Purpose . Prognostic significance of fluorine-18 fluorodeoxyglucose positron emission tomography ( 18 F-FDG-PET) in anal squamous cell carcinoma (SCC) has been evaluated in several studies; however, the results seem to be controversial and no consensus exists about its predictive capability. The current meta-analysis was carried out to comprehensively investigate the prognostic significance of 18 F-FDG-PET parameters in patients with anal SCC. Methods . A comprehensive literature search of PubMed/MEDLINE and Scopus databases was performed to retrieve pertinent articles published until August 5th 2018, concerning the prognostic significance of 18 F-FDG-PET in patients with anal SCC. No language restriction was used. Several prognostic factors were reported for progression-free survival (PFS) and overall survival (OS) including pretreatment maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), inguinal nodal uptake, and metabolic response to therapy. Results . Eleven studies (741 patients) were included. The pooled hazard ratio (HR) for the probability of PFS was 5.36 (95% confidence interval (95% CI): 3.12–9.21, p<0.001) for metabolic response to therapy and 1.98 (95% CI: 1.26–3.12, p=0.003) for SUVmax. The pooled HR for the probability of OS was 5.87 (3.02–11.39, p<0.0001) for metabolic response to therapy. On the other hand, the study revealed that the pooled HRs of MTV and inguinal nodal uptake for PFS were 1.56 (95% CI: 0.96–2.53, p=0.072) and 1.79 (95% CI: 1–3.21, p=0.051), respectively. Conclusions . Our findings propose that some 18 F-FDG-PET parameters could serve as prognostic indicators in anal SCC, but further larger studies are needed in this setting.
Image artefacts continue to pose challenges in clinical molecular imaging, resulting in misdiagnoses, additional radiation doses to patients and financial costs. Mismatch and halo artefacts occur frequently in gallium-68 (
Cytokine genes, including interleukin-10 (IL-10), are known to play important roles in the pathogenesis of juvenile idiopathic arthritis (JIA). This study aims to determine whether the IL-10 polymorphisms confer susceptibility to JIA.A meta-analysis was performed on the associations between the IL-10 -1082 G/A, -592 C/A, and -819 C/T polymorphisms and JIA. A total number of 7 studies involving 1,785 patients and 6,142 controls were considered in the meta-analysis.Meta-analysis of the IL-10 -592 C/A and -819 C/T polymorphisms showed no association with JIA in the study participants, or in Caucasian or Middle Eastern participants. Meta-analysis of the IL-10 -1082 A allele in all study participants, Caucasian and Middle Eastern, showed significant associations with RA (overall ORs were 1.17, 1.15, and 1.41, respectively). Meta-analysis of the AA versus GG genotype of the IL-10 -1082 G/A polymorphism revealed significant associations with JIA (OR = 3.66, 95% CI = 1.44-9.29, P = 0.006) in participants from Middle Eastern countries. Additionally, meta-analysis of the GG versus AA+GA genotypes of the IL-10 -1082 G/A polymorphism revealed the GG genotype as the protective factor against JIA in the Middle Eastern subgroup (OR = 0.44, 95% CI = 0.20-0.94, P = 0,04). Moreover, meta-analysis of the IL-10 -1082 A allele in 4 studies on Hardy-Weinberg equilibrium showed a significant association with JIA (OR = 1.17, 95% CI = 1.07-1.28, P = 0.0009). No association was found between the IL-10 (-1082, -819, -592) ACC, ATA, and GCC haplotypes and JIA.These results suggest that the IL-10 -1082 G/A polymorphism confers susceptibility to JIA.
The prostate-specific membrane antigen (PSMA) is an excellent target for theranostic applications in prostate cancer. However, PSMA-targeted radioligand therapy can cause undesirable effects due to high accumulation of PSMA radiotracers in salivary glands and kidneys. This study assessed orally administered monosodium glutamate (MSG) as a potential means of reducing kidney and salivary gland radiation exposure using a PSMA-targeting radiotracer. Methods: This prospective, double-blind, placebo-controlled study enrolled 10 patients with biochemically recurrent prostate cancer. Each subject served as his own control. PET/CT imaging sessions using 2-(3-{1-carboxy-5-[(6-18F-fluoro-pyridine-3-carbonyl)-amino]-pentyl}-ureido)-pentanedioic acid (18F-DCFPyL) were performed 3–7 d apart, after oral administration of either 12.7 g of MSG or placebo. Data from the 2 sets of images were analyzed by placing regions of interest on lacrimal, parotid, and submandibular glands; left ventricle; liver; spleen; kidneys; bowel; urinary bladder; gluteus muscle; and malignant lesions. The results from MSG and placebo scans were compared by paired analysis of the region-of-interest data. Results: In total, 142 pathologic lesions along with normal tissues were analyzed. As hypothesized a priori, there was a significant decrease in SUVmax corrected for lean body mass (SULmax) on images obtained after MSG administration in the parotids (24% ± 14%, P = 0.001), submandibular glands (35% ± 11%, P < 0.001), and kidneys (23% ± 26%, P = 0.014). Significant decreases were also observed in the lacrimal glands (49% ± 13%, P < 0.001), liver (15% ± 6%, P < 0.001), spleen (28% ± 13%, P = 0.001), and bowel (44% ± 13%, P < 0.001). A mildly lower blood pool SULmean was observed after MSG administration (decrease of 11% ± 13%, P = 0.021). However, significantly lower radiotracer uptake in terms of SULmean, SULpeak, and SULmax was observed in malignant lesions on scans performed after MSG administration than on the placebo studies (SULmax median decrease, 33%; range, −1% to 75%; P < 0.001). No significant adverse events occurred after placebo or MSG administration, and vital signs were stable. Conclusion: Orally administered MSG significantly decreased salivary gland, kidney, and other normal-organ PSMA radiotracer uptake in human subjects, using 18F-DCFPyL as an exemplar. However, MSG caused a corresponding reduction in tumor uptake, which may limit the benefits of this approach for diagnostic and therapeutic applications.
Abstract Background Prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) is becoming standard of care for men with biochemical recurrence (BCR) of prostate cancer. The implications of a negative PSMA PET/CT scan in this population remain unclear. This study aims to assess the outcome of patients with BCR post radical prostatectomy (RP) who have negative [ 18 F]DCFPyL PET/CT scan at relapse. Methods This is a post-hoc subgroup analysis of a prospective non randomized clinical trial. One hundred and one patients (median age, 75 years) with BCR after RP, who tested negative on [ 18 F]DCFPyL PET/CT and subsequently either underwent salvage radiotherapy (sRT) with or without androgen deprivation therapy (ADT) or were followed without active treatment, were included. Freedom from progression (FFP) after negative PSMA PET/CT was determined based on follow-up imaging selected as per clinical practice. Uni- and multivariate Cox regression analyses were performed to examine the association of patients' characteristics, tumor-specific variables, and treatment with clinical progression at the last follow-up. FFP at 1-, 2-, and 3-year were reported using Kaplan Meier analysis. Results The median PSA level at PET/CT was 0.56 ng/mL (range, 0.4–11.3). Sixty five (64%) patients were followed without receiving further treatment, and 36 (36%) received sRT (18% to the prostate bed only and 18% to the prostate bed and pelvic lymph nodes) within 3 months of the PSMA PET. Seventeen of the sRT patients (17 of 36, 47%) received concomitant androgen deprivation therapy (ADT). Median follow-up was 39 months. Subsequent clinical progression was detected in 21 patients (21%), with 52% in pelvic lymph nodes, 52% in the prostatic fossa, 19% in distant lymph nodes, 14% in lungs, and 10% in bones. The FFP was 95% (95% CI: 91%-99%) at 12 months, 87% (95% CI: 81%-94%) at 24 months, and 79% (95% CI: 71%-88%) at 36 months. Multivariate Cox regression analysis revealed that an initial International Society of Urological Pathology (ISUP) grade 5 was significantly associated with clinical progression at the last follow-up (hazard ratio, 5.1, P value, 0.04). Furthermore, the receipt of sRT correlated significantly with lower clinical progression at the last follow-up (hazard ratio, 0.2, P value, 0.03), whereas other clinical and tumor-specific parameters did not. Following surveillance-only and sRT, 29% (19 of 65) and 6% (2 of 36) of patients, respectively, showed clinical progression. In the sRT group, no significant difference was observed in FFP between patients who underwent sRT to the prostatic fossa versus those who received sRT to the prostatic fossa and pelvic lymph nodes, although the numbers in these groups were small. Conclusions This study suggests that salvage radiotherapy is associated with a decreased or delayed clinical progression in patients with biochemical recurrence following radical prostatectomy who have negative PSMA PET/CT scan results. The analysis also underscores the prognostic significance of the initial ISUP grade, with ISUP grade 5 being associated with worse outcomes. Trial registration Registered September 14, 2016; NCT02899312 .
Automatic and accurate segmentation of lesions in images of metastatic castration-resistant prostate cancer has the potential to enable personalized radiopharmaceutical therapy and advanced treatment response monitoring. The aim of this study is to develop a convolutional neural networks-based framework for fully-automated detection and segmentation of metastatic prostate cancer lesions in whole-body PET/CT images. 525 whole-body PET/CT images of patients with metastatic prostate cancer were available for the study, acquired with the [18F]DCFPyL radiotracer that targets prostate-specific membrane antigen (PSMA). U-Net (1)-based convolutional neural networks (CNNs) were trained to identify lesions on paired axial PET/CT slices. Baseline models were trained using batch-wise dice loss, as well as the proposed weighted batch-wise dice loss (wDice), and the lesion detection performance was quantified, with a particular emphasis on lesion size, intensity, and location. We used 418 images for model training, 30 for model validation, and 77 for model testing. In addition, we allowed our model to take n = 0,2, …, 12 neighboring axial slices to examine how incorporating greater amounts of 3D context influences model performance. We selected the optimal number of neighboring axial slices that maximized the detection rate on the 30 validation images, and trained five neural networks with different architectures. Model performance was evaluated using the detection rate, Dice similarity coefficient (DSC) and sensitivity. We found that the proposed wDice loss significantly improved the lesion detection rate, lesion-wise DSC and lesion-wise sensitivity compared to the baseline, with corresponding average increases of 0.07 (p-value = 0.01), 0.03 (p-value = 0.01) and 0.04 (p-value = 0.01), respectively. The inclusion of the first two neighboring axial slices in the input likewise increased the detection rate by 0.17, lesion-wise DSC by 0.05, and lesion-wise mean sensitivity by 0.16. However, there was a minimal effect from including more distant neighboring slices. We ultimately chose to use a number of neighboring slices equal to 2 and the wDice loss function to train our final model. To evaluate the model's performance, we trained three models using identical hyperparameters on three different data splits. The results showed that, on average, the model was able to detect 80% of all testing lesions, with a detection rate of 93% for lesions with maximum standardized uptake values (SUVmax) greater than 5.0. In addition, the average median lesion-wise DSC was 0.51 and 0.60 for all the lesions and lesions with SUVmax>5.0, respectively, on the testing set. Four additional neural networks with different architectures were trained, and they both yielded stronger performance of segmenting lesions whose SUVmax>5.0 compared to the rest of lesions. Our results demonstrate that prostate cancer metastases in PSMA PET/CT images can be detected and segmented using CNNs. The segmentation performance strongly depends on the intensity, size, and the location of lesions, and can be improved by using specialized loss functions. Specifically, the models performed best in detection of lesions with SUVmax>5.0. Another challenge was to accurately segment lesions close to the bladder. Future work will focus on improving the detection of lesions with lower SUV values by designing custom loss functions that take into account the lesion intensity, using additional data augmentation techniques, and reducing the number of false lesions by developing methods to better separate signal from noise.
Vasculitis of ascending aorta detected on FDG PET/CT in a patient with fever of unknown origin A 59-year-old man was admitted for fever of unknown origin.Fever was associated with chills.His medical record revealed the history of aortic valve replacement 11 years earlier, as well as enterococcal endocarditis 4 months prior to the current admission.The patient was found to have normal left ventricular size with borderline systolic function, left ventricular hypertrophy, right ventricle at the upper limit of normal size, mild systolic dysfunction and mild transvalvular aortic insufficiency on transthoracic echocardiography; while no vegetations were observed on transesophageal echocardiography.Sequential blood cultures were negative; however, a blood culture sample obtained 5 days prior to last admission was shown to be positive for enterococci.In addition, persistently increased levels of erythrocyte sedimentation rate and C reactive protein at 48 mm/hour and 39 mg/L were noted, respectively.Subsequently, the patient underwent fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography (F-18 FDG-PET/CT) in search for the origin of the fever, which depicted increased radiopharmaceutical uptake in the aortic root with upward extension to the ascending aorta (figure 1), without any abnormal uptake of the prosthetic aortic valve in the non-attenuation corrected images.Rest of the whole body scan was unremarkable.Based on scan pattern, compatible with aortitis, the patient underwent antibiotic treatment with ampicillin/sulbactam. Fever immediately disappeared, and the inflammatory parameters as we all as patient's clinical situation improved.The patient is currently receiving antibiotics to fulfil the 8 weeks duration.Multiple imaging modalities, providing different and often complementary findings among a wide array of aortitis presentations and potential complications, are used in the evaluation of both inflammatory and non-inflammatory aortic diseases.Inflammatory cell infiltration of different levels of aortic wall, caused by various immunological, infectious or traumatic factors, as the presenting cause of aortitis, is the rationale for nuclear imaging including F-18 FDG PET, which applies the metabolic accumulation of F-18 FDG in the inflammatory milieu, mainly in monocytes.Limited spatial resolution of PET and its inability to provide precise anatomic characterisation warrant coregistration of CT or MRI for anatomic localisation.Inconclusive CT findings in the early stages of aortitis indicate the need for a more sensitive modality. 1PET is known to be the most sensitive test for detection of the early vessel inflammation.
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