A direct comparison in diagnostic performance of CDUS, FDG-PET/CT and MRI in patients suspected of giant cell arteritis.

OBJECTIVES: This study directly compares diagnostic performance of Colour Duplex Ultrasound (CDUS), Fluor-18-deoxyglucose Positron Emission Tomography Computed Tomography (FDG-PET/CT) and Magnetic Resonance Imaging (MRI) in patients suspected of giant cell arteritis (GCA). METHODS: Patients with suspected GCA were included in a nested-case control pilot study. CDUS, whole body FDG-PET/CT and cranial MRI were performed within 5 working days after initial clinical evaluation. Clinical diagnosis after six months follow-up by experienced rheumatologists in the field of GCA, blinded for imaging, was used as reference standard. Diagnostic performance of the imaging modalities was determined. Stratification for GCA subtype was performed and imaging results were evaluated in different risk stratification groups. RESULTS: In total, 23 patients with GCA and 19 patients suspected of but not diagnosed with GCA were included. Sensitivity was 69.6% (95%CI 50.4%-88.8%) for CDUS, 52.2% (95%CI 31.4%-73.0%) for FDG-PET/CT and 56.5% (95%CI 35.8%-77.2%) for MRI. Specificity was 100% for CDUS, FDG-PET/CT and MRI. FDG-PET/CT was negative for GCA in all isolated cranial GCA patients (n = 8), while MRI was negative in all isolated extracranial GCA patients (n = 4). In 4 GCA patients with false-negative (n = 2; intermediate and high risk) or inconclusive (n = 2; low and intermediate risk) CDUS results, further imaging confirmed diagnosis. CONCLUSIONS: Sensitivity of CDUS was highest, while specificity was excellent in all imaging modalities. Nevertheless, confidence intervals of all imaging modalities were overlapping. Following EULAR recommendations, CDUS can be used as a first test to diagnose GCA. With insufficient evidence for GCA, further testing considering GCA subtype is warranted.

Comparing Diagnostic Performance of Short and Long [18F]FDG-PET Acquisition Times in Giant Cell Arteritis.

(1) Background: In giant cell arteritis (GCA), the assessment of cranial arteries using [18F]fluorodeoxyglucose ([18F]FDG) positron emission tomography (PET) combined with low-dose computed tomography (CT) may be challenging due to low image quality. This study aimed to investigate the effect of prolonged acquisition time on the diagnostic performance of [18F]FDG PET/CT in GCA. (2) Methods: Patients with suspected GCA underwent [18F]FDG-PET imaging with a short acquisition time (SAT) and long acquisition time (LAT). Two nuclear medicine physicians (NMPs) reported the presence or absence of GCA according to the overall image impression (gestalt) and total vascular score (TVS) of the cranial arteries. Inter-observer agreement and intra-observer agreement were assessed. (3) Results: In total, 38 patients were included, of whom 20 were diagnosed with GCA and 18 were without it. Sensitivity and specificity for GCA on SAT scans were 80% and 72%, respectively, for the first NMP, and 55% and 89% for the second NMP. On the LAT scans, these values were 65% and 83%, and 75% and 83%, respectively. When using the TVS, LAT scans showed especially increased specificity (94% for both NMPs). Observer agreement was higher on the LAT scans compared with that on the SAT scan. (4) Conclusions: LAT combined with the use of the TVS may decrease the number of false-positive assessments of [18F]FDG PET/CT. Additionally, LAT and TVS may increase both inter and intra-observer agreement.

Diagnostic accuracy of dynamic CZT-SPECT in coronary artery disease. A systematic review and meta-analysis.

BACKGROUND: With the appearance of cadmium-zinc-telluride (CZT) cameras, dynamic myocardial perfusion imaging (MPI) has been introduced, but comparable data to other MPI modalities, such as quantitative coronary angiography (CAG) with fractional flow reserve (FFR) and positron emission tomography (PET), are lacking. This study aimed to evaluate the diagnostic accuracy of dynamic CZT single-photon emission tomography (SPECT) in coronary artery disease compared to quantitative CAG, FFR, and PET as reference. MATERIALS AND METHODS: Different databases were screened for eligible citations performing dynamic CZT-SPECT against CAG, FFR, or PET. PubMed, OvidSP (Medline), Web of Science, the Cochrane Library, and EMBASE were searched on the 5th of July 2020. Studies had to meet the following pre-established inclusion criteria: randomized controlled trials, retrospective trails or observational studies relevant for the diagnosis of coronary artery disease, and performing CZT-SPECT and within half a year the methodological references. Studies which considered coronary stenosis between 50% and 70% as significant based only on CAG were excluded. Data extracted were sensitivity, specificity, likelihood ratios, and diagnostic odds ratios. Quality was assessed with QUADAS-2 and statistical analysis was performed using a bivariate model. RESULTS: Based on our criteria, a total of 9 studies containing 421 patients were included. For the assessment of CZT-SPECT, the diagnostic value pooled analysis with a bivariate model was calculated and yielded a sensitivity of 0.79 (% CI 0.73 to 0.85) and a specificity of 0.85 (95% CI 0.74 to 0.92). Diagnostic odds ratio (DOR) was 17.82 (95% CI 8.80 to 36.08, P < 0.001). Positive likelihood ratio (PLR) and negative likelihood ratio (NLR) were 3.86 (95% CI 2.76 to 5.38, P < 0.001) and 0.21 (95% CI 0.13 to 0.33, P < 0.001), respectively. CONCLUSION: Based on the results of the current systematic review and meta-analysis, dynamic CZT-SPECT MPI demonstrated a good sensitivity and specificity to diagnose CAD as compared to the gold standards. However, due to the heterogeneity of the methodologies between the CZT-SPECT MPI studies and the relatively small number of included studies, it warrants further well-defined study protocols.

Integrated analysis of pain, health-related quality of life, and analgesic use in patients with metastatic castration-resistant prostate cancer treated with Radium-223.

BACKGROUND: Radium-223 (Ra-223), an alpha-emitting radiopharmaceutical, established an improved overall survival and health-related quality of life (HRQoL) in symptomatic metastatic castration-resistant prostate cancer (mCRPC) patients. However, effects on pain were not specifically evaluated. Here we assess integrated HRQoL, pain, and opioid use in a contemporary, more extensively pretreated, symptomatic and asymptomatic mCRPC population. METHODS: mCRPC patients scheduled for Ra-223 treatment were included and analyzed for HRQoL, pain, and opioid use, using Functional Assessment of Cancer Therapy-Prostate (FACT-P) and Brief Pain Inventory-Short Form (BPI-SF) questionnaires and recording of opioid use and dosage, respectively. Primary outcome measure was the percentage of patients experiencing a complete pain response (score of 0 on the BPI-SF Worst pain item and no increase in daily use of analgesics). A complete or partial pain response (better BPI-SF score and decrease in opioid use) and a better or no change in HRQoL was evaluated as an integrated overall clinical response (IOCR). Secondary endpoints included the time to pain progression (TPP) and Total FACT-P deterioration (TTFD), defined as time from first Ra-223 treatment to clinical meaningful increase in BPI-SF Worst pain item score and Total FACT-P score, respectively. RESULTS: This registry included 300 patients, of whom 105 (35%) were evaluable for FACT-P and BPI-SF during Ra-223 treatment. Forty-five (43%) patients had pain at baseline (PAB) (BPI-SF Worst pain score 5-10 points) and 60 (57%) had no pain at baseline (no-PAB) (BPI-SF Worst pain score 0-4 points). Complete pain response was achieved in 31.4% of the patients, while 58% had an IOCR. The median TTP and TTFD were 5.6 and 5.7 months, respectively, while the difference between PAB and no-PAB patients was not significant. CONCLUSIONS: In contemporary, extensively pretreated mCRPC patients, Ra-223 treatment induced complete pain responses while integrated analysis of HRQoL, pain response, and opioid use demonstrated that the majority of patients derive clinical benefit.

A prospective observational registry evaluating clinical outcomes of Radium-223 treatment in a nonstudy population.

The ALSYMPCA study established a 3.6 month Overall Survival (OS) benefit in metastatic Castration Resistant Prostate Cancer (mCRPC) patients treated with Radium-223 dichloride (Ra-223) over placebo. Here we report clinical outcomes of Ra-223 treatment in a nonstudy population. In this prospective registry, patients from 20 Dutch hospitals were included prior to Ra-223 treatment. Clinical parameters collected included previous treatments and Adverse Events. Primary outcome was 6 months Symptomatic Skeletal Event (SSE)-free survival, while secondary outcomes included Progression-Free Survival (PFS) and Overall Survival (OS). Of the 305 patients included, 300 were evaluable. The mean age was 73.6 years, 90% had ≥6 bone metastases and 74.1% were pretreated with Docetaxel, 19.5% with Cabazitaxel and 80.5% with Abiraterone and/or Enzalutamide. Of all patients, 96.7% were treated with Ra-223 and received a median of 5 cycles. After a median follow-up of 13.2 months, 6 months SSE-free survival rate was 83%, median PFS was 5.1 months and median OS was 15.2 months. Six months SSE-free survival rate and OS were comparable with those reported in ALSYMPCA. "Previous Cabazitaxel treatment" and "bone-only metastases" were independent predictors of a shorter and longer PFS, respectively, while above-median LDH and "bone-only metastases" were independent predictors of shorter and longer OS, respectively. Toxicity was similar as reported in the ALSYMPCA trial. These results suggest that in a nonstudy population, Ra-223 treatment is well-tolerated, equally effective as in the ALSYMPCA population and that patients not previously treated with Cabazitaxel benefit most from Ra-223.

Incidental congenital coronary artery vascular fistulas in adults: Evaluation with adenosine-13N-ammonia PET-CT.

AIM: To assess the functionality of congenital coronary artery fistulas (CAFs) using adenosine stress 13N-ammonia positron emission tomography computed tomography (PET-CT). METHODS: Congenital CAFs were incidentally detected during coronary angiography (CAG) procedures in 11 adult patients (six males and five females) with a mean age of 64.3 years (range 41-81). Patients were collected from three institutes in the Netherlands. The characteristics of the fistulas (origin, pathway and termination), multiplicity of the origins and pathways of the fistulous vessels were assessed by CAG. Five patients underwent adenosine pharmacologic stress 13N-ammonia PET-CT to assess myocardial perfusion and the functional behavior of the fistula. RESULTS: Eleven patients with 12 CAFs, 10 unilateral and one bilateral, originating from the left anterior descending coronary artery (n = 8), right coronary artery (n = 2) and circumflex (n = 2). All fistulas were of the vascular type, terminating into either the pulmonary artery (n = 11) or coronary sinus (n = 1). The CAG delineated the characteristics of the fistula (origin, pathway and termination). Multiplicity of the origins and pathways of the fistulous vessels were common in most fistulas (8/12, 67% and 9/12, 75%, respectively). Multiplicity was common among the different fistula components (23/36, 64%). Adenosine pharmacologic stress 13N-ammonia PET-CT revealed normal myocardial perfusion and ejection fraction in all but one patient, who showed a reduced ejection fraction. CONCLUSION: PET-CT may be helpful for assessing the functional status of congenital CAFs in selected patients regarding clinical decision-making. Studies with a larger patient series are warranted.

Optimized dose regimen for whole-body FDG-PET imaging.

BACKGROUND: The European Association of Nuclear Medicine procedure guidelines for whole-body fluorodeoxyglucose positron-emission tomography (FDG-PET) scanning prescribe a dose proportional to the patient's body mass. However, clinical practice shows degraded image quality in obese patients indicating that using an FDG dose proportional to body mass does not overcome size-related degradation of the image quality. The aim of this study was to optimize the administered FDG dose as a function of the patient's body mass or a different patient-dependent parameter, providing whole-body FDG-PET images of a more constant quality. METHODS: Using a linear relation between administered dose and body mass, FDG-PET imaging was performed on two PET/computed tomography scanners (Biograph TruePoint and Biograph mCT, Siemens). Image quality was assessed by the signal-to-noise ratio (SNR) in the liver in 102 patients with a body mass of 46 to 130 kg. Moreover, the best correlating patient-dependent parameter was derived, and an optimized FDG dose regimen was determined. This optimized dose regimen was validated on the Biograph TruePoint system in 42 new patients. Furthermore, this relation was verified by a simulation study, in which patients with different body masses were simulated with cylindrical phantoms. RESULTS: As expected, both PET systems showed a significant decrease in SNR with increasing patient's body mass when using a linear dosage. When image quality was fitted to the patient-dependent parameters, the fit with the patient's body mass had the highest R2. The optimized dose regimen was found to be Anew= c/t × m2, where m is the body mass, t is the acquisition time per bed position and c is a constant (depending on scanner type). Using this relation, SNR no longer varied with the patient's body mass. This quadratic relation between dose and body mass was confirmed by the simulation study. CONCLUSION: A quadratic relation between FDG dose and the patient's body mass is recommended. Both simulations and clinical observations confirm that image quality remains constant across patients when this quadratic dose regimen is used.

Targeted lymph node biopsy in mediastinoscopy using 3D FDG-PET/CT movies: a feasibility study.

In non-small-cell lung cancer, positive lymph nodes with increased fluorodeoxyglucose (FDG) uptake may be missed by mediastinoscopy. Lack of pathological confirmation may lead to radical, but unnecessary lung surgery. To minimize these false-negative results, the feasibility and potential value of three-dimensional (3D) FDG-PET/computed tomography (CT) movies were investigated to improve targeted lymph node biopsy during mediastinoscopies. PET/CT images were rendered in 3D volumes with multiplanar reconstructions and maximum intensity projections and reviewed in 3D 'fly-through' and 'fly-around' movies. These movies were developed and optimized by the Departments of Surgery and Nuclear Medicine. Twenty-two consecutive patients with non-small-cell lung cancer were included, of whom eight were FDG-PET positive for mediastinal lymph nodes. 3D FDG-PET/CT movies were presented to surgeons before mediastinoscopy. Surgical consequences were investigated, including sensitivity and the negative predictive value of mediastinoscopy. Results were compared with those of a retrospective study in which 3D techniques were not used. During mediastinoscopies, the 3D-PET/CT movies were found to be helpful in the surgical localization of FDG-positive lymph nodes. It led to more confidence in the surgical approach. The sensitivity and negative predictive value were 86 and 94%, respectively. Although not statistically significant, these results were higher compared with those of the retrospective study (75 and 92%, respectively). 3D FDG-PET/CT guidance during mediastinoscopy is feasible. The movies seem to lead to targeted biopsy of lymph nodes. They may reduce false-negative mediastinoscopies and improve staging of lung cancer. 3D FDG-PET/CT can be seen as a promising tool for further implementation of image-guided surgery.

Adrenal metastasis from a primary papillary thyroid carcinoma.

Distant metastases of a papillary thyroid carcinoma (PTC) is rare, and usually involves the lung or the bones. Adrenal metastasis of a PTC has been described only in three patients. We describe a 74-year-old woman with adrenal metastasis of a PTC, detected with a total body iodine scan and a PET-CT scan.