Evaluating cancer genetic services in a safety net system: overcoming barriers for a lasting impact beyond the CHARM research project.

Underserved patients face substantial barriers to receiving cancer genetic services. The Cancer Health Assessments Reaching Many (CHARM) study evaluated ways to increase access to genetic testing for individuals in underserved populations at risk for hereditary cancer syndromes (HCS). Here, we report the successful implementation of CHARM in a low-resource environment and the development of sustainable processes to continue genetic risk assessment in this setting.

Engaging Patient Advisory Committees to Inform a Genomic Cancer Risk Study: Lessons for Future Efforts.

Introduction The Cancer Health Assessments Reaching Many study seeks to reduce disparities in genomic care. Two patient advisory committees (PACs) were formed, 1 of English speakers and 1 of Spanish speakers, to vet study processes and materials. Stakeholder engagement in research is relatively new, and we know little about how stakeholders view their engagement.

Discordant Patient and Clinician Perspectives on the Potential Value of Genetic Services in Safety-Net Clinics.

Purpose: As new genetic services become available, their implementation in safety-net settings must be studied.

Methods: We interviewed stakeholders (patients and primary care clinicians) from federally qualified health centers to discuss the utility, acceptability, and priority of new genetic services. We presented scenarios tailored for each audience describing carrier testing, diagnostic testing for a developmental delay, and hereditary cancer syndrome testing.

Assessing the implications of positive genomic screening results.

Before population screening of 'healthy' individuals is widely adopted, it is important to consider the harms and benefits of receiving positive results and how harms and benefits may differ by age. Participants in a preventive genomic screening study were screened for 17 genes associated with 11 conditions. We interviewed 11 participants who received positive results.

Design of a randomized controlled trial for genomic carrier screening in healthy patients seeking preconception genetic testing.

Population-based carrier screening is limited to well-studied or high-impact genetic conditions for which the benefits may outweigh the associated harms and costs. As the cost of genome sequencing declines and availability increases, the balance of risks and benefits may change for a much larger number of genetic conditions, including medically actionable additional findings. We designed an RCT to evaluate genomic clinical sequencing for women and partners considering a pregnancy.

A survey of current practices for genomic sequencing test interpretation and reporting processes in US laboratories.

Purpose: While the diagnostic success of genomic sequencing expands, the complexity of this testing should not be overlooked. Numerous laboratory processes are required to support the identification, interpretation, and reporting of clinically significant variants. This study aimed to examine the workflow and reporting procedures among US laboratories to highlight shared practices and identify areas in need of standardization.

A standardized, evidence-based protocol to assess clinical actionability of genetic disorders associated with genomic variation.

Purpose: Genome and exome sequencing can identify variants unrelated to the primary goal of sequencing. Detecting pathogenic variants associated with an increased risk of a medical disorder enables clinical interventions to improve future health outcomes in patients and their at-risk relatives. The Clinical Genome Resource, or ClinGen, aims to assess clinical actionability of genes and associated disorders as part of a larger effort to build a central resource of information regarding the clinical relevance of genomic variation for use in precision medicine and research.

Generating a taxonomy for genetic conditions relevant to reproductive planning.

As genome or exome sequencing (hereafter genome-scale sequencing) becomes more integrated into standard care, carrier testing is an important possible application. Carrier testing using genome-scale sequencing can identify a large number of conditions, but choosing which conditions/genes to evaluate as well as which results to disclose can be complicated. Carrier testing generally occurs in the context of reproductive decision-making and involves patient values in a way that other types of genetic testing may not.

Patients' ratings of genetic conditions validate a taxonomy to simplify decisions about preconception carrier screening via genome sequencing.

Advances in genome sequencing and gene discovery have created opportunities to efficiently assess more genetic conditions than ever before. Given the large number of conditions that can be screened, the implementation of expanded carrier screening using genome sequencing will require practical methods of simplifying decisions about the conditions for which patients want to be screened. One method to simplify decision making is to generate a taxonomy based on expert judgment.

"Is It Worth Knowing?" Focus Group Participants' Perceived Utility of Genomic Preconception Carrier Screening.

As genome sequencing technology advances, research is needed to guide decision-making about what results can or should be offered to patients in different clinical settings. We conducted three focus groups with individuals who had prior preconception genetic testing experience to explore perceived advantages and disadvantages of genome sequencing for preconception carrier screening, compared to usual care. Using a discussion guide, a trained qualitative moderator facilitated the audio-recorded focus groups.

Universal tumor screening for Lynch syndrome: Assessment of the perspectives of patients with colorectal cancer regarding benefits and barriers.

Background: Universal tumor screening for Lynch syndrome, the most common form of hereditary colorectal cancer (CRC), has been recommended among all patients newly diagnosed with CRC. However, there is limited literature regarding patient perspectives of tumor screening for Lynch syndrome among patients with CRC who are not selected for screening based on family history criteria.

Methods: A total of 145 patients aged 39 to 87 years were administered surveys assessing perceived risk, patient perspectives, and potential benefits of and barriers to tumor screening for Lynch syndrome.

Systematic review of the predictive effect of MSI status in colorectal cancer patients undergoing 5FU-based chemotherapy.

Background: We systematically reviewed the evidence for the interaction of microsatellite instability status (MSI) and treatment with 5FU in colorectal cancer to determine how well MSI status predicts health outcomes in patients undergoing 5FU-based chemotherapy.

Methods: We conducted a search of four electronic databases through June 2013. We considered studies that included both colorectal cancer patients treated with 5FU-based chemotherapy and untreated patients with survival outcomes presented by MSI status.

Stakeholder perspectives on implementing a universal Lynch syndrome screening program: a qualitative study of early barriers and facilitators.

Purpose: Evidence-based guidelines recommend that all newly diagnosed colon cancer be screened for Lynch syndrome (LS), but best practices for implementing universal tumor screening have not been extensively studied. We interviewed a range of stakeholders in an integrated health-care system to identify initial factors that might promote or hinder the successful implementation of a universal LS screening program.

Methods: We conducted interviews with health-plan leaders, managers, and staff.

Leveraging biospecimen resources for discovery or validation of markers for early cancer detection.

Validation of early detection cancer biomarkers has proven to be disappointing when initial promising claims have often not been reproducible in diagnostic samples or did not extend to prediagnostic samples. The previously reported lack of rigorous internal validity (systematic differences between compared groups) and external validity (lack of generalizability beyond compared groups) may be effectively addressed by utilizing blood specimens and data collected within well-conducted cohort studies. Cohort studies with prediagnostic specimens (eg, blood specimens collected prior to development of clinical symptoms) and clinical data have recently been used to assess the validity of some early detection biomarkers.

Family history and the natural history of colorectal cancer: systematic review.

Purpose: Family history of colorectal cancer (CRC) is a known risk factor for CRC and encompasses both genetic and shared environmental risks.

Methods: We conducted a systematic review to estimate the impact of family history on the natural history of CRC and adherence to screening.

Results: We found high heterogeneity in family-history definitions, the most common definition being one or more first-degree relatives.

Practical barriers and ethical challenges in genetic data sharing.

The underlying ethos of dbGaP is that access to these data by secondary data analysts facilitates advancement of science. NIH has required that genome-wide association study data be deposited in the Database of Genotypes and Phenotypes (dbGaP) since 2003. In 2013, a proposed updated policy extended this requirement to next-generation sequencing data.

Approaches to integrating germline and tumor genomic data in cancer research.

Cancer is characterized by a diversity of genetic and epigenetic alterations occurring in both the germline and somatic (tumor) genomes. Hundreds of germline variants associated with cancer risk have been identified, and large amounts of data identifying mutations in the tumor genome that participate in tumorigenesis have been generated. Increasingly, these two genomes are being explored jointly to better understand how cancer risk alleles contribute to carcinogenesis and whether they influence development of specific tumor types or mutation profiles.

Evidence synthesis and guideline development in genomic medicine: current status and future prospects.

Purpose: With the accelerated implementation of genomic medicine, health-care providers will depend heavily on professional guidelines and recommendations. Because genomics affects many diseases across the life span, no single professional group covers the entirety of this rapidly developing field.

Methods: To pursue a discussion of the minimal elements needed to develop evidence-based guidelines in genomics, the Centers for Disease Control and Prevention and the National Cancer Institute jointly held a workshop to engage representatives from 35 organizations with interest in genomics (13 of which make recommendations).

Does KRAS testing in metastatic colorectal cancer impact overall survival? A comparative effectiveness study in a population-based sample.

Purpose: Epidermal growth factor receptor (EGFR) inhibitors are approved for treating metastatic colorectal cancer (CRC); KRAS mutation testing is recommended prior to treatment. We conducted a non-inferiority analysis to examine whether KRAS testing has impacted survival in CRC patients.

Patients And Methods: We included 1186 metastatic CRC cases from seven health plans.

Oncologists' attitudes toward KRAS testing: a multisite study.

Recent discoveries promise increasingly to help oncologists individually tailor anticancer therapy to their patients' molecular tumor characteristics. One such promising molecular diagnostic is Kirsten ras (KRAS) tumor mutation testing for metastatic colorectal cancer (mCRC) patients. In the current study, we examined how and why physicians adopt KRAS testing and how they subsequently utilize the information when discussing treatment strategies with patients.

A genome-wide search for linkage of estimated glomerular filtration rate (eGFR) in the Family Investigation of Nephropathy and Diabetes (FIND).

Objective: Estimated glomerular filtration rate (eGFR), a measure of kidney function, is heritable, suggesting that genes influence renal function. Genes that influence eGFR have been identified through genome-wide association studies. However, family-based linkage approaches may identify loci that explain a larger proportion of the heritability.

Comparative effectiveness research in cancer genomics and precision medicine: current landscape and future prospects.

A major promise of genomic research is information that can transform health care and public health through earlier diagnosis, more effective prevention and treatment of disease, and avoidance of drug side effects. Although there is interest in the early adoption of emerging genomic applications in cancer prevention and treatment, there are substantial evidence gaps that are further compounded by the difficulties of designing adequately powered studies to generate this evidence, thus limiting the uptake of these tools into clinical practice. Comparative effectiveness research (CER) is intended to generate evidence on the "real-world" effectiveness compared with existing standards of care so informed decisions can be made to improve health care.

Underutilization of Lynch syndrome screening in a multisite study of patients with colorectal cancer.

Purpose: The aim of this study was to examine Lynch syndrome screening of patients with metastatic colorectal cancer in integrated health-care-delivery organizations.

Methods: We determined the availability of Lynch syndrome screening criteria and actual Lynch syndrome screening in the medical records of 1,188 patients diagnosed with metastatic colorectal cancer between 2004 and 2009 at seven institutions in the Cancer Research Network.

Results: We found infrequent use of Lynch syndrome screening (41/1,188).