An observational study in Lung Cancer, Genetic Disease and Genetic Predisposition, sponsored by Dana-Farber Cancer Institute. Recruiting at 2 sites in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-08-26.
Sponsored by Dana-Farber Cancer Institute · Observational
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.
Dana-Farber Cancer Institute (DFCI), DFCI affiliates, satellites, or other sites clinics
Cohort 1: individuals with or with high risk of carrying an EGFR T790M or other EGFR germline variant identified in blood or saliva, including via somatic single or multi-gene panel testing (MGPT). This includes both probands and family members.
Cohort 2: individuals with or with high risk of carrying non-EGFR germline variants suggestive of a potential inherited lung cancer risk, identified in blood or saliva, including via somatic single or multi-gene panel testing (MGPT). This includes both probands and family members.
Cohort 3: individuals with lung cancer who are not known to carry a pathogenic or likely pathogenic variant, and with one of the following:
For each cohort, the following applies:
Exclusion Criteria:
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.
Genetic: Data and Specimen Collection
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.
Genetic: Data and Specimen Collection
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
Genetic: Data and Specimen Collection
* 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
Prevalence of rare germline EGFR mutations
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
Time frame: 3 years
Prevalence of rare germline non-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
Time frame: 3 years
Prevalence of rare pathogenic or likely pathogenic germline variants in familial lung cancers
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
Time frame: 3 years
Prevalence of rare pathogenic or likely pathogenic germline variants in lung cancer patients with multiple primary cancers or multi-focal NSCLC
To determine prevalence of rare pathogenic or likely pathogenic germline variants in lung cancer patients with multiple primary cancers or multi-focal NSCLC
Time frame: 3 years
Preliminary Assessment of History of Lung Cancers
To make a preliminary assessment of the natural history of lung cancers occurring in patients with germline EGFR mutations
Time frame: 3 years
Estimate of Prevalence of Lung Nodules
To generate an initial estimate of the prevalence of CT-detected lung nodules in individuals with germline EGFR mutations
Time frame: 3 years
Repository of Specimens and Data
Prospective registry of patients and families with hereditary or familial lung cancer to collect clinicopathologic information and biologic specimens.
Time frame: 3 years
Plan to share: Yes — 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.
Supporting information: Study protocol, Sap, Icf
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