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  • 1
    Online Resource
    Online Resource
    Relevance of estrogen activating STS and inactivating SULT1E1 enzymes and estrogen receptors [alpha/beta] in patients with advanced ovarian cancer
    Bioscientifica ; 2014
    In:  Endocrine Abstracts ( 2014-04-17)
    Details
    In: Endocrine Abstracts, Bioscientifica, ( 2014-04-17)
    Type of Medium: Online Resource
    ISSN: 1479-6848
    URL: Article
    DOI: 10.1530/endoabs.35.P650
    Language: Unknown
    Publisher: Bioscientifica
    Publication Date: 2014
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  • 2
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    Treatment Guided By Next Generation Functional Drug Screening Provides Clinical Benefit in Advanced Aggressive Hematological Malignancies: Final Evaluation of the Open Label, Single Arm Exalt Trial
    American Society of Hematology ; 2020
    In:  Blood Vol. 136, No. Supplement 1 ( 2020-11-5), p. 2-4
    Details
    In: Blood, American Society of Hematology, Vol. 136, No. Supplement 1 ( 2020-11-5), p. 2-4
    Abstract: Background: Aggressive hematological malignancies in relapsed/refractory setting bear a dire prognosis with low cure rates and short survival. Matching these patients to therapies is challenged by complexity due to spatial and temporal tumor evolution and incomplete understanding of genotype to phenotype correlations. Direct functional testing could address these impediments. The EXALT trial is an interventional, one-arm study designed to assess the clinical value of next generation functional drug screening (ngFDS). An interim analysis on 17 patients suggested a clinical benefit (Snijder et al., Lancet Hematol. 2017). Methods: We applied image-based ngFDS to quantify differential ex-vivo sensitivity of primary patient tumor cells to respective non-tumor cells towards 136 small molecule drugs, including EMA approved for any indication or experimental. We screened bone marrow, peripheral blood or lymph node material from 143 patients who suffered from late stage aggressive hematological malignancies (acute leukemias, aggressive B- and T-cell lymphomas) , discussed the results in a multidisciplinary tumor board and recommended treatments to physicians (A). The primary endpoint of this study was the percentage of patients reaching a PFS-ratio (PFS(ngFDS treatment)/PFS(previous treatment)) of ≥1.3 with an H0 hypothesis & lt; 15% patients. The secondary endpoint was overall response rate (ORR) defined as proportion of patients reaching complete remission (CR) or partial remission (PR). Additionally, we performed a post hoc analysis to evaluate the matching of ngFDS to drugs used in actual treatment (matching score of received treatment). Results: 56 (39%) patients were evaluable and treated according to ngFDS based recommendations. With 30 of 56 (54%) ngFDS guided patients experiencing a PFS ratio of ≥1.3, the primary study endpoint was reached. 11 patients (37%) had ongoing response at censoring date (B). The median follow-up was 718 days. The median number of days from sampling to treatment was 21 (range 4-77). The ngFDS treatment regimens consisted of a median of 2 drugs (range: 1-6). ORR was 55% for all evaluable ngFDS treated patients, 60% for the lymphoid subgroup and 41% for the myeloid subgroup. Patients on ngFDS guided treatment with performance status ECOG ≤ 1 had a median PFS of 207 days compared to a median PFS of 29 days for patients with higher ECOG (p & lt; 0.001, C). 24 of 39 (62%) patients with ECOG ≤ 1 had a PFS ratio of ≥1.3 (D). In disease specific subgroup analysis median PFS of T-cell lymphoma patients was 235 days versus 60 days for B-cell lymphoma patients (p = 0.018, E). Age (≤60 vs. & gt;60), sex, lineage (myeloid vs. lymphoid), number of previous treatment lines (≤2 vs. & gt;2), and clinical presentation (leukemia vs. lymphoma) did not have an impact on PFS of ngFDS guided treatment. Post hoc analysis including additional 17 non-ngFDS treated patients demonstrated that only patients receiving treatment with a positive ngFDS matching score demonstrated clinical benefit (HR: 0.53, p=0.005; vs. HR: 1.4, p=0.4). ngFDS matched treatments resulted in higher PFS for patients with tumor samples that had a cancer cell fraction of 10-50% in comparison to patients with samples of lower or higher cancer cell percentage (HR:0.35, p=0.01). Conclusion: ngFDS could be integrated in the routine clinical work flow. ngFDS guided treatments led to high rates of PFS prolongation compared to previous treatments of individual patients. ngFDS guided treatment is feasible and effective in patients with late stage aggressive hematological malignancies. These results prompted a prospective randomized trial comparing treatment guidance based on ngFDS or comprehensive genomic profiling or physician's choice (EXALT-2 trial, NCT04470947). Figure Disclosures Vladimer: Allcyte GmbH: Current Employment, Current equity holder in private company, Other: Founder. Jaeger:Karyopharm: Honoraria; Amgen: Honoraria; Gilead: Honoraria, Research Funding; BMS/Celgene: Consultancy, Honoraria, Research Funding; True North: Honoraria, Research Funding; Miltenyi: Consultancy, Honoraria; CDR Life AG: Consultancy, Research Funding; F. Hoffmann-La Roche: Honoraria, Research Funding; Infinity: Honoraria; Takeda: Honoraria; Novartis: Consultancy, Honoraria, Research Funding; AbbVie: Honoraria. Krall:Allcyte GmbH: Current Employment, Current equity holder in private company, Other: Founder. Valent:Allcyte GmbH: Research Funding; Cellgene: Honoraria, Research Funding; Pfizer: Honoraria. Wolf:Celgene: Honoraria, Research Funding. Zielinski:MSD: Consultancy, Honoraria, Speakers Bureau; Roche: Consultancy, Honoraria, Speakers Bureau; Novartis: Consultancy, Honoraria, Speakers Bureau; BMS: Consultancy, Honoraria, Speakers Bureau; Imugene: Consultancy, Honoraria, Speakers Bureau; Ariad: Consultancy, Honoraria, Speakers Bureau; Pfizer: Consultancy, Honoraria, Speakers Bureau; Merrimack: Consultancy, Honoraria, Speakers Bureau; Merck KGaA: Consultancy, Honoraria, Speakers Bureau; Fibrogen: Consultancy, Honoraria, Speakers Bureau; AstraZeneca: Consultancy, Honoraria, Speakers Bureau; Tesaro: Consultancy, Honoraria, Speakers Bureau; Gilead: Consultancy, Honoraria, Speakers Bureau; Servier: Consultancy, Honoraria, Speakers Bureau; Shire: Consultancy, Honoraria, Speakers Bureau; Eli Lilly: Consultancy, Honoraria, Speakers Bureau; Athenex: Consultancy, Honoraria, Speakers Bureau. Superti-Furga:Allcyte GmbH: Current equity holder in private company, Other: Founder. Snijder:Allcyte GmbH: Current equity holder in private company, Other: Founder. Staber:Roche: Consultancy, Honoraria, Research Funding; Astra Zeneca: Consultancy, Honoraria; Celgene/ BMS: Consultancy, Honoraria; msd: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Gilead: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood-2020-140831
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2020
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 3
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    Regimes, Social Risks and the Welfare Mix: Unpacking Attitudes to Pensions and Childcare in Germany and the UK Through Deliberative Forums
    Cambridge University Press (CUP) ; 2020
    In:  Journal of Social Policy Vol. 49, No. 1 ( 2020-01), p. 61-79
    Details
    In: Journal of Social Policy, Cambridge University Press (CUP), Vol. 49, No. 1 ( 2020-01), p. 61-79
    Abstract: Modern welfare regimes rest on a range of actors – state, market, family/households, employers and charities – but austerity programmes diminish the contribution of the state. While changes in this ‘welfare mix’ require support from the population, attitude studies have focused mainly on people’s views on state responsibilities, using welfare regime theory to explain differences. This paper contributes to our understanding of the welfare mix by including other providers such as the market, the family or employers, and also introduces social risk theories, contrasting new and old risks. Regime theory implies differences will persist over time, but risk theory suggests that growing similarities in certain risks may tend to promote international convergence. This article examines attitudes to the roles of state, market, family, charity/community and employer for pension and childcare in Germany and the UK. We collected data using deliberative forums, a new method in social policy research that allows citizens space to pursue extended lightly moderated discussion and permits researchers to analyse people’s justifications for their attitudes. Our research indicated patterns of convergence especially in preferences for childcare, but that regime predominates in people’s justifications for their attitudes: regime differences in attitudes are resilient.
    Type of Medium: Online Resource
    ISSN: 0047-2794 , 1469-7823
    URL: Article
    DOI: 10.1017/S004727941800079X
    Language: English
    Publisher: Cambridge University Press (CUP)
    Publication Date: 2020
    detail.hit.zdb_id: 1478899-8
    SSG: 3,4
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  • 4
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    Functional Precision Medicine Provides Clinical Benefit in Advanced Aggressive Hematologic Cancers and Identifies Exceptional Responders
    American Association for Cancer Research (AACR) ; 2022
    In:  Cancer Discovery Vol. 12, No. 2 ( 2022-02-01), p. 372-387
    Details
    In: Cancer Discovery, American Association for Cancer Research (AACR), Vol. 12, No. 2 ( 2022-02-01), p. 372-387
    Abstract: Personalized medicine aims to match the right drug with the right patient by using specific features of the individual patient's tumor. However, current strategies of personalized therapy matching provide treatment opportunities for less than 10% of patients with cancer. A promising method may be drug profiling of patient biopsy specimens with single-cell resolution to directly quantify drug effects. We prospectively tested an image-based single-cell functional precision medicine (scFPM) approach to guide treatments in 143 patients with advanced aggressive hematologic cancers. Fifty-six patients (39%) were treated according to scFPM results. At a median follow-up of 23.9 months, 30 patients (54%) demonstrated a clinical benefit of more than 1.3-fold enhanced progression-free survival compared with their previous therapy. Twelve patients (40% of responders) experienced exceptional responses lasting three times longer than expected for their respective disease. We conclude that therapy matching by scFPM is clinically feasible and effective in advanced aggressive hematologic cancers. Significance: This is the first precision medicine trial using a functional assay to instruct n-of-one therapies in oncology. It illustrates that for patients lacking standard therapies, high-content assay-based scFPM can have a significant value in clinical therapy guidance based on functional dependencies of each patient's cancer. See related commentary by Letai, p. 290. This article is highlighted in the In This Issue feature, p. 275
    Type of Medium: Online Resource
    ISSN: 2159-8274 , 2159-8290
    URL: Article
    DOI: 10.1158/2159-8290.CD-21-0538
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2022
    detail.hit.zdb_id: 2607892-2
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  • 5
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    Arzneimittelinteraktionen im Überblick : Fallvignette: Akute Blutung durch Arzneimittelinteraktion: Die CLL-Patientin und der Helicobacter pylori
    Springer Science and Business Media LLC ; 2018
    In:  Wiener klinische Wochenschrift Education Vol. 13, No. 1-4 ( 2018-12), p. 13-27
    Details
    In: Wiener klinische Wochenschrift Education, Springer Science and Business Media LLC, Vol. 13, No. 1-4 ( 2018-12), p. 13-27
    Type of Medium: Online Resource
    ISSN: 1863-3579 , 1863-3765
    URL: Article
    DOI: 10.1007/s11812-018-0091-2
    Language: German
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2018
    detail.hit.zdb_id: 2325844-5
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  • 6
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    Image-based ex-vivo drug screening for patients with aggressive haematological malignancies: interim results from a single-arm, open-label, pilot study
    Elsevier BV ; 2017
    In:  The Lancet Haematology Vol. 4, No. 12 ( 2017-12), p. e595-e606
    Details
    In: The Lancet Haematology, Elsevier BV, Vol. 4, No. 12 ( 2017-12), p. e595-e606
    Type of Medium: Online Resource
    ISSN: 2352-3026
    URL: Article
    DOI: 10.1016/S2352-3026(17)30208-9
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2017
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  • 7
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    Changing preferences towards redistribution: How deliberation shapes welfare attitudes
    Wiley ; 2018
    In:  Social Policy & Administration Vol. 52, No. 5 ( 2018-09), p. 969-982
    Details
    In: Social Policy & Administration, Wiley, Vol. 52, No. 5 ( 2018-09), p. 969-982
    Abstract: The article departs from the argument that research on welfare attitudes is, so far, dominated by large‐scale survey‐studies, which allow for generalizable insights into citizens' preferences and evaluations, but are necessarily limited in their ability to capture the dynamic and contextual aspects of attitude formation. In order to broaden the horizon of welfare attitudes' research, this article introduces a new qualitative method, namely deliberative forums. In these large group discussions—originally developed for participatory decision‐making—attitudes, opinions, and preferences are core aspects of the deliberation process, and the article argues that by observing deliberation, we can observe attitude construction “ in vivo ”. The evidence from a two‐day German deliberation event illustrates in an exploratory manner how information, reasoning, and group processes can influence people's evaluations and expressed policy preferences with regard to redistribution. By linking participants' answers from a survey before and after the event to their statements during the discussions, the article not only shows that the preferences for redistribution people expressed in the survey answers are often higher after the deliberative event, but also seeks to make sense of attitudinal dynamics on the basis of the qualitative material by pointing towards the role of information, reasoning, and group processes.
    Type of Medium: Online Resource
    ISSN: 0144-5596 , 1467-9515
    URL: Issue
    URL: Article
    DOI: 10.1111/spol.2018.52.issue-5
    DOI: 10.1111/spol.12398
    Language: English
    Publisher: Wiley
    Publication Date: 2018
    detail.hit.zdb_id: 2021111-9
    detail.hit.zdb_id: 2271794-8
    SSG: 2
    SSG: 3,4
    SSG: 3,6
    SSG: 3,7
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  • 8
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    Unravelling deservingness: Which criteria do people use to judge the relative deservingness of welfare target groups? A vignette-based focus group study
    SAGE Publications ; 2020
    In:  Journal of European Social Policy Vol. 30, No. 4 ( 2020-10), p. 389-403
    Details
    In: Journal of European Social Policy, SAGE Publications, Vol. 30, No. 4 ( 2020-10), p. 389-403
    Abstract: Previous research suggests that European citizens share consistent attitudes towards the relative deservingness of different target groups of social policy, such as perceiving elderly people as most deserving, unemployed people as less deserving and immigrants as least deserving. Yet, it is unclear which criteria people apply when making these judgements. In this article, we explore the reasoning behind deservingness judgements. We analyse how four focus groups – from the middle class, the working class, young people and elderly people – discuss and rank various vignettes representing welfare target groups. Our focus groups’ rankings mirror the well-established rank order of welfare target groups, and we also introduce further target groups: median-income families, low-income earners, and well-off earners. Our analyses of reasoning patterns show that depending on the target group specific combinations of deservingness criteria suggested in the literature (e.g. need, reciprocity, identity, control) are applied, and we suggest adding a further criterion emphasizing future returns on invested resources (‘social investment’). Furthermore, by comparing focus groups, we find that different groups back up similar rankings by differing criteria, suggesting that below the surface of a ‘common deservingness culture’ linger class and other differences in perceiving welfare deservingness.
    Type of Medium: Online Resource
    ISSN: 0958-9287 , 1461-7269
    URL: Article
    DOI: 10.1177/0958928720905285
    RVK:
    MN 1000
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2020
    detail.hit.zdb_id: 1082229-X
    detail.hit.zdb_id: 1482723-2
    SSG: 3,4
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  • 9
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    Legitimizing Inequality : The Moral Repertoires of Meritocracy in Four Countries
    Brill ; 2020
    In:  Comparative Sociology Vol. 19, No. 4-5 ( 2020-11-16), p. 542-584
    Details
    In: Comparative Sociology, Brill, Vol. 19, No. 4-5 ( 2020-11-16), p. 542-584
    Abstract: Do people in different countries understand and frame the principle of meritocracy differently? This question is the starting point for this cross-national analysis of the moral repertoires of meritocracy in four countries: Germany, Norway, Slovenia and the United Kingdom. The authors pursue a mixed methods approach, using data from the European Social Survey 2016 and qualitative data from group discussions. In these discussions, citizens openly talked about issues like inequality and social policy, which allows us to study their understandings and framings of meritocracy. The authors show that the issue of unequal rewards does not only find different levels of support, but also that people – corresponding to the context they live in – have different understandings of which merits should count. The authors identify a ‘market success meritocracy’ in the UK, a work-centred understanding in Germany, a ‘common good meritocracy’ in Norway, and non-salience of this issue in Slovenia.
    Type of Medium: Online Resource
    ISSN: 1569-1322 , 1569-1330
    URL: Article
    DOI: 10.1163/15691330-BJA10017
    Language: Unknown
    Publisher: Brill
    Publication Date: 2020
    detail.hit.zdb_id: 2080573-1
    SSG: 3,4
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