Prospective comparison of F-18-PSMA-1007 PET/CT, whole-body MRI and CT in primary nodal staging of unfavourable intermediate- and high-risk prostate cancer

Purpose To prospectively compare F-18-prostate-specific membrane antigen (PSMA)-1007 positron emission tomography (PET)/CT, whole-body magnetic resonance imaging (WBMRI) including diffusion-weighted imaging (DWI) and standard computed tomography (CT), in primary nodal staging of prostate cancer (PCa). Methods Men with newly diagnosed unfavourable intermediate- or high-risk PCa prospectively underwent F-18-PSMA-1007 PET/CT, WBMRI with DWI and contrast-enhanced CT within a median of 8 days. Six readers (two for each modality) independently reported pelvic lymph nodes as malignant, equivocal or benign while blinded to the other imaging modalities. Sensitivity, specificity and accuracy were reported according to optimistic (equivocal lesions interpreted as benign) and pessimistic (equivocal lesions interpreted as malignant) analyses. The reference standard diagnosis was based on multidisciplinary consensus meetings where available histopathology, clinical and follow-up data were used. Results Seventy-nine patients completed all the imaging modalities, except for one case of interrupted WBMRI. Thirty-one (39%) patients had pelvic lymph node metastases, which were detected in 27/31 (87%), 14/31 (45%) and 8/31 (26%) patients by F-18-PSMA-1007 PET/CT, WBMRI with DWI and CT, respectively (optimistic analysis). In 8/31 (26%) patients, only F-18-PSMA-1007 PET/CT detected malignant lymph nodes, while the other two imaging modalities were reported as negative. At the patient level, sensitivity and specificity values for F-18-PSMA-1007 PET/CT, WBMRI with DWI and CT in optimistic analysis were 0.87 (95%CI 0.71-0.95) and 0.98 (95%CI 0.89-1.00), 0.37 (95%CI 0.22-0.55) and 0.98 (95%CI 0.89-1.00) and 0.26 (95%CI 0.14-0.43) and 1.00 (95%CI 0.93-1.00), respectively. Conclusion F-18-PSMA-1007 PET/CT showed significantly greater sensitivity in nodal staging of primary PCa than did WBMRI with DWI or CT, while maintaining high specificity.Peer reviewe

A Prospective Comparison of F-18-prostate-specific Membrane Antigen-1007 Positron Emission Tomography Computed Tomography, Whole-body 1.5 T Magnetic Resonance Imaging with Diffusion-weighted Imaging, and Single-photon Emission Computed Tomography/Computed Tomography with Traditional Imaging in Primary Distant Metastasis Staging of Prostate Cancer (PROSTAGE)

Background: Computed tomography (CT) and bone scintigraphy (BS) are the imaging modalities currently used for distant metastasis staging of prostate cancer (PCa). Objective: To compare standard staging modalities with newer and potentially more accurate imaging modalities. Design, setting, and participants: This prospective, single-centre trial (NCT03537391) enrolled 80 patients with newly diagnosed high-risk PCa (International Society of Urological Pathology grade group >= 3 and/or prostate-specific antigen [PSA] >= 20 and/or cT >= T3; March 2018-June 2019) to undergo primary metastasis staging with two standard and three advanced imaging modalities. Outcome measurements and statistical analysis: The participants underwent the following five imaging examinations within 2 wk of enrolment and without a prespecified sequence: BS, CT, Tc-99m-hydroxymethylene diphosphonate (Tc-99m-HMDP) single-photon emission computed tomography (SPECT)-CT, 1.5 T whole-body magnetic resonance imaging (WBMRI) using diffusion-weighted imaging, and F-18-prostate-specific membrane antigen-1007 (F-18-PSMA-1007) positron emission tomography(PET)-CT. Each modality was reviewed by two independent experts blinded to the results of the prior studies, who classified lesions as benign, equivocal, or malignant. Pessimistic and optimistic analyses were performed to resolve each equivocal diagnosis. The reference standard diagnosis was defined using all available information accrued during at least 12 mo of clinical follow-up. Patients with equivocal reference standard diagnoses underwent MRI and/or CT to search for the development of anatomical correspondence. PSMA PET-avid lesions without histopathological verification were rated to be malignant only if there was a corresponding anatomical finding suspicious for malignancy at the primary or follow-up imaging. Results and limitations: Seventy-nine men underwent all imaging modalities except for one case of interrupted MRI. The median interval per patient between the first and the last imaging study was 8 d (interquartile range [IQR]: 6-9). The mean age was 70 yr (standard deviation: 7) and median PSA 12 ng/mL (IQR:7-23). The median follow-up was 435 d (IQR: 378-557). Metastatic disease was detected in 20 (25%) patients. The imaging modality F-18-PSMA-1007 PET-CT had superior sensitivity and highest inter-reader agreement. The area under the receiver-operating characteristic curve (AUC) values for bone metastasis detection with PSMA PET-CT were 0.90 (95% confidence interval [CI]: 0.85-0.95) and 0.91 (95% CI: 0.87-0.96) for readers 1 and 2, respectively, while the AUC values for BS, CT, SPECT-CT, and WBMRI were 0.71 (95% CI: 0.58-0.84) and 0.8 (95% CI: 0.67-0.92), 0.53 (95% CI: 0.39-0.67) and 0.66 (95% CI: 0.54-0.77), 0.77 (95% CI: 0.65-0.89) and 0.75 (95% CI: 0.62-0.88), and 0.85 (95% CI: 0.74-0.96) and 0.67 (95% CI: 0.54-0.80), respectively, for the other four pairs of readers. The imaging method F-18-PSMA-1007 PET-CT detected metastatic disease in 11/20 patients in whom standard imaging was negative and influenced clinical decision making in 14/79 (18%) patients. In 12/79 cases, false positive bone disease was reported only by PSMA PET-CT. Limitations included a nonrandomised study setting and few histopathologically validated suspicious lesions. Conclusions: Despite the risk of false positive bone lesions, F-18-PSMA-1007 PET-CT outperformed all other imaging methods studied for the detection of primary distant metastasis in high-risk PCa. Patient summary: In this report, we compared the diagnostic performance of conventional and advanced imaging. It was found that F-18-prostate-specific membrane antigen-1007 positron emission tomography/computed tomography (F-18-PSMA-1007 PET-CT) was superior to the other imaging modalities studied for the detection of distant metastasis at the time of initial diagnosis of high-risk prostate cancer. PSMA PET-CT also appears to detect some nonmetastatic bone lesions. (C) 2020 The Author(s). Published by Elsevier B.V. on behalf of European Association of Urology.Peer reviewe

Serum Lipidomics Meets Cardiac Magnetic Resonance Imaging: Profiling of Subjects at Risk of Dilated Cardiomyopathy

Peer reviewe

A multi-centre randomized controlled trial comparing arthroscopic osteochondroplasty and lavage with arthroscopic lavage alone on patient important outcomes and quality of life in the treatment of young adult (18-50) Femoroacetabular impingement

Background: Several cross-sectional studies have estimated that the prevalence of femoroacetabular impingement (FAI) ranges from 14-17% among asymptomatic young adults to almost 95% among competitive athletes. With FAI, there is abnormal contact between the proximal femur and the acetabulum, resulting in abnormal mechanics with terminal motion such as hip flexion and rotation. This condition results from bony anomalies of the acetabular rim (Pincer) and or femoral head/neck junction (CAM) and typically causes hip pain and decreased hip function. The development of hip pain potentially serves as an indicator for early cartilage and labral damage that may result in hip osteoarthritis. Although surgical correction of the misshaped bony anatomy and associated intra-articular soft tissue damage of the hip is thought to improve hip pain and alter the natural history of degenerative disease, the supportive evidence is based upon low quality observational studies. The Femoroacetabular Impingement RandomiSed controlled Trial (FIRST) compares outcomes following surgical correction of the impingement morphology (arthroscopic osteochondroplasty) with/without labral repair versus arthroscopic lavage of the hip joint in adults aged 18 to 50 diagnosed with FAI. Methods and design: FIRST is a multi-centre, randomized controlled trial with a sample size of 220 patients. Exclusion criteria include the presence of hip syndromes, previous surgery or trauma to the affected hip, and significant medical comorbidities. The primary outcome is pain and the secondary outcomes include patient function, quality of life, complications, and cost-effectiveness - all within one year of follow-up. Patients are stratified based on centre and impingement sub-type. Patients, outcome assessors, data analysts, and the Steering Committee are blinded to surgical allocation. Using an intention-to-treat approach, outcome analyses will be performed using an analysis of covariance and descriptive statistics. Discussion: Symptomatic FAI is associated with chronic hip pain, functional limitations, and secondary osteoarthritis. Therefore, optimizing treatment has the potential to improve the lives millions of young, active persons who are diagnosed with this condition. Few orthopaedic surgical trials have similar potential to shift the paradigm of care dramatically towards (or away) from surgical bony and soft tissue interventions.Peer reviewe

Birth and expansion of innovation ecosystems: A case study of copper production

Despite the growing attention innovation ecosystems have received from scholars and practitioners, rather little is known about the crucial birth and expansion phases that these ecosystems experience. Through a single case in the complex product system (CoPS) environment, this paper investigates the development of an innovation ecosystem between 1980 and 2007. The findings demonstrate that the ecosystem’s birth phase includes sub-phases, namely, invention and start-up, where the ecosystem is reconfigured to find the appropriate form and the proper actors to satisfy the first customer’s requirements. Moreover, the duration of the expansion phase is found to be remarkably long, suggesting that within the CoPS setting, expansion may also include two or more sub-phases

A bibliometric review on innovation systems and ecosystems: a research agenda

Purpose The ecosystem perspective on innovation and business has emerged as the secret sauce of innovative organizations. While its theoretical foundations are premised on innovation system literature, the broad adoption of the ecosystem concept has resulted in conceptual ambiguity. The purpose of this paper is to tackle the ambiguous use of innovation ecosystem terminology and structure a conceptual frame for the field, identifying definitions of an innovation ecosystem and how the concept has been established in previous literature. Design/methodology/approach This paper examines the ambiguous use of terminology by reviewing the literature with bibliometric coupling and co-citation analysis by which thematic differences in ecosystem literature were identified. The study gathered the scientific publications from Thomson Reuters Web of Sciences Core Collection (n=4,681) from 1990 to 2015. Findings Six major bibliometrically coupled clusters were identified, of which the three largest clusters are innovation system studies, regional innovation studies and technological innovation studies. In addition, further analysis shows an emerging cluster that is focused on ecosystems, having its roots in eight seminal papers. This ecosystem research cluster includes seven sub-clusters, such as innovation ecosystem studies, business ecosystem studies and studies focusing on ecosystem development. Research limitations/implications The authors’ approach highlights how a lot of recent ecosystem studies actually belong to previous, well-developed research streams. However, there is also a separate, emergent research stream that includes the innovation and ecosystem studies. As a research implication, the paper concludes by suggesting the research agenda for further studies. Originality/value Even though literature on innovation systems and ecosystems is extensive literature, no studies have captured the emergence of the ecosystems approach and its relation with the systems of innovation literature

Editorial: Platforms and ecosystems

Introduces the research papers included in a Special Issue that arose out of the newly created ISPIM special interest group on Platforms and Ecosystems. Each article was developed from a paper presented at the ISPIM Innovation Conference in Vienna, Austria, June 18–21, 2017

Disruptive change and the reconfiguration of innovation ecosystems

This conceptual paper extends the traditional view of disruptive change, which considers the effects of rivalry between an incumbent and new entrant firm, by examining the impact of disruption upon the ‘innovation ecosystem’ in its entirety – the group of organisations that collaborate in creating a holistic value proposition for the end-user. Following Adner’s “ecosystem-as-structure” perspective, we develop propositions that anticipate structural differences between incumbent and disruptive innovation ecosystems, and then review these propositions in the context of three historical, disruptive innovation cases; Bakelite (a synthetic plastic), microwave oven, and photocopier. Through these cases, we illustrate that the manner of innovation ecosystem reconfiguration is likely to depend on the design attributes of the product, as well as the type of disruption experienced. We conclude by reflecting upon contemporary cases of disruption enabled through digital technologies, and proposing a framework that can guide future research