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A multidisciplinary team-based approach with lifestyle modification and symptom management to address the impact of androgen deprivation therapy in prostate cancer: A randomized phase II study.
Pollock, Y, Zhang, L, Kenfield, SA, Van Blarigan, EL, Rodvelt, T, Rabow, M, Macaire, G, Weinberg, R, Topp, K, Friedlander, T, et al
Urologic oncology. 2021;(10):730.e9-730.e15
Abstract
BACKGROUND Androgen deprivation therapy (ADT) is associated with numerous toxicities that are potentially modifiable. We sought to evaluate the impact of participation in a multidisciplinary clinic, STAND (Supportive Therapy in Androgen Deprivation) Clinic, designed to provide individualized lifestyle modification and management of ADT-related side effects. METHODS This phase II study recruited men with prostate cancer who had started ADT <6 months prior to enrollment, and in whom ADT was planned for at least 12 months following enrollment. Patients were randomized in a 1:1 ratio to either the STAND Clinic or usual care. Patients randomized to the STAND Clinic were provided monthly multidisciplinary assessment and counseling on exercise, nutrition, and symptom management for 12 months on a rotating schedule. Primary outcome was change from baseline to 12 months in percent body fat. Feasibility outcomes were also assessed by measuring percentage of completed visits. Secondary outcomes included change from baseline to 12 months in 3 domains: (1) metabolic impact and bone health, (2) quality of life (QOL), and (3) physical activity. RESULTS A total of 25 men were randomized to STAND clinic, and 23 were randomized to usual care. The study did not meet its accrual target of 32 men in each arm and was closed early due to lack of financial support. Overall, 91% (295 of 325) of STAND clinic visits were completed. Eighteen out of the 25 patients in STAND clinic arm (72%) completed all 12 months of STAND clinic visits, and 80% (20 of 25) completed the first 6 months. For all primary and secondary outcomes, there were no statistically significant differences between treatment arms. CONCLUSION Individualized and comprehensive management of ADT toxicities in a multidisciplinary clinic was well attended by patients. However, we did not find any differences in the outcomes assessed between the intervention arm and control.
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Ferumoxytol-Enhanced MR Lymphography for Detection of Metastatic Lymph Nodes in Genitourinary Malignancies: A Prospective Study.
Turkbey, B, Czarniecki, M, Shih, JH, Harmon, SA, Agarwal, PK, Apolo, AB, Citrin, DE, Gulley, JL, Harisinghani, M, Madan, RA, et al
AJR. American journal of roentgenology. 2020;(1):105-113
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Abstract
OBJECTIVE. The objective of our study was to evaluate the utility of ferumoxytol-enhanced MR lymphography (MRL) in detection of metastatic lymph nodes (LNs) in patients with prostate, bladder, and kidney cancer. SUBJECTS AND METHODS. This phase 2 single-institution study enrolled patients with confirmed prostate (arm 1), bladder (arm 2), and kidney (arm 3) cancer and evidence of suspected LN involvement. Participants underwent ferumoxytol-enhanced MRL 24 and 48 hours after IV injection of 7.5 mg Fe/kg of ferumoxytol. A retrospective quantitative analysis was performed to determine the optimal timing for ferumoxytol-enhanced MRL using percentage change in normalized signal intensity (SI) from baseline to 24 and 48 hours after injection, which were estimated using the linear mixed-effects model in which time (24 vs 48 hours), diseases status, and time and disease status interaction were the fixed-effects independent variables. Differences in normalized SI values between subgroups of lesions were estimated by forming fixed-effects contrasts and tested by the Wald test. RESULTS. Thirty-nine patients (n = 30, arm 1; n = 6, arm 2; n = 3, arm 3) (median age, 65 years) with 145 LNs (metastatic, n = 100; benign, n = 45) were included. LN-based sensitivity, specificity, positive predictive value, and negative predictive value of ferumoxytol-enhanced MRL was 98.0%, 64.4%, 86.0%, and 93.5%, respectively. Sensitivity and specificity of ferumoxytol-enhanced MRL did not vary by LN size. Metastatic LNs showed a significantly higher percentage decrease of normalized SI on MRL at 24 hours after ferumoxytol injection than at 48 hours after ferumoxytol injection (p = 0.023), whereas the normalized SI values for nonmetastatic LNs were similar at both imaging time points (p = 0.260). CONCLUSION. Ferumoxytol-enhanced MRL shows high sensitivity in the detection of metastatic LNs in genitourinary cancers independent of LN size. The SI difference between benign and malignant LNs on ferumoxytol-enhanced MRL appears similar 24 and 48 hours after ferumoxytol injection, suggesting that imaging can be performed safely within 1 or 2 days of injection. Although ferumoxytol-enhanced MRL can be useful in settings without an available targeted PET agent, issues of iron overload and repeatability of ferumoxytol-enhanced MRL remain concerns for this method.
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Conventional vs machine learning-based treatment planning in prostate brachytherapy: Results of a Phase I randomized controlled trial.
Nicolae, A, Semple, M, Lu, L, Smith, M, Chung, H, Loblaw, A, Morton, G, Mendez, LC, Tseng, CL, Davidson, M, et al
Brachytherapy. 2020;(4):470-476
Abstract
PURPOSE The purpose of this study was to evaluate the noninferiority of Day 30 dosimetry between a machine learning-based treatment planning system for prostate low-dose-rate (LDR) brachytherapy and the conventional, manual planning technique. As a secondary objective, the impact of planning technique on clinical workflow efficiency was also evaluated. MATERIALS AND METHODS 41 consecutive patients who underwent I-125 LDR monotherapy for low- and intermediate-risk prostate cancer were accrued into this single-institution study between 2017 and 2018. Patients were 1:1 randomized to receive treatment planning using a machine learning-based prostate implant planning algorithm (PIPA system) or conventional, manual technique. Treatment plan modifications by the radiation oncologist were evaluated by computing the Dice coefficient of the prostate V150% isodose volume between either the PIPA-or conventional-and final approved plans. Additional evaluations between groups evaluated the total planning time and dosimetric outcomes at preimplant and Day 30. RESULTS 21 and 20 patients were treated using the PIPA and conventional techniques, respectively. No significant differences were observed in preimplant or Day 30 prostate D90%, V100%, rectum V100, or rectum D1cc between PIPA and conventional techniques. Although the PIPA group had a larger proportion of patients with plans requiring no modifications (Dice = 1.00), there was no significant difference between the magnitude of modifications between each arm. There was a large significant advantage in mean planning time for the PIPA arm (2.38 ± 0.96 min) compared with the conventional (43.13 ± 58.70 min) technique (p >> 0.05). CONCLUSIONS A machine learning-based planning workflow for prostate LDR brachytherapy has the potential to offer significant time savings and operational efficiencies, while producing noninferior postoperative dosimetry to that of expert, conventional treatment planners.
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Comparison of 18F-sodium fluoride PET/CT, 18F-fluorocholine PET/CT and diffusion-weighted MRI for the detection of bone metastases in recurrent prostate cancer: a cost-effectiveness analysis in France.
Gauthé, M, Zarca, K, Aveline, C, Lecouvet, F, Balogova, S, Cussenot, O, Talbot, JN, Durand-Zaleski, I
BMC medical imaging. 2020;(1):25
Abstract
BACKGROUND The diagnostic performance of 18F-sodium fluoride positron emission tomography/computed tomography (PET/CT) (NaF), 18F-fluorocholine PET/CT (FCH) and diffusion-weighted whole-body magnetic resonance imaging (DW-MRI) in detecting bone metastases in prostate cancer (PCa) patients with first biochemical recurrence (BCR) has already been published, but their cost-effectiveness in this indication have never been compared. METHODS We performed trial-based and model-based economic evaluations. In the trial, PCa patients with first BCR after previous definitive treatment were prospectively included. Imaging readings were performed both on-site by local specialists and centrally by experts. The economic evaluation extrapolated the diagnostic performances of the imaging techniques using a combination of a decision tree and Markov model based on the natural history of PCa. The health states were non-metastatic and metastatic BCR, non-metastatic and metastatic castration-resistant prostate cancer and death. The state-transition probabilities and utilities associated with each health state were derived from the literature. Real costs were extracted from the National Cost Study of hospital costs and the social health insurance cost schedule. RESULTS There was no significant difference in diagnostic performance among the 3 imaging modalities in detecting bone metastases. FCH was the most cost-effective imaging modality above a threshold incremental cost-effectiveness ratio of 3000€/QALY when imaging was interpreted by local specialists and 9000€/QALY when imaging was interpreted by experts. CONCLUSIONS FCH had a better incremental effect on QALY, independent of imaging reading and should be preferred for detecting bone metastases in patients with biochemical recurrence of prostate cancer. TRIAL REGISTRATION NCT01501630. Registered 29 December 2011.
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Dose-Dependent Increases in Ellagitannin Metabolites as Biomarkers of Intake in Humans Consuming Standardized Black Raspberry Food Products Designed for Clinical Trials.
Roberts, KM, Grainger, EM, Thomas-Ahner, JM, Hinton, A, Gu, J, Riedl, K, Vodovotz, Y, Abaza, R, Schwartz, SJ, Clinton, SK
Molecular nutrition & food research. 2020;(10):e1900800
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SCOPE Black raspberry (BRB) phytochemicals demonstrate anti-carcinogenic properties in experimental models, including prostate cancer. Two BRB foods, a confection and nectar, providing a consistent and reproducible product for human clinical studies are designed and characterized. METHODS AND RESULTS Men with clinically localized prostate cancer are sequentially enrolled to a control group or one of four intervention groups (confection or nectar, 10 or 20 g dose; n = 8 per group) for 4 weeks prior to prostatectomy. Primary outcomes include: safety, adherence, and ellagitannin metabolism. Adherence to the intervention is >96%. No significant (≥grade II) toxicities are detected. Urinary urolithins (A, B, C, and D) and dimethyl ellagic acid (DMEA) quantified by Ultra high performance liquid chromatography tandem mass spectroscopy (UPLC/MS/MS) indicate a dose-dependent excretion yet heterogeneous patterns among men. Men in the BRB confection groups have greater urinary excretion of the microbial urinary metabolites urolithin A and DMEA, suggesting that this food matrix provides greater colonic microflora exposure. CONCLUSION Fully characterized BRB confections and nectar are ideal for food-based large phase III human clinical studies. BRB products provide a bioavailable source of BRB phytochemicals, however large inter individual variation in polyphenol metabolism suggests that host genetics, microflora, and other factors are critical to understanding bioactivity and metabolism.
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Prospective Comparison of PET Imaging with PSMA-Targeted 18F-DCFPyL Versus Na18F for Bone Lesion Detection in Patients with Metastatic Prostate Cancer.
Rowe, SP, Li, X, Trock, BJ, Werner, RA, Frey, S, DiGianvittorio, M, Bleiler, JK, Reyes, DK, Abdallah, R, Pienta, KJ, et al
Journal of nuclear medicine : official publication, Society of Nuclear Medicine. 2020;(2):183-188
Abstract
Bone metastases in prostate cancer (PCa) have important prognostic significance, and imaging modalities used for PCa staging should have high sensitivity for detecting such lesions. Prostate-specific membrane antigen (PSMA)-targeted PET radiotracers are promising new agents for imaging PCa. We undertook a head-to-head comparison of PSMA-targeted 2-(3-{1-carboxy-5-[(6-18F-fluoro-pyridine-3-carbonyl)-amino]-pentyl}-ureido)-pentanedioic acid (18F-DCFPyL) PET to Na18F PET to determine which modality was more sensitive for the detection of lesions suggestive of bone metastases in a group of patients with metastatic PCa. Methods: Patients with progressive, metastatic PCa were prospectively imaged with both 18F-DCFPyL and Na18F PET/CT, with both scans occurring within 24 h of each other. A consensus 2-reader central review was performed to identify all bone lesions suggestive of sites of PCa involvement on both scans, and maximized SUVs corrected for body weight (SUVmax) and lean body mass (SULmax) were recorded. Soft-tissue lesions were also noted on both scans, and SUVmax, SULmax, and PSMA reporting and data system (RADS) version 1.0 scores were recorded. Data from the 2 scans were compared using a generalized estimating equation. Results: In total, 16 patients meeting all inclusion criteria were enrolled in this study, and 15 of the 16 (93.8%) were imaged with both PET radiotracers. In total, 405 bone lesions suggestive of sites of PCa were identified on at least 1 scan. On 18F-DCFPyL PET/CT, 391 (96.5%) were definitively positive, 4 (1.0%) were equivocally positive, and 10 (2.5%) were negative. On Na18F PET/CT, the corresponding values were 388 (95.8%), 4 (1.0%), and 13 (3.2%). Of the definitively negative lesions on 18F-DCFPyL PET, 8 of 10 (80.0%) were sclerotic and 2 of 10 (20.0%) were infiltrative or marrow-based. Additionally, 12 of 13 (92.3%) of the definitively negative lesions on Na18F PET were infiltrative or marrow-based and 1 of 13 (7.7%) was lytic. Also identified were 78 PSMA-RADS-4, 17 PSMA-RADS-5, and 1 PSMA-RADS-3C soft-tissue lesions. Conclusion: PET/CT imaging using 18F-DCFPyL and Na18F PET had nearly identical sensitivities for the detection of bone lesions in patients with metastatic PCa. As would be expected, PSMA-targeted PET provides more information on soft-tissue disease. There may be little additional value to imaging PCa patients with Na18F after a PSMA-targeted PET scan has already been performed.
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Standardization of acquisition protocols using PET/CT with 18F-Choline in prostate cancer.
Garcia, JR, Cozar, M, Soler, M, Bassa, P, Riera, E, Buxeda, M, Valls, E, Ferrer, J
Revista espanola de medicina nuclear e imagen molecular. 2020;(4):204-211
Abstract
AIM: To standardize acquisition protocols for 18F-Choline PET/CT to prevent from urine interference, to determine the best time point for the whole-body study, and to assess whether "dual point" acquisition allows for differentiating malignant vs. benign lesions. METHODS One hundred consecutive patients with prostate cancer were prospectively studied. Immediately after 18F-Choline injection, a pelvis study was acquired, and a whole-body was subsequently obtained 1 and 2 hours p.i. Mean SUVmax was obtained in regions and for every sequential imaging. Mean analysis (χ2) and SUV percentage change (2/1 hours; 1 hours/0 min) were obtained. Metabolic pattern dynamics were assessed: accumulative vs. clearance. Patient follow-up after therapy and directed classification whenever ethically possible were performed. RESULTS Fifty-three prostate foci, without disturbing urinary activity was ever found on early images. Accumulative pattern in 42, with percentage increase was: 0 min/1 hour: +16.7% (χ20.94); 1/2 hours: +10,0% (χ2 0.83). Clearance pattern in 11, with percentage decrease: 0 min/1 hour: -21.4% (χ20.91): -7.7% (χ20.85), corresponding in 7 to initial staging and in 4 post-radiotherapy biochemical recurrence. Every infradiaphragmatic uptake (n: 24) showed accumulative pattern, with percentage increase of +9.1% (χ20.97), all of them depicted on early imaging. As for 12 supradiaphragmantic uptake, 8 of them showed clearance pattern with percentage decrease: -13.0% (χ20.95). Accumulative pattern showed in 4 of them with percentage increase +13.0% (χ2 0.96), thus being assessed as invasive/malignant. Every bone uptake (n: 18) showed accumulative pattern, with percentage increase: +17.1% (χ20.95), all of them depicted on 1 hour imaging. CONCLUSIONS As for prostate assessment is concerned, dual point at 0 min/1 hour proved to be the best procedure. As for supradiaphragmatic lymph-nodes detection, dual point with 1/2 hours performed best. As for infradiaphragmatic and bone involvement, as well as for inconclusive findings, the 2 hour imaging increased our diagnostic confidence.
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WATER II (80-150 mL) procedural outcomes.
Desai, M, Bidair, M, Bhojani, N, Trainer, A, Arther, A, Kramolowsky, E, Doumanian, L, Elterman, D, Kaufman, RP, Lingeman, J, et al
BJU international. 2019;(1):106-112
Abstract
OBJECTIVES To present early safety and feasibility data from a multicentre prospective study (WATER II) of aquablation in the treatment of symptomatic men with large-volume benign prostatic hyperplasia (BPH). METHODS Between September and December 2017, 101 men with moderate-to-severe BPH symptoms and prostate volume of 80-150 mL underwent aquablation in a prospective multicentre international clinical trial. Baseline demographics and standardized postoperative management variables were carefully recorded in a central independently monitored database. Surgeons answered analogue scale questionnaires on intra-operative technical factors and postoperative management. Adverse events up to 1 month were adjudicated by an independent clinical events committee. RESULTS The mean (range) prostate volume was 107 (80-150) mL. The mean (range) operating time was 37 (15-97) min and aquablation resection time was 8 (3-15) min. Adequate adenoma resection was achieved with a single pass in 34 patients and with additional passes in 67 patients (mean 1.8 treatment passes), all in a single operating session. Haemostasis was achieved using either a Foley balloon catheter placed in the bladder under traction (n = 98, mean duration 18 h) or direct tamponade using a balloon inflated in the prostate fossa (n = 3, mean duration 15 h). No patient required electrocautery for haemostasis at the time of the primary procedure. The mean length of stay after the procedure was 1.6 days (range same day to 6 days). The Clavien-Dindo grade ≥2 event rate observed at 1 month was 29.7%. Bleeding complications were recorded in 10 patients (9.9%) during the index procedure hospitalization prior to discharge, and included six (5.9%) peri-operative transfusions. CONCLUSIONS Aquablation is feasible and safe in treating men with men with large prostates (80-150 mL). The 6-month efficacy data are being accrued and will be presented in future publications (ClinicalTrials.gov number, NCT03123250).
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No Added Value of 18F-Sodium Fluoride PET/CT for the Detection of Bone Metastases in Patients with Newly Diagnosed Prostate Cancer with Normal Bone Scintigraphy.
Zacho, HD, Jochumsen, MR, Langkilde, NC, Mortensen, JC, Haarmark, C, Hendel, HW, Jensen, JB, Petersen, LJ
Journal of nuclear medicine : official publication, Society of Nuclear Medicine. 2019;(12):1713-1716
Abstract
The aim of this study was to determine if additional 18F-sodium fluoride PET/CT (NaF PET/CT) improves the prognostic accuracy in the initial staging of prostate cancer patients with normal bone scintigraphy undergoing prostatectomy. Methods: A prospective cohort study examined NaF PET/CT in intermediate- or high-risk prostate cancer with negative bone scintigraphy who were scheduled for prostatectomy. Biochemical response: PSA levels < 0.2 ng/mL at 6 wk and 6 mo postoperatively, PSA level ≥ 0.2 ng/mL was biochemical failure. Results: Eighty-one patients were included in the study; 75 patients (93%) achieved biochemical responses, 6 patients had biochemical failure. NaF PET/CT indicated bone metastasis in 1 patient (1.2%), was equivocal in 7 patients (8.6%), without bone metastases in 73 patients (90.1%). Eight patients with bone metastases or equivocal results on NaF PET/CT exhibited biochemical responses. All patients with biochemical failure had negative NaF PET/CT and bone scintigraphy for bone metastases. Conclusion: NaF PET/CT has no added value for bone staging in intermediate- and high-risk prostate cancer patients with normal bone scintigraphy results undergoing prostatectomy.
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Community pharmacy lifestyle intervention to increase physical activity and improve cardiovascular health of men with prostate cancer: a phase II feasibility study.
Lemanska, A, Poole, K, Griffin, BA, Manders, R, Saxton, JM, Turner, L, Wainwright, J, Faithfull, S
BMJ open. 2019;(6):e025114
Abstract
OBJECTIVES To assess the feasibility and acceptability of a community pharmacy lifestyle intervention to improve physical activity and cardiovascular health of men with prostate cancer. To refine the intervention. DESIGN Phase II feasibility study of a complex intervention. SETTING Nine community pharmacies in the UK. INTERVENTION Community pharmacy teams were trained to deliver a health assessment including fitness, strength and anthropometric measures. A computer algorithm generated a personalised lifestyle prescription for a home-based programme accompanied by supporting resources. The health assessment was repeated 12 weeks later and support phone calls were provided at weeks 1 and 6. PARTICIPANTS 116 men who completed treatment for prostate cancer. OUTCOME MEASURES The feasibility and acceptability of the intervention and the delivery model were assessed by evaluating study processes (rate of participant recruitment, consent, retention and adverse events), by analysing delivery data and semi-structured interviews with participants and by focus groups with pharmacy teams. Physical activity (measured with accelerometry at baseline, 3 and 6 months) and patient reported outcomes (activation, dietary intake and quality of life) were evaluated. Change in physical activity was used to inform the sample size calculations for a future trial. RESULTS Out of 403 invited men, 172 (43%) responded and 116 (29%) participated. Of these, 99 (85%) completed the intervention and 88 (76%) completed the 6-month follow-up (attrition 24%). Certain components of the intervention were feasible and acceptable (eg, community pharmacy delivery), while others were more challenging (eg, fitness assessment) and will be refined for future studies. By 3 months, moderate to vigorous physical activity increased on average by 34 min (95% CI 6 to 62, p=0.018), but this was not sustained over 6 months. CONCLUSIONS The community pharmacy intervention was feasible and acceptable. Results are encouraging and warrant a definitive trial to assess the effectiveness of the refined intervention.