The PiGeOn project: Protocol for a longitudinal study examining psychosocial, behavioural and ethical issues and outcomes in cancer tumour genomic profiling

© 2018 The Author(s). Background: Genomic sequencing in cancer (both tumour and germline), and development of therapies targeted to tumour genetic status, hold great promise for improvement of patient outcomes. However, the imminent introduction of genomics into clinical practice calls for better understanding of how patients value, experience, and cope with this novel technology and its often complex results. Here we describe a protocol for a novel mixed-methods, prospective study (PiGeOn) that aims to examine patients' psychosocial, cognitive, affective and behavioural responses to tumour genomic profiling and to integrate a parallel critical ethical analysis of returning results. Methods: This is a cohort sub-study of a parent tumour genomic profiling programme enrolling patients with advanced cancer. One thousand patients will be recruited for the parent study in Sydney, Australia from 2016 to 2019. They will be asked to complete surveys at baseline, three, and fivemonths. Primary outcomes are: knowledge, preferences, attitudes and values. A purposively sampled subset of patients will be asked to participate in three semi-structured interviews (at each time point) to provide deeper data interpretation. Relevant ethical themes will be critically analysed to iteratively develop or refine normative ethical concepts or frameworks currently used in the return of genetic information. Discussion: This will be the first Australian study to collect longitudinal data on cancer patients' experience of tumour genomic profiling. Findings will be used to inform ongoing ethical debates on issues such as how to effectively obtain informed consent for genomic profiling return results, distinguish between research and clinical practice and manage patient expectations. The combination of quantitative and qualitative methods will provide comprehensive and critical data on how patients cope with 'actionable' and 'non-actionable' results. This information is needed to ensure that when tumour genomic profiling becomes part of routine clinical care, ethical considerations are embedded, and patients are adequately prepared and supported during and after receiving results

The PiGeOn project: Protocol of a longitudinal study examining psychosocial and ethical issues and outcomes in germline genomic sequencing for cancer

© 2018 The Author(s). Background: Advances in genomics offer promise for earlier detection or prevention of cancer, by personalisation of medical care tailored to an individual's genomic risk status. However genome sequencing can generate an unprecedented volume of results for the patient to process with potential implications for their families and reproductive choices. This paper describes a protocol for a study (PiGeOn) that aims to explore how patients and their blood relatives experience germline genomic sequencing, to help guide the appropriate future implementation of genome sequencing into routine clinical practice. Methods: We have designed a mixed-methods, prospective, cohort sub-study of a germline genomic sequencing study that targets adults with cancer suggestive of a genetic aetiology. One thousand probands and 2000 of their blood relatives will undergo germline genomic sequencing as part of the parent study in Sydney, Australia between 2016 and 2020. Test results are expected within12-15 months of recruitment. For the PiGeOn sub-study, participants will be invited to complete surveys at baseline, three months and twelve months after baseline using self-administered questionnaires, to assess the experience of long waits for results (despite being informed that results may not be returned) and expectations of receiving them. Subsets of both probands and blood relatives will be purposively sampled and invited to participate in three semi-structured qualitative interviews (at baseline and each follow-up) to triangulate the data. Ethical themes identified in the data will be used to inform critical revisions of normative ethical concepts or frameworks. Discussion: This will be one of the first studies internationally to follow the psychosocial impact on probands and their blood relatives who undergo germline genome sequencing, over time. Study results will inform ongoing ethical debates on issues such as informed consent for genomic sequencing, and informing participants and their relatives of specific results. The study will also provide important outcome data concerning the psychological impact of prolonged waiting for germline genomic sequencing. These data are needed to ensure that when germline genomic sequencing is introduced into standard clinical settings, ethical concepts are embedded, and patients and their relatives are adequately prepared and supported during and after the testing process

Patient information leaflets (PILs) for UK randomised controlled trials : a feasibility study exploring whether they contain information to support decision making about trial participation

Peer reviewedPublisher PD

Patient perspectives on molecular tumor profiling: "why wouldn't you?"

© 2019 The Author(s). Aim: This study explored the attitudes of patients with advanced cancer towards MTP and return of results, prior to undergoing genomic testing within a research program. Methods: Participants were recruited as part of the longitudinal PiGeOn (Psychosocial Issues in Genomics in Oncology) study involving patients with advanced/metastatic solid cancer who had exhausted therapeutic options and who were offered MTP in order to identify cognate therapies. Twenty patients, selected by purposive sampling, were interviewed around the time they gave consent to MTP. Interviews were audio recorded, transcribed and analysed using thematic analysis. Themes identified in the transcripts were cross-validated via qualitative responses to the PiGeOn study survey (n = 569; 63%). Results: All interviewed participants gave consent to MTP without reservation. Three themes were identified and further supported via the survey responses: (1) Obvious agreement to participate, primarily because of desire for new treatments and altruism. (2) The black box - while participant knowledge of genomics was generally poor, faith in their oncologists and the scientific process encouraged them to proceed with testing; and (3) Survival is the priority - receiving treatment to prolong life was the priority for all participants, and other issues such as identification of a germline variant were generally seen as ancillary. Conclusion: Having advanced cancer seemed to abrogate any potential concerns about MTP. Participants valued the research for varied reasons, but this was secondary to their priority to survive. While no negative attitudes toward MTP emerged, limitations in understanding of genomics were evident

Body Fluid Cytokine Levels in Mild Cognitive Impairment and Alzheimer’s Disease: a Comparative Overview

This article gives a comprehensive overview of cytokine and other inflammation associated protein levels in plasma, serum and cerebrospinal fluid (CSF) of patients with Alzheimer's disease (AD) and mild cognitive impairment (MCI). We reviewed 118 research articles published between 1989 and 2013 to compare the reported levels of 66 cytokines and other proteins related to regulation and signaling in inflammation in the blood or CSF obtained from MCI and AD patients. Several cytokines are evidently regulated in (neuro-) inflammatory processes associated with neurodegenerative disorders. Others do not display changes in the blood or CSF during disease progression. However, many reports on cytokine levels in MCI or AD are controversial or inconclusive, particularly those which provide data on frequently investigated cytokines like tumor necrosis factor alpha (TNF-α) or interleukin-6 (IL-6). The levels of several cytokines are possible indicators of neuroinflammation in AD. Some of them might increase steadily during disease progression or temporarily at the time of MCI to AD conversion. Furthermore, elevated body fluid cytokine levels may correlate with an increased risk of conversion from MCI to AD. Yet, research results are conflicting. To overcome interindividual variances and to obtain a more definite description of cytokine regulation and function in neurodegeneration, a high degree of methodical standardization and patients collective characterization, together with longitudinal sampling over years is essential

Light isovector resonances in π-p →π-π-π+p at 190 GeV/c

We have performed the most comprehensive resonance-model fit of π-π-π+ states using the results of our previously published partial-wave analysis (PWA) of a large data set of diffractive-dissociation events from the reaction π-+p→π-π-π++precoil with a 190 GeV/c pion beam. The PWA results, which were obtained in 100 bins of three-pion mass, 0.5<2.5 GeV/c2, and simultaneously in 11 bins of the reduced four-momentum transfer squared, 0.1<1.0 (GeV/c)2, are subjected to a resonance-model fit using Breit-Wigner amplitudes to simultaneously describe a subset of 14 selected waves using 11 isovector light-meson states with JPC=0-+, 1++, 2++, 2-+, 4++, and spin-exotic 1-+ quantum numbers. The model contains the well-known resonances π(1800), a1(1260), a2(1320), π2(1670), π2(1880), and a4(2040). In addition, it includes the disputed π1(1600), the excited states a1(1640), a2(1700), and π2(2005), as well as the resonancelike a1(1420). We measure the resonance parameters mass and width of these objects by combining the information from the PWA results obtained in the 11 t′ bins. We extract the relative branching fractions of the ρ(770)π and f2(1270)π decays of a2(1320) and a4(2040), where the former one is measured for the first time. In a novel approach, we extract the t′ dependence of the intensity of the resonances and of their phases. The t′ dependence of the intensities of most resonances differs distinctly from the t′ dependence of the nonresonant components. For the first time, we determine the t′ dependence of the phases of the production amplitudes and confirm that the production mechanism of the Pomeron exchange is common to all resonances. We have performed extensive systematic studies on the model dependence and correlations of the measured physical parameters

Corrigendum to "Transverse extension of partons in the proton probed in the sea-quark range by measuring the DVCS cross section" [Phys. Lett. B 793 (2019) 188]

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Measurement of P T -weighted Sivers asymmetries in leptoproduction of hadrons

The transverse spin asymmetries measured in semi-inclusive leptoproduction of hadrons, when weighted with the hadron transverse momentum PT , allow for the extraction of important transverse-momentumdependent distribution functions. In particular, the weighted Sivers asymmetries provide direct information on the Sivers function, which is a leading-twist distribution that arises from a correlation between the transverse momentum of an unpolarised quark in a transversely polarised nucleon and the spin of the nucleon. Using the high-statistics data collected by the COMPASS Collaboration in 2010 with a transversely polarised proton target, we have evaluated two types of PT -weighted Sivers asymmetries, which are both proportional to the product of the first transverse moment of the Sivers function and of the fragmentation function. The results are compared to the standard unweighted Sivers asymmetries and used to extract the first transverse moments of the Sivers distributions for u and d quark