RESUMEN
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).
Asunto(s)
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
Pancreatic ductal adenocarcinoma (PDAC) is the only leading cause of cancer death without an early detection strategy. In retrospective studies, 0.5-1% of subjects >50 years of age who newly develop biochemically-defined diabetes have been diagnosed with PDAC within 3 years of meeting new onset hyperglycemia and diabetes (NOD) criteria. The Enriching New-onset Diabetes for Pancreatic Cancer (ENDPAC) algorithm further risk stratifies NOD subjects based on age and changes in weight and diabetes parameters. We present the methodology for the Early Detection Initiative (EDI), a randomized controlled trial of algorithm-based screening in patients with NOD for early detection of PDAC. We hypothesize that study interventions (risk stratification with ENDPAC and imaging with Computerized Tomography (CT) scan) in NOD will identify earlier stage PDAC. EDI uses a modified Zelen's design with post-randomization consent. Eligible subjects will be identified through passive surveillance of electronic medical records and eligible study participants randomized 1:1 to the Intervention or Observation arm. The sample size is 12,500 subjects. The ENDPAC score will be calculated only in those randomized to the Intervention arm, with 50% (n = 3125) expected to have a high ENDPAC score. Consenting subjects in the high ENDPAC group will undergo CT imaging for PDAC detection and an estimate of potential harm. The effectiveness and efficacy evaluation will compare proportions of late stage PDAC between Intervention and Observation arm per randomization assignment or per protocol, respectively, with a planned interim analysis. The study is designed to improve the detection of sporadic PDAC when surgical intervention is possible.
Asunto(s)
Adenocarcinoma , Diabetes Mellitus , Hiperglucemia , Neoplasias Pancreáticas , Adenocarcinoma/diagnóstico por imagen , Algoritmos , Preescolar , Diabetes Mellitus/diagnóstico , Detección Precoz del Cáncer , Humanos , Hiperglucemia/diagnóstico , Neoplasias Pancreáticas/diagnóstico por imagen , Estudios RetrospectivosRESUMEN
ABSTRACT: Advancements in pancreatic ductal adenocarcinoma (PDAC) prevention, diagnosis, and treatment rely on representative and robust clinical trial participation. Given the severity of PDAC, along with the lack of effective early detection approaches, the need for accessible screening tools and new treatments is dire. Unfortunately, enrollment barriers often result in low participant accrual rates for PDAC studies and illustrate the challenging terrain researchers are facing. Research participation along with access to preventative care has been further impacted by the coronavirus disease 2019 pandemic. In this review, we use the Comprehensive Model for Information Seeking to discuss underexplored factors that influence patient participation in clinical studies. Adequate staffing, flexible scheduling, effective patient and physician communication, and culturally responsive messaging, along with the use of telehealth, can support enrollment objectives. Clinical research studies are a key component of health care, informing medical advancements, and improving outcomes. By leveraging health-related antecedents and information carrier factors, researchers can more effectively address barriers to participation and implement potential evidence-based mitigating strategies. While this work focuses on the PDAC research context, the lessons delineated here are applicable to the wider cancer research setting.
Asunto(s)
COVID-19 , Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Humanos , Participación del Paciente , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/terapia , Carcinoma Ductal Pancreático/terapia , Neoplasias PancreáticasRESUMEN
ABSTRACT: The potential of artificial intelligence (AI) applied to clinical data from electronic health records (EHRs) to improve early detection for pancreatic and other cancers remains underexplored. The Kenner Family Research Fund, in collaboration with the Cancer Biomarker Research Group at the National Cancer Institute, organized the workshop entitled: "Early Detection of Pancreatic Cancer: Opportunities and Challenges in Utilizing Electronic Health Records (EHR)" in March 2021. The workshop included a select group of panelists with expertise in pancreatic cancer, EHR data mining, and AI-based modeling. This review article reflects the findings from the workshop and assesses the feasibility of AI-based data extraction and modeling applied to EHRs. It highlights the increasing role of data sharing networks and common data models in improving the secondary use of EHR data. Current efforts using EHR data for AI-based modeling to enhance early detection of pancreatic cancer show promise. Specific challenges (biology, limited data, standards, compatibility, legal, quality, AI chasm, incentives) are identified, with mitigation strategies summarized and next steps identified.
Asunto(s)
Inteligencia Artificial , Congresos como Asunto , Detección Precoz del Cáncer/métodos , Registros Electrónicos de Salud/estadística & datos numéricos , Neoplasias Pancreáticas/diagnóstico , Investigación Biomédica/métodos , Investigación Biomédica/estadística & datos numéricos , Humanos , Difusión de la Información/métodosRESUMEN
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.
Asunto(s)
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 JovenRESUMEN
ABSTRACT: Despite considerable research efforts, pancreatic cancer is associated with a dire prognosis and a 5-year survival rate of only 10%. Early symptoms of the disease are mostly nonspecific. The premise of improved survival through early detection is that more individuals will benefit from potentially curative treatment. Artificial intelligence (AI) methodology has emerged as a successful tool for risk stratification and identification in general health care. In response to the maturity of AI, Kenner Family Research Fund conducted the 2020 AI and Early Detection of Pancreatic Cancer Virtual Summit (www.pdac-virtualsummit.org) in conjunction with the American Pancreatic Association, with a focus on the potential of AI to advance early detection efforts in this disease. This comprehensive presummit article was prepared based on information provided by each of the interdisciplinary participants on one of the 5 following topics: Progress, Problems, and Prospects for Early Detection; AI and Machine Learning; AI and Pancreatic Cancer-Current Efforts; Collaborative Opportunities; and Moving Forward-Reflections from Government, Industry, and Advocacy. The outcome from the robust Summit conversations, to be presented in a future white paper, indicate that significant progress must be the result of strategic collaboration among investigators and institutions from multidisciplinary backgrounds, supported by committed funders.
Asunto(s)
Inteligencia Artificial , Biomarcadores de Tumor/genética , Carcinoma Ductal Pancreático/genética , Detección Precoz del Cáncer/métodos , Genómica/métodos , Neoplasias Pancreáticas/genética , Carcinoma Ductal Pancreático/diagnóstico , Carcinoma Ductal Pancreático/terapia , Humanos , Comunicación Interdisciplinaria , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/terapia , Pronóstico , Análisis de SupervivenciaRESUMEN
OBJECTIVES: The aim of this study was to evaluate depression in pancreatic cancer (PC) patients before and after a cancer diagnosis using a US-based healthcare database. We also sought to study the impact of treatment of depression in PC patients on all-cause mortality. METHODS: Pancreatic cancer patients with comorbid depression in Explorys (1999-2019) were compared with controls using odds ratios with 95% confidence intervals. Rates of depression diagnosed within 6 months, 1 year, and 3 years before and after a PC diagnosis were recorded. Patients who developed depression after a PC diagnosis were further categorized into those treated for depression using mental health professionals (MHPs), pharmacologic treatment, or both (2015-2019). RESULTS: Of the 62,450 PC patients, 10,220 (16.4%) were diagnosed with depression before PC and 8130 (13%) were diagnosed with depression after PC. Patients diagnosed with depression after PC had a significantly higher all-cause mortality than patients with PC alone (P < 0.0001). Involvement of MHP significantly improved all-cause mortality (P = 0.0041). CONCLUSIONS: Most post-PC depression is diagnosed in the first 6 months after a PC diagnosis. Although depression significantly increases PC mortality, integrating MHP in the care of PC patients with depression improves outcomes.
Asunto(s)
Depresión/diagnóstico , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/psicología , Adolescente , Adulto , Anciano , Antidepresivos/uso terapéutico , Ansiedad/diagnóstico , Depresión/tratamiento farmacológico , Fatiga/diagnóstico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neoplasias Pancreáticas/mortalidad , Calidad de Vida , Factores de Riesgo , Tasa de Supervivencia , Factores de Tiempo , Adulto JovenRESUMEN
A diagnosis of pancreatic cancer is devastating owing to its poor prognosis, with a 5-year survival rate of only 9%. Currently, most individuals are diagnosed at a late stage when treatment options are limited. Early detection of pancreatic cancer provides the greatest hope for making substantial improvements in survival. The Kenner Family Research Fund in partnership with the American Pancreatic Association has sponsored a series of fora to stimulate discussion and collaboration on early detection of pancreatic cancer. At the first forum in 2014, "Early Detection of Sporadic Pancreatic Cancer Summit Conference," a strategic plan was set forth by an international group of interdisciplinary scientific representatives and subsequently The Strategic Map for Innovation was generated. The current conference report is the third forum in the series, "Early Detection of Pancreatic Cancer: The Role of Industry in the Development of Biomarkers," which was held in Boston, Massachusetts, on October 27, 2016. This report provides an overview of examples of innovative initiatives by industry and confirms the critical need for collaboration among industry, government, research institutions, and advocacy groups in order to make pancreatic cancer more easily detectable in its earlier stages, when it is more treatable.
Asunto(s)
Biomarcadores de Tumor/análisis , Industria Farmacéutica/métodos , Detección Precoz del Cáncer , Neoplasias Pancreáticas/diagnóstico , Investigación Biomédica/métodos , Investigación Biomédica/tendencias , Congresos como Asunto , Conducta Cooperativa , Difusión de Innovaciones , Industria Farmacéutica/tendencias , Humanos , Cooperación Internacional , Técnicas de Diagnóstico Molecular/métodos , Técnicas de Diagnóstico Molecular/tendenciasRESUMEN
The implementation of effective early detection programs has significantly improved treatment, prognosis, and life expectancy in breast, prostate, and colorectal cancers. Early-detection methods need to be developed for pancreatic ductal adenocarcinoma (PDAC), where progress during the past decades has remained slow. Addressing this need, the forum "Early Detection: Lessons Learned from Other Cancers" was held in November 2015 and presented by the Kenner Family Research Fund in partnership with the American Pancreatic Association. Leading experts from breast, prostate, and colorectal cancers described the development of early detection methods in their respective fields. Emerging opportunities for scientific advancement were subsequently identified that hold the greatest promise for the future of early detection in PDAC, including a 4-part strategic map of necessary actionable items. Knowledge from other fields must be applied to achieve large-scale change within the arena of PDAC. A major breakthrough in early detection of PDAC will occur only through a definitive interdisciplinary collaborative effort involving a critical mass of committed academic research institutions, government agencies, industry leaders, and philanthropies.
Asunto(s)
Neoplasias Pancreáticas , Carcinoma Ductal Pancreático , Detección Precoz del Cáncer , Humanos , Páncreas , PronósticoRESUMEN
A meeting of North American Pancreatic Cancer Organizations planned by Kenner Family Research Fund and Pancreatic Cancer Action Network was held on July 15-16, 2015, in New York City. The meeting was attended by 32 individuals from 20 nonprofit groups from the United States and Canada. The objectives of this inaugural convening were to share mission goals and initiatives, engage as leaders, cultivate potential partnerships, and increase participation in World Pancreatic Cancer Day. The program was designed to provide opportunities for informal conversations, as well as facilitated discussions to meet the stated objectives. At the conclusion of the meeting, the group agreed that enhancing collaboration and communication will result in a more unified approach within the field and will benefit individuals diagnosed with pancreatic cancer. As a first step, the group will actively collaborate to participate in World Pancreatic Cancer Day, which is planned for November 13, 2015, and seeks to raise the level of visibility about the disease globally.
Asunto(s)
Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/terapia , Canadá , Comunicación , Conducta Cooperativa , Humanos , Objetivos Organizacionales , Investigadores/economía , Investigadores/educación , Apoyo a la Investigación como Asunto/economía , Sociedades Médicas/organización & administración , Estados UnidosRESUMEN
Innovation leading to significant advances in research and subsequent translation to clinical practice is urgently necessary in early detection of sporadic pancreatic cancer. Addressing this need, the Early Detection of Sporadic Pancreatic Cancer Summit Conference was conducted by Kenner Family Research Fund in conjunction with the 2014 American Pancreatic Association and Japan Pancreas Society Meeting. International interdisciplinary scientific representatives engaged in strategic facilitated conversations based on distinct areas of inquiry: Case for Early Detection: Definitions, Detection, Survival, and Challenges; Biomarkers for Early Detection; Imaging; and Collaborative Studies. Ideas generated from the summit have led to the development of a Strategic Map for Innovation built upon 3 components: formation of an international collaborative effort, design of an actionable strategic plan, and implementation of operational standards, research priorities, and first-phase initiatives. Through invested and committed efforts of leading researchers and institutions, philanthropic partners, government agencies, and supportive business entities, this endeavor will change the future of the field and consequently the survival rate of those diagnosed with pancreatic cancer.
Asunto(s)
Investigación Biomédica/organización & administración , Carcinoma Ductal Pancreático/diagnóstico , Detección Precoz del Cáncer , Neoplasias Pancreáticas/diagnóstico , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Biopsia , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/metabolismo , Carcinoma Ductal Pancreático/mortalidad , Carcinoma Ductal Pancreático/patología , Carcinoma Ductal Pancreático/terapia , Conducta Cooperativa , Diagnóstico por Imagen , Difusión de Innovaciones , Detección Precoz del Cáncer/métodos , Humanos , Comunicación Interdisciplinaria , Cooperación Internacional , Técnicas de Diagnóstico Molecular , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/mortalidad , Neoplasias Pancreáticas/patología , Neoplasias Pancreáticas/terapia , Valor Predictivo de las Pruebas , PronósticoRESUMEN
Pancreatic cancer (PC) is estimated to become the second leading cause of cancer death in the United States by 2020. Early detection is the key to improving survival in PC. Addressing this urgent need, the Kenner Family Research Fund conducted the inaugural Early Detection of Sporadic Pancreatic Cancer Summit Conference in 2014 in conjunction with the 45th Anniversary Meeting of the American Pancreatic Association and Japan Pancreas Society. This seminal convening of international representatives from science, practice, and clinical research was designed to facilitate challenging interdisciplinary conversations to generate innovative ideas leading to the creation of a defined collaborative strategic pathway for the future of the field. An in-depth summary of current efforts in the field, analysis of gaps in specific areas of expertise, and challenges that exist in early detection is presented within distinct areas of inquiry: Case for Early Detection: Definitions, Detection, Survival, and Challenges; Biomarkers for Early Detection; Imaging; and Collaborative Studies. In addition, an overview of efforts in familial PC is presented in an addendum to this article. It is clear from the summit deliberations that only strategically designed collaboration among investigators, institutions, and funders will lead to significant progress in early detection of sporadic PC.