[177Lu]Lu-PSMA-617 plus enzalutamide in patients with metastatic castration-resistant prostate cancer (ENZA-p): an open-label, multicentre, randomised, phase 2 trial.

BACKGROUND: Enzalutamide and lutetium-177 [177Lu]Lu-prostate-specific membrane antigen (PSMA)-617 both improve overall survival in patients with metastatic castration-resistant prostate cancer. Androgen and PSMA receptors have a close intracellular relationship, with data suggesting complementary benefit if targeted concurrently. In this study, we assessed the activity and safety of enzalutamide plus adaptive-dosed [177Lu]Lu-PSMA-617 versus enzalutamide alone as first-line treatment for metastatic castration-resistant prostate cancer. METHODS: ENZA-p was an open-label, randomised, controlled phase 2 trial done at 15 hospitals in Australia. Participants were men aged 18 years or older with metastatic castration-resistant prostate cancer not previously treated with docetaxel or androgen receptor pathway inhibitors for metastatic castration-resistant prostate cancer, gallium-68 [68Ga]Ga-PSMA-PET-CT (PSMA-PET-CT) positive disease, Eastern Cooperative Oncology Group performance status of 0-2, and at least two risk factors for early progression on enzalutamide. Participants were randomly assigned (1:1) by a centralised, web-based system using minimisation with a random component to stratify for study site, disease burden, use of early docetaxel, and previous treatment with abiraterone acetate. Patients were either given oral enzalutamide 160 mg daily alone or with adaptive-dosed (two or four doses) intravenous 7·5 GBq [177Lu]Lu-PSMA-617 every 6-8 weeks dependent on an interim PSMA-PET-CT (week 12). The primary endpoint was prostate-specific antigen (PSA) progression-free survival, defined as the interval from the date of randomisation to the date of first evidence of PSA progression, commencement of non-protocol anticancer therapy, or death. The analysis was done in the intention-to-treat population, using stratified Cox proportional hazards regression. This trial is registered with ClinicalTrials.gov, NCT04419402, and participant follow-up is ongoing. FINDINGS: 162 participants were randomly assigned between Aug 17, 2020, and July 26, 2022. 83 men were assigned to the enzalutamide plus [177Lu]Lu-PSMA-617 group, and 79 were assigned to the enzalutamide group. Median follow-up in this interim analysis was 20 months (IQR 18-21), with 32 (39%) of 83 patients in the enzalutamide plus [177Lu]Lu-PSMA-617 group and 16 (20%) of 79 patients in the enzalutamide group remaining on treatment at the data cutoff date. Median age was 71 years (IQR 64-76). Median PSA progression-free survival was 13·0 months (95% CI 11·0-17·0) in the enzalutamide plus [177Lu]Lu-PSMA-617 group and 7·8 months (95% CI 4·3-11·0) in the enzalutamide group (hazard ratio 0·43, 95% CI 0·29-0·63, p<0·0001). The most common adverse events (all grades) were fatigue (61 [75%] of 81 patients), nausea (38 [47%]), and dry mouth (32 [40%]) in the enzalutamide plus [177Lu]Lu-PSMA-617 group and fatigue (55 [70%] of 79), nausea (21 [27%]), and constipation (18 [23%]) in the enzalutamide group. Grade 3-5 adverse events occurred in 32 (40%) of 81 patients in the enzalutamide plus [177Lu]Lu-PSMA-617 group and 32 (41%) of 79 patients in the enzalutamide group. Grade 3 events that occurred only in the enzalutamide plus [177Lu]Lu-PSMA-617 group included anaemia (three [4%] of 81 participants) and decreased platelet count (one [1%] participant). No grade 4 or 5 events were attributed to treatment on central review in either group. INTERPRETATION: The addition of [177Lu]Lu-PSMA-617 to enzalutamide improved PSA progression-free survival providing evidence of enhanced anticancer activity in patients with metastatic castration-resistant prostate cancer with risk factors for early progression on enzalutamide and warrants further evaluation of the combination more broadly in metastatic prostate cancer. FUNDING: Prostate Cancer Research Alliance (Movember and Australian Federal Government), St Vincent's Clinic Foundation, GenesisCare, Roy Morgan Research, and Endocyte (a Novartis company).

The Evaluation of Gastric Emptying Using Nuclear Scintigraphy Compared to Three-Dimensional Multi-detector Computed Tomography (3D-MDCT) Gastric Volumetry in the Assessment of Poor Weight Loss Following Sleeve Gastrectomy.

BACKGROUND: Poor weight loss and weight regain are principal challenges following laparoscopic sleeve gastrectomy (LSG). There is a lack of standardised assessments and diagnostic tests to stratify the status post-LSG and determine whether anatomical or physiological problem exists. We aimed to compare nuclear scintigraphy gastric emptying with CT volumetric analysis of sleeve anatomy and determine the impact of anatomy on physiological function and its correlation with weight loss. MATERIALS AND METHODS: Patients greater than 12 months post-LSG were categorised into optimal weight loss (OWL) (n = 29) and poor weight loss groups (PWL) (n = 50). All patients underwent a protocolised nuclear scintigraphy and three-dimensional multi-detector computed tomography (3D-MDCT) gastric volumetry imaging. RESULTS: Post-operative % total weight loss in OWL was 26.2 ± 10.5% vs. 14.2 ± 10.7% in the PWL group (p value < 0.0001). The PWL group had significantly more delayed gastric emptying half-time than OWL (34.1 ± 18.8 vs. 19.5 ± 4.7, p value < 0.0001). Gastric emptying half-time showed statistically significant correlations with weight loss parameters (BMI; r = 0.215, p value 0.048, %EWL; r = - 0.336, p value 0.002 and %TWL; r = - 0.379, p value < 0.001). The median gastric volume on 3D-MDCT did not differ between the OWL (246 (IQR 50) ml) and PWL group (262 (IQR 129.5) ml), p value 0.515. Nuclear scintigraphy gastric emptying half-time was the most highly discriminant measure. A threshold of 21.2 min distinguished OWL from PWL patients with 86.4% sensitivity and 68.4% specificity. CONCLUSION: Nuclear scintigraphy is a potentially highly accurate tool in the functional assessment of sleeve gastrectomy physiology. It appears to perform better as a diagnostic test than volumetric assessment. Gastric volume did not correlate with weight loss outcomes. We have established diagnostic criteria of greater than 21 min to assess sleeve failure, which is linked to suboptimal weight loss outcomes.

18 F-FDG PET/CT features of immune-related adverse events and pitfalls following immunotherapy.

18 F-FDG PET/CT scanning is routinely performed to stage and evaluate the treatment response in many malignancies. Immunotherapy is a rapidly growing treatment option for many cancers, and both clinicians and imaging specialists need to be familiar with 18 F-FDG PET/CT imaging characteristics unique to patients on this type of treatment. In particular, many immune-related adverse events (irAEs) can be detected on 18 F-FDG PET/CT and early accurate identification is critical to reduce treatment related morbidity and incorrect interpretation of malignant disease status. This pictorial essay reviews frequently encountered irAEs in clinical practice and their appearances on 18 F-FDG PET/CT along with a brief discussion on pseudoprogression and hyperprogression.

Clinical utility of stimulated cholescintigraphy using a standardized Ensure-Plus fatty meal protocol in patients with suspected functional gallbladder disorder: a retrospective study of seven-years clinical experience.

BACKGROUND: The clinical utility of fatty meal stimulated cholescintigraphy particularly using a standardized formulation in patients with suspected functional gallbladder disorder has not been extensively studied. We present our seven-year clinical experience using an Ensure plus protocol. METHODS: A retrospective study was performed on patients undergoing stimulated cholescintigraphy using Ensure Plus for evaluation of suspected functional gallbladder disorder. A gallbladder ejection fraction (GBEF) of <33% was considered abnormal. RESULTS: Of the 173 patients evaluated, 57 (33%) had an abnormal GBEF, 112 (65%) had a normal GBEF and 4 (2%) had no gallbladder visualization. Of the 57 patients with an abnormal GBEF, symptom improvement occurred in 30/31 (97%) who underwent cholecystectomy and in 17/26 (65%) who were managed conservatively (p = 0.003). Of the 112 patients with a normal GBEF, symptom improvement occurred in 8/10 (80%) who underwent cholecystectomy and 74/102 (73%) who were managed conservatively (p = 1.000). In the subgroup of 102 patients with a normal GBEF managed conservatively, those without symptomatic improvement had lower GBEFs compared to those with symptomatic improvement (median GBEF 46% versus 57%, p = 0.019). CONCLUSION: Our retrospective results support a clinical role for stimulated cholescintigraphy using Ensure Plus in the evaluation of patients with suspected functional gallbladder disorder. While an abnormal GBEF predicts good surgical outcome, our results suggest that using an absolute GBEF cut off value of <33% may not apply to all patients and hence GBEF results should only be used as an adjunct in the surgical decision-making process.

Head-to-head comparison of cerebral blood flow single-photon emission computed tomography and 18 F-fluoro-2-deoxyglucose positron emission tomography in the diagnosis of Alzheimer disease.

BACKGROUND: Clinical diagnosis of Alzheimer disease (AD) is only 70% accurate. Reduced cerebral blood flow (CBF) and metabolism in parieto-temporal and posterior cingulate cortex may assist diagnosis. While widely accepted that 18 F-fluoro-2-deoxyglucose positron emission tomography (18 F-FDG PET) has superior accuracy to CBF-SPECT for AD, there are very limited head-to-head data from clinically relevant populations and these studies relied on clinical diagnosis as the reference standard. AIMS: To compare directly the accuracy of CBF-SPECT and 18 F-FDG PET in patients referred for diagnostic studies in detecting ß-amyloid PET confirmed AD. METHODS: A total of 126 patients, 56% with mild cognitive impairment and 44% with dementia, completed both CBF-SPECT and 18 F-FDG PET as part of their diagnostic assessment, and subsequently underwent ß-amyloid PET for research purposes. Transaxial slices and Neurostat 3D-SSP analyses of 18 F-FDG PET and CBF-SPECT scans were independently reviewed by five nuclear medicine clinicians blinded to all other data. Operators selected the most likely diagnosis and their diagnostic confidence. Accuracy analysis used final diagnosis incorporating ß-amyloid PET as the reference standard. RESULTS: Clinicians reported high diagnostic confidence in 83% of 18 F-FDG PET compared to 67% for CBF-SPECT (P = 0.001). All reviewers showed individually higher accuracy using 18 F-FDG PET. Based on majority read, the combined area under the receiver operating characteristic curve in diagnosing AD was 0.71 for 18 F-FDG PET and 0.61 for CBF-SPECT (P = 0.02). The sensitivity of 18 F-FDG PET and CBF-SPECT was 76% versus 43% (P < 0.001), while specificity was 74% versus 83% (P = 0.45). CONCLUSIONS: 18 F-FDG PET is superior to CBF-SPECT in detecting AD among patients referred for the assessment of cognitive impairment.

Excellent suppression of physiological myocardial FDG activity in patients with cardiac sarcoidosis.

INTRODUCTION: Suppression of physiological myocardial FDG activity is vital in patients undergoing PET/CT for assessment of known or suspected cardiac sarcoidosis. This study aims to evaluate the efficacy of physiological myocardial FDG suppression following a protocol change to a 24-h high fat very low carbohydrate (HFVLC) diet and prolonged fast. METHODS: A retrospective review of patients undergoing FDG PET/CT for the evaluation of cardiac sarcoidosis was performed. Prior to June-2018, patients were prepared with a single very high-fat low carbohydrate meal followed by a 12-18 h fast (group 1). After June-2018, a protocol change was initiated with patients prepared with a HFVLC diet for 24-h followed by a 12-18 h fast (group 2). Focal myocardial activity was classified as positive, absent activity as negative and diffuse/focal on diffuse activity as indeterminate. RESULTS: A total of 94 FDG PET/CT scans were included with 46 scans in group 1 and 48 scans in group 2. Studies were classified as positive, negative or indeterminate in 25 (54%), 7 (15%) and 14 (30%) scans in group 1 and in 13 (27%), 33 (69%) and 2 (4%) scans in group 2, respectively. In scans classified as negative, myocardial FDG activity was less than mediastinal blood pool activity in 5/7 (71%) scans in group 1 and 33/33 (100%) scans in group 2. CONCLUSION: Excellent myocardial FDG suppression can be achieved using a 24-h HFVLC diet and prolonged fast, resulting in a very low indeterminate scan rate in patients with known or suspected cardiac sarcoidosis.

Metastatic clear cell renal cell carcinoma demonstrating intense uptake on 68Ga-DOTATATE positron emission tomography: Three case reports and a review of the literature.

68Ga-DOTATATE positron emission tomography (PET) is a molecular imaging technology which has shown superiority over 111In-octreotide scanning for the detection and staging of neuroendocrine tumors. We report three patients with pancreatic masses that were ultimately diagnosed as clear cell renal cell carcinoma (ccRCC) metastases on histopathology. During their initial diagnostic assessment, the three patients underwent both 18F-fluorodeoxyglucose (18F-FDG) and 68Ga-DOTATATE PET. While all three patients' lesions showed variable 18F-FDG avidity, uptake on 68Ga-DOTATATE PET was comparatively intense. The small case series illustrates the need to consider ccRCC in the differential diagnosis of 68Ga-DOTATATE avid lesions.

Variability of Liver Shear Wave Measurements Using a New Ultrasound Elastographic Technique.

OBJECTIVES: A new 2-dimensional (2D) shear wave elastographic (SWE) device has been developed for the noninvasive assessment of liver fibrosis. Guidelines on measurement acquisition parameters are not yet well established for this technique. Our study aimed to assess 2D SWE measurement variability and to determine the number of measurements required per patient to reliably assess liver stiffness. METHODS: Two-dimensional SWE was assessed in 55 patients with mixed-etiology chronic liver disease on an Aplio 500 ultrasound system (Toshiba Medical Systems Corporation, Tochigi, Japan). Ten measurements were obtained per patient by an operator blinded to all preceding readings. Results were analyzed with clinical information obtained from medical records. RESULTS: The median interquartile range/median ratio for 2D SWE was 0.131 (quartiles 1-3, 0.089-0.174). Five readings provided an approximation within 0.11 m/s, or 4.2% of the median velocity of 10 measurements. Factors associated with increased measurement variability included body mass index (ρ = 0.388; P = .01), increased skin-to-liver capsule distance (ρ = 0.426; P = .002), and measurements taken within 1.5 cm of the liver capsule (P < .001). Measurements with heterogeneous shear wave profiles (indicated by a region of interest [ROI] SD/speed ratio > 0.15) showed greater deviation from the set's median velocity than those with an ROI SD/speed ratio of 0.15 or lower (0.42 versus 0.22 m/s; P = .001). CONCLUSIONS: Two-dimensional SWE showed low overall measurement variability, with a minimum of 5 readings providing equivalent precision to the existing method using 10 samples. Obesity, increasing abdominal wall thickness, subcapsular measurements and an ROI SD/speed ratio of greater than 0.15 were all associated with increased measurement variability. The ROI SD/speed ratio warrants further evaluation as a quality assessment metric, to allow objective operator assessment of individual 2D SWE measurement reliability in real time.