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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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Extraprostatic Uptake of 18F-Fluciclovine: Differentiation of Nonprostatic Neoplasms From Metastatic Prostate Cancer.
Robertson, MS, Sakellis, CG, Hyun, H, Jacene, HA
AJR. American journal of roentgenology. 2020;(3):641-648
Abstract
OBJECTIVE. Fluciclovine is a synthetic radiolabeled amino acid analog used for imaging of biochemical recurrent prostate cancer. Uptake of fluciclovine is mediated by several amino acid transporters, including alanine-serine-cysteine transporter 2 and large neutral amino acid transporters, which are known to be overexpressed in other malignancies. CONCLUSION. Knowledge of the common patterns of prostate cancer recurrence, in addition to what other neoplasms can show uptake, is critical for accurate study interpretation.
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A randomized phase 2 study of temsirolimus and cetuximab versus temsirolimus alone in recurrent/metastatic, cetuximab-resistant head and neck cancer: The MAESTRO study.
Seiwert, TY, Kochanny, S, Wood, K, Worden, FP, Adkins, D, Wade, JL, Sleckman, BG, Anderson, D, Brisson, RJ, Karrison, T, et al
Cancer. 2020;(14):3237-3243
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Abstract
BACKGROUND Patients with cetuximab-resistant, recurrent/metastatic head and neck squamous cell carcinoma (HNSCC) have poor outcomes. This study hypothesized that dual blockade of mammalian target of rapamycin and epidermal growth factor receptor (EGFR) would overcome cetuximab resistance on the basis of the role of phosphoinositide 3-kinase signaling in preclinical models of EGFR resistance. METHODS In this multicenter, randomized clinical study, patients with recurrent/metastatic HNSCC with documented progression on cetuximab (in any line in the recurrent/metastatic setting) received 25 mg of temsirolimus weekly plus cetuximab at 400/250 mg/m2 weekly (TC) or single-agent temsirolimus (T). The primary outcome was progression-free survival (PFS) in the TC arm versus the T arm. Response rates, overall survival, and toxicity were secondary outcomes. RESULTS Eighty patients were randomized to therapy with TC or T alone. There was no difference for the primary outcome of median PFS (TC arm, 3.5 months; T arm, 3.5 months). The response rate was 12.5% in the TC arm (5 responses, including 1 complete response [2.5%]) and 2.5% in the T arm (1 partial response; P = .10). Responses were clinically meaningful in the TC arm (range, 3.6-9.1 months) but not in the T-alone arm (1.9 months). Fatigue, electrolyte abnormalities, and leukopenia were the most common grade 3 or higher adverse events and occurred in less than 20% of patients in both arms. CONCLUSIONS The study did not meet its primary endpoint of improvement in PFS. However, TC induced responses in cetuximab-refractory patients with good tolerability. The post hoc observation of activity in patients with acquired resistance (after prior benefit from cetuximab monotherapy) may warrant further investigation.
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Comparison of 5 Different PET Radiopharmaceuticals for the Detection of Recurrent Medullary Thyroid Carcinoma: A Network Meta-analysis.
Lee, SW, Shim, SR, Jeong, SY, Kim, SJ
Clinical nuclear medicine. 2020;(5):341-348
Abstract
PURPOSE The aim of this study is to investigate and compare the performance of different PET radiopharmaceuticals for the detection of recurrent medullary thyroid carcinoma (MTC) by performing a network meta-analysis (NMA) using direct comparison studies with 2 or more PET radiopharmaceuticals. METHODS PubMed and EMBASE were searched for the studies evaluating the performance of PET or PET/CT for the detection of recurrent MTC. The NMA was performed for different PET radiopharmaceuticals in both patient- and lesion-based analyses and with a threshold of serum calcitonin or carcinoembryonic antigen (CEA) levels and calcitonin doubling time. The consistency was evaluated by examining the agreement between direct and indirect treatment effects, and publication bias was assessed by funnel plot asymmetry tests. The surface under the cumulative ranking curve values were obtained to calculate the probability of each PET modality being the most effective diagnostic method. RESULTS A total of 306 patients from 14 direct comparison studies using 5 different PET radiopharmaceuticals (F-FDG, F-DOPA, Ga-somatostatin analogs, 3-O-methyl-6-[F]fluoro-DOPA, and C-methionine) for the detection of recurrent MTC was included. The detection rate of F-DOPA PET was significantly higher than that of FDG PET in both patient- and lesion-based analyses (patient-based analysis: odds ratio, 2.44; 95% confidence interval, 1.4-4.31; lesion-based analysis: odds ratio, 5.74; 95% confidence interval, 1.65-23.4). Among all PET radiopharmaceuticals, F-DOPA showed the highest surface under the cumulative ranking curve value in both patient- and lesion-based analyses regardless of serum calcitonin or CEA levels and calcitonin doubling time. CONCLUSIONS The results from this NMA indicate that F-DOPA PET clearly showed a best performance for the detection of recurrent MTC in both patient- and lesion-based analyses regardless of serum calcitonin or CEA levels and calcitonin doubling time.
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S-1 and Oxaliplatin Versus Tegafur-uracil and Leucovorin as Postoperative Adjuvant Chemotherapy in Patients With High-risk Stage III Colon Cancer (ACTS-CC 02): A Randomized, Open-label, Multicenter, Phase III Superiority Trial.
Sunami, E, Kusumoto, T, Ota, M, Sakamoto, Y, Yoshida, K, Tomita, N, Maeda, A, Teshima, J, Okabe, M, Tanaka, C, et al
Clinical colorectal cancer. 2020;(1):22-31.e6
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Abstract
BACKGROUND The efficacy of S-1 plus oxaliplatin (SOX) as postoperative adjuvant chemotherapy for colon cancer has not been established. This randomized phase III study was designed to verify the superiority of SOX over tegafur-uracil and leucovorin (UFT/LV) in patients with high-risk stage III colon cancer (any T, N2, or positive nodes around the origin of the feeding arteries). PATIENTS AND METHODS Patients who underwent curative resection for pathologically confirmed high-risk stage III colon cancer were randomly assigned to receive either UFT/LV (300 mg/m2 of UFT and 75 mg/day of LV on days 1-28, every 35 days, 5 cycles) or SOX (100 mg/m2 of oxaliplatin on day 1 and 80 mg/m2 of S-1 on days 1-14, every 21 days, 8 cycles). The primary endpoint was disease-free survival (DFS). RESULTS A total of 478 patients in the UFT/LV group and 477 patients in the SOX group were included in the primary analysis. The 3-year DFS was 60.6% (95% confidence interval [CI], 56.0%-64.9%) in the UFT/LV group and 62.7% (95% CI, 58.1%-66.9%) in the SOX group. The stratified hazard ratio for DFS was 0.90 (95% CI, 0.74-1.09; stratified log-rank test, P = .2780). In the N2b subgroup, the 3-year DFS was 46.0% (95% CI, 37.5%-54.0%) in the UFT/LV group and 54.7% (95% CI, 45.7%-62.7%) in the SOX group (hazard ratio, 0.76; 95% CI, 0.55-1.05). CONCLUSION As postoperative adjuvant chemotherapy, SOX was not superior to UFT/LV in terms of DFS in patients with high-risk stage III colon cancer.
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E-Coaching: the DianaWeb study to prevent breast cancer recurrences.
Gianfredi, V, Nucci, D, Balzarini, M, Acito, M, Moretti, M, Villarini, A, Villarini, M
La Clinica terapeutica. 2020;(1):e59-e65
Abstract
INTRODUCTION Breast cancer is the most common cancer in women worldwide, for which the survival rate is increasing over time. Growing evidence are showing that the effect of lifestyle could have the same weight of the effect of the usual clinical-pathological risk factors on survival rate. The DianaWeb study responds to the pressing request of patients diagnosed with breast cancer to know the most advanced point of scientific research on the prevention of recurrences, to have a virtual space to meet, where to receive advice and practical information for the daily management the lifestyle change. DianaWeb is a community-based participatory research, dedicated to breast cancer patients, aimed to monitor lifestyle, provide them tips to encourage sustainable lifestyle changes, and to analyze clinical outcomes. In order to achieve these aims, DianaWeb uses a specific interactive website (http://www.dianaweb.org/). METHODS The web architecture has been designed essential and light, with a rigorous implantation that brings the figure of the woman to the center. In order to humanized the project the acronym used to identify the study was Diana (Diet and Androgens), a classical female name, who was illustrated as a female avatar, aimed to symbolize all women. The graphical interface was developed using seven pastel tones colors, which become a fundamental elements of the layout, such as frame, navigation menu, and separation interspaces. RESULTS The project started in 2015, and in 4 days the web site was visited by more than 1000 people. A total of 2823 persons enrolled in the study, but 2182 did not send the full documentations, 61 persons abandoned the study, 641 timely answered to the questionnaires. CONCLUSIONS The high number of participants' interaction within the web page, confirmed the high usability of the web page and the great interest of patients. Prevention of breast cancer recurrences with low cost technologies, easily available to everybody, is a priority for both public health and public finances.
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hERG1 and CA IX expression are associated with disease recurrence in surgically resected clear cell renal carcinoma.
Lastraioli, E, Pillozzi, S, Mari, A, Tellini, R, Duranti, C, Baldazzi, V, Venturini, S, Minervini, A, Lapini, A, Nesi, G, et al
European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology. 2020;(1):209-215
Abstract
BACKGROUND In search of novel prognostic biomarkers for clear cell renal carcinoma (ccRCC), we analysed the expression of several proteins related to angiogenesis and hypoxia. METHODS A monocentric study on 30 consecutive surgical samples from surgically-treated ccRCC patients with a 10-year follow up was performed. The following proteins were analysed by immunohistochemistry: Vascular Endothelial Growth Factor- A (VEGF-A), Platelet-Derived Growth Factor β Receptor (PDGFRβ), VEGF-receptor 1 (Flt1), VEGF-receptor 2 (KDR), Glucose Transporter 1 (GLUT1), Carbonic anhydrase IX (CA-IX) and the hERG1 potassium channel. Data were analysed in conjunction with the clinico-pathological characteristics of the patients and follow up. RESULTS All the proteins were expressed in the samples, with statistically significant associations of VEGF-A with PDGFRβ and Flt1 and hERG1 with CA IX. Notably, hERG1 and CAIX co-immunoprecipitated in primary ccRCC samples and survival analysis showed that the positivity for hERG1 and CA IX had a negative impact on Recurrence Free Survival (RFS) at the univariate analysis. At the multivariate analysis only hERG1 maintained its statistically significant negative impact. CONCLUSIONS hERG1 expression can be exploited to predict recurrence in surgically-treated ccRCC patients. hERG1 channels form a multiprotein complex with the pH regulator CA IX in primary ccRCC samples their potential use as therapeutic target might be suggested.
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Hemoglobin A1c Levels Modify Associations between Dietary Acid Load and Breast Cancer Recurrence.
Wu, T, Hsu, FC, Wang, S, Luong, D, Pierce, JP
Nutrients. 2020;(2)
Abstract
BACKGROUND Metabolic acidosis promotes cancer metastasis. No prospective studies have examined the association between dietary acid load and breast cancer recurrence among breast cancer survivors, who are susceptible to metabolic acidosis. Hyperglycemia promotes cancer progression and acid formation; however, researchers have not examined whether hyperglycemia can modify the association between dietary acid load and breast cancer recurrence. METHODS We studied 3081 early-stage breast cancer survivors enrolled in the Women's Healthy Eating and Living study who provided dietary information through 24-h recalls at baseline and during follow-up and had measurements of hemoglobin A1c (HbA1c) at baseline. We assessed dietary acid load using two common dietary acid load scores, potential renal acid load (PRAL) score and net endogenous acid production (NEAP) score. RESULTS After an average of 7.3 years of follow-up, dietary acid load was positively associated with recurrence when baseline HbA1c levels were ≥ 5.6% (median level) and ≥5.7% (pre-diabetic cut-point). In the stratum with HbA1c ≥ 5.6%, comparing the highest to the lowest quartile of dietary acid load, the multivariable-adjusted hazard ratio was 2.15 (95% confidence interval [CI] 1.34-3.48) for PRAL and was 2.31 (95% CI 1.42-3.74) for NEAP. No associations were observed in the stratum with HbA1c levels were <5.6%. P-values for interactions were 0.01 for PRAL and 0.05 for NEAP. CONCLUSIONS Our study demonstrated for the first time that even at or above normal to high HbA1c levels, dietary acid load was associated with increased risk of breast cancer recurrence among breast cancer survivors. IMPACTS Our study provides strong evidence for developing specific dietary acid load guidelines based on HbA1c levels.
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PSMA-targeted Radiotracers versus 18F Fluciclovine for the Detection of Prostate Cancer Biochemical Recurrence after Definitive Therapy: A Systematic Review and Meta-Analysis.
Tan, N, Oyoyo, U, Bavadian, N, Ferguson, N, Mukkamala, A, Calais, J, Davenport, MS
Radiology. 2020;(1):44-55
Abstract
Background National guidelines endorse fluorine 18 (18F) fluciclovine PET/CT for the detection of prostate cancer (PCa) in men with biochemically recurrent PCa. The comparative performance between fluciclovine and gallium 68 or 18F prostate-specific membrane antigen (PSMA) PET/CT, a newer examination, is unclear. Purpose To compare the detection of biochemical recurrence using fluciclovine versus PSMA-targeted radiotracers in patients with a prostate-specific antigen (PSA) level less than 2 ng/mL. Materials and Methods With use of the Preferred Reporting Items for a Systematic Review and Meta-Analysis of Diagnostic Test Accuracy, or PRISMA-DTA, guidelines, a systematic review of PubMed and EMBASE databases between 2012 and 2019 was performed. Studies of fluciclovine PET/CT or PSMA PET/CT in biochemical recurrence were identified. PSA levels, clinical data, and reference standards were obtained when available. A random-effects model was applied to pooled estimates and 95% confidence intervals (CIs) around the prevalence of a positive examination, stratified according to PSA tier. Results Quantitative analysis included 482 patients (median age, 67 years; interquartile range, 67-67 years) in six fluciclovine studies and 3217 patients (median age, 68 years; interquartile range, 67-70 years) in 38 PSMA studies. Pooled detection rates for PSMA and fluciclovine were 45% (95% CI: 38%, 52%) and 37% (95% CI: 25%, 49%), respectively, for a PSA level less than 0.5 ng/mL (P = .46); 59% (95% CI: 52%, 66%) and 48% (95% CI: 34%, 61%) for a PSA level of 0.5-0.9 ng/mL (P = .19); and 80% (95% CI: 75%, 85%) and 62% (95% CI: 54%, 70%) for a PSA level of 1.0-1.9 ng/mL (P = .01). A reference standard was positive in 703 of 735 patients (96%) in the PSMA cohort and 247of 256 (97%) in the fluciclovine cohort. Conclusion Patient-level detection rates for biochemically recurrent prostate cancer were greater for prostate-specific membrane antigen-targeted radiotracers than fluciclovine for prostate specific antigen levels of 1.0-1.9 ng/mL. © RSNA, 2020 Online supplemental material is available for this article.
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Current Imaging Techniques for and Imaging Spectrum of Prostate Cancer Recurrence and Metastasis: A Pictorial Review.
Tanaka, T, Yang, M, Froemming, AT, Bryce, AH, Inai, R, Kanazawa, S, Kawashima, A
Radiographics : a review publication of the Radiological Society of North America, Inc. 2020;(3):709-726
Abstract
Relapsing level of prostate-specific antigen (PSA) after initial curative-intent local therapy for organ-confined prostate cancer is often the first sign of recurrence. However, PSA level recurrence does not enable accurate differentiation of locally recurrent tumor from metastatic disease or a combination of both. Metastatic prostate cancer most frequently involves bones and lymph nodes, followed by other organs such as the liver, lung, pleura, adrenal gland, ureter, peritoneum, penis, testis, and meninges. Conventional imaging including CT and bone scintigraphy has long been the standard of care but has limited sensitivity in depicting early local recurrence or metastatic disease. Multiparametric MRI has been shown to be more sensitive in detecting locally recurrent tumor in the prostatectomy bed as well as in situ recurrence in a prostate gland that has been treated with radiation therapy or thermal ablation. In addition, lesions detected with multiparametric MRI may be amenable to targeted biopsy for definitive diagnosis of recurrence. PET/CT or PET/MRI using the U.S. Food and Drug Administration (FDA)-approved tracers carbon 11 choline or fluorine 18 fluciclovine has demonstrated markedly increased sensitivity and specificity for diagnosis of early metastatic disease such as small-volume lymph node metastasis, as have a range of investigational gallium 68 prostate-specific membrane antigen (PSMA) radioactive PET tracers. With recent advances in imaging modalities and techniques, more accurate early detection, localization, and characterization of recurrent prostate cancer have become possible. The authors present a contemporary review of the strengths and limitations of conventional and advanced imaging modalities in evaluation of patients with recurrent prostate cancer and a systematic review of the clinical and imaging features of locally recurrent and metastatic disease.©RSNA, 2020See discussion on this article by Barwick and Castellucci.