Faculty Bibliography

INTRODUCTION/BACKGROUND:Radiographic progression-free survival (rPFS) based on Prostate Cancer Working Group 2 (PCWG2) has been increasingly used as a meaningful imaging-based intermediate endpoint (IBIE) for overall survival (OS) in patients with metastatic castration-resistant prostate cancer (mCRPC). In randomized phase III trials, rPFS showed good correlation with OS at the individual trial level. We aimed to assess the correlation between the hazard ratios (HR) of IBIE and OS among PCWG2-based randomized trials. MATERIALS AND METHODS:PubMed and EMBASE databases were systematically searched for randomized trials evaluating systemic treatments on mCRPC using PCWG2 up to April 15, 2020. Hazard ratios for OS and IBIEs were extracted and their correlation was assessed using weighted linear regression. Subgroup analyses were performed according to various clinical settings: prior chemotherapy, drug category, type of IBIE (rPFS vs. composite IBIE, latter defined as progression by imaging and one or a combination of PSA, pain, skeletal-related events, and performance status), and publication year. RESULTS: = 0.32-0.91). CONCLUSION:IBIEs in the era of PCWG2 correlate well with OS in randomized trials for systemic drugs in patients with mCRPC. PCWG2-based rPFS should be used instead of a composite IBIE that includes PSA and other clinical variables.

The aim of the study was to evaluate the performance of the Prophet forecasting procedure, part of the Facebook open-source Artificial Intelligence portfolio, for forecasting variations in radiological examination volumes. Daily CT and MRI examination volumes from our institution were extracted from the radiology information system (RIS) database. Data from January 1, 2015, to December 31, 2019, was used for training the Prophet algorithm, and data from January 2020 was used for validation. Algorithm performance was then evaluated prospectively in February and August 2020. Total error and mean error per day were evaluated, and computational time was logged using different Markov chain Monte Carlo (MCMC) samples. Data from 610,570 examinations were used for training; the majority were CTs (82.3%). During retrospective testing, prediction error was reduced from 19 to < 1 per day in CT (total 589 to 17) and from 5 to < 1 per day (total 144 to 27) in MRI by fine-tuning the Prophet procedure. Prospective prediction error in February was 11 per day in CT (9934 predicted, 9667 actual) and 1 per day in MRI (2484 predicted, 2457 actual) and was significantly better than manual weekly predictions (p = 0.001). Inference with MCMC added no substantial improvements while vastly increasing computational time. Prophet accurately models weekly, seasonal, and overall trends paving the way for optimal resource allocation for radiology exam acquisition and interpretation.

PURPOSE/OBJECTIVE:Zr-immunoPET tracers. METHODS:for normal liver and sites of disease and liver signal-to-noise ratio were measured. RESULTS:Q.Clear reconstructions with β = 3600 provided the highest scores for image quality. Images reconstructed with β-values of 3600 or 5200 using only 50% or 25% of the original counts provided comparable or better image quality scores than standard OSEM reconstruction images using 100% of counts. CONCLUSION/CONCLUSIONS:Zr-immunoPET tracers.

BACKGROUND:Identification of pretherapeutic predictive markers in gastro-esophageal cancer is essential for individual-oriented treatment. This study evaluated the relationship of multimodality parameters derived from intravoxel incoherent motion method (IVIM), 18F-FDG-positron emission tomography (PET), computed tomography (CT) perfusion and dynamic contrast enhanced magnetic resonance imaging (MRI) in patients with gastro-esophageal cancer and investigated their histopathological correlation. METHODS:Thirty-one consecutive patients (28 males; median age 63.9 years; range 37-84 years) with gastro-esophageal adenocarcinoma (N.=22) and esophageal squamous cell carcinoma (N.=9) were analyzed. IVIM parameters: pseudodiffusion (D*), perfusion fraction (fp), true diffusion (D) and the threshold b-value (bval); PET-parameters: SUV<inf>max</inf>, metabolic tumor volume (MTV) and total lesion glycolysis (TLG); CT perfusion parameters: blood flow (BF), blood volume (BV) and mean transit time (MTT); and MR perfusion parameters: time to enhance, positive enhancement integral, time-to-peak (TTP), maximum-slope-of-increase, and maximum-slope-of-decrease were determined, and correlated to each other and to histopathology. RESULTS:IVIM and PET parameters showed significant negative correlations: MTV and bval (r<inf>s</inf> =-0.643, P=0.002), TLG and bval (r<inf>s</inf>=-0.699, P<0.01) and TLG and fp (r<inf>s</inf>=-0.577, P=0.006). Positive correlation was found for TLG and D (r<inf>s</inf>=0.705, P=0.000). Negative correlation was found for bval and staging (r<inf>s</inf>=0.590, P=0.005). Positive correlation was found for positive enhancement interval and BV (r<inf>s</inf>=0.547, P=0.007), BF and regression index (r<inf>s</inf>=0.753, P=0.005) and for time-to-peak and staging (r<inf>s</inf>=0.557, P=0.005). CONCLUSIONS:IVIM parameters (bval, fp, D) provide quantitative information and correlate with PET parameters (MTV, TLG) and staging. IVIM might be a useful tool for additional characterization of gastro-esophageal cancer.

PURPOSE/OBJECTIVE:To evaluate the influence of body phased-array (BPA) receive coil setups on signal-to-noise ratio (SNR) and image quality (IQ) in prostate MRI. METHODS:This prospective study evaluated axial T2-weighted images (T2W-TSE) and DWI of the prostate in ten healthy volunteers with 18-channel (18CH), 30-channel and 60-channel (60CH) BPA receive coil setups. SNR and ADC values were assessed in the peripheral and transition zones (TZ). Two radiologists rated IQ features. Differences in qualitative and quantitative image features between BPA receive coil setups were compared. After correction for multiple comparisons, p-values <0.004 for quantitative and p-values <0.017 for qualitative image analysis were considered statistically significant. RESULTS:Significantly higher SNR was found in T2W-TSE images in the TZ using 60CH BPA compared to 18CH BPA coil setups (15.20 ± 4.22 vs. 7.68 ± 2.37; p = 0.001). There were no significant differences between all other quantitative (T2W-TSE, p = 0.007-0.308; DWI, p = 0.024-0.574) and qualitative image features (T2W-TSE, p = 0.083-1.0; DWI, p = 0.046-1.0). CONCLUSION/CONCLUSIONS:60CH BPA receive coil setup showed marginal SNR improvement in T2W-TSE images. Good IQ could be achieved with 18CH BPA coil setups.

PURPOSE:Ga-labeled prostate-specific membrane antigen (PSMA-PET/MRI) to detect and localize primary sigPCa (ISUP grade group 3 and/or cancer core length ≥ 6 mm) and guide biopsy. METHODS:Prospective, open-label, single-center, non-randomized, diagnostic accuracy study including patients with suspected PCa by elevation of prostate-specific antigen (PSA) level and a suspicious lesion (PIRADS ≥3) on multiparametric MRI (mpMRI). Forty-two patients underwent PSMA-PET/MRI followed by both PSMA-PET/MRI-guided and section-based saturation template biopsy between May 2017 and February 2019. Primary outcome was the accuracy of PSMA-PET/MRI for biopsy guidance using section-based saturation template biopsy as the reference standard. RESULTS:SigPCa was found in 62% of the patients. Patient-based sensitivity, specificity, negative and positive predictive value, and accuracy for sigPCa were 96%, 81%, 93%, 89%, and 90%, respectively. One patient had PSMA-negative sigPCa. Eight of nine false-positive lesions corresponded to cancer on prostatectomy and one in six false-negative lesions was negative on prostatectomy. CONCLUSION:PSMA-PET/MRI has a high accuracy for detecting sigPCa and is a promising tool to select patients with suspicion of PCa for biopsy. TRIAL REGISTRATION:This trial was retrospectively registered under the name "Positron Emission Tomography/Magnetic Resonance Imaging (PET/MRI) Guided Biopsy in Men with Elevated PSA" (NCT03187990) on 06/15/2017 ( https://clinicaltrials.gov/ct2/show/NCT03187990 ).

Human brown adipose tissue (BAT) is a thermogenic tissue activated by the sympathetic nervous system in response to cold exposure. It contributes to energy expenditure (EE) and takes up glucose and lipids from the circulation. Studies in rodents suggest that BAT contributes to the transient rise in EE after food intake, so-called diet-induced thermogenesis (DIT). We investigated the relationship between human BAT activity and DIT in response to glucose intake in 17 healthy volunteers. We assessed DIT, cold-induced thermogenesis (CIT), and maximum BAT activity at three separate study visits within 2 wk. DIT was measured by indirect calorimetry during an oral glucose tolerance test. CIT was assessed as the difference in EE after cold exposure of 2-h duration as compared with warm conditions. Maximal activity of BAT was assessed by 18-F-fluoro-deoxyglucose (¹⁸F-FDG) ¹⁸F-FDG-PET/MRI after cold exposure and concomitant pharmacological stimulation with mirabegron. Seventeen healthy men (mean age = 23.4 yr, mean body mass index = 23.2 kg/m²) participated in the study. EE increased from 1,908 (±181) kcal/24 h to 2,128 (±277) kcal/24 h (P < 0.0001, +11.5%) after mild cold exposure. An oral glucose load increased EE from 1,911 (±165) kcal/24 h to 2,096 (±167) kcal/24 h at 60 min (P < 0.0001, +9.7%). The increase in EE in response to cold was significantly associated with BAT activity (R

BACKGROUND:Positron emission tomography (PET) targeting the prostate-specific membrane antigen (PSMA) has superior sensitivity over conventional imaging (CI) to stage prostate cancer (PCa) and therefore is increasingly used in staging to stratify patients before radical therapy. Whether this improved diagnostic accuracy translates into improved outcome after radical prostatectomy (RPE) has not yet been shown. Therefore, the aim of this study was to compare the oncological outcome after RPE between patients that underwent preoperative staging with CI or PSMA-PET for intermediate and high-risk PCa. METHODS:We retrospectively selected all patients that underwent RPE for intermediate- or high-risk PCa at our institution before PSMA-PET introduction (between March 2014 and September 2016) and compared the oncologic outcome of patients staged with PSMA-PET (between October 2016 and October 2018). Oncological pre-surgical risk parameters (age, PSA, D'Amico score, biopsy-ISUP, and cT stage) were compared between the groups. Oncological outcome was determined as PSA persistence, nerve-sparing rate, and surgical margin status. Wilcoxon rank-sum, Fisher's, and chi-square tests where used for statistical testing. RESULTS:One hundred five patients were included, 53 in the CI group and 52 in the PSMA-group. Patients in the PSMA group had higher ISUP grade (p < 0.001) and D'Amico score (p < 0.05). The rate of free surgical margins and PSA persistence after RPE was 64% and 17% for the CI and 77% and 6% for the PSMA group (p = 0.15 and 0.13, respectively). Subgroup analysis with high-risk patients revealed PSA persistence in 7% (3/44) in the PSMA group and 25% (7/28) in the CI group (p = 0.04). Limitations include the retrospective design and choline-PET for some patients in the CI group. CONCLUSION:Immediate outcome after RPE was not worse in the PSMA group compared with the CI group, despite a higher-risk cohort. In a comparison of only high-risk patients, PSMA-PET staging was associated with a significantly lower rate of postsurgical PSA persistence.

PURPOSE/OBJECTIVE:To report the incidence of urinary tract malignancies (UTM) and to compare the diagnostic accuracy of cytology with cystoscopy, renal ultrasound (US) and computed tomography (CT) in patients with hematuria. METHODS:A retrospective analysis was conducted of patients who underwent cystoscopy, cytology, US and CT for hematuria between 2011 and 2017. Age, gender, BMI, smoking status, and results of further diagnostic interventions including transurethral resection of the bladder (TURB), ureterorenoscopy (URS), renal biopsy and imaging were extracted from medical charts. Logistic regression to identify risk factors for UTM was performed. Discriminatory accuracy of US, CT and cytology was assessed by 2 × 2 tables. RESULTS:Of 847 patients, 432 (51%) presented with non-visible hematuria (NVH) and 415 (49%) with visible hematuria (VH). Of all patients with NVH, seven (1.6%) had bladder cancer (BCA), three (< 1%) had renal cell cancer (RCC) and no single patient had upper tract urothelial cancer (UTUC). Of the patients with VH, 62 (14.9%) were diagnosed with BCA, 7 (1.6%) with RCC and 4 (< 1%) with UTUC. In multivariable analysis VH, higher age, smoking and lower BMI were associated with an increased risk for UTM. The specificity/negative predictive value of US for the detection of RCC or UTUC in patients with NVH and VH were 96%/100% and 95%/99%, respectively. CONCLUSION/CONCLUSIONS:Due to the low incidence of UTM, the necessity of further diagnostics should be questioned in patients with NVH. In contrast, patients with VH are at considerable risk for BCA, and cystoscopy and upper tract imaging is justified.

BACKGROUND:Statins are commonly prescribed for primary and secondary prevention of atherosclerotic disease. They reduce cholesterol biosynthesis by inhibiting hydroxymethylglutaryl-coenzyme A-reductase (HMG-CoA-reductase) and therefore mevalonate synthesis. Several studies reported a small, but significant increase in the diagnosis of diabetes mellitus with statin treatment. The molecular mechanisms behind this adverse effect are not yet fully understood. Brown adipose tissue (BAT), which plays a role in thermogenesis, has been associated with a reduced risk of insulin resistance. Statins inhibit adipose tissue browning and have been negatively linked to the presence of BAT in humans. We therefore speculated that inhibition of BAT by statins contributes to increased insulin resistance in humans. METHODS:A prospective study was conducted in 17 young, healthy men. After screening whether significant cold-induced thermogenesis (CIT) was present, participants underwent glucose tolerance testing (oGTT) and assessment of BAT activity by FDG-PET/MRI after cold-exposure and treatment with a β3-agonist. Fluvastatin 2x40mg per day was then administered for two weeks and oGTT and FDG-PET/MRI were repeated. RESULTS:0.14, p=0.16, respectively). CONCLUSIONS:Treatment with fluvastatin for two weeks reduced serum lipid levels but increased glucose AUC in young, healthy men, indicating reduced glucose tolerance. This was not associated with changes in cold-induced BAT activity.