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      Oncologists' and Cancer Patients' Views on Whole-Exome Sequencing and Incidental Findings: Results from The CanSeq Study

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          Abstract

          Purpose

          While targeted sequencing improves outcomes for many cancer patients, how somatic and germline whole-exome sequencing (WES) will integrate into care remains uncertain.

          Methods

          We conducted surveys and interviews, within a study of WES integration at an academic center, to determine oncologists' attitudes about WES and to identify lung and colorectal cancer patients' preferences for learning WES findings.

          Results

          167 patients (85% white, 58% female, mean age 60) and 27 oncologists (22% female) participated. Although oncologists had extensive experience ordering somatic tests (median 100/year), they had little experience ordering germline tests. Oncologists intended to disclose most WES results to patients but anticipated numerous challenges in using WES. Patients had moderately low levels of genetic knowledge (mean 4 correct of 7). Most patients chose to learn results that could help select a clinical trial, pharmacogenetic and positive prognostic results, and results suggesting inherited predisposition to cancer and treatable non-cancer conditions (all ≥95%). Fewer chose to receive negative prognostic results (84%) and results suggesting predisposition to untreatable non-cancer conditions (85%).

          Conclusion

          The majority of patients want most cancer-related and incidental WES results. Patients' low levels of genetic knowledge and oncologists' inexperience with large-scale sequencing presage challenges to implementing paired WES in practice.

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          Most cited references24

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          • Article: not found

          Measuring numeracy without a math test: development of the Subjective Numeracy Scale.

          Basic numeracy skills are necessary before patients can understand the risks of medical treatments. Previous research has used objective measures, similar to mathematics tests, to evaluate numeracy. To design a subjective measure (i.e., self-assessment) of quantitative ability that distinguishes low- and high-numerate individuals yet is less aversive, quicker to administer, and more usable for telephone and Internet surveys than existing numeracy measures. Paper-and-pencil questionnaires. The general public (N = 703) surveyed at 2 hospitals. Forty-nine subjective numeracy questions were compared to measures of objective numeracy. An 8-item measure, the Subjective Numeracy Scale (SNS), was developed through several rounds of testing. Four items measure people's beliefs about their skill in performing various mathematical operations, and 4 measure people's preferences regarding the presentation of numerical information. The SNS was significantly correlated with Lipkus and others' objective numeracy scale (correlations: 0.63-0.68) yet was completed in less time (24 s/item v. 31 s/item, P < 0.05) and was perceived as less stressful (1.62 v. 2.69, P < 0.01) and less frustrating (1.92 v. 2.88, P < 0.01). Fifty percent of participants who completed the SNS volunteered to participate in another study, whereas only 8% of those who completed the Lipkus and others scale similarly volunteered (odds ratio = 11.00, 95% confidence interval = 2.14-56.65). The SNS correlates well with mathematical test measures of objective numeracy but can be administered in less time and with less burden. In addition, it is much more likely to leave participants willing to participate in additional research and shows much lower rates of missing or incomplete data.
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            Whole-exome sequencing and clinical interpretation of FFPE tumor samples to guide precision cancer medicine

            Translating whole exome sequencing (WES) for prospective clinical use may impact the care of cancer patients; however, multiple innovations are necessary for clinical implementation. These include: (1) rapid and robust WES from formalin-fixed paraffin embedded (FFPE) tumor tissue, (2) analytical output similar to data from frozen samples, and (3) clinical interpretation of WES data for prospective use. Here, we describe a prospective clinical WES platform for archival FFPE tumor samples. The platform employs computational methods for effective clinical analysis and interpretation of WES data. When applied retrospectively to 511 exomes, the interpretative framework revealed a “long tail” of somatic alterations in clinically important genes. Prospective application of this approach identified clinically relevant alterations in 15/16 patients. In one patient, previously undetected findings guided clinical trial enrollment leading to an objective clinical response. Overall, this methodology may inform the widespread implementation of precision cancer medicine.
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              Controlled 15-year trial on screening for colorectal cancer in families with hereditary nonpolyposis colorectal cancer.

              Identification of the hereditary nonpolyposis colorectal cancer (HNPCC) syndrome enables prevention of colorectal cancer (CRC) by means of colonoscopy and polypectomies. We evaluated the efficacy of screening in a controlled trial over 15 years. Incidence of CRC and survival were compared in 2 cohorts of at-risk members of 22 families with HNPCC. Colonic screening at 3-year intervals was arranged for 133 subjects; 119 control subjects had no screening. Genetic testing was offered to subjects in whose families the causative mutation was known. CRC developed in 8 screened subjects (6%) compared with 19 control subjects (16 %; P = 0.014). The CRC rate was reduced by 62%. In mutation-positive subjects alone, the CRC rates were 18% in screened subjects and 41% in controls (P = 0.02). The decrease resulted from the removal of adenomas in 13 mutation-positive individuals (30%) and in 6 subjects with unknown mutation status (40%). All CRCs in the study group were local, causing no deaths, compared with 9 deaths caused by CRC in the controls. The overall death rates were 10 vs. 26 subjects in the study and control groups (P = 0.003), 4 vs. 12 in mutation-positive subjects (P = 0.05). Colonoscopic screening at 3-year intervals more than halves the risk of CRC, prevents CRC deaths, and decreases overall mortality by about 65% in HNPCC families.
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                Author and article information

                Journal
                9815831
                22061
                Genet Med
                Genet. Med.
                Genetics in medicine : official journal of the American College of Medical Genetics
                1098-3600
                1530-0366
                17 January 2016
                11 February 2016
                15 August 2016
                : 10.1038/gim.2015.207
                Affiliations
                [1 ]Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA
                [2 ]Harvard Medical School, Boston, MA
                [3 ]Department of Medicine, Brigham & Women's Hospital, Boston, MA
                [4 ]Massachusetts General Hospital, Boston, MA
                [5 ]Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA
                [6 ]Department of Pathology, Brigham & Woman's Hospital, Boston, MA
                [7 ]Broad Institute, Cambridge, MA
                [8 ]Department of Medical Ethics and Health Policy, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA
                Author notes
                Corresponding Author: Stacy W. Gray, Center for Population Sciences, Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Ave, Dana 1123-a, Boston, MA 02215, stacyw_gray@ 123456dfci.harvard.edu (to be published with article), phone: 617-582-9651, fax: 617-394-2870
                Article
                NIHMS744791
                10.1038/gim.2015.207
                4981555
                26866579
                6156bd85-63e9-4f7f-aa27-181e0b4410c6

                Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms

                History
                Categories
                Article

                Genetics
                sequencing,cancer,incidental findings,return of results
                Genetics
                sequencing, cancer, incidental findings, return of results

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