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  1. AU="Hollifield, Lucas"
  2. AU="de Bessa, Jose"
  3. AU="Rami S. Al-Fodeh"

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  1. Article ; Online: Case Series of Men with the Germline APC I1307K variant and Treatment-Emergent Neuroendocrine Prostate Cancer.

    Economides, Minas P / Nakazawa, Mari / Lee, Jonathan W / Li, Xiaochun / Hollifield, Lucas / Chambers, Rachelle / Sarfaty, Michal / Goldberg, Judith D / Antonarakis, Emmanuel S / Wise, David R

    Clinical genitourinary cancer

    2023  Volume 22, Issue 1, Page(s) e31–e37.e1

    Abstract: Introduction: Somatic mutations in the Wnt signaling gene Adenomatous Polyposis Coli (APC) promote metastatic prostate cancer (PCa) progression. Less is known regarding the impact of germline APC mutations on PCa outcomes. We sought to investigate the ... ...

    Abstract Introduction: Somatic mutations in the Wnt signaling gene Adenomatous Polyposis Coli (APC) promote metastatic prostate cancer (PCa) progression. Less is known regarding the impact of germline APC mutations on PCa outcomes. We sought to investigate the prevalence of aggressive variant PCa (AVPC) and treatment-emergent neuroendocrine PCa (t-NEPC) in patients with the germline APC I1307K variant, an alteration found in 7% of Ashkenazi Jewish men.
    Materials and methods: We report a retrospective cohort study comparing patients with PCa and either APC I1307K germline mutation, APC somatic mutations, or unselected patients. Proportions of patients with AVPC among all the cases were estimated along with 95% Clopper-Pearson exact confidence intervals (CI). Odds ratios with 95% CI were provided for the prevalence of t-NEPC and AVPC in patients with germline APC I1307K compared to patients with frameshift alterations in APC.
    Results: From 2016-2022, 18 patients with PCa at 3 institutions with the germline APC (I1307K) mutation were identified. Clinically-defined AVPC was found in 8 of the 15 cases with metastatic disease (53%; 95% CI: 26%-79%). Combined somatic alterations in two or more of RB1, TP53 or PTEN (molecularly-defined AVPC) were found in 5/18 cases (28%; 95% CI: 10%-54%). When compared to 20 patients with APC somatic frameshift mutations, patients with the germline APC I1307K variant had a significantly increased risk of AVPC (OR 7.2; 95% CI 1.27, 40.68).
    Conclusion: PCa that develops in the presence of the germline APC I1307K mutation appear to be enriched for clinically-defined and molecularly-defined AVPC and in particular, for t-NEPC.
    MeSH term(s) Male ; Humans ; Germ-Line Mutation ; Colorectal Neoplasms/epidemiology ; Colorectal Neoplasms/genetics ; Retrospective Studies ; Adenomatous Polyposis Coli/genetics ; Prostatic Neoplasms/drug therapy ; Prostatic Neoplasms/genetics ; Prostatic Neoplasms/pathology ; Germ Cells/pathology
    Language English
    Publishing date 2023-06-28
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ZDB-ID 2225121-2
    ISSN 1938-0682 ; 1558-7673
    ISSN (online) 1938-0682
    ISSN 1558-7673
    DOI 10.1016/j.clgc.2023.06.013
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: TARGET: A Randomized, Noninferiority Trial of a Pretest, Patient-Driven Genetic Education Webtool Versus Genetic Counseling for Prostate Cancer Germline Testing.

    Loeb, Stacy / Keith, Scott W / Cheng, Heather H / Leader, Amy E / Gross, Laura / Sanchez Nolasco, Tatiana / Byrne, Nataliya / Hartman, Rebecca / Brown, Lauren H / Pieczonka, Christopher Michael / Gomella, Leonard G / Kelly, William Kevin / Lallas, Costas D / Handley, Nathan / Mille, Patrick Johnston / Mark, James Ryan / Brown, Gordon Andrew / Chopra, Sameer / McClellan, Alexandra /
    Wise, David R / Hollifield, Lucas / Giri, Veda N

    JCO precision oncology

    2024  Volume 8, Page(s) e2300552

    Abstract: Purpose: Germline genetic testing (GT) is important for prostate cancer (PCA) management, clinical trial eligibility, and hereditary cancer risk. However, GT is underutilized and there is a shortage of genetic counselors. To address these gaps, a ... ...

    Abstract Purpose: Germline genetic testing (GT) is important for prostate cancer (PCA) management, clinical trial eligibility, and hereditary cancer risk. However, GT is underutilized and there is a shortage of genetic counselors. To address these gaps, a patient-driven, pretest genetic education webtool was designed and studied compared with traditional genetic counseling (GC) to inform strategies for expanding access to genetic services.
    Methods: Technology-enhanced acceleration of germline evaluation for therapy (TARGET) was a multicenter, noninferiority, randomized trial (ClinicalTrials.gov identifier: NCT04447703) comparing a nine-module patient-driven genetic education webtool versus pretest GC. Participants completed surveys measuring decisional conflict, satisfaction, and attitudes toward GT at baseline, after pretest education/counseling, and after GT result disclosure. The primary end point was noninferiority in reducing decisional conflict between webtool and GC using the validated Decisional Conflict Scale. Mixed-effects regression modeling was used to compare decisional conflict between groups. Participants opting for GT received a 51-gene panel, with results delivered to participants and their providers.
    Results: The analytic data set includes primary outcome data from 315 participants (GC [n = 162] and webtool [n = 153]). Mean difference in decisional conflict score changes between groups was -0.04 (one-sided 95% CI, -∞ to 2.54;
    Conclusion: The results of the TARGET study support the use of patient-driven digital webtools for expanding access to pretest genetic education for PCA GT. Further studies to optimize patient experience and evaluate them in diverse patient populations are warranted.
    MeSH term(s) Humans ; Male ; Genetic Counseling/methods ; Genetic Testing ; Germ Cells ; Health Knowledge, Attitudes, Practice ; Prostatic Neoplasms/diagnosis ; Prostatic Neoplasms/genetics ; Prostatic Neoplasms/therapy
    Language English
    Publishing date 2024-03-07
    Publishing country United States
    Document type Equivalence Trial ; Journal Article ; Multicenter Study ; Randomized Controlled Trial
    ISSN 2473-4284
    ISSN (online) 2473-4284
    DOI 10.1200/PO.23.00552
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Technology-enhanced AcceleRation of Germline Evaluation for Therapy (TARGET): A randomized controlled trial of a pretest patient-driven webtool vs. genetic counseling for prostate cancer germline testing.

    Loeb, Stacy / Cheng, Heather H / Leader, Amy / Gross, Laura / Nolasco, Tatiana Sanchez / Byrne, Nataliya / Wise, David R / Hollifield, Lucas / Brown, Lauren H / Slater, Elias / Pieczonka, Christopher / Gomella, Leonard G / Kelly, William K / Trabulsi, Edouard J / Handley, Nathan / Lallas, Costas D / Chandrasekar, Thenappan / Mille, Patrick / Mann, Mark /
    Mark, James Ryan / Brown, Gordon / Chopra, Sameer / Wasserman, Jenna / Phillips, Jade / Somers, Patrick / Giri, Veda N

    Contemporary clinical trials

    2022  Volume 119, Page(s) 106821

    Abstract: Background: Germline testing has an increasingly important role in prostate cancer care. However, a relative shortage of genetic counselors necessitates alternate strategies for delivery of pre-test education for germline testing. This study, funded by ... ...

    Abstract Background: Germline testing has an increasingly important role in prostate cancer care. However, a relative shortage of genetic counselors necessitates alternate strategies for delivery of pre-test education for germline testing. This study, funded by the Prostate Cancer Foundation, seeks to address the need for novel methods of delivery of pre-test germline education beyond traditional germline counseling to facilitate informed patient decision-making for germline testing.
    Methods: This is a two-armed randomized controlled trial (RCT) with a target enrollment of 173 participants with prostate cancer per study arm (total anticipated n = 346). Patients who meet criteria for germline testing based on tumor features, family history or Ashkenazi Jewish ancestry are being recruited from 5 US sites including academic, private practice and Veterans healthcare settings. Consenting participants are randomized to the interactive pretest webtool or germline counseling with assessment of key patient-reported outcomes involved in informed decision-making for germline testing.
    Results: Participants complete surveys at baseline, after pretest education/counseling, and following disclosure of germline results. The primary outcome of the study is decisional conflict for germline testing. Secondary outcomes include genetic knowledge, satisfaction, uptake of germline testing, and understanding of results.
    Conclusion: Our hypothesis is that the web-based genetic education tool is non-inferior to traditional genetic counseling regarding key patient-reported outcomes involved in informed decision-making for germline testing. If proven, the results would support deploying the webtool across various practice settings to facilitate pre-test genetic education for individuals with prostate cancer and developing collaborative care strategies with genetic counseling.
    Clinicaltrials: gov Identifier: NCT04447703.
    MeSH term(s) Acceleration ; Genetic Counseling ; Genetic Testing ; Germ Cells ; Humans ; Male ; Prostatic Neoplasms ; Technology
    Language English
    Publishing date 2022-06-14
    Publishing country United States
    Document type Journal Article ; Randomized Controlled Trial ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 2182176-8
    ISSN 1559-2030 ; 1551-7144
    ISSN (online) 1559-2030
    ISSN 1551-7144
    DOI 10.1016/j.cct.2022.106821
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 1581: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)

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