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1.
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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2.
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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3.
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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4.
Comparison of PSMA-PET/CT, choline-PET/CT, NaF-PET/CT, MRI, and bone scintigraphy in the diagnosis of bone metastases in patients with prostate cancer: a systematic review and meta-analysis.
Zhou, J, Gou, Z, Wu, R, Yuan, Y, Yu, G, Zhao, Y
Skeletal radiology. 2019;(12):1915-1924
Abstract
OBJECTIVE A systematic review and meta-analysis to compare the diagnostic performance of prostate-specific membrane antigen (PSMA)-PET/CT, choline-PET/CT, Sodium Fluoride (NaF) PET/CT, MRI, and bone scintigraphy (BS) in detecting bone metastases in patients with prostate cancer. METHODS We searched PubMed and Embase for articles published between January 1990 and September 2018. Two evaluators independently extracted the sensitivity, specificity, the numbers of true and false positives, and true and false negatives. We calculated the pooled sensitivity, specificity, and 95% confidence intervals (CI) for each method. We calculated the tests' diagnostic odds ratios (DOR); drew the summary receiver operating characteristic (SROC) curves; and obtained the areas under the curves (AUC), Q* values, and 95% CIs. RESULTS The per-patient pooled sensitivities of PSMA-PET/CT, choline-PET/CT, NaF-PET/CT, MRI, and BS were 0.97, 0.87, 0.96, 0.91, and 0.86, respectively. The pooled specificities were 1.00, 0.99, 0.97, 0.96, and 0.95, respectively. The pooled DOR values were 504.16, 673.67, 242.63, and 114.44, respectively. The AUC were 1.00, 0.99, 0.99, 0.98, and 0.95, respectively. The per-lesion pooled sensitivities of PSMA-PET/CT, choline-PET/CT, NaF-PET/CT, MRI, and bone imaging were 0.88, 0.80, 0.97, 0.81 and 0.68, respectively. CONCLUSIONS According to the meta-analysis, PSMA-PET/CT had the highest per-patient sensitivity and specificity in detecting bone metastases with prostate cancer. The sensitivities of NaF-PET/CT and MRI were better than those for choline-PET/CT and BS. The specificity of PSMA-PET/CT was significantly better than BS. Others were similar. For per-lesion, NaF-PET/CT had the highest sensitivity, PSMA-PET/CT had higher sensitivity than choline-PET/CT and MRI, and BS had the lowest sensitivity.
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5.
Patient-reported health-related quality of life for men treated with low-dose-rate prostate brachytherapy as monotherapy with 125-iodine, 103-palladium, or 131-cesium: Results of a prospective phase II study.
Blanchard, P, Pugh, TJ, Swanson, DA, Mahmood, U, Chen, HC, Wang, X, Graber, WJ, Kudchadker, RJ, Bruno, T, Feeley, T, et al
Brachytherapy. 2018;(2):265-276
Abstract
PURPOSE To compare quality of life (QoL) after brachytherapy with one of the three approved radioactive isotopes. METHODS AND MATERIALS Patients with mostly favorable intermediate-risk prostate cancer were treated on this prospective phase II trial with brachytherapy as monotherapy, without hormonal therapy. QoL was recorded at baseline and each follow-up by using the Expanded Prostate Cancer Index Composite instrument. The minimal clinically important difference was defined as half the standard deviation of the baseline score for each domain. Mixed effect models were used to compare the different isotopes, and time-driven activity-based costing was used to compute costs. RESULTS From 2006 to 2013, 300 patients were treated with iodine-125 (I-125, n = 98, prescribed dose [PD] = 145 Gy), palladium-103 (Pd-103, n = 102, PD = 125 Gy), or cesium-131 (Cs-131, n = 100, PD = 115 Gy). Median age was 64.9 years. Median follow-up time was 5.1 years for the entire cohort, and 7.1, 4.8 and 3.3 years for I-125, Pd-103, and Cs-131 groups, respectively. All three isotope groups showed an initial drop in QoL at first follow-up, which gradually improved over the first 2 years for urinary and bowel domains. QoL profiles were similar between I-125 and Pd-103, whereas Cs-131 showed a statistically significant decrease in QoL regarding bowel and sexual function at 12 months compared with Pd-103. However, these differences did not reach the minimal clinically important difference. Compared with I-125, the use of Pd-103 or Cs-131 resulted in cost increases of 18% and 34% respectively. CONCLUSIONS The three different isotopes produced a similar QoL profile. Statistically significant differences favored Pd-103/I-125 over Cs-131 for bowel and sexual QoL, but this did not reach clinical significance.
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6.
Intraindividual Comparison of 18F-PSMA-1007 and 18F-DCFPyL PET/CT in the Prospective Evaluation of Patients with Newly Diagnosed Prostate Carcinoma: A Pilot Study.
Giesel, FL, Will, L, Lawal, I, Lengana, T, Kratochwil, C, Vorster, M, Neels, O, Reyneke, F, Haberkon, U, Kopka, K, et al
Journal of nuclear medicine : official publication, Society of Nuclear Medicine. 2018;(7):1076-1080
Abstract
The introduction of 18F-labeled prostate-specific membrane antigen (PSMA)-targeted PET/CT tracers, first 18F-DCFPyL (2-(3-{1-carboxy-5-[(6-18F-fluoro-pyridine-3-carbonyl)-amino]-pentyl}-ureido)-pentanedioic acid) and more recently 18F-PSMA-1007 (((3S,10S,14S)-1-(4-(((S)-4-carboxy-2-((S)-4-carboxy-2-(6-18F-fluoronicotinamido)butanamido)butanamido)methyl)phenyl)-3-(naphthalen-2-ylmethyl)-1,4,12-trioxo-2,5,11,13-tetraazahexadecane-10,14,16-tricarboxylic acid)), have demonstrated promising results for the diagnostic workup of prostate cancer. This clinical study presents an intraindividual comparison to evaluate tracer-specific characteristics of 18F-DCFPyL versus 18F-PSMA-1007. Methods: Twelve prostate cancer patients, drug-naïve or before surgery, received similar activities of about 250 MBq of 18F-DCFPyL and 18F-PSMA-1007 48 h apart and were imaged 2 h after injection on the same PET/CT scanner using the same reconstruction algorithm. Normal-organ biodistribution and tumor uptake were quantified using SUVmaxResults: PSMA-positive lesions were detected in 12 of 12 prostate cancer patients. Both tracers, 18F-DCFPyL and 18F-PSMA-1007, detected the same lesions. No statistical significance could be observed when comparing the SUVmax of 18F-DCFPyL and 18F-PSMA-1007 for local tumor, lymph node metastases, and bone metastases. With regard to normal organs, 18F-DCFPyL had statistically significant higher uptake in kidneys, urinary bladder, and lacrimal gland. Vice versa, significantly higher uptake of 18F-PSMA-1007 in muscle, submandibular and sublingual gland, spleen, pancreas, liver, and gallbladder was observed. Conclusion: Excellent imaging quality was achieved with both 18F-DCFPyL and 18F-PSMA-1007, resulting in identical clinical findings for the evaluated routine situations. Nonurinary excretion of 18F-PSMA-1007 might present some advantage with regard to delineation of local recurrence or pelvic lymph node metastasis in selected patients; the lower hepatic background might favor 18F-DCFPyL in late stages, when rare cases of liver metastases can occur.
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7.
[Toxicity and quality of life comparison of iodine 125 brachytherapy and stereotactic radiotherapy for prostate cancers].
Gnep, K, Lizée, T, Campillo-Gimenez, B, Delpon, G, Droupy, S, Perrier, L, de Crevoisier, R
Cancer radiotherapie : journal de la Societe francaise de radiotherapie oncologique. 2017;(6-7):478-490
Abstract
Quality of life is a major issue for good prognostic prostate cancer, for which brachytherapy is one of the reference treatments. Stereotactic Body Radiotherapy (SBRT) is a recent alternative however not yet validated as a standard treatment. This review of the literature reports and compares the toxicities and the quality of life, either after exclusive brachytherapy with iodine 125 or after SBRT. The comparison is made with the limitations of the absence of randomized trial comparing the two treatment techniques. Acute toxicity appears to be lower after SBRT compared to brachytherapy (from 10 to 40 % versus 30 to 40 %, respectively). Conversely, acute and late gastrointestinal toxicity (from 0 to 21 % and from 0 to 10 % of grade 2, respectively) appears more frequent with SBRT. Late urinary toxicity seems identical between both techniques (from 20 to 30 % of grade 2), with a possible urinary flare syndrome. Both treatments have an impact on erectile dysfunction, although it is not possible to conclude that a technique is superior because of the limited data on SBRT. SBRT has better bowel and urinary (irritation or obstruction) quality of life scores than brachytherapy; while sexual and urinary incontinence remain the same. The absence of randomized trial comparing SBRT with brachytherapy for prostate cancers does not allow to conclude on the superiority of one technique over another, thus justifying a phase III medicoeconomic evaluation.
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8.
Dosimetric comparison between treatment plans of patients treated with low-dose-rate vs. high-dose-rate interstitial prostate brachytherapy as monotherapy: Initial findings of a randomized clinical trial.
Major, T, Polgár, C, Jorgo, K, Stelczer, G, Ágoston, P
Brachytherapy. 2017;(3):608-615
Abstract
PURPOSE The aim of this study was to compare the dosimetry of intraoperative dose plans of prostate cancer patients treated with low-dose-rate (LDR) and high-dose-rate (HDR) interstitial brachytherapy (BT). METHODS AND MATERIALS A randomized clinical trial was initiated at our institution to compare the results and side effects of LDR and HDR BT as monotherapy in the treatment of early, organ-confined prostate cancer patients. Eighty-seven patients were randomly assigned to receive HDR afterloading BT with one fraction of 19 Gy or permanent LDR 125I seed BT with 145 Gy. Inverse optimization algorithms were used for planning. Stranded seeds were implanted using live ultrasound imaging after preimplant treatment planning. Final dosimetry of HDR treatments was based on updated needle and contour positions. Statistical comparisons with nonparametric test were performed between the corresponding dose-volume parameters. RESULTS The V100 and V150 were 99% and 61%, respectively, for LDR, whereas 98% and 32% for HDR treatments. The D90 was less for HDR (122% vs. 110%). The dose distributions were more homogeneous and conformal with HDR technique (dose homogeneity index, 0.39 vs. 0.67; conformal index, 0.65 vs. 0.80). The urethra and rectum received significantly less dose with HDR. The D10 and D30 for urethra were 133% and 128%, respectively, for LDR and 114% and 111% for HDR treatments. The [Formula: see text] for rectum was 68% and 55% for LDR and HDR technique, respectively. CONCLUSIONS Both techniques provided acceptable target volume coverage with a slightly higher value with the LDR technique. The dose distributions were more homogeneous and conformal, and both urethra and rectum were better protected with the HDR technique.
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9.
Randomized, placebo-controlled trial evaluating the safety of one-year administration of green tea catechins.
Kumar, NB, Pow-Sang, J, Spiess, PE, Park, J, Salup, R, Williams, CR, Parnes, H, Schell, MJ
Oncotarget. 2016;(43):70794-70802
Abstract
PURPOSE Although preclinical, epidemiological and prior clinical trial data suggest that green tea catechins (GTCs) may reduce prostate cancer (PCa) risk, several preclinical studies and case reports have reported liver toxicities and acute gastrointestinal bleeding. Based on these observations, regulatory bodies have required stringent inclusion criteria with frequent, excessive toxicity monitoring and early stopping rules in clinical trials. These requirements have impeded recruitment and retention of subjects in chemoprevention trials and subsequent progress in agent development efforts. EXPERIMENTAL DESIGN We conducted a placebo-controlled, randomized clinical trial of Polyphenon E® (PolyE®), a proprietary mixture of decaffeinated GTCs, containing 400 mg (-)-epigallocatechin-3-gallate (EGCG) per day, in 97 men with high-grade prostatic intraepithelial neoplasia (HGPIN) and/or atypical small acinar proliferation (ASAP). PolyE® containing 200 mg EGCG was administered with food, BID. A secondary study endpoint in this trial was a comparison of the overall one-year treatment related adverse events and grade 3 or higher adverse event on the two study arms. Monthly assessments of toxicity (CTCAE 4.0), concomitant medications and organ function, including hepatic panel, PT/PTT and LDH, were performed. RESULTS Daily intake of a standardized, decaffeinated, catechin mixture containing 200 mg EGCG BID taken with food for 1 year accumulated in plasma and was well tolerated and did not produce treatment related adverse effects in men with baseline HGPIN or ASAP. CONCLUSION The current data provides evidence of safety of decaffeinated, catechin mixture containing 200 mg EGCG BID to be further tested for prostate cancer prevention or other indications.
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10.
(11)C-methylaminoisobutyric acid (MeAIB) PET for evaluation of prostate cancer: compared with (18)F-fluorodeoxyglucose PET.
Arimoto, MK, Higashi, T, Nishii, R, Kagawa, S, Takahashi, M, Kishibe, Y, Yamauchi, H, Ishitoya, S, Oonishi, H, Nakamoto, Y, et al
Annals of nuclear medicine. 2016;(8):553-62
Abstract
OBJECTIVE α-N-methyl-(11)C-methylaminoisobutyric acid ((11)C-MeAIB) is a selective substrate of system A amino acid transport, and known to accumulate in malignant lesions. The aim of this study was to evaluate the utility of MeAIB PET for the assessment of prostate cancer, compared with FDG PET. METHODS Thirty-four men (age range 57-77 years) with prostate cancer were prospectively enrolled, and underwent MeAIB PET and FDG PET between January 2011 and January 2013. MeAIB PET and FDG PET were performed at 20 and 50 min post-injection, respectively. SUVmax of the prostate was calculated, and visual analysis was conducted for MeAIB and FDG PET studies. MRI images were visually evaluated if available. All patients received total prostatectomy subsequently, and imaging findings were compared with pathological results, including T stage, Gleason score, and tumor size. The patient-based and lesion-based sensitivity and specificity were calculated according to pathological significant cancer. RESULTS Mean value of SUVmax of (11)C-MeAIB PET and (18)F-FDG PET in prostate cancer were 3.18 (±1.90, range; 1.55-9.57) and 3.88 (±2.85, range; 2.04-14.47). MeAIB PET and FDG PET were positive by visual analysis in 47.1 % (16/34) and 44.1 % (15/34) of the patients. MRI was positive in 51.5 % (17/33). Pathological stage and Gleason score were as follows: Stage 2 (n = 23), 3 (n = 8), and 4 (n = 3); Gleason score 6 (n = 13), 7 (n = 16), 8 (n = 3), and 9 (n = 2). The sensitivities tended to be higher according to higher pathological T stage or Gleason sum score for both MeAIB and FDG PET studies. Visual analysis of both MeAIB PET and FDG PET had significant correlation with extraprostatic extension (p < 0.05). MeAIB PET and FDG PET had complementary results by visual analysis in the assessment of prostate cancer. The patient-based sensitivity of MeAIB PET, FDG PET, and MRI were 51.6, 48.4, and 56.7 %, respectively. The patient-based specificity of these modalities was 100 % for each modality. CONCLUSIONS MeAIB PET has better diagnostic results than FDG PET for the assessment of significant prostate cancer, and these PET studies showed complementary results. MRI has even better diagnostic results than (11)C-MeAIB PET. MeAIB accumulates in prostate cancer, which indicates that the system A amino acid transport pathway is activated in prostate cancer.