Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Symptoms and General Pathology

Diseases and Abnormalities at or Before Birth

Lung Neoplasms

Genetic Predisposition to Disease

Disease Susceptibility

Genetic Diseases, Inborn

Disease Attributes

Individuals known to carry or at risk for carrying germline EGFR mutations (e.g., T790M, R776G/H/X, V769M, V834L, V843I, P848L, and others that will be identified). Patients with lung cancer with a somatic EGFR mutation prior to the initiation of treatment or who are found to have a suspected germline EGFR mutation via ctDNA analysis are also eligible.

Individuals known to carry or at risk for carrying non-EGFR germline mutations (e.g., HER2, BRCA2, MET, YAP1, and others that will be identified). Patients with lung cancer with a somatic variant suggestive of a possible hereditary lung cancer risk are also eligible.

Individuals and families with history of lung cancer where no pathogenic germline variant has been identified, but ascertained through history of one or more of the following:

* Multi-generational or first-degree relative with lung cancer
* Personal history of multiple primary lung cancers or other neoplasms
* Multi-focal lung cancer

* Provide blood and/or saliva sample
* Answer short questionnaires
* Consider consenting to other optional parts of the research such as:

  * use stored tissue samples related to prior cancer treatment
  * Allow access to deceased relatives' medical records and stored specimens
  * Provide blood 1x per year for up to 5 years
  * Provide contact information of family members

Data and Specimen Collection

Pasi A Jänne, MD, PhD

Jaclyn LoPiccolo, MD, PhD

Pasi A Janne, MD, PhD

The purpose of this research study is to learn more about the inherited risk for developing lung cancer.

Lung cancer is largely tobacco related, but the contribution of inherited susceptibility has been less well-studied, particularly among never-smokers. The goal of this study is to learn more about genetic susceptibility to lung cancer by studying individuals and families with known pathogenic germline mutations and/or family histories suggestive for heritable lung cancer, specifically in cases where tobacco exposure is minimal. Patients will be identified through somatic multi-gene panel testing (MGPT) as well as through reported personal and family histories of one or multiple cancers.

The overriding goal of this protocol is to follow patients with known germline mutations and strong family histories of lung cancer to better determine their risk of lung cancer and inform a screening paradigm based on this risk. This will allow us to observe the natural history of this disease and better understand the mechanisms underlying lung tumorigenesis in patients with susceptible germline backgrounds. These patients and their families will be enrolled as individuals with or without lung cancer who meet the following criteria: 1) individuals known to carry or at risk for carrying a germline EGFR mutation (T790M or other), identified through family members or by somatic genotyping at diagnosis, 2) individuals known to carry or at risk for carrying a pathogenic germline mutation in genes other than EGFR and with family history of lung cancer, or 3) individuals with no known germline mutation but with minimal exposure to tobacco and family history of lung cancer, personal history of other primary cancers, or multi-focal lung cancer.

This study is designed to create a data and specimen repository as well as follow patients over time to learn how to better predict lung cancer risk for those with certain genetic changes and family history of lung cancer, and to better understand how and why lung cancer develops in families.

The research study procedures include screening for eligibility, collection of information from participants' medical record, short questionnaires, and collecting blood and/or saliva samples. Procedures may also include use of tissue samples, access to medical records and stored specimens from deceased relatives, and contact information of family members.

It is expected that about 500 people will participant in this study.

Investigating Hereditary Risk In Thoracic Cancers (INHERIT)

The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to: \[contact information for Sponsor Investigator or designee\]. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.

To determine the prevalence of rare germline EGFR T790M or other (e.g., EGFR V843I and R776H) mutations in lung cancer patients and in relatives of carriers of germline EGFR mutations

To determine the prevalence of rare germline non-EGFR mutations (e.g., HER2, BRCA2, MET, YAP1) in lung cancer patients and in relatives of carriers of germline non-EGFR mutations

To determine prevalence of rare pathogenic or likely pathogenic germline variants in individuals and families where lung cancer has occurred in multiple generations or across multiple family members of the same generation

To determine prevalence of rare pathogenic or likely pathogenic germline variants in lung cancer patients with multiple primary cancers or multi-focal NSCLC

To make a preliminary assessment of the natural history of lung cancers occurring in patients with germline EGFR mutations

To generate an initial estimate of the prevalence of CT-detected lung nodules in individuals with germline EGFR mutations

Prospective registry of patients and families with hereditary or familial lung cancer to collect clinicopathologic information and biologic specimens.

Dana-Farber Cancer Institute

Principal Investigator

Digestive System Diseases

Gland and Hormone Related Diseases

Rare Diseases

Pancreatic Neoplasms

Adenocarcinoma

Pancreatitis

Pancreatitis, Chronic

Carcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Gastrointestinal Diseases

Pancreatic Diseases

Chronic Disease

Chronic Graft Versus Host Disease

Pancreatic Cancer

Anti-Infective Agents

All Drugs and Chemicals

Carbamide Peroxide

Bilirubin

Chronic pancreatitis, due to cystic fibrosis

Persons with a confirmed diagnosis of Peutz-Jeghers syndrome (STK11 mutation) or familial melanoma syndrome (CDKN2A mutation), hereditary pancreatitis (PRSS1 mutation)

Persons with a confirmed diagnosis of hereditary syndromes and at the same time with the condition of at least one relative of the first or second degree with a diagnosis of pancreatic ductal adenocarcinoma in family anamnesis; i.e. Lynch syndrome (mut: MLH1, MSH2, MSH6 a PMS2, EPCAM), HBOC (mut: BRCA1, BRCA2, PALB2, ATM), familial adenomatous polyposis (mut: APC), Li-Fraumeni syndrome (mut: TP53)

Persons with positive family anamnesis of pancreatic ductal adenocarcinoma without proven hereditary syndrome

endoscopic ultrasonography - frequency defined by arm

endoscopic ultrasonography

magnetic resonance - frequency defined by arm

magnetic resonance

hematology, biochemistry, Na+, K+, Cl-, Ca2+, bilirubin, ALT, AST, GGT, ALP, lactate dehydrogenase, creatinine, urea, fasting glycemia, HbA1c, alpha-amylase, LPS, albumin, total protein, CA19-9, CEA

laboratory examination

Martina Lojova, Ph.D.

Dita Kozakova, Ing.

Petr Karasek, MD

Jana Halamkova, MD

Helena Coupkova, MD

Anna Ondrackova, MD

Marketa Palacova, MD

Radim Nemecek, MD

Lumir Kunovsky, MD

Jan Trna, MD

Lenka Foretova, MD

Zdenka Cermakova, MD

Jan Kristek, MD

Roman Hrstka, Ph.D.

Pancreatic cancer is one of the diseases with the worst prognosis, which is mainly due to the initial asymptomatic prognosis. Unfortunately, the incidence of this disease in the Czech Republic is still increasing. In a certain proportion of patients, it is possible to predict the disease, e.g. due to family burdens. Regular follow-up of such individuals is the subject of the SCREPAN study: "Pancreatic Cancer Screening in High-Risk Persons".

Pancreatic ductal adenocarcinoma (PDAC) is one of the cancers with the worst prognosis. Mortality in this disease is almost equal to the incidence. In the Czech Republic, the incidence of this cancer has an upward trend, in 2017, 21.2 new cases per 100,000 people were reported, which represents a more than double increase compared to the data from the 1970s.

Pancreatic cancer is associated with an extremely poor prognosis for several reasons. It is usually diagnosed at an advanced stage, which is often due to the asymptomatic course of the disease or non-specific symptoms, the lack of sensitive and specific tumor markers, and difficult diagnosis by imaging methods in the early stages. Five-year survival, regardless of clinical stage, is between 7-9%.

Resectable disease is diagnosed in only 10% of patients, in which the 5-year survival rate is 37 %, locally advanced unresectable disease is detected in about 30 % of patients with a 5-year survival of 12 %, and metastatic disease is found in about 60 % of patients, with a 5-year survival rate of only around 3 %.

The poor prognosis of this disease is also due to the limited possibilities of screening and curative intervention for a short "lead time" in rapidly metastatic disease.

Pancreatic cancer screening is not suitable for the non-selected population. On the contrary, it is important for individuals with a high risk of developing this disease. In these subjects, early diagnosis during screening demonstrated a higher number of curative resections and longer survival.

Pancreatic Cancer Screening in a Population at High Risk

Number of participants (in risk population) with newly diagnosed pancreatic cancer

Comparison of magnetic resonance versus endoscopic ultrasonography yield

Comparison of magnetic resonance versus endoscopic ultrasonography cost effectiveness

KRAS mutation status defined by number of positive droplets on drop digital PCR using material from liquid biopsy

Masaryk University

Masaryk Memorial Cancer Institute

Skin and Connective Tissue Diseases

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Breast Neoplasms

Syndrome

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Neoplastic Syndromes, Hereditary

Hereditary Breast and Ovarian Cancer Syndrome

Breast Diseases

Skin Diseases

Endocrine Gland Neoplasms

Ovarian Diseases

Adnexal Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Genital Neoplasms, Female

Urogenital Neoplasms

Endocrine System Diseases

Gonadal Disorders

Ovarian Cancer

Ovarian Epithelial Cancer

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.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Investigating Hereditary Risk In Thoracic Cancers (INHERIT)	NCT05587439	Lung Cancer Genetic Disease Genetic Predisp... Hereditary Dise...	Data and Specim...	18 Years -	Dana-Farber Cancer Institute
Investigating Hereditary Risk In Thoracic Cancers (INHERIT)	NCT05587439	Lung Cancer Genetic Disease Genetic Predisp... Hereditary Dise...	Data and Specim...	18 Years -	Dana-Farber Cancer Institute
Pancreatic Cancer Screening in a Population at High Risk	NCT06330441	Pancreatic Duct... Hereditary Dise... Pancreatitis, C...	endoscopic ultr... magnetic resona... laboratory exam...	18 Years -	Masaryk Memorial Cancer Institute
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

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