. 46.0%, compared with 59.1% vs. 14.3% by 2-[ 18 F]FDG-PET/CT. Correspondingly, 2-year disease-specific survival were 83.3% vs. 77.8% for CE-CT and 84.6% vs. 61.9% for 2-[ 18 F]FDG-PET/CT. Tumor response on 2-[ 18 F]FDG-PET/CT was significantly associated with progression-free (HR: 3.49, P < 0.001) and disease-specific survival (HR 2.35, P = 0.008), while no association was found for tumor response on CE-CT. In conclusion, 2-[ 18 F]FDG-PET/CT appears a better predictor of progression-free and disease-specific survival than CE-CT when used to monitor metastatic breast cancer. In addition, we found low concordance between response categorization between the two modalities., Trial Registration: Clinical., Trials: gov. NCT03358589. Registered 30/11/2017-Retrospectively registered, http://www., Clinicaltrials: gov., (© 2023. The Author(s).)

This study aimed to compare contrast-enhanced CT (CE-CT) and 18 F-FDG PET/CT for response monitoring in metastatic breast cancer using the standardized response evaluation criteria RECIST 1.1 and PERCIST. The objective was to examine whether progressive disease was detected systematically earlier by one of the modalities. Methods: Women with biopsy-verified metastatic breast cancer were enrolled prospectively and monitored using combined CE-CT and 18 F-FDG PET/CT every 9-12 wk to evaluate response to first-line treatment. CE-CT scans and RECIST 1.1 were used for clinical decision-making without accessing the 18 F-FDG PET/CT scans. At study completion, 18 F-FDG PET/CT scans were unmasked and assessed according to PERCIST. Visual assessment was used if response criteria could not be applied. The modality-specific time to progression was defined as the time from the baseline scan until the first scan demonstrating progression. Paired comparative analyses for CE-CT versus 18 F-FDG PET/CT were applied, and the primary endpoint was earlier detection of progression by one modality. Secondary endpoints were time to detection of progression, response categorization, visualization of changes in response over time, and measurable disease according to RECIST and PERCIST. Results: In total, 87 women were evaluable, with a median of 6 (1-11) follow-up scans. Progression was detected first by 18 F-FDG PET/CT in 43 (49.4%) of 87 patients and first by CE-CT in 1 (1.15%) of 87 patients ( P  < 0.0001). Excluding patients without progression ( n  = 32), progression was seen first on 18 F-FDG PET/CT in 78.2% (43/55) of patients. The median time from detection of progression by 18 F-FDG PET/CT to that of CE-CT was 6 mo (95% CI, 4.3-6.4 mo). At baseline, 76 (87.4%) of 87 patients had measurable disease according to PERCIST and 51 (58.6%) of 87 patients had measurable disease according to RECIST 1.1. Moreover, 18 F-FDG PET/CT provided improved visualization of changes in response over time, as seen in the graphical abstract. Conclusion: Disease progression was detected earlier by 18 F-FDG PET/CT than by CE-CT in most patients, with a potentially clinically relevant median 6-mo delay for CE-CT. More patients had measurable disease according to PERCIST than according to RECIST 1.1. The magnitude of the final benefit for patients is a perspective for future research., (© 2023 by the Society of Nuclear Medicine and Molecular Imaging.)

Background: Carotid atherosclerosis is a major cause of stroke, traditionally diagnosed late. Positron emission tomography/computed tomography (PET/CT) with 18 F-sodium fluoride (NaF) detects arterial wall micro-calcification long before macro-calcification becomes detectable by ultrasound, CT or magnetic resonance imaging. However, manual PET/CT processing is time-consuming and requires experience. We compared a convolutional neural network (CNN) approach with manual segmentation of the common carotids., Methods: Segmentation in NaF-PET/CT scans of 29 healthy volunteers and 20 angina pectoris patients were compared for segmented volume (Vol) and mean, maximal, and total standardized uptake values (SUVmean, SUVmax, and SUVtotal). SUVmean was the average of SUVmeans within the VOI, SUVmax the highest SUV in all voxels in the VOI, and SUVtotal the SUVmean multiplied by the Vol of the VOI. Intra and Interobserver variability with manual segmentation was examined in 25 randomly selected scans., Results: Bias for Vol, SUVmean, SUVmax, and SUVtotal were 1.33 ± 2.06, -0.01 ± 0.05, 0.09 ± 0.48, and 1.18 ± 1.99 in the left and 1.89 ± 1.5, -0.07 ± 0.12, 0.05 ± 0.47, and 1.61 ± 1.47, respectively, in the right common carotid artery. Manual segmentation lasted typically 20 min versus 1 min with the CNN-based approach. Mean Vol deviation at repeat manual segmentation was 14% and 27% in left and right common carotids., Conclusions: CNN-based segmentation was much faster and provided SUVmean values virtually identical to manually obtained ones, suggesting CNN-based analysis as a promising substitute of slow and cumbersome manual processing., (© 2022 The Authors. Clinical Physiology and Functional Imaging published by John Wiley & Sons Ltd on behalf of Scandinavian Society of Clinical Physiology and Nuclear Medicine.)

Background: Artificial intelligence (AI) is known to provide effective means to accelerate and facilitate clinical and research processes. So in this study it was aimed to compare a AI-based method for cardiac segmentation in positron emission tomography/computed tomography (PET/CT) scans with manual segmentation to assess global cardiac atherosclerosis burden., Methods: A trained convolutional neural network (CNN) was used for cardiac segmentation in 18 F-sodium fluoride PET/CT scans of 29 healthy volunteers and 20 angina pectoris patients and compared with manual segmentation. Parameters for segmented volume (Vol) and mean, maximal, and total standardized uptake values (SUVmean, SUVmax, SUVtotal) were analyzed by Bland-Altman Limits of Agreement. Repeatability with AI-based assessment of the same scans is 100%. Repeatability (same conditions, same operator) and reproducibility (same conditions, two different operators) of manual segmentation was examined by re-segmentation in 25 randomly selected scans., Results: Mean (± SD) values with manual vs. CNN-based segmentation were Vol 617.65 ± 154.99 mL vs 625.26 ± 153.55 mL (P = .21), SUVmean 0.69 ± 0.15 vs 0.69 ± 0.15 (P = .26), SUVmax 2.68 ± 0.86 vs 2.77 ± 1.05 (P = .34), and SUVtotal 425.51 ± 138.93 vs 427.91 ± 132.68 (P = .62). Limits of agreement were - 89.42 to 74.2, - 0.02 to 0.02, - 1.52 to 1.32, and - 68.02 to 63.21, respectively. Manual segmentation lasted typically 30 minutes vs about one minute with the CNN-based approach. The maximal deviation at manual re-segmentation was for the four parameters 0% to 0.5% with the same and 0% to 1% with different operators., Conclusion: The CNN-based method was faster and provided values for Vol, SUVmean, SUVmax, and SUVtotal comparable to the manually obtained ones. This AI-based segmentation approach appears to offer a more reproducible and much faster substitute for slow and cumbersome manual segmentation of the heart., (© 2021. American Society of Nuclear Cardiology.)

Background: We aimed to establish and test an automated AI-based method for rapid segmentation of the aortic wall in positron emission tomography/computed tomography (PET/CT) scans., Methods: For segmentation of the wall in three sections: the arch, thoracic, and abdominal aorta, we developed a tool based on a convolutional neural network (CNN), available on the Research Consortium for Medical Image Analysis (RECOMIA) platform, capable of segmenting 100 different labels in CT images. It was tested on 18 F-sodium fluoride PET/CT scans of 49 subjects (29 healthy controls and 20 angina pectoris patients) and compared to data obtained by manual segmentation. The following derived parameters were compared using Bland-Altman Limits of Agreement: segmented volume, and maximal, mean, and total standardized uptake values (SUVmax, SUVmean, SUVtotal). The repeatability of the manual method was examined in 25 randomly selected scans., Results: CNN-derived values for volume, SUVmax, and SUVtotal were all slightly, i.e., 13-17%, lower than the corresponding manually obtained ones, whereas SUVmean values for the three aortic sections were virtually identical for the two methods. Manual segmentation lasted typically 1-2 hours per scan compared to about one minute with the CNN-based approach. The maximal deviation at repeat manual segmentation was 6%., Conclusions: The automated CNN-based approach was much faster and provided parameters that were about 15% lower than the manually obtained values, except for SUVmean values, which were comparable. AI-based segmentation of the aorta already now appears as a trustworthy and fast alternative to slow and cumbersome manual segmentation., (© 2021. American Society of Nuclear Cardiology.)

To examine 2-year changes in carotid and aortic 18 F-sodium fluoride (NaF) uptake in both healthy controls and angina pectoris patients. Twenty-nine healthy subjects and 20 angina pectoris patients underwent 90-min NaF-PET/CT twice 2 years apart. The carotids and three sections of the aorta (arch, thoracic, abdominal) were manually segmented. NaF uptake was expressed as the mean and total standardized uptake values without and with partial volume correction (SUVmean, SUVtotal and pvcSUVmean, pvcSUVtotal). Insignificant tendencies were higher NaF uptake in angina patients at both time points with less uptake in healthy subjects and higher uptake in angina patients after 2 years. Thus, aortic pvcSUVmean of angina patients was 1.14 ± 0.35 and 1.29 ± 0.71 at baseline and after 2 years vs. 0.99 ± 0.31 and 0.95 ± 0.28 in healthy subjects. A similar pattern was observed for the carotid pvcSUVmean. NaF uptake at baseline could not predict a change in CT-calcification after 2 years. NaF uptake in all parts of the aorta correlated positively with age. There was an insignificant, but consistent, tendency for slightly higher arterial NaF uptake in the angina group indicating more ongoing microcalcification at both time points in patients than healthy subjects. The 2-year changes were in both groups very small suggesting that the atherosclerotic process is slow, albeit with a tendency of slight decreases among healthy controls and slight increases in angina patients despite statin therapy in half of these., (© 2021. The Author(s), under exclusive licence to Springer Nature B.V.)

Purpose: The goal of this study was to assess global cerebral glucose uptake in subjects with known cardiovascular risk factors by employing a quantitative 18F-fluorodeoxyglucose-PET/computed tomography (FDG-PET/CT) technique. We hypothesized that at-risk subjects would demonstrate decreased global brain glucose uptake compared to healthy controls., Methods: We compared 35 healthy male controls and 14 male subjects at increased risk for cardiovascular disease (CVD) as assessed by the systematic coronary risk evaluation (SCORE) tool. All subjects were grouped into two age-matched cohorts: younger (<50 years) and older (≥50 years). The global standardized uptake value mean (Avg SUVmean) was measured by mapping regions of interest of the entire brain across the supratentorial structures and cerebellum. Wilcoxon's rank-sum test was used to assess the differences in Avg SUVmean between controls and at-risk subjects., Results: Younger subjects demonstrated higher brain Avg SUVmean than older subjects. In addition, in both age strata, the 10-year risk for fatal CVD according to the SCORE tool was significantly greater in the at-risk groups than in healthy controls (younger: P = 0.0304; older: P = 0.0436). In the younger cohort, at-risk subjects demonstrated significantly lower brain Avg SUVmean than healthy controls (P = 0.0355). In the older cohort, at-risk subjects similarly had lower Avg SUVmean than controls (P = 0.0343)., Conclusions: Global brain glucose uptake appears to be influenced by chronic cardiovascular risk factors. Therefore, FDG-PET/CT may play a role in determining the importance of CVD on brain function and has potential for monitoring the efficacy of various therapeutic interventions., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Atherosclerotic burden has become the focus of cardiovascular risk assessment. PET/computed tomography (CT) imaging with the tracers 18F-fluorodeoxyglucose and 18F-sodium fluoride shows arterial wall inflammation and microcalcification, respectively. Arterial uptake of both tracers is modestly age dependent. 18F-sodium fluoride uptake is consistently associated with risk factors and more easily measured in the heart. Because of extremely high sensitivity, ultrashort acquisition, and minimal radiation to the patient, total-body PET/CT provides unique opportunities for atherosclerosis imaging: disease screening and delayed and repeat imaging with global disease scoring and parametric imaging to better characterize the atherosclerosis of individual patients., Competing Interests: Disclosure This review was not funded. The authors have nothing to disclose., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Aims: To investigate the benefit of utilizing 18 F-sodium fluoride (NaF) PET/CT over calcium and Framingham scoring for potential preventative coronary artery disease (CAD) intervention., Methods and Results: This retrospective study included 136 participants (ages 21-75, BMI 18-43 kg/m 2 ): 86 healthy controls and 50 patients. CT heart segmentations were superimposed onto PET images and standard uptake values (SUV) were calculated by a semi-auto segmentation method of drawing volumes of interest around the heart. Intergroup comparisons were made matching 37 patient/control pairs based on age, gender, and BMI. ROC curves were generated to determine how well SUV and Framingham methods predicted patient status. Regressions including all 136 participants were performed between SUV, age, and BMI. Patients exhibited higher average SUV (SUV mean ; P = 0.006) and Framingham scores (P = 0.02) than controls. However, ROC curves indicated that SUV mean could discriminate patients from controls (AUC = 0.63, P = 0.049), but Framingham scores could not (AUC = 0.44, P = 0.38). Calcium scores and maximum SUV (SUV max ) did not differ between patients and controls. SUV mean correlated with age and BMI among females (age, partial R 2 = 0.16, P = 0.001; BMI, partial R 2 = 0.12, P = 0.004) and males (age, partial R 2 = 0.28, P < 0.0001; BMI, partial R 2 = 0.22, P < 0.0001)., Conclusion: Unlike calcium scores, NaF PET/CT-derived values differed between patients and controls. Framingham risk score patterns echoed those of SUV mean , but were not sensitive enough to predict patient status. SUV mean values increased with age and BMI. Therefore, incorporation of NaF PET/CT into routine prognostic CAD assessment might prove beneficial for assessing early stage plaque calcification in coronary arteries., Trial Registration: ClinicalTrials.gov (NCT01724749).

Objective: We aimed to determine whether NaF-PET/CT or FDG-PET/CT can detect abdominal aortic molecular calcification and inflammation in patients with rheumatoid arthritis (RA)., Methods: In this study, 18 RA patients (4 women, 14 men; mean age 56.0 ± 11.7) and 18 healthy controls (4 women, 14 men; mean age 55.8 ± 11.9) were included. The controls were matched to patients by sex and age (± 4 years). All subjects of this study underwent NaF-PET/CT scanning 90 min following the administration of NaF. FDG-PET/CT imaging was performed 180 min following intravenous FDG injection. Using OsiriX software, the global mean standardized uptake value (global SUVmean) in abdominal aorta was calculated for both FDG and NaF. The NaF SUVmean and FDG SUVmean were divided by the blood pool activity providing target-to-background ratios (TBR) namely, NaF-TBRmean and FDG-TBRmean. The CT calcium volume score was obtained using a growing region algorithm based on Hounsfield units., Results: The average NaF-TBRmean score among RA patients was significantly greater than that of healthy controls (median 1.61; IQR 1.49-1.88 and median 1.40; IQR 1.23-1.52, P = 0.002). The average CT calcium volume score among RA patients was also significantly greater than that of healthy controls (median 1.96 cm 3 ; IQR 0.57-5.48 and median 0.004 cm 3 ; IQR 0.04-0.05, P < 0.001). There was no significant difference between the average FDG-TBRmean scores in the RA patients when compared to healthy controls (median 1.29; IQR 1.13-1.52 and median 1.29; IQR 1.13-1.52, respectively, P = 0.98)., Conclusion: Quantitative assessment with NaF-PET/CT identifies increased molecular calcification in the wall of the abdominal aorta among patients with RA as compared with healthy controls, while quantitative assessment with FDG-PET/CT did not identify a difference in aortic vessel wall FDG uptake between the RA and healthy control groups.

Despite increased focus on prevention as well as improved treatment possibilities, lung cancer remains among the most frequent and deadliest cancer diagnoses worldwide. Even lung cancer patients treated with curative intent have a high risk of relapse, leading to a dismal prognosis. More knowledge on the efficacy of surveillance with both current and new technologies as well as on the impact on patient treatment, quality of life, and survival are urgently needed. We therefore designed a randomized phase 3 trial. In one arm, every other computed tomography (CT) scan is replaced by positron emission tomography/CT, the other arm is the standard follow-up scheme with CT. The standard arm is identical to the current national Danish follow-up program. The primary endpoint is to compare the number of relapses treatable with curative intent in the 2 arms. We aim to include 750 patients over a 3-year period. Additionally, we will test the feasibility of noninvasive lung cancer diagnostics and surveillance in the form of circulating tumor DNA analysis. For this purpose, blood samples are collected before treatment and at each following control. The blood samples are stored in a biobank for later analysis and will not be used for guiding patient treatment decisions., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Positron emission tomography/x-ray computed tomography (PET/CT) has long been discussed as a promising modality for response evaluation in cancer. When designing respective clinical trials, several design issues have to be addressed, especially the number/timing of PET/CT scans, the approach for quantifying metabolic activity, and the final translation of measurements into a rule. It is unclear how well these issues have been tackled in quest of an optimised use of PET/CT in response evaluation. Medline via Ovid and Science Citation Index via Web of Science were systematically searched for articles from 2015 on cancer patients scanned with PET/CT before and during/after treatment. Reports were categorised as being either developmental or evaluative, i.e. focusing on either the establishment or the evaluation of a rule discriminating responders from non-responders. Of 124 included papers, 112 (90 %) were accuracy and/or prognostic studies; the remainder were response-curve studies. No randomised controlled trials were found. Most studies were prospective (62 %) and from single centres (85 %); median number of patients was 38.5 (range 5-354). Most (69 %) of the studies employed only one post-baseline scan. Quantification was mainly based on SUVmax (91 %), while change over time was most frequently used to combine measurements into a rule (79 %). Half of the reports were categorised as developmental, the other half evaluative. Most development studies assessed only one element (35/62, 56 %), most frequently the choice of cut-off points (25/62, 40 %). In summary, the majority of studies did not address the essential open issues in establishing PET/CT for response evaluation. Reasonably sized multicentre studies are needed to systematically compare the many different options when using PET/CT for response evaluation.

Purpose: We present a novel computed tomography-based tissue segmentation methodology for determining volume and global uptake of FDG of the thigh muscles and correlate these parameters with age., Materials and Methods: A total of 71 subjects from a prospective clinical trial (NCT01724749) were included. PET/CT scans were acquired 180 minutes after intravenous injection of FDG. A 3D growing region algorithm with neighborhood Hounsfield unit threshold between one and 150 was used to highlight the muscle. FDG uptake was expressed as the average mean standardized uptake value normalized for lean body mass (average SULmean). Femur volume was used to normalize thigh muscle volume to calculate normalized volume and correlate with age., Results: We found a significant negative correlation between normalized volume and age (left side r = -0.262, P = 0.02; right side r = -0.286, P = 0.01). No statistically significant difference was found between SUL and age or between SUL and BMI. There was no statistically significant difference in muscle volume on the two sides. Statistically significant difference was noted in the global metabolic activity (SUL) between the two sides (left 0.39 ± 0.06, right 0.42 ± 0.08, P < 0.001), with 56/71 (78.8%) subjects having higher uptake on the right side., Conclusion: FDG-PET/CT using CT-based segmentation is a novel imaging modality assessing the volume and global metabolic activity of the thigh muscles. It could be possible to utilize this methodology for the research and understanding of lower limb muscle pathophysiology.

Aim: To test the feasibility of a fully automated artificial intelligence-based method providing PET measures of prostate cancer (PCa)., Methods: A convolutional neural network (CNN) was trained for automated measurements in 18 F-choline (FCH) PET/CT scans obtained prior to radical prostatectomy (RP) in 45 patients with newly diagnosed PCa. Automated values were obtained for prostate volume, maximal standardized uptake value (SUV max ), mean standardized uptake value of voxels considered abnormal (SUV mean ) and volume of abnormal voxels (Vol abn ). The product SUV mean  × Vol abn was calculated to reflect total lesion uptake (TLU). Corresponding manual measurements were performed. CNN-estimated data were compared with the weighted surgically removed tissue specimens and manually derived data and related to clinical parameters assuming that 1 g ≈ 1 ml of tissue., Results: The mean (range) weight of the prostate specimens was 44 g (20-109), while CNN-estimated volume was 62 ml (31-108) with a mean difference of 13·5 g or ml (95% CI: 9·78-17·32). The two measures were significantly correlated (r = 0·77, P<0·001). Mean differences (95% CI) between CNN-based and manually derived PET measures of SUVmax, SUVmean, Vol abn (ml) and TLU were 0·37 (-0·01 to 0·75), -0·08 (-0·30 to 0·14), 1·40 (-2·26 to 5·06) and 9·61 (-3·95 to 23·17), respectively. PET findings Vol abn and TLU correlated with PSA (P<0·05), but not with Gleason score or stage., Conclusion: Automated CNN segmentation provided in seconds volume and simple PET measures similar to manually derived ones. Further studies on automated CNN segmentation with newer tracers such as radiolabelled prostate-specific membrane antigen are warranted., (© 2019 Scandinavian Society of Clinical Physiology and Nuclear Medicine. Published by John Wiley & Sons Ltd.)

Purpose: PET/MRI was introduced for clinical use in 2011 and is now an established modality for the imaging of brain and certain pelvic cancers, whereas clinical use for the imaging of other forms of cancer is not yet widespread. We therefore systematically investigated what has been published on the use of PET/MRI compared to PET/CT in the imaging of cancers outside the brain, focusing on clinical areas of application related to diagnosis, staging and restaging., Methods: A systematic search of PubMed/MEDLINE, Embase and the Cochrane Library was performed. Studies evaluating the diagnostic performance of simultaneous PET/MRI in cancer patients were chosen., Results: A total of 3,138 publications were identified and 116 published during the period 2012-2018 were included and were grouped according to the major cancer forms: 13 head and neck (HNC), 9 breast (BC), 21 prostate (PC), 14 gynaecological, 13 gastrointestinal (GIC), and 46 various cancers. Data from studies comparing PET/MRI and PET/CT for staging/restaging suggested the superiority of 18 F-FDG PET/MRI for the detection of tumour extension and retropharyngeal lymph node metastases in nasopharyngeal cancer, and for the detection of liver metastases and possibly bone marrow metastases in high-risk BC. FDG PET/MRI tended to be inferior for the detection of lung metastases in HNC and BC. 68 Ga-PSMA-11 PET/MRI was superior to PET/CT for the detection of local PC recurrence. FDG PET/MRI was superior to FDG PET/CT for the detection of local tumour invasion in cervical cancer and had higher accuracy for the detection of liver metastases in colorectal cancer., Conclusion: The scoping review methodology resulted in the identification of a huge number of records, of which less than 5% were suitable for inclusion and only a limited number allowed conclusions on the advantages/disadvantages of PET/MRI compared to PET/CT in the oncological setting. There was evidence to support the use of FDG PET/MRI in staging of nasopharyngeal cancer and high-risk BC. Preliminary data indicate the superiority of PET/MRI for the detection of local recurrence in PC, local tumour invasion in cervical cancer, and liver metastases in colorectal cancer. These conclusions are based on small datasets and need to be further explored.

Objective: To investigate whether a 18F-FDG PET/CT (PET/CT)-based diagnostic strategy adds decisive new information compared to conventional imaging in the evaluation of salivary gland tumours and the detection of cervical lymph node metastases, distant metastases, and synchronous cancer in patients with salivary gland carcinoma., Methods: The study was a blinded prospective cohort study. Data were collected consecutively through almost 3 years. All patients underwent conventional imaging-magnetic resonance imaging (MRI) and chest X-ray (CXR)-in addition to PET/CT prior to surgery. Final diagnosis was obtained by histopathology. MRI/CXR and PET/CT were interpreted separately by experienced radiologists and nuclear medicine physicians. Interpretation included evaluation of tumour site, cervical lymph node metastases, distant metastases, and synchronous cancer., Results: Ninety-one patients were included in the study. Thirty-three patients had primary salivary gland carcinoma and eight had cervical lymph node metastases. With PET/CT, the sensitivity was 92% and specificity 29% regarding tumour site. With MRI/CXR, the sensitivity and specificity were 90% and 26%, respectively. Regarding cervical lymph node metastases in patients with salivary gland carcinoma, the sensitivity with PET/CT was 100% and with MRI/CXR 50%. PET/CT diagnosed distant metastases in five patients, while MRI/CXR detected these in two patients. Finally, PET/CT diagnosed two synchronous cancers, whereas MRI/CXR did not detect any synchronous cancers., Conclusions: Compared with MRI/CXR PET/CT did not improve discrimination of benign from malignant salivary gland lesions. However, PET/CT may be advantageous in primary staging and in the detection of distant metastases and synchronous cancers.

Purpose: To compare multidisciplinary team conference (MDTC) decisions regarding treatment intent based on either chest X-ray + MRI of the head and neck (CXR/MRI) or 18 F-FDG-PET/CT (PET/CT) in patients with recurrent head and neck squamous cell carcinoma (HNSCC)., Methods: Prospective blinded cohort study based on paired data. Consecutive patients with suspected recurrent HNSCC were invited to participate. All included patients underwent CXR/MRI and PET/CT before diagnostic biopsy. An ordinary MDTC using all available imaging data was conducted as per standard practice. After at least three months (to eliminate recall bias in the team), the first project MDTC, based on either CXR/MRI or PET/CT, was conducted, and the tumor board made conclusions regarding treatment. After an additional three months, a second project MDTC was conducted using the complementary imaging strategy. The separate treatment strategies were compared using McNemar's test., Results: A total of 110 patients (90 males and 20 females, median age 66 years, range 40-87) were included. The initial primary tumor originated from the pharynx in 56 (51%) patients, oral cavity in 17 (15%) patients, and larynx in 37 (34%) patients. Based on CXR/MRI, 87 patients (79%) were recommended curative treatment and 23 (21%) palliative treatment. Based on PET/CT, the MDTC decided that 52 (47%) patients were suitable for curative treatment and 58 (53%) for palliative treatment. The absolute difference of 32% was statistically significant (95% CI: 22-42%, p < 0.001)., Conclusions: PET/CT affected MDTC decisions in patients with recurrent HNSCC towards less curative and more palliative treatment., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

The purpose of this study was to examine whether staging with 18 F-FDG PET/CT better predicts survival in patients with recurrent head and neck squamous cell carcinoma (HNSCC) than chest x-ray (CXR) plus head and neck MRI or chest CT (CCT) plus head and neck MRI. Methods: This was a prospective cohort study based on paired data. Consecutive patients with histologically verified HNSCC recurrence were enrolled from September 2013 to March 2016. All patients underwent CXR/MRI, CCT/MRI, and PET/CT on the same day and before biopsy. All imaging studies underwent masked interpretation by separate teams of experienced nuclear physicians or radiologists. Recurrent carcinomas were categorized as localized (equivalent to primary stages I-II), locally advanced (equivalent to primary stages III-IVB), or metastatic (equivalent to primary stage IVC). Discriminative abilities for each imaging strategy with respect to cancer-specific and stage-based survival were compared using Kaplan-Meier analysis, Cox proportional-hazards regression with the Harrell concordance index (C-index), and net reclassification improvement. Results: In total, 110 patients (90 men and 20 women; median age, 66 y; range, 40-87 y) were included. PET/CT significantly changed the assigned tumor stage when compared with imaging strategies based on CXR/MRI or CCT/MRI ( P < 0.001 for both). Kaplan-Meier analysis of PET/CT-based staging showed progressively worsened prognosis with localized, locally advanced, or metastatic disease (log-rank test, P < 0.001), whereas CXR/MRI and CCT/MRI were unable to distinguish between these groups in terms of survival (log-rank test, P = 0.18 and P = 0.58, respectively). Overall discriminative ability in predicting cancer-specific mortality was significantly greater for PET/CT (C-index, 0.72) than for CXR/MRI (C-index, 0.55) ( P = 0.001) and CCT/MRI (C-index, 0.55)( P < 0.001). The addition of PET/CT to either CXR/MRI or CCT/MRI was associated with a significantly positive net reclassification improvement ( P < 0.001 for both). Conclusion: Contrary to standard imaging strategies, PET/CT-based staging in recurrent HNSCC was able to significantly discriminate among the survival courses of patients with local, locally advanced, or metastatic disease and predict their respective survival probability., (© 2019 by the Society of Nuclear Medicine and Molecular Imaging.)

Purpose: Suspected serious disease (SSD) is a disease designation often given to patients with one or more non-specific symptoms of severe disease that could be due to cancer; the optimal diagnostic strategy is largely left to the clinician's discretion. Being a sensitive non-invasive whole-body imaging modality 18 F-FDG-PET/CT may have a potential role in this cancer-prevalent group of patients to confirm or refute suspected malignancy. We aimed to investigate the diagnostic value of 18 F-FDG-PET/CT in SSD using long-term follow-up as reference., Methods: We retrospectively studied results obtained in all SSD patients referred for 18 F-FDG-PET/CT at a single institution in 2010-2011 retrieving the following clinical data in all patients: journal entries, examinations, and evaluations made from 6 months before the scan and until the latest recorded entry. A true positive PET scan was a positive scan with a subsequently biopsy-confirmed diagnosis of cancer in the same target organ, whereas a false positive scan had no subsequent cancer diagnosis. A true negative PET scan was a negative scan without a cancer diagnosis during follow-up, whereas a false negative PET scan was one with a subsequently confirmed cancer diagnosis., Results: Ninety-three patients, aged 67 years (range 25-89) were included and followed for up to 7.3 years (median 6). Of these, 21 [22.6% (95% CI 15.3-32.1)] turned out to have cancer. With 18 F-FDG-PET/CT, the sensitivity was 81.0% (95% CI 60.0-92.3), specificity 76.4% (95% CI 65.4-84.7), positive predictive value 50% (95% CI 34.1-65.9), and negative predictive value 93.2% (95% CI 83.8-97.3). Five patients with negative scans were subsequently diagnosed with cancer., Conclusion: Cancer prevalence is substantial among patients with SSD. 18 F-FDG-PET/CT is a promising option in this setting, in particular because a high negative predictive value equals a low incidence of cancer during follow-up. Further studies are needed to establish the role of 18 F-FDG-PET/CT in SSD.

Objective: We aimed to assess the feasibility of quantifying fluorine-18-fluorodexoglucose ( 18 F-FDG) and 18 F-sodium fluoride ( 18 F-NaF) uptake in abdominal aorta and examine their association with age and cardiovascular risk factors., Subjects and Methods: Our study comprised 123 subjects (48±14 years of age, 62 men) including 78 healthy volunteers and 45 patients with chest pain syndrome, who originally enrolled in the CAMONA study in Odense, Denmark (NCT01724749). All subjects underwent 18 F-FDG positron emission tomography/computed tomography (PET/CT) and 18 F-NaF PET/CT on separate days, 180min and 90min after administration of tracers, respectively. The global tracer uptake value (GTUV) in the abdominal aorta was determined as sum of the product of each slice area and its corresponding average standardized uptake value (SUV mean), divided by the sum of those slice areas. In addition, for each subject, the 10 years Framingham risk score (FRS) was calculated. The correlations between 18 F-NaF and 18 F-FDG GTUV with age and 10 years FRS were assessed in all, healthy and patient subjects., Results: There was a significant, positive correlation between subjects' age and 18 F-NaF GTUV (r=0.35, P<0.001), but not 18 F-FDG GTUV (r=0.06, P=0.53). Also, there was a significant, positive correlation between 10 years FRS and 18 F-NaF GTUV (r=0.30, P<0.001), but not 18 F-FDG GTUV (r=0.01, P=0.95). Individual differences in 18 F-FDG and 1 18 F-NaF uptake were large in both healthy subjects and patients., Conclusion: In this study, the global uptake of 18 F-NaF in abdominal aorta was positively associated with age and 10 years FRS in all subjects, healthy and patient groups, whereas the global uptake of 18 F-FDG was not.

Objective: This proof of concept study investigated whether dual time point FDG-PET/CT with image acquisition after 1 and 3 h could be useful in preoperative staging of patients undergoing robot-assisted radical prostatectomy and extended pelvic lymph node dissection for high-risk prostate cancer., Results: Twenty patients with high-risk prostate cancer underwent dual time point FDG-PET/CT before undergoing surgery. Histologically confirmed lymph node metastases were found in 9/20 (45%). A median of 19 (range 10-41; n = 434) lymph nodes were removed per patient. Pelvic lymph nodes with detectable FDG uptake were seen in two patients only, but the FDG-avid lesion on PET did not correspond with pathological findings in either patient. We found a significant increase in maximal standardized uptake value of the prostate of around 30% between early and late imaging. We found no correlation between clinical findings after radical prostatectomy and PET measurements.

Combined myocardial flow reserve (MFR) by PET and CT coronary angiography (CTA) is a promising tool for assessment of coronary artery disease. Prior analyses of MFR/CTA has been performed as side-by-side interpretation, not as volume rendered, full hybrid analysis, with fused MFR/CTA. We aimed to: (i) establish a method for full hybrid analysis of MFR/CTA, (ii) validate the inter- and intra-observer reproducibility of MFR values, and (iii) determine the diagnostic value of side-by-side versus full hybrid MFR/CTA with 15-O-water PET. Forty-four outpatients scheduled for invasive coronary angiography (ICA) were enrolled prospectively. All underwent rest/stress 15-O-water PET/CTA with ICA as reference. Within two observers of different experience, the Pearson r at global and territorial level exceeded 0.953 for rest, stress, and MFR values, as determined by Carimas software. Within and between observers, the mean differences between rest, stress, and MFR values were close to zero and the confidence intervals for 95% limits of agreement were narrow. The diagnostic performance of full hybrid PET/CTA did not outperform the side-by-side approach, but performed better than MFR without CTA at vessel level: specificity 93% (95% confidence limits: 89-97%) versus 76% (64-88%), p = 0.0004; positive predictive value 71% (55-86%) versus 51% (37-65%), p = 0.0001; accuracy 90% (84-95%) versus 77% (69-84%), p = 0.0009. MFR showed high reproducibility within and between observers of different experience. The full hybrid model was not superior to side-by-side interpretation of MFR/CTA, but proved better than MFR alone at vessel level with regard to specificity, positive predictive value, and accuracy.

Purpose: In patients with newly diagnosed head and neck squamous cell carcinoma (HNSCC), we wanted to examine the differences in overall treatment decisions, i.e. curative versus palliative treatment intent, reached by a multidisciplinary team conference (MDTC) based on 18F-fluoro-deoxy-glucose-positron emission tomography/computed tomography (PET/CT) or chest X-ray + MRI of the head and neck (CXR/MRI)., Patients and Methods: This was a prospective blinded cohort study based on paired data. Consecutive patients with histologically verified primary HNSCC were invited to participate. All included patients underwent CXR/MRI and PET/CT before diagnostic biopsy. An ordinary MDTC using all available imaging was conducted as per standard practice. After at least 3 months (to eliminate recall bias in the team), the first project MDTC was conducted, based on either CXR/MRI or PET/CT, and the tumor board drew conclusions regarding treatment. After an additional 3 months, a second project MDTC was conducted using the complementary imaging modality., Results: A total of 307 patients were included. Based on CXR/MRI, 303 patients (99%) were recommended for curative treatment and only four patients (1%) for palliative treatment. Based on PET/CT, the MDTC concluded that 278 (91%) patients were suitable for curative treatment and 29 (9%) patients for palliative treatment. The absolute difference of 8% was statistically significant (95% CI: 4.8%-11.5%, p < 0.001)., Conclusions: A PET/CT-based imaging strategy significantly changed the decisions regarding treatment intent made by a MDTC for patients diagnosed with HNSCC, when compared with the standard imaging strategy of CXR/MRI.

Our purpose was to examine whether staging of head and neck squamous cell carcinoma (HNSCC) by upfront 18 F-FDG PET/CT (i.e., on the day of biopsy and before the biopsy) discriminates survival better than the traditional imaging strategies based on chest x-ray plus head and neck MRI (CXR/MRI) or chest CT plus head and neck MRI (CCT/MRI). Methods: We performed a masked prospective cohort study based on paired data. Consecutive patients with histologically verified primary HNSCC were recruited from Odense University Hospital from September 2013 to March 2016. All patients underwent CXR/MRI, CCT/MRI, and PET/CT on the same day. Tumors were categorized as localized (stages I and II), locally advanced (stages III and IVB), or metastatic (stage IVC). Discriminative ability for each imaging modality with respect to HNSCC staging were compared using Kaplan-Meier analysis, Cox proportional hazards regression with the Harrell C-index, and net reclassification improvement. Results: In total, 307 patients with histologically verified HNSCC were included. Use of PET/CT significantly altered the stratification of tumor stage when compared with either CXR/MRI or CCT/MRI (χ 2 , P < 0.001 for both). Cancer stages based on PET/CT, but not CXR/MRI or CCT/MRI, were associated with significant differences in mortality risk on Kaplan-Meier analyses ( P ≤ 0.002 for all PET/CT-based comparisons). Furthermore, overall discriminative ability was significantly greater for PET/CT (C-index, 0.712) than for CXR/MRI (C-index, 0.675; P = 0.04) or CCT/MRI (C-index, 0.657; P = 0.02). Finally, PET/CT was significantly associated with a positive net reclassification improvement when compared with CXR/MRI (0.184, P = 0.03) but not CCT/MRI (0.094%, P = 0.31). Conclusion: Tumor stages determined by PET/CT were associated with more distinct prognostic properties in terms of survival than those determined by standard imaging strategies., (© 2018 by the Society of Nuclear Medicine and Molecular Imaging.)

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a group of autoimmune diseases characterized by systemic inflammation in small- to medium-sized blood vessels. Although immunosuppressive therapy has greatly improved the prognosis for these patients, there are still significant comorbidities, such as cancer and infection, associated with AAV. These comorbidities are often indistinguishable from an underlying AAV disease relapse, and create a clinical conundrum, as these conditions are normally contraindications for immunosuppressive treatment. Thus, it is important to be able to rule out these comorbidities before initiation of immunosuppressive treatment. We examined F-fluoro-deoxy-glucose positron emission tomography combined with computed tomography (FDG-PET/CT)'s value in ruling out cancer or infection in patients with AAV.Data were obtained retrospectively for a clinically based cohort of AAV patients who underwent FDG-PET/CT during 2009 to 2014 owing to a suspicion of cancer, infection, or both cancer and infection indistinguishable from disease relapse. FDG-PET/CT conclusions were compared to the final diagnoses after follow-up analysis (mean 43 months).A total of 19 patients were included who underwent a total of 26 scans. The results of FDG-PET/CT outcome compared to final diagnosis were: 9 true positives, 3 false positives, 13 true negatives, and 1 false negative. The diagnostic probabilities for FDG-PET/CT with respect to overall comorbidity (i.e., cancer or infection) were: sensitivity 90% ( 95% confidence interval [CI] 60%-98%), specificity 81% ( 95% CI 57%-93%), positive predictive value 75% (95% CI 47%-91%), negative predictive value 93% (95% CI 68%-99%), and accuracy 84% (95% CI 66%-94%).FDG-PET/CT had a high negative predictive value and ruled out the comorbidities correctly in all but one case of urinary tract infection, a well-known limitation. Our study showed FGD-PET/CT's promise as an effective tool for ruling out cancer or infection in patients with AAV albeit in a limited population.

Background: Cancer of unknown primary (CUP) is a heterogeneous group of cancers, so called when a biopsy from a patient reveals malignancy without giving a clue to where in the body the primary tumor is located. Whole-body 18-fluorine-fluorodeoxyglucose positron-emission-tomography/computed tomography (18F-FDG PET/CT) is widely used for diagnosis and staging of most cancers. We hypothesized that 18F-FDG PET/CT-especially if used early-is suitable for the detection of the primary tumor in patients with CUP., Objective: To assess the ability of 18F-FDG PET/CT to detect the primary tumor in adult CUP patients., Data Sources: PubMed/Medline, Embase, and Web of Science., Study Eligibility Criteria: Studies on CUP from extracervical metastases in which every patient had received an 18F-FDG PET/CT scan and at least one 18F-FDG PET/CT-positive finding was confirmed by biopsy or clinical follow-up., Study Appraisal: PRISMA and QUADAS-2 were applied., Synthesis Methods: The pooled detection rate (DR) of 18F-FDG PET/CT was assessed with a fixed-effects model. Heterogeneity among studies was assessed with the I-squared statistic., Results: A total of 2953 articles were identified from which N = 82 were assessed by full text and N = 20, comprising 1942 adult patients, were included in the study. Median (range) number of patients and DR was N = 72 (21-316) and 36.3% (9.8%-75.3%), respectively. Two-thirds of included studies were retrospective, and the pooled DR was 40.93% (95% confidence interval: 38.99%-42.87%). There was large heterogeneity between studies (I-squared = 95.9%), randomization was not applied, CUP diagnosis was not standardized, and workup (if described) was characterized by multiple testing procedures resulting in a highly selected, challenging patient group., Conclusions: Despite great heterogeneity in diagnostic workup and in studies in general, an overall DR of 40.93% suggests that upfront application of 18F-FDG PET/CT may have a role in CUP by obviating a great many futile diagnostic procedures. To what degree 18F-FDG PET/CT used early in the course of disease may improve the detection rate could not be deducted from selected articles. A large, prospective, preferably randomized, study on the potential benefit of using 18F-FDG PET/CT up front in CUP patients is warranted to judge if and when 18F-FDG PET/CT should be applied in these patients.

Objective: Patients presenting with cystic lesions in the neck without obvious signs of malignancy constitute a diagnostic challenge since fine needle aspiration is often insufficient and a diagnosis may not be reached until surgical resection/biopsy is performed. The differential diagnosis of a cystic cervical mass comprises a variety of benign conditions, but malignancy must be ruled out. We examined the diagnostic performance of fluorine-18 fluorodeoxyglucose ( 18 F-FDG) PET/CT to identify malignancy., Methods: We retrospectively included consecutive patients referred from the Department of ENT Head and Neck Surgery for 18 F-FDG PET/CT-scans because of a solitary neck cyst. Scan results were compared to histopathology and follow-up., Results: The study comprised 58 patients. Twenty patients (34%) were diagnosed with cancer during follow-up. PET/CT suggested malignancy in 34 patients (19 true positive, 15 false positive) and showed no malignancy in 24 (23 true negative, 1 false negative). The sensitivity, specificity, accuracy, positive and negative predictive values were 95% (76-99%), 61% (45-74%), 72% (60-82%), 56% (39-71%), and 96% (80-99%), respectively (95% confidence intervals in brackets). The primary tumor was identified in 14 out of the 20 patients with confirmed cancer. Increased metabolism, as evaluated by PET, was the only imaging characteristic among several others, which associated independently with malignancy in the cystic neck lesions, odds ratio 1.27 (1.07-1.50), p = 0.006., Conclusion: 18 F-FDG PET/CT could reliably rule out malignancy (NPV 96%), albeit with a high frequency of false positive scans, requiring further diagnostic work-up. Increased metabolism was the best imaging parameter to differentiate between malignant and benign lesions.

Objective: Increased focal colorectal uptake of fluorine-18-fluorodeoxyglucose ( 18 F-FDG) is reported to occur in 1%-3% of patients undergoing 18 F-FDG positron emission tomography/computed tomography (PET/CT) for disease outside the bowel. However, there is no consensus on how to deal with this finding in the clinic. Due to the non-specific appearance of such lesions and a certain rate of false positive findings, patients may by subjected to unnecessary invasive procedures or, conversely, cancers may be overlooked if the risk of malignancy is downplayed. The purpose of this study was to examine the incidence and clinical significance of focal colorectal incidentalomas (FCI) at our institution and to assess the potential benefit of using semi-quantitative measures instead of visual interpretation to discern malignant from benign lesions., Subjects and Methods: We identified all patients in 2011 with a report of FCI. We reviewed patient charts with regard to basic characteristics, indications for and results of 18 F-FDG-PET/CT and subsequent workup including colonoscopy and histopathological analyses, and applied post hoc semi-quantitative analysis. Out of 4,829 patients, twenty-five met the inclusion criteria (mean age 71 years, 13 females, 12 males)., Results: Of the 25 included patients, eight presented with no pathologic or non-malignant findings (e.g. inflammation), while ten had polyps/adenomas and seven a hitherto undiagnosed colorectal cancer. Semi-quantitative SUVmax values and ROC analysis based cut-off values could not reliably discriminate benign from premalignant or malignant disease., Conclusion: It is the opinion of the authors that 18 F-FDG PET/CT scan may identify incidentally sites of colorectal carcinoma but cannot discriminate them from polyps/adenomas. Nevertheless, incidental focal bowel uptake should always be reported and/or further evaluated.

Purpose: The purpose of this study was to determine the ability of dual time-point (DTP) PET/CT with (18)F-FDG to discriminate between malignant and benign lymphadenopathies. The relationship between DTP FDG uptake and glucose metabolism/hypoxia markers in lymphadenopathies was also assessed., Methods: Patients with suspected lymphoma or recently diagnosed treatment-naive lymphoma were prospectively enrolled for DTP FDG PET/CT (scans 60 min and 180 min after FDG administration). FDG-avid nodal lesions were segmented to yield volume and standardized uptake values (SUV), including SUVmax, SUVmean, cSUVmean (with partial volume correction), total lesion glycolysis (TLG) and cTLG (with partial volume correction). Expression of glucose transporter-1 (GLUT-1), hexokinase-II (HK-II), glucose-6-phosphatase (G6Pase) and hypoxia-inducible factor-1alpha (HIF-1alpha) were assessed with immunohistochemistry and enzyme activity was determined for HK and G6Pase., Results: FDG uptake was assessed in 203 lesions (146 malignant and 57 benign). Besides volume, there were significant increases over time for all parameters, with generally higher levels in the malignant lesions. The retention index (RI) was not able to discriminate between malignant and benign lesions. Volume, SUVmax, TLG and cTLG for both scans were able to discriminate between the two groups statistically, but without complete separation. Glucose metabolism/hypoxia markers were assessed in 15 lesions. TLG and cTLG were correlated with GLUT-1 expression on the 60-min scan. RI-max and RI-mean and SUVmax, SUVmean and cSUVmean on the 60-min scan were significantly correlated with HK-II expression., Conclusion: RI was not able to discriminate between malignant and benign lesions, but some of the SUVs were able to discriminate on the 60-min and 180-min scans. Furthermore, FDG uptake was correlated with GLUT-1 and HK-II expression.

Purpose: To prospectively investigate the diagnostic accuracy of [(18)F]fluorodeoxyglucose (FDG)-positron emission tomography (PET)/computed tomography (CT) with dual-time-point imaging, contrast-enhanced CT (ceCT), and bone scintigraphy (BS) in patients with suspected breast cancer recurrence., Patients and Methods: One hundred women with suspected recurrence of breast cancer underwent 1-hour and 3-hour FDG-PET/CT, ceCT, and BS within approximately 10 days. The study was powered to estimate the precision of the individual imaging tests. Images were visually interpreted using a four-point assessment scale, and readers were blinded to other test results. The reference standard was biopsy along with treatment decisions and clinical follow-up (median, 17 months)., Results: FDG-PET/CT resulted in no false negatives and fewer false positives than the other imaging techniques. Accuracy of results were similar for 1-hour and 3-hour FDG-PET/CT. For distant recurrence, the area under the receiver operating curve was 0.99 (95% CI, 0.97 to 1) for FDG-PET/CT, 0.84 (95% CI, 0.73 to 0.94) for ceCT, and 0.86 (95% CI, 0.77 to 0.94) for the combined ceCT+BS. Of 100 patients, 22 (22%) were verified with distant recurrence, and 18 of these had bone involvement. Nineteen patients (19%) had local recurrence only. In exploratory analyses, diagnostic accuracy of FDG-PET/CT was better than ceCT alone or ceCT combined with BS in diagnosing distant, bone, and local recurrence, shown by a greater area under the receiver operating curve and higher sensitivity, specificity, and superior likelihood ratios., Conclusion: FDG-PET/CT was accurate in diagnosing recurrence in breast cancer patients. It allowed for distant recurrence to be correctly ruled out and resulted in only a small number of false-positive cases. Exploratory findings suggest that FDG-PET/CT has greater accuracy than conventional imaging technologies in this patient group., (© 2016 by American Society of Clinical Oncology.)

Arteriosclerosis and its sequelae are the most common cause of death in diabetic patients and one of the reasons why diabetes has entered the top 10 causes of death worldwide, fatalities having doubled since 2000. The literature in the field claims almost unanimously that arteriosclerosis is more frequent or develops more rapidly in diabetic than non-diabetic subjects, and that the disease is caused by arterial inflammation, the control of which should therefore be the goal of therapeutic efforts. These views are mostly based on indirect methodologies, including studies of artery wall thickness or stiffness, or on conventional CT-based imaging used to demonstrate tissue changes occurring late in the disease process. In contrast, imaging with positron emission tomography and computed tomography (PET/CT) applying the tracers 18F-fluorodeoxyglucose (FDG) or 18F-sodium fluoride (NaF) mirrors arterial wall inflammation and microcalcification, respectively, early in the course of the disease, potentially enabling in vivo insight into molecular processes. The present review provides an overview of the literature from the more than 20 and 10 years, respectively, that these two tracers have been used for the study of atherosclerosis, with emphasis on what new information they have provided in relation to diabetes and which questions remain insufficiently elucidated. [ABSTRACT FROM AUTHOR]

This study aimed to compare the prognostic value of quantitative measures of [18F]-fluorodeoxyglucose positron emission tomography with integrated computed tomography (FDG-PET/CT) for the response monitoring of patients with metastatic breast cancer (MBC). In this prospective study, 22 patients with biopsy-verified MBC diagnosed between 2011 and 2014 at Odense University Hospital (Denmark) were followed up until 2019. A dual-time-point FDG-PET/CT scan protocol (1 and 3 h) was applied at baseline, when MBC was diagnosed. Baseline characteristics and quantitative measures of maximum standardized uptake value (SUVmax), mean standardized uptake value (SUVmean), corrected SUVmean (cSUVmean), metabolic tumor volume (MTV), total lesion glycolysis (TLG), and corrected TLG (cTLG) were collected. Survival time was analyzed using the Kaplan–Meier method and was regressed on MTV, TLG, and cTLG while adjusting for clinicopathological characteristics. Among the 22 patients included (median age: 59.5 years), 21 patients (95%) died within the follow-up period. Median survival time was 29.13 months (95% Confidence interval: 20.4–40 months). Multivariable Cox proportional hazards regression analyses of survival time showed no influence from the SUVmean, cSUVmean, or SUVmax, while increased values of MTV, TLG, and cTLG were significantly associated with slightly higher risk, with hazard ratios ranging between 1.0003 and 1.004 (p = 0.007 to p = 0.026). Changes from 1 to 3 h were insignificant for all PET measures in the regression model. In conclusion, MTV and TLG are potential prognostic markers for overall survival in MBC patients. [ABSTRACT FROM AUTHOR]

This study measures the total graft of 18F-sodium fluoride (NaF) uptake in non-instrumented posterolateral lumbar fusion (niPLF) patients one month after surgery and correlates it with the difference in the clinical findings between the baseline and one year after surgery. The walking distance (WLK-D), visual analog scale of back pain (VAS-B), VAS score of leg pain (VAS-L), tandem test (TAN), Oswestry Disability Index questionnaire (ODI), and European Quality of Life-5 Dimensions questionnaire (EQ-5D) were assessed before surgery and one year after. The graft NaF uptake was analyzed quantitatively with a fixed threshold algorithm resulting in the total graft uptake (SUVtotal) and partial volume corrected SUVtotal (cSUVtotal). Only 4 out of 18 patients experienced fusion; they had an insignificantly lower median total graft uptakes, i.e., 1178 SUVtotal vs. 1224 SUVtotal (p = 0.73) and 1282 cSUVtotal vs. 1231 cSUVtotal (p = 0.35), respectively. Similarly, fused patients experienced insignificantly larger pain decreases, i.e., median VAS-B 4.3 vs. 3.8 (p = 0.92) and VAS-L −6.4 vs. −4.4 (p = 0.2). We found an insignificant trend for a lower NaF uptake and less pain in fused patients. The NaF uptake did not correlate with the chronological change in the clinical parameters. [ABSTRACT FROM AUTHOR]

18F-fluorodeoxyglucose positron emission tomography with integrated computed tomography (FDG-PET/CT) and contrast-enhanced computed tomography (CT) can be used for response evaluation in metastatic breast cancer (MBC). In this study, we aimed to review literature comparing the PET Response Criteria in Solid Tumors (PERCIST) with Response Evaluation Criteria in Solid Tumors (RECIST) in patients with MBC. We made a systematic search in Embase, PubMed/Medline, and Cochrane Library using a modified PICO model. The population was MBC patients and the intervention was PERCIST or RECIST. Quality assessment was performed using the QUADAS-2 checklist. A total of 1975 articles were identified. After screening by title/abstract, 78 articles were selected for further analysis of which 2 duplicates and 33 abstracts/out of focus articles were excluded. The remaining 43 articles provided useful information, but only one met the inclusion and none of the exclusion criteria. This was a retrospective study of 65 patients with MBC showing one-year progression-free survival for responders versus non-responders to be 59% vs. 27% (p = 0.2) by RECIST compared to 64% vs. 0% (p = 0.0001) by PERCIST. This systematic literature review identified a lack of studies comparing the use of RECIST (with CE-CT) and PERCIST (with FDG-PET/CT) for response evaluation in metastatic breast cancer. The available sparse literature suggests that PERCIST might be more appropriate than RECIST for predicting prognosis in patients with MBC. [ABSTRACT FROM AUTHOR]

Purpose: In this systematic review and individual patient data (IPD) meta-analysis, we analysed the diagnostic performance of [18F]FDG PET/CT in detecting primary tumours in patients with CUP and evaluated whether the location of the predominant metastatic site influences the diagnostic performance.A systematic literature search from January 2005 to February 2024 was performed to identify articles describing the diagnostic performance of [18F]FDG PET/CT for primary tumour detection in CUP. Individual patient data retrieved from original articles or obtained from corresponding authors were grouped by the predominant metastatic site. The diagnostic performance of [18F]FDG PET/CT in detecting the underlying primary tumour was compared between predominant metastatic sites.A total of 1865 patients from 32 studies were included. The largest subgroup included patients with predominant bone metastases (n = 622), followed by liver (n = 369), lymph node (n = 358), brain (n = 316), peritoneal (n = 70), lung (n = 67), and soft tissue (n = 23) metastases, leaving a small group of other/undefined metastases (n = 40). [18F]FDG PET/CT resulted in pooled detection rates to identify the primary tumour of 0.74 (for patients with predominant brain metastases), 0.54 (liver-predominant), 0.49 (bone-predominant), 0.46 (lung-predominant), 0.38 (peritoneal-predominant), 0.37 (lymph node-predominant), and 0.35 (soft-tissue-predominant).This individual patient data meta-analysis suggests that the ability of [18F]FDG PET/CT to identify the primary tumour in CUP depends on the distribution of metastatic sites. This finding emphasises the need for more tailored diagnostic approaches in different patient populations. In addition, alternative diagnostic tools, such as new PET tracers or whole-body (PET/)MRI, should be investigated.Methods: In this systematic review and individual patient data (IPD) meta-analysis, we analysed the diagnostic performance of [18F]FDG PET/CT in detecting primary tumours in patients with CUP and evaluated whether the location of the predominant metastatic site influences the diagnostic performance.A systematic literature search from January 2005 to February 2024 was performed to identify articles describing the diagnostic performance of [18F]FDG PET/CT for primary tumour detection in CUP. Individual patient data retrieved from original articles or obtained from corresponding authors were grouped by the predominant metastatic site. The diagnostic performance of [18F]FDG PET/CT in detecting the underlying primary tumour was compared between predominant metastatic sites.A total of 1865 patients from 32 studies were included. The largest subgroup included patients with predominant bone metastases (n = 622), followed by liver (n = 369), lymph node (n = 358), brain (n = 316), peritoneal (n = 70), lung (n = 67), and soft tissue (n = 23) metastases, leaving a small group of other/undefined metastases (n = 40). [18F]FDG PET/CT resulted in pooled detection rates to identify the primary tumour of 0.74 (for patients with predominant brain metastases), 0.54 (liver-predominant), 0.49 (bone-predominant), 0.46 (lung-predominant), 0.38 (peritoneal-predominant), 0.37 (lymph node-predominant), and 0.35 (soft-tissue-predominant).This individual patient data meta-analysis suggests that the ability of [18F]FDG PET/CT to identify the primary tumour in CUP depends on the distribution of metastatic sites. This finding emphasises the need for more tailored diagnostic approaches in different patient populations. In addition, alternative diagnostic tools, such as new PET tracers or whole-body (PET/)MRI, should be investigated.Results: In this systematic review and individual patient data (IPD) meta-analysis, we analysed the diagnostic performance of [18F]FDG PET/CT in detecting primary tumours in patients with CUP and evaluated whether the location of the predominant metastatic site influences the diagnostic performance.A systematic literature search from January 2005 to February 2024 was performed to identify articles describing the diagnostic performance of [18F]FDG PET/CT for primary tumour detection in CUP. Individual patient data retrieved from original articles or obtained from corresponding authors were grouped by the predominant metastatic site. The diagnostic performance of [18F]FDG PET/CT in detecting the underlying primary tumour was compared between predominant metastatic sites.A total of 1865 patients from 32 studies were included. The largest subgroup included patients with predominant bone metastases (n = 622), followed by liver (n = 369), lymph node (n = 358), brain (n = 316), peritoneal (n = 70), lung (n = 67), and soft tissue (n = 23) metastases, leaving a small group of other/undefined metastases (n = 40). [18F]FDG PET/CT resulted in pooled detection rates to identify the primary tumour of 0.74 (for patients with predominant brain metastases), 0.54 (liver-predominant), 0.49 (bone-predominant), 0.46 (lung-predominant), 0.38 (peritoneal-predominant), 0.37 (lymph node-predominant), and 0.35 (soft-tissue-predominant).This individual patient data meta-analysis suggests that the ability of [18F]FDG PET/CT to identify the primary tumour in CUP depends on the distribution of metastatic sites. This finding emphasises the need for more tailored diagnostic approaches in different patient populations. In addition, alternative diagnostic tools, such as new PET tracers or whole-body (PET/)MRI, should be investigated.Conclusion: In this systematic review and individual patient data (IPD) meta-analysis, we analysed the diagnostic performance of [18F]FDG PET/CT in detecting primary tumours in patients with CUP and evaluated whether the location of the predominant metastatic site influences the diagnostic performance.A systematic literature search from January 2005 to February 2024 was performed to identify articles describing the diagnostic performance of [18F]FDG PET/CT for primary tumour detection in CUP. Individual patient data retrieved from original articles or obtained from corresponding authors were grouped by the predominant metastatic site. The diagnostic performance of [18F]FDG PET/CT in detecting the underlying primary tumour was compared between predominant metastatic sites.A total of 1865 patients from 32 studies were included. The largest subgroup included patients with predominant bone metastases (n = 622), followed by liver (n = 369), lymph node (n = 358), brain (n = 316), peritoneal (n = 70), lung (n = 67), and soft tissue (n = 23) metastases, leaving a small group of other/undefined metastases (n = 40). [18F]FDG PET/CT resulted in pooled detection rates to identify the primary tumour of 0.74 (for patients with predominant brain metastases), 0.54 (liver-predominant), 0.49 (bone-predominant), 0.46 (lung-predominant), 0.38 (peritoneal-predominant), 0.37 (lymph node-predominant), and 0.35 (soft-tissue-predominant).This individual patient data meta-analysis suggests that the ability of [18F]FDG PET/CT to identify the primary tumour in CUP depends on the distribution of metastatic sites. This finding emphasises the need for more tailored diagnostic approaches in different patient populations. In addition, alternative diagnostic tools, such as new PET tracers or whole-body (PET/)MRI, should be investigated. [ABSTRACT FROM AUTHOR]

• Heterogeneity among studies on PET or PET-CT in malignant pleural effusions. • Few low-risk bias studies on PET or PET-CT in malignant pleural effusions. • Visual image analysis of PET-CT adds value to work-up of malignant pleural effusion. The role of PET and integrated PET-CT in the diagnostic workup of suspected malignant pleural effusions is unknown. Earlier systematic reviews (published 2014 and 2015) both included pleural pathology without effusion, and reached contradictory conclusions. Five studies have been published since the latest review. This systematic review and meta-analysis aims to summarise the evidence of PET and integrated PET-CT in predicting pleural malignancy in patients suspected of having malignant pleural effusions. A meta-analysis based on a systematic literature search in Cochrane Library, Medline, EMBASE and Clinicaltrials.gov was performed. Diagnostic studies evaluating the performance of PET or PET-CT in patients with suspected malignant pleural effusion, using pleural fluid cytology or histopathology as the reference test, and presenting sufficient data for constructing a 2x2 table were included. The quality of the studies was assessed by the Quality Assessment of Diagnostic Accuracy Studies-2 score. Subgroup analyses on image modality, interpretation method and known malignancy status pre index-test application were planned. Seven studies with low risk of bias were included. The pooled ability to separate benign from malignant effusions varied with image modality, interpretation method and known malignancy status pre index-test application. In studies using PET-CT, visual/qualitative image analysis was superior to semi-quantitative with positive (LR +) and negative likelihood ratio (LR-) of 9.9 (4.5–15.3) respectively 0.1 (0.1–0.2). There was considerable heterogeneity among studies. In conclusion, visual/qualitative image analysis of integrated PET-CT seems to add relevant information in the work-up of suspected malignant pleural effusions with LR + and LR- close to rigorous pre-set cut-offs of > 10 and < 0.1. However, the quality of evidence was low due to inter-study heterogeneity, and inability to assess meta-bias. Clinical Trial Registration : The protocol was uploaded to the PROSPERO database (CRD42020213319) on the 13th of October 2020. [ABSTRACT FROM AUTHOR]