A Mixed-Methods Approach to Assessing Barriers and Facilitators to Cancer Genetics Care in Black and Latino/a Individuals Impacted by Pancreatic Cancer: The Racial/ethnic Equity in GENetic Education, Risk Assessment, and TEsting (REGENERATE) Study.

Purpose: Pancreatic ductal adenocarcinoma (PDAC) disproportionately impacts Black and Latino/a communities, who are less likely to receive genetic counseling/testing referrals, hindering early cancer detection/prevention access. This study aims to determine the barriers/facilitators to PDAC genetics care/surveillance among Black and Latino/a populations.

Methods: This is a concurrent mixed-methods study that utilized electronic surveys and semi-structured focus groups/in-depth interviews (02/14/2022-12/21/2022).

Neoplasia Detection Through Colonic Surveillance Among Young Individuals With MSH6 / PMS2 -Associated Lynch Syndrome.

Introduction: The age to initiate colonoscopy in MSH6 / PMS2 -associated Lynch syndrome (LS) remains uncertain. In this study, we characterize colonoscopy findings among young individuals with MSH6 / PMS2 -associated LS.

Methods: Retrospective review of a multi-institutional cohort of individuals with MSH6/PMS2 -associated LS undergoing colonoscopy before the age of 50 years was performed.

Cancer Incidence and Mortality in Familial Adenomatous Polyposis Syndrome.

Background: Risk-reducing colectomy in familial adenomatous polyposis syndrome is the standard of care. This has increased the importance of surveillance for extracolonic malignancies in postcolectomy individuals.

Objective: We sought to define the present-day incidence of all cancers and mortality in familial adenomatous polyposis.

Comparison of PREMM5 and PREMMplus Risk Assessment Models to Identify Lynch Syndrome.

Purpose: Clinical risk assessment models can identify patients with hereditary cancer susceptibility, but it is unknown how multigene cancer syndrome prediction models compare with syndrome-specific models in assessing risk for individual syndromes such as Lynch syndrome (LS). Our aim was to compare PREMMplus (a 19-gene cancer risk prediction model) with PREMM5 (a LS gene-specific model) for LS identification.

Methods: We analyzed data from two cohorts of patients undergoing germline testing from a commercial laboratory (n = 12,020) and genetics clinic (n = 6,232) with personal and/or family histories of LS-associated cancer.

Feasibility of an electronic patient-facing cancer family history tool in medically underserved populations.

Purpose: We developed an electronic patient-facing family history collection tool including B-RST 3.0, PREMM risk assessments and "limited family knowledge/structure" information designed for primary care settings. We evaluated the tool's performance compared with genetic-counselor-collected information for clinical risk stratification in a population with barriers to access.

Prevalence and Distribution of Unexpected Actionable Germline Pathogenic Variants Identified on Broad-Based Multigene Panel Testing Among Patients With Cancer.

Purpose: In patients with a variety of malignancies undergoing multigene panel testing (MGPT), we examined the frequency of a pathogenic/likely pathogenic variant (PV) that would not have been predicted on the basis of the patient's personal and family history of cancer.

Methods: This is a retrospective review of patients with cancer ascertained from a single academic cancer center who underwent broad-based MGPT of ≥20 cancer predisposition genes not selected on the basis of personal or family cancer history from 2015 to 2021. Low-penetrance variants and recessive inheritance genes were excluded.

Risk Factors for Serrated Polyps: Results From a Large, Multicenter Colonoscopy-Based Study.

Introduction: Risk factors for serrated polyps (SPs) are not well understood.

Methods: Multivariable analyses of data from a multicenter colonoscopy-based study estimated odds ratios for having either a sessile serrated lesion or traditional serrated adenoma according to participant characteristics.

Results: Six thousand seventy-eighty participants were included in the analyses (565 with either a sessile serrated lesion or traditional serrated adenoma).

Community Collaboration to Advance Racial/Ethnic Equity in Colorectal Cancer Screening: Protocol for a Multilevel Intervention to Improve Screening and Follow-up in Community Health Centers.

Introduction: Colorectal cancer (CRC) screening utilization is low among low-income, uninsured, and minority populations that receive care in community health centers (CHCs). There is a need for evidence-based interventions to increase screening and follow-up care in these settings.

Methods: A multilevel, multi-component pragmatic cluster randomized controlled trial is being conducted at 8 CHCs in two metropolitan areas (Boston and Los Angeles), with two arms: (1) Mailed FIT outreach with text reminders, and (2) Mailed FIT-DNA with patient support.

Gastrointestinal Cancer Precursor Conditions and Their Detection.

Gastrointestinal cancers are a leading cause of cancer morbidity and mortality. Many gastrointestinal cancers develop from cancer precursor lesions, which are commonly found in individuals with hereditary cancer syndromes. Hereditary cancer syndromes have advanced our understanding of cancer development and progression and have facilitated the evaluation of cancer prevention and interception efforts.

Expanding access to genetic testing for pancreatic cancer.

Among individuals with pancreatic ductal adenocarcinoma (PDAC) 5-10% have a pathogenic germline variant (PGV) in a PDAC susceptibility gene. Guidelines recommend genetic testing among all individuals with PDAC. Additionally, at-risk relatives of PDAC patients benefit from their own genetic education, risk assessment, and testing.

A Randomized Trial of Two Remote Health Care Delivery Models on the Uptake of Genetic Testing and Impact on Patient-Reported Psychological Outcomes in Families With Pancreatic Cancer: The Genetic Education, Risk Assessment, and Testing (GENERATE) Study.

Background & Aims: Genetic testing uptake for cancer susceptibility in family members of patients with cancer is suboptimal. Among relatives of patients with pancreatic ductal adenocarcinoma (PDAC), The GENetic Education, Risk Assessment, and TEsting (GENERATE) study evaluated 2 online genetic education/testing delivery models and their impact on patient-reported psychological outcomes.

Methods: Eligible participants had ≥1 first-degree relative with PDAC, or ≥1 first-/second-degree relative with PDAC with a known pathogenic germline variant in 1 of 13 PDAC predisposition genes.

PREMM5 distinguishes sporadic from Lynch syndrome-associated MMR-deficient/MSI-high colorectal cancer.

Current algorithms for diagnosing Lynch syndrome (LS) include multistep molecular tumor tests to distinguish LS-associated from sporadic colorectal cancer (CRC), which add cost and complexity to the evaluation. We hypothesized that PREMM5, a clinical LS prediction tool, could be an alternative approach to screen for LS, thereby lessening the need for specialized molecular diagnostics. We reviewed a consecutively ascertained institutional cohort of 1058 CRC patients on whom pathologic and clinical data were available, including prior LS germline testing.

Young-onset colorectal cancer.

In the past decades the incidence of colorectal cancer (CRC) in people under the age of 50 years has increased, which is referred to as early-onset CRC or young-onset CRC (YO-CRC). YO-CRC is expected to account for 11% of colon cancers and 23% of rectal cancers by 2030. This trend is observed in different parts of the world and in both men and women.

Clinical factors associated with skin neoplasms in individuals with Lynch syndrome in a longitudinal observational cohort.

Background: Little is known about patient-specific risk factors for skin neoplasia in individuals with Lynch syndrome (LS).

Objective: Identify clinical factors associated with development of skin neoplasms in LS.

Methods: Clinical data were systematically collected on a cohort of LS carriers (confirmed pathogenic germline variants in MLH1, MSH2, MSH6, PMS2, or EPCAM) age ≥18 undergoing clinical genetics care at Dana-Farber Cancer Institute from January 2000 to March 2020.

MyLynch: A Patient-Facing Clinical Decision Support Tool for Genetically-Guided Personalized Medicine in Lynch Syndrome.

Lynch syndrome (LS) is a hereditary cancer susceptibility condition associated with varying cancer risks depending on which of the five causative genes harbors a pathogenic variant; however, lifestyle and medical interventions provide options to lower those risks. We developed MyLynch, a patient-facing clinical decision support (CDS) web application that applies genetically-guided personalized medicine (GPM) for individuals with LS. The tool was developed in R Shiny through a patient-focused iterative design process.

A validation of models for prediction of pathogenic variants in mismatch repair genes.

Purpose: Models used to predict the probability of an individual having a pathogenic homozygous or heterozygous variant in a mismatch repair gene, such as MMRpro, are widely used. Recently, MMRpro was updated with new colorectal cancer penetrance estimates. The purpose of this study was to evaluate the predictive performance of MMRpro and other models for individuals with a family history of colorectal cancer.

Development and Validation of the PREMMplus Model for Multigene Hereditary Cancer Risk Assessment.

Purpose: With the availability of multigene panel testing (MGPT) for hereditary cancer risk assessment, clinicians need to assess the likelihood of pathogenic germline variants (PGVs) across numerous genes in parallel. This study's aim was to develop and validate a clinical prediction model (PREMMplus) for MGPT risk assessment.

Materials And Methods: PREMMplus was developed in a single-institution cohort of 7,280 individuals who had undergone MGPT.

The Multicenter Cancer of Pancreas Screening Study: Impact on Stage and Survival.

Purpose: To report pancreas surveillance outcomes of high-risk individuals within the multicenter Cancer of Pancreas Screening-5 (CAPS5) study and to update outcomes of patients enrolled in prior CAPS studies.

Methods: Individuals recommended for pancreas surveillance were prospectively enrolled into one of eight CAPS5 study centers between 2014 and 2021. The primary end point was the stage distribution of pancreatic ductal adenocarcinoma (PDAC) detected (stage I higher-stage).

Literacy-adapted, electronic family history assessment for genetics referral in primary care: patient user insights from qualitative interviews.

Background: Risk assessment for hereditary cancer syndromes is recommended in primary care, but family history is rarely collected in enough detail to facilitate risk assessment and referral - a roadblock that disproportionately impacts individuals with healthcare access barriers. We sought to qualitatively assess a literacy-adapted, electronic patient-facing family history tool developed for use in diverse, underserved patient populations recruited in the Cancer Health Assessments Reaching Many (CHARM) Study.

Methods: Interview participants were recruited from a subpopulation of CHARM participants who experienced barriers to tool use in terms of spending a longer time to complete the tool, having incomplete attempts, and/or providing inaccurate family history in comparison to a genetic counselor-collected standard.