Symptoms and General Pathology

All Conditions

Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

Diseases and Abnormalities at or Before Birth

Skin and Connective Tissue Diseases

Rare Diseases

Syndrome

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Neoplastic Syndromes, Hereditary

Hereditary Breast and Ovarian Cancer Syndrome

Genetic Diseases, Inborn

Ovarian Cancer

Ovarian Epithelial Cancer

This will be typical genetic counseling that a patient would receive in a traditional genetic counseling setting.

This will be genetic counseling that is modified for a lower literacy patient and will include fewer technical terms and less complicated genetic information.

After participants at high risk for a hereditary cancer syndrome receive exome sequencing, they will receive modified genetic counseling to help them understand the results.

Modified genetic counseling

After participants at high risk for a hereditary cancer syndrome receive exome sequencing, they will receive traditional genetic counseling to help them understand the results.

Traditional genetic counseling

Michael Leo, PhD

Benjamin S Wilfond, MD

The CHARM (Cancer Health Assessment Reaching Many) study will assess the utility of clinical exome sequencing and how it affects care in diverse populations. The study population includes adults at risk for hereditary cancer syndromes.

The primary objective is to implement a hereditary cancer risk assessment program in healthy 18-49 year-olds in primary care settings within a vertically integrated health delivery system (Kaiser Permanente) and a federal qualified health center (Denver Health). The investigators will assess clinical exome sequencing implementation and interpretation, as well as tailored interactions for low health literacy including a contextualized consent process, and a modified approach to results disclosure and genetic counseling. The investigators will also assess the clinical utility (healthcare utilization and adherence to recommended care) and personal utility of primary and additional results from clinical exome sequencing, and evaluate the ethical and policy implications of considering personal utility of genomic information decisions for health care coverage.

Aim 1. Implement a hereditary cancer risk-assessment program in healthy 18-49-year-old adults in primary care settings, with stakeholder input, and offer exome sequencing to clarify risk.

Aim 1A. Identify and recruit 880 adult participants at-risk of a hereditary cancer syndrome.

Aim 1B: Generate medical exome sequence data and interpret variants. Aim 1C: Disclose findings from medical exome sequencing, incorporate results into the electronic medical record (EMR), and facilitate downstream patient management and coordination of care with the provider.

Aim 1D. Engage stakeholders to tailor and optimize the program in diverse populations.

Aim 2. Evaluate and tailor for diverse populations the critical interactions in the program, including the consent process, choices for reporting additional findings, and the response to results disclosure.

Aim 2A. Design, implement, and assess a contextualized consent process to support informed decision-making about participation in research about medical exome sequencing.

Aim 2B. Design, implement, and compare a novel decision aid in the second half of the study for selecting the optional categories of additional findings with the approach we developed in CSER1 that offered a category checklist.

Aim 2C. Design, implement, and compare a modified (communication-focused) approach to results disclosure, genetic counseling, and decision making with a standard (information-focused) approach.

Aim 3. Evaluate the clinical utility (including personal utility) of using exome sequencing to diagnose individuals with hereditary cancer syndromes and provide additional findings.

Aim 3A: Measure the yield of reportable findings for hereditary cancer syndromes and additional findings.

Aim 3B: Evaluate subsequent healthcare utilization for all study participants and adherence to recommended care among individuals who are identified with a hereditary cancer syndrome in diverse settings.

Aim 3C. Assess the personal utility of exome sequencing, including primary and additional findings.

Aim 4. Address pragmatic and ethical challenges to the integration of genomic medicine into clinical and health systems decision-making.

Aim 4A: Develop and pilot a system that integrates genomic, clinical, and healthcare utilization data to inform clinicians and patients acting on genomic information and to reduce care gaps in patient management.

Aim 4B: Advance the analysis of the ethical and policy implications of incorporating personal utility of genomic information into the decision framework for healthcare coverage.

All participants will receive exome sequencing. The randomization will be into one of two types of genetic counseling - traditional and modified.

The participant will not know if they are receiving traditional or modified genetic counseling.

Cancer Health Assessments Reaching Many

Exome Sequencing in Diverse Populations in Colorado & Oregon

Genotype and Phenotype data will be uploaded to ANVIL. Variant data will be uploaded to ClinVar.

Number of people found to have a pathogenic variant in one of the cancer genes associated with Lynch syndrome or hereditary breast and ovarian cancer

Number of people with pathogenic variants found in genes related to medically actionable hereditary conditions

Number of people with pathogenic variants found in genes related to common carrier conditions

Downstream healthcare utilization of specific recommended procedures (e.g., colonoscopy, mammography, surgery) will be compared between participants in the traditional genetic counseling arm, the modified genetic counseling arm, and patients at high risk for a hereditary cancer syndrome that do not join the study (usual care)

Measurement of participant's understanding of the recommended care based on their genetic test result will be assessed using a validated survey tool

Measurement of patient's understanding of the genetic test results will be assessed using a validated survey tool

Measurement of the patient's satisfaction of genetic counseling will be assessed using a validated survey tool

Measurement of the degree to which participants shared their genetic test results with various family members will be assessed using a validated survey tool

Measurement of the participant's perceived utility of obtaining genetic testing and counseling will be assessed using validated survey tools that assess lifestyle behaviors and self-reported health/quality of life.

National Human Genome Research Institute (NHGRI)

University of Washington

Seattle Children's Hospital

University of California, San Francisco

Denver Health and Hospital Authority

Emory University

Dana-Farber Cancer Institute

Columbia University

Kaiser Permanente

Carcinoma, Renal Cell

Kidney Neoplasms

Birt-Hogg-Dube Syndrome

Carcinoma

Urologic Neoplasms

Urogenital Neoplasms

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Kidney Diseases

Urologic Diseases

Male Urogenital Diseases

Adenocarcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Renal Cell Carcinoma

Antineoplastic Agents

All Drugs and Chemicals

Gastrointestinal Agents

Anti-Infective Agents

Everolimus

Lactitol

Sirolimus

Temsirolimus

MTOR Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Immunosuppressive Agents

Immunologic Factors

Birt-Hogg-Dube Syndrome (BHD)-associated renal tumors

Everolimus is a commercial agent and is supplied by Novartis.

Ramaprasad Srinivasan, M.D.

Background:

- Research has shown that the drug everolimus can stop cancer cells from growing. It is approved for people with advanced kidney cancer. Researchers want to see if it also helps people with two other types of kidney cancer.

Objective:

- To see if everolimus is safe and effective in people with Birt-Hogg-Dube Syndrome (BHD)-associated kidney cancer or sporadic (nonfamilial) chromophobe renal cancer.

Eligibility:

- People ages 18 and over with BHD-associated kidney cancer or advanced sporadic chromophobe renal cancer.

Design:

* Participants will be screened with:
* Medical history, physical exam, and blood and urine tests.
* Computed tomography (CT) scan or magnetic resonance imaging (MRI) scan. They will lie in a machine that takes pictures of their chest/abdomen/pelvis.
* They may also be screened with:
* Another scan, of the brain or neck.
* Bone scan.
* Positron emission tomography scan with fludeoxyglucose (FDG-PET).
* Heart and lung tests.
* Tests for hepatitis.
* Participants will take a tablet once a day by mouth for up to a year. They will keep a diary of when they take the tablet and any symptoms.
* During the study, participants will have physical exams and urine and blood tests. They will have scans of the chest/abdomen/pelvis. They may have FDG-PET and bone scans.
* Participants will have tests for hepatitis and may have a tumor sample taken.
* Participants will have a follow-up visit 4-5 weeks finishing taking the drug. They will have a physical exam and blood tests. They may have scans and/or hepatitis tests.
* Participants will be called about every 3-6 months after the study ends to see how they are doing

Background:

* Birt-Hogg-Dube (BHD) is a hereditary cancer syndrome with clinical manifestations including cutaneous fibrofolliculomas, lung cysts/pneumothorax, and renal cell carcinoma (RCC). RCC occurs in approximately 30% of patients with BHD. It presents at an early age of onset and is commonly bilateral and multifocal.
* Tumors associated with BHD can have variable histology, however approximately 85% of these tumors have a chromophobe component (either alone or part of a hybrid tumor mixed with elements of oncocytoma).
* The current management includes surgical resection with partial nephrectomy when tumors reach 3 cm. While significant morbidity can be associated with repeat, partial nephrectomy with this approach, most patients can maintain renal function and do not develop systemic disease. There are no proven systemic therapy options for BHD to date.
* Germline mutations in the gene Folliculin (FLCN) are the genetic hallmark of BHD and can be found in greater than 90% of patients. FLCN is believed to function like a classic tumor suppressor gene with a second hit in the wild type allele (somatic mutation or loss of heterozygosity) occurring in the majority of renal tumors.
* BHD is in the family of hamartomatous disorders similar to Tuberous Sclerosis Complex (TSC) and Cowden Syndrome, and studies have found activation of the phosphoinositide 3-kinase (PI3K)/mTOR pathway in BHD renal tumors. FLCN is believed be part of a complex that interacts with 5' AMP-activated protein kinase (AMPK) and is involved with regulation of mTOR activity. In vitro and in vivo models of FLCN loss demonstrate activation of both mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2).
* Preclinical data from conditional FLCN knockout mice demonstrate that treatment with sirolimus can reverse renal manifestations.
* We hypothesize that mTOR inhibition with everolimus treatment will be clinically active in BHD associated RCC.

Objectives:

-To determine the overall response rate with everolimus treatment in subjects with BHD-associated renal tumors.

Eligibility:

-Patients with renal cell carcinoma (RCC) associated with Birt-Hogg-Dube Syndrome (BHD).

Design:

* This is an open label, phase II study to evaluate the efficacy and safety of everolimus therapy in patients with BHD associated renal tumors. Up to 16 evaluable patients will be enrolled.
* Tumor response rate will be measured by Response Evaluation Criteria in Solid Tumors (RECIST) and efficacy analysis will be done.
* Secondary endpoints will evaluate growth rates (cm/year) while on therapy.
* Additionally, reduction in the size of lung cysts and cutaneous fibrofolliculomas will be evaluated.

Everolimus Therapy in People With Birt-Hogg-Dube Syndrome (BHD)-Associated Kidney Cancer or Sporadic Chromophobe Renal Cancer

Phase 2 Study of Everolimus Therapy in Patients With Birt-Hogg-Dube Syndrome (BHD)-Associated Kidney Cancer or Sporadic Chromophobe Renal Cancer

Overall best response is defined as the best response recorded from the start of the treatment until disease progression/recurrence (taking as reference for progressive disease the smallest measurements recorded since the treatment started). Response was assessed by the Response Evaluation in Solid Tumors (RECIST) criteria v1.1. Progressive disease is at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes baseline sum if that is the smallest on study). The sum must also demonstrate an absolute increase of at least 5mm. Note: the appearance of one or more new lesions is also progression. Complete response is disappearance of all target lesions. Partial response is at least a 30% decrease in the sum of the diameters of target lesions. Stable disease is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum of diameters while on study.

Progression-free survival is defined as the time interval from start of treatment to documented evidence of disease progression. Progression is at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes baseline sum if that is the smallest on study). The sum must also demonstrate an absolute increase of at least 5mm. Note: the appearance of one or more new lesions is also progression. Progressive disease was assessed by the Response Evaluation in Solid Tumors (RECIST) criteria v1.1.

Overall Survival is defined as the time between the first day of treatment to the day of death.

Here is the count of participants with non-serious adverse events assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0). A non-serious adverse event is any untoward medical occurrence.

National Cancer Institute (NCI)

Principla Investigator

Birt-Hogg-Dube Syndrome (BHD)-associated renal tumors

Everolimus: Everolimus is a commercial agent and is supplied by Novartis.

Age, Categorical

Age, Continuous

Sex: Female, Male

White

Asian

A person not meeting definition of Hispanic/Latino

Race/Ethnicity, Customized

United States

Region of Enrollment

Dr. Ramaprasad Srinivasan

Complete Response

Partial Response

Stable Disease

Progressive Disease

Overall Response Rate With Everolimus Treatment.

Because all the 3 patients were alive without progression as of date of off study their median time to progression cannot be determined.

Progression-free Survival (PFS)

Because all the 3 patients were alive as of date of off study, their median time to death is unknown.

Overall Survival (OS)

Count of Participants With Non-serious Adverse Events Assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0)

Overall Study

All individuals at risk of a hereditary cancer syndrome with or without a known germline mutation from clinical genetic testing.

Raymond Kim, MD

This study will investigate the utility of integrative sequencing of individuals and families at risk of hereditary cancer syndromes and will uncover novel contributors to tumourigenesis. Integrative sequencing refers to:

1. Whole genome sequencing (WGS) of the germline (inherited) genome
2. Whole exome sequencing (WES) or targeted/panel sequencing of tumour(s) (somatic, tumour-specific mutations)
3. DNA methylation (methylome) analysis of tumour(s)
4. RNA sequencing (transcriptome) of tumour(s)

Eligible patients receiving genetic care at Princess Margaret Cancer Centre and the University Health Network may be approached by their genetic counsellor for participation in this study.

Archival tumor tissue, whole blood at baseline for germ-line DNA analysis

Integrative Sequencing In Germline and Hereditary Tumours

University Health Network, Toronto

Breast Neoplasms

Pharmaceutical Solutions

The mainstream genetic testing (MGT) model of cancer genetic services involves a non-genetics healthcare provider, such as the primary care provider, who engages patients in the counseling, consenting, and ordering of genetic testing. The provider/care team discloses the genetic test results and refers patients for genetic counseling only when genetic test results are abnormal. By eliminating the pre- and post-test counseling visits with a genetics provider, the MGT model has the potential to provide scalable access to genetic services.

The enhanced standard of care model (SOC+) is the current referral model of cancer genetic services delivery with an enhancement to include screening for and resources to address health literacy. This model begins with a health care provider's recognition, identification and then referral of a patient to a genetic counselor where genetic testing takes place if appropriate. This model is time- and resource- intensive and may not be scalable.

Mainstream Genetic Testing Model of Cancer Genetics Service Delivery

Mainstream Genetic Testing Model

Enhanced Standard of Care Model of Cancer Genetic Service Delivery

Enhanced Standard of Care Model

The goal of this clinical trial is for researchers to compare the effectiveness of a mainstreamed model of genetic testing (MGT) with an enhanced standard of care model (SOC+) on the uptake of genetic testing among at risk patients in an urban Federally Qualified Health Center (primary care) setting using a hybrid-effectiveness study design.

Aim 1 is to compare the effectiveness of MGT and SOC+ interventions on the uptake of genetic testing among Black patients receiving primary care in an urban federally qualified health center (FQHC) system using a randomized trial study design. The hypothesis is that the uptake of testing will be higher among patients receiving services through MGT compared with SOC+ model.

Aim 2 is to evaluate the implementation outcomes (acceptability, feasibility and sustainability) and the barriers and facilitators of cancer genetic service delivery approaches within primary care at FQHCs via qualitative interviews with patients, primary care providers and clinic staff, and organizational leaders, guided by the Explore, Prepare, Implement, Sustain (EPIS) implementation framework.

Randomization of cancer genetic service models will occur at the clinic level. Participants (patients, provider and staff) will be recruited to participate in interviews about their experience with each model of care in the clinical trial.

More than 15 years after the release of evidence-based guidelines recommending hereditary cancer risk assessment and testing for at-risk individuals, less than 1 in 5 patients eligible for cancer genetic testing receive this evidence-based care.1-2 Utilization of cancer genetics services is significantly lower among Black patients compared with White patients. Addressing racial inequities in cancer genetic services is crucial, given that (1) 10-15% of cancers are caused by inherited mutations; and (2) early identification of high risk Black patients can reduce disparities in cancer morbidity and mortality through prevention and early detection.

Multilevel social determinants of health (SDoH) limit Black patients' access to cancer genetic services. At the clinic level, Black populations often engage in care with clinics with limited resources to systematically identify at-risk patients, have no or few genetic specialists, and, have to outsource genetic services to other, potentially distant, healthcare systems. At the interpersonal level, primary care providers lack confidence and knowledge to deliver cancer genetics services9 and genetic specialists may not have trustworthy relationships with Black patients. At the patient level, Black patients often face economic, cultural, and educational barriers to genetic services.

There is an urgent need to develop innovative, multi-level, streamlined, and sustainable system wide solutions to enhance cancer genetic services access and use. Extant standard of care (SOC) at best resolves patient-level barriers through staff assistance for low literacy, culturally targeted education materials, and access to free/low-cost services. Our team has recently implemented an enhanced SOC (SOC+) in underserved clinical settings, which uses universal standardized hereditary cancer risk assessments (HCRA) to identify at-risk patients, informs providers about the need for referrals, and provides patient-level interventions to enhance uptake (e.g., financial assistance, literacy support). Despite better identification of at- risk patients, uptake of genetic services remains low with a number of challenges remaining at provider (complexity of and confidence with care) and clinic levels (time and resource intensive).

To address these challenges, our proposal will examine the effectiveness and implementation of an alternative mainstream model of cancer genetic testing (MGT) into primary care. MGT leverages patients' established relationship with their primary care provider (PCP) and care team to address provider and clinic-level access issues. Specifically, patients receive risk assessment and genetic testing in their medical homes, during regular visits, without referral to a specialist. MGT thus efficiently reduces clinic-level demand for specialists and referrals to specialty care; leverages trusted patient-provider relationships; and maintains some benefits of SOC and SOC+ interventions. Past studies on MGT models have focused primarily on cancer patients in oncology settings; thus, we have limited understanding of how well MGT may address population- level disparities widely across primary care sites with higher patient volumes and fewer clinic resources. To address this problem, we propose to systematically test this alternative approach to reducing racial/ethnic disparities through a hybrid effectiveness-implementation design. Specifically, we will:

Aim 1. Compare the effectiveness of MGT and SOC+ interventions on the uptake of genetic testing among Black patients receiving primary care in an urban federally qualified health center (FQHC) system using a randomized trial study design. Hypothesis: Uptake of testing will be higher among patients receiving services through MGT compared with SOC+ model.

Aim 2. Evaluate the implementation outcomes (acceptability, feasibility and sustainability) and the barriers and facilitators of cancer genetic service delivery approaches within primary care at FQHCs via qualitative interviews with patients, primary care providers and clinic staff, and organizational leaders, guided by the Explore, Prepare, Implement, Sustain (EPIS) implementation framework.

Our work offers innovative solutions to increase equitable delivery of cancer prevention services and overcome major gaps in the implementation of guideline-based care. Our project leverages: (1) an unique, established, and robust partnership between a federally qualified health center (FQHC), an academic institution, and specialty health services; and, (2) a robust, transdisciplinary research team and advisory committee, employed to ensure that the MGT model provides high quality care and is an acceptable and sustainable model that can work for other FQHC systems after external funding ends. Successful integration, based on our hybrid-effectiveness design, will inform the development of best practice solutions for cancer genetic services delivery in underserved clinical settings. Ultimately, this will reduce racial disparities in cancer.

clinical trial with a hybrid effectiveness-implementation design

Implementation of Population Breast Cancer Genetic Services in Federally Qualified Health Centers (FQHC)

Developing and Optimizing Best Practice Solutions for Implementation of Population Based Cancer Genetic Services in Federally Qualified Health Centers

compare the uptake of genetic testing among patients in both models of cancer genetic delivery who screen positive on hereditary cancer risk asserssment (HCRA)

Time from screening positive on HCRA to genetic testing

Qualitative interviews with patients and providers in the clinical trial, guided by the Explore, Prepare, Implement, Sustain (EPIS) implementation framework.

University of Illinois at Chicago

Principal Investigator

Genetic Predisposition to Disease

Disease Susceptibility

Breast Diseases

Skin Diseases

Endocrine Gland Neoplasms

Ovarian Diseases

Adnexal Diseases

Genital Diseases, Female

Genital Diseases

Genital Neoplasms, Female

Endocrine System Diseases

Gonadal Disorders

Disease Attributes

This sequential arm contains three types of communication to be employed following non-response to the previous type. The initial communication will be a direct message to the patient via the MyPennMedicine. The subsequent message will be sent as a text via the Way To Health app(lication). The final communication will be a nudge to the patient's physician which will send upon opening the patient's chart and will remain as a flag thereafter.

The intervention includes 3 message types: an EHR message, followed by a text message, followed by physician nudge. Each subsequent type will be activated if the previous type does not yield a response.

Sequential EHR Communications

The goal of this sequential study design is to increase genetic testing in those meeting national clinical guidelines. The main question it aims to answer is: which intervention is most effective in uptake of genetic testing for the target population? Participants will receive genetic testing and counseling that may initiate life-saving screenings.

Germline genetic testing is recommended by the National Cancer Center Network (NCCN) for individuals with a personal history of ovarian cancer, young-onset (\<50 years) breast cancer, and a family history of ovarian cancer or male breast cancer, among others. Recent publications demonstrate that the uptake of genetic testing is under-utilized, overall, and rates are consistently lower in minority populations. EHR-based algorithms will be used to identify patients of two Penn Medicine Ob/Gyn practices for whom genetic testing is recommended based on NCCN guidelines and to test pragmatic methods using messages delivered to patients or clinicians to encourage testing. The ACC Electronic Phenotyping Core developed the algorithms based on cancer registry data along with family history fields and this study will develop and test messages directed at patients and clinicians to encourage testing. The aims are:

1. Identification of at-risk populations through electronic health record (EHR) searches followed by patient nudges (MPM and then Way To Health) to increase the uptake of genetic counseling referral and testing in patients at gynecology practices at Dickens Center and Penn Medicine Radnor.
2. In patients who have not responded to patient nudges (Aim 1), test a provider nudge to increase the uptake of genetic counseling referral and testing in gynecology practices at Dickens Center and Penn Medicine Radnor (Aim 2).

Eligible patients will be sent a message through the patient portal to encourage genetic counseling and testing. If the patient does not respond, they will be sent a text message. Should there be no response, the patient's clinician will receive a nudge

Sequential EHR Based Interventions to Increase Genetic Testing for Breast and Ovarian Cancer Predisposition

Sequential EHR Based Interventions to Increase Genetic Testing for Breast and Ovarian Cancer Predisposition Across Diverse Patient Populations in Gynecology Practices at Penn Medicine

The total number of referrals signed by the patient's Ob/Gyn provider for genetic counseling and testing.

Scheduling and completion of genetic counseling appointments will be monitored through EHR. MPM stands for MyPennMedicine message which will be sent directly to the patient through the medical record.

Scheduling and completion of genetic counseling appointments will be monitored through EHR. The provider nudge will be delivered as a Best Practice Alert (BPA) upon opening the patient's chart.

The proportion of eligible participants who open the invitation to receive genetic counseling and testing compared to the total amount of eligible participants sent an MPM.

The proportion of eligible participants who respond to a text message invitation to receive genetic counseling and testing compared to the total amount of eligible participants sent a Way To Health (WTH) text.

Abramson Cancer Center at Penn Medicine

Tissue Adhesions

Endometrial Neoplasms

Uterine Neoplasms

Uterine Diseases

The inclusion of subjects in the GENEPY network follows the genealogical study of a case (index): relatives are identified as potentially at risk. In accordance with the recommendations, but also generally at the wish of the patients (Claes 2003), the index case is then asked to inform its relatives and to propose them to go to an oncogenetic consultation of their choice. If these people reside in the Midi Pyrenees Toulouse oncogenetic consultation is open to them. If following this consultation a mutation is identified or that their genetic risk is considered important, they are proposed to join the GENEPY network for their monitoring.

inclusion of subjects in the GENEPY network

Edith Chipoulet, Msc

Anne-Laure Fize, MSc

Anne-Laure Fize, Msc

Laurence Gladieff, PhD

In order to best meet the needs of all those affected by the genetic risk of cancer in our region, it is important to identify the factors likely to influence the course leading to the GENEPY surveillance network. The aim of this study is to evaluatie the adhesion to the network of care of people at genetic risk of cancer in Midi-Pyrénées (GENEPY).

This network has been open since November 2015 for people who are genetically predisposed to breast / ovarian cancer. The extension to digestive pathologies (HNPCC syndrome, PAF) is in progress. It concerns not only the persons carrying a mutation also those belonging to a family without identified mutation but whose risk of predisposition is important.

The GENEPY network is based on a collaboration between oncogenetic consultations in the region and professionals practicing in institutions (private, public) and liberal: general practitioners, gynecologists, radiologists, oncologists, gastroenterologists, psychologists ...

It is therefore a multicentric and multidisciplinary network, which aims to promote the local care of people genetically predisposed (or considered at high risk of genetic predisposition), while ensuring a high level of competence, to guarantee an optimal and equitable care on the whole of Midi Pyrenees.

The diagnosis of a new genetic disease in an individual is likely to have implications for other family members who may themselves be at risk of developing the disease and / or passing it on to their children.

The inclusion of subjects in the GENEPY network follows the genealogical study of a case (index) : relatives are identified as potentially at risk. In accordance with the recommendations, but also generally at the wish of the patients, the index case is then asked to inform its relatives and to propose them to go to an oncogenetic consultation of their choice. If these people reside in the Midi Pyrenees Toulouse oncogenetic consultation is open to them. If following this consultation a mutation is identified or that their genetic risk is considered important, they are proposed to join the GENEPY network for their monitoring.

Evaluation of the Adhesion to the GENEPY Network

Evaluation of the Adhesion to the Network of Care of People at Genetic Risk of Cancer in Midi-Pyrénées (GENEPY)

Network membership rate : comparison between the number of relatives who received the invitation and the number of them who joined the network.

Age of the relative of the patient who answered the questionnaire

sex of the relative of the patient who answered the questionnaire

distance from the offer of care and level of deprivation (for the relative of the patient who answered the questionnaire)

relationship of the relatives with the index case according to the latter contact

Patient's agreement to communicate about his illness to his relative

satisfaction of people who have joined the network (scale of values by questionnaire)

satisfaction of general practitioners (scale of values by questionnaire)

Institut Claudius Regaud

Subjects will receive a text message initiating a chatbot conversation that relies on natural language processing to gather personal and family cancer. Subjects are identified by the chatbot as meeting National Comprehensive Cancer Network (NCCN) high-risk criteria. Next, subjects undergo pre-test genetic counseling via the chatbot and then clinicians are notified (via the chatbot portal) that the subject meets high-risk criteria. For subjects meeting high-risk criteria (based on the chatbot evaluation), the clinician will complete genetic counseling and recommend genetic testing during the visit. For subjects interested in genetic testing, the clinician will order genetic testing.

Personal and family cancer history will be collected by the clinician during the subject's visit. Clinicians will evaluate the patient's personal/family history according to National Comprehensive Cancer Network (NCCN) high-risk criteria. For subjects recognized by the clinician as meeting NCCN criteria, the clinician will complete genetic counseling and recommend genetic testing. For subjects interested in genetic testing, the clinician will order genetic testing.

A chatbot is a software program designed to simulate human conversation, typically via text. Chatbots utilize natural language processing to gather patient data, anticipate questions, and predict responses. In this study, the Chatbot will simulate a text-like conversation with patients via a smartphone and use this platform to deal with the time-consuming nature of family history collection. The chatbots can then triage the collected family history against medical guidelines to determine which patients warrant genetic testing. For those patients meeting criteria for genetic testing, the chatbot can offer pre-test education and assist physicians with ordering genetic testing for interested patients meeting high-risk criteria.

Chatbot

Melissa K Frey, MD, MS

Isabelle Chandler

Denise Howard, MD, MPH

Michael Kim, MD

Julia Cron, MD, FACOG

Melissa K Frey, MD

David Fishman, MD

In this study, the investigators aim to compare a mobile health platform, known as a 'chatbot,' that leverages artificial intelligence and natural language processing to scale communication, to 'usual care' that patients would receive. This comparison will enable the investigators to determine if the chatbot system can improve rates of recommendation for genetic testing among patients at elevated risk of harboring a familial cancer syndrome in an all-Medicaid gynecology clinic. Furthermore, the investigators aim to evaluate facilitators of inequity in regard to patient access to and utilization of genetic testing services.

2-arm randomized controlled trial of a chatbot for personal/family history intake vs. usual care (intake via the clinician interview). Enrolled patients will be randomized in a 1:1 ratio.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Cancer Health Assessments Reaching Many	NCT03426878	Hereditary Canc...	Modified geneti... Traditional gen...	18 Years - 49 Years	Kaiser Permanente
Everolimus Therapy in People With Birt-Hogg-Dube Syndrome (BHD)-Associated Kidney Cancer or Sporadic Chromophobe Renal Cancer	NCT02504892	Renal Cancer Birt-Hogg-Dube ...	Everolimus	18 Years - 100 Years	National Institutes of Health Clinical Center (CC)
Integrative Sequencing In Germline and Hereditary Tumours	NCT03857594	Hereditary Canc... High-Risk Mutation Germline Mutati...		18 Years -	University Health Network, Toronto
Implementation of Population Breast Cancer Genetic Services in Federally Qualified Health Centers (FQHC)	NCT05664867	Hereditary Canc...	Mainstream Gene... Enhanced Standa...	25 Years -	University of Illinois at Chicago
Sequential EHR Based Interventions to Increase Genetic Testing for Breast and Ovarian Cancer Predisposition	NCT05721326	Genetic Predisp... Breast Cancer F... Ovarian Cancer Hereditary Brea... Hereditary Canc... Hereditary Dise... Gene Mutation-R...	Sequential EHR ...	25 Years - 100 Years	Abramson Cancer Center at Penn Medicine
Evaluation of the Adhesion to the GENEPY Network	NCT03979612	Hereditary Canc... Hereditary Brea... Hereditary Colo...	inclusion of su...	18 Years -	Institut Claudius Regaud
Chatbot to Maximize Hereditary Cancer Genetic Risk Assessment	NCT05562778	Gynecologic Can... Hereditary Canc...	Chatbot	18 Years -	Weill Medical College of Cornell University
Implementation of Population Breast Cancer Genetic Services in Federally Qualified Health Centers (FQHC)	NCT05664867	Hereditary Canc...	Mainstream Gene... Enhanced Standa...	25 Years -	University of Illinois at Chicago

Spots Global Cancer Trial Database for hereditary cancer syndrome