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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. We also include an additional CHC in Rapid City (South Dakota) that follows a parallel protocol for FIT-DNA but is not randomized due to lack of a comparison group. Eligible individuals in participating clinics are primary care patients ages 45-75, at average-risk for CRC, and overdue for CRC screening. Participants with abnormal screening results are offered navigation for follow-up colonoscopy and CRC risk assessment. RESULTS: The primary outcome is the completion rate of CRC screening at 90 days. Secondary outcomes include the screening completion rate at 180 days and the rate of colonoscopy completion within 6 months among participants with an abnormal result. Additional goals are to enhance our understanding of facilitators and barriers to CRC risk assessment in CHC settings. CONCLUSIONS: This study assesses the effectiveness of two multilevel interventions to increase screening participation and follow-up after abnormal screening in under-resourced clinical settings, informing future efforts to address CRC disparities. TRIAL REGISTRATION: NCT05714644.
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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. Common gastrointestinal hereditary cancer syndromes, including their organ-specific cancer risk and surveillance recommendations, are reviewed in this article. The management of common gastroesophageal, pancreatic, and colonic precursor lesions is also discussed, regardless of their genetic background. Further research is needed to advance chemoprevention and immunoprevention strategies.
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Neoplasias Gastrointestinales , Humanos , Neoplasias Gastrointestinales/terapia , Neoplasias Gastrointestinales/diagnóstico , Neoplasias Gastrointestinales/genética , Neoplasias Gastrointestinales/etiología , Lesiones Precancerosas/diagnóstico , Lesiones Precancerosas/genética , Lesiones Precancerosas/patología , Lesiones Precancerosas/terapia , Predisposición Genética a la Enfermedad , Detección Precoz del Cáncer , Síndromes Neoplásicos Hereditarios/diagnóstico , Síndromes Neoplásicos Hereditarios/genética , Síndromes Neoplásicos Hereditarios/terapiaRESUMEN
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. Participants were randomized by family, between May 8, 2019, and June 1, 2021. Arm 1 participants underwent a remote interactive telemedicine session and online genetic education. Arm 2 participants were offered online genetic education only. All participants were offered germline testing. The primary outcome was genetic testing uptake, compared by permutation tests and mixed-effects logistic regression models. We hypothesized that Arm 1 participants would have a higher genetic testing uptake than Arm 2. Validated surveys were administered to assess patient-reported anxiety, depression, and cancer worry at baseline and 3 months postintervention. RESULTS: A total of 424 families were randomized, including 601 participants (n = 296 Arm 1; n = 305 Arm 2), 90% of whom completed genetic testing (Arm 1 [87%]; Arm 2 [93%], P = .014). Arm 1 participants were significantly less likely to complete genetic testing compared with Arm 2 participants (adjusted ratio [Arm1/Arm2] 0.90, 95% confidence interval 0.78-0.98). Among participants who completed patient-reported psychological outcomes questionnaires (Arm 1 [n = 194]; Arm 2 [n = 206]), the intervention did not affect mean anxiety, depression, or cancer worry scores. CONCLUSIONS: Remote genetic education and testing can be a successful and complementary option for delivering genetics care. (Clinicaltrials.gov, number NCT03762590).
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Carcinoma Ductal Pancreático , Predisposición Genética a la Enfermedad , Pruebas Genéticas , Neoplasias Pancreáticas , Medición de Resultados Informados por el Paciente , Telemedicina , Humanos , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/psicología , Neoplasias Pancreáticas/diagnóstico , Masculino , Femenino , Persona de Mediana Edad , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/psicología , Carcinoma Ductal Pancreático/diagnóstico , Carcinoma Ductal Pancreático/terapia , Predisposición Genética a la Enfermedad/psicología , Medición de Riesgo , Anciano , Ansiedad/psicología , Ansiedad/diagnóstico , Ansiedad/etiología , Adulto , Depresión/diagnóstico , Depresión/genética , Depresión/psicología , Asesoramiento Genético/psicología , Mutación de Línea Germinal , Familia/psicologíaRESUMEN
BACKGROUND: Hereditary diffuse gastric cancer (HDGC) is an autosomal-dominant syndrome most often caused by pathogenic variants in CDH1. The International Gastric Cancer Linkage Consortium (IGCLC) recently updated its criteria for genetic testing. The purpose of this study was to estimate the sensitivity of IGCLC's 2020 criteria for identifying carriers of CDH1 pathogenic variants and to formulate a new set of criteria that is simpler and more sensitive. METHODS: Medical histories of 112 CDH1 mutation carriers, identified predominantly by multigene panel testing, and their 649 family members were reviewed. The percentage of subjects fulfilling the IGCLC 2015 and 2020 criteria was calculated, once without making any assumptions about unavailable pathology, and once assuming gastric cancer to be diffuse when pathology was unavailable. For comparison, we calculated the percentage of subjects who fulfilled our proposed criteria. RESULTS: When making no assumptions about missing pathology, a small (19%) and equal percentage of CDH1 mutation carriers fulfilled the IGCLC 2015 and 2020 criteria. When assuming unspecified gastric cancer to be diffuse, 45 out of 112 (40%) subjects met the 2015 criteria and 53 out of 112 (47%) met the 2020 criteria. Eighty-seven per cent (97/112) fulfilled our proposed criteria. CONCLUSION: In consecutive cases, mostly unselected for clinical criteria of HDGC, the IGCLC 2020 criteria are, at best, marginally more sensitive than previous iterations, but they are also more cumbersome. Unavailable cancer pathology reports are a real-world obstacle to their proper application. Our proposed Yale criteria both address this issue and offer significantly greater sensitivity than the IGCLC 2020 criteria.
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Adenocarcinoma , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/genética , Neoplasias Gástricas/patología , Linaje , Pruebas Genéticas , Cadherinas/genética , Adenocarcinoma/genética , Mutación de Línea Germinal , Predisposición Genética a la Enfermedad , Antígenos CD/genéticaRESUMEN
Up to 10% of patients with pancreatic ductal adenocarcinoma (PDAC) carry underlying germline pathogenic variants in cancer susceptibility genes. The GENetic Education Risk Assessment and TEsting (GENERATE) study aimed to evaluate novel methods of genetic education and testing in relatives of patients with PDAC. Eligible individuals had a family history of PDAC and a relative with a germline pathogenic variant in APC, ATM, BRCA1, BRCA2, CDKN2A, EPCAM, MLH1, MSH2, MSH6, PALB2, PMS2, STK11, or TP53 genes. Participants were recruited at six academic cancer centers and through social media campaigns and patient advocacy efforts. Enrollment occurred via the study website (https://GENERATEstudy.org) and all participation, including collecting a saliva sample for genetic testing, could be done from home. Participants were randomized to one of two remote methods that delivered genetic education about the risks of inherited PDAC and strategies for surveillance. The primary outcome of the study was uptake of genetic testing. From 5/8/2019 to 5/6/2020, 49 participants were randomized to each of the intervention arms. Overall, 90 of 98 (92%) of randomized participants completed genetic testing. The most frequently detected pathogenic variants included those in BRCA2 (N = 15, 17%), ATM (N = 11, 12%), and CDKN2A (N = 4, 4%). Participation in the study remained steady throughout the onset of the Coronavirus disease (COVID-19) pandemic. Preliminary data from the GENERATE study indicate success of remote alternatives to traditional cascade testing, with genetic testing rates over 90% and a high rate of identification of germline pathogenic variant carriers who would be ideal candidates for PDAC interception approaches. PREVENTION RELEVANCE: Preliminary data from the GENERATE study indicate success of remote alternatives for pancreatic cancer genetic testing and education, with genetic testing uptake rates over 90% and a high rate of identification of germline pathogenic variant carriers who would be ideal candidates for pancreatic cancer interception.
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Proteína BRCA1/genética , Proteína BRCA2/genética , Predisposición Genética a la Enfermedad , Pruebas Genéticas/métodos , Mutación de Línea Germinal , Neoplasias Pancreáticas/genética , Medición de Riesgo/métodos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/patología , Carcinoma Ductal Pancreático/terapia , Femenino , Humanos , Masculino , Persona de Mediana Edad , Modelos Genéticos , Neoplasias Pancreáticas/patología , Neoplasias Pancreáticas/terapia , Participación del Paciente , Factores de Riesgo , Encuestas y Cuestionarios , Telemedicina , Adulto JovenAsunto(s)
Atención Ambulatoria , Gastroenterología , Enfermedades Gastrointestinales/terapia , Accesibilidad a los Servicios de Salud , Disparidades en Atención de Salud , Telemedicina , Adulto , Anciano , Femenino , Enfermedades Gastrointestinales/diagnóstico , Enfermedades Gastrointestinales/etnología , Humanos , Masculino , Massachusetts/epidemiología , Persona de Mediana Edad , Visita a Consultorio Médico , Medición de Riesgo , Factores de Riesgo , Factores Socioeconómicos , Teléfono , Comunicación por VideoconferenciaRESUMEN
BACKGROUND: Population-based literature suggests severe acute respiratory syndrome coronavirus 2 infection may disproportionately affect racial/ethnic minorities; however, patient-level observations of hospitalization outcomes by race/ethnicity are limited. Our aim in this study was to characterize coronavirus disease 2019 (COVID-19)-associated morbidity and in-hospital mortality by race/ethnicity. METHODS: This was a retrospective analysis of 9 Massachusetts hospitals including all consecutive adult patients hospitalized with laboratory-confirmed COVID-19. Measured outcomes were assessed and compared by patient-reported race/ethnicity, classified as white, black, Latinx, Asian, or other. Student t test, Fischer exact test, and multivariable regression analyses were performed. RESULTS: A total of 379 patients (aged 62.9 ± 16.5 years; 55.7% men) with confirmed COVID-19 were included (49.9% white, 13.7% black, 29.8% Latinx, 3.7% Asian), of which 376 (99.2%) were insured (34.3% private, 41.2% public, 23.8% public with supplement). Latinx patients were younger, had fewer cardiopulmonary disorders, were more likely to be obese, more frequently reported fever and myalgia, and had lower D-dimer levels compared with white patients (P < .05). On multivariable analysis controlling for age, gender, obesity, cardiopulmonary comorbidities, hypertension, and diabetes, no significant differences in in-hospital mortality, intensive care unit admission, or mechanical ventilation by race/ethnicity were found. Diabetes was a significant predictor for mechanical ventilation (odds ratio [OR], 1.89; 95% confidence interval [CI], 1.11-3.23), while older age was a predictor of in-hospital mortality (OR, 4.18; 95% CI, 1.94-9.04). CONCLUSIONS: In this multicenter cohort of hospitalized COVID-19 patients in the largest health system in Massachusetts, there was no association between race/ethnicity and clinically relevant hospitalization outcomes, including in-hospital mortality, after controlling for key demographic/clinical characteristics. These findings serve to refute suggestions that certain races/ethnicities may be biologically predisposed to poorer COVID-19 outcomes.
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COVID-19 , Adulto , Anciano , Comorbilidad , Minorías Étnicas y Raciales , Etnicidad , Femenino , Hospitalización , Humanos , Masculino , Estudios Retrospectivos , SARS-CoV-2RESUMEN
Autoimmune enteropathy is a rare but severe disorder with significant immune-mediated changes. We present a 54-year-old woman with history of refractory ulcerative colitis status post total colectomy with end ileostomy who presented 1 month after her surgery with high ostomy output of 4 L/d. After a negative workup, ileoscopy with biopsies showed severe chronic active ileitis. Enteroscopy revealed diffuse chronic enteritis concerning for autoimmune enteropathy. She was started on budesonide and intravenous solumedrol, but her ostomy output remained high. She was then started on cyclosporine and later tacrolimus with significant clinical improvement and normalization of ostomy output on tacrolimus.