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

Rare Diseases

Carcinoma, Non-Small-Cell Lung

Carcinoma

Small Cell Lung Carcinoma

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Small Cell Lung Cancer

Tumor and saliva specimens from participants with non-small cell lung cancer (NSCLC) or small cell lung cancer (SCLC) diagnosed at age 45 or younger

* Provide research team access to relevant medical records
* Answer two (2) short questionnaires at time of consent
* Provide up to 5 tubes (37 ml) of blood at or near the time of consent, and/or saliva sample
* Consider consenting to other optional parts of the research such as:

  * Providing additional blood or tissue samples in the future (optional)
  * Providing permission for obtainment of stored tissue specimens from lung cancer surgeries or biopsies from the pathology departments where they have been stored (optional)

Jessica Line, MD

Jessica Lin, MD

Daniel Costa, MD PhD

The purpose of this research study is to learn more about lung cancer (NSCLC or SCLC) diagnosed in adults at ages 45 or younger.

This research study looks to enroll as many people diagnosed with lung cancer at 45 years old or younger in order to:

* Better understand causes of lung cancer in individuals 45 years old and younger, which is a rare disease
* Better estimate lung cancer risks and potential risk factors for lung cancer in individuals 45 years old and younger
* Examine tumor (somatic) or normal (germline) genetic changes that may be shared among young lung cancer patients
* Improve opportunities for screening and treatment of lung cancer in individuals 45 years old and younger

Study procedures will include:

* Collecting information from participants' medical record and two (2) short questionnaires
* Collecting blood and/or saliva samples
* Collecting tumor tissue samples (optional)

It is expected that about 500 people will take part in this research study. Participants will be in this study until it closes or the participant withdraws consent.

Biology of Young Lung Cancer Study: The YOUNG LUNG Study

Prospective registry of young lung cancer specimens for exploratory tumor and germline genomics, transcriptomics/proteomics, and future biomarker study.

Targetable alterations are defined as any somatic alteration in a driver oncogene for which a Food and Drug Administration-approved therapy exists, for which an off-label therapy exists, or for which a clinical trial exists (including but not limited to EGFR, KRAS, ALK, ROS1, RET, MET, BRAF, and TRK). Results will be summarized using descriptive statistics.

Unknown driver genes include genes not currently known to be driver oncogenes in lung cancer, and for which no directed treatment exists. Results will be summarized using descriptive statistics.

Pathogenic or likely pathogenic variants based on classification by the American College of Medical Genetics and Genomics (ACMG). Results will be summarized using descriptive statistics.

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
Biology of Young Lung Cancer Study: The YOUNG LUNG Study	NCT05265429	Non Small Cell ... Small Cell Lung...	Data and Specim...	15 Years - 45 Years	Dana-Farber Cancer Institute
Biology of Young Lung Cancer Study: The YOUNG LUNG Study	NCT05265429	Non Small Cell ... Small Cell Lung...	Data and Specim...	15 Years - 45 Years	Dana-Farber Cancer Institute

Spots Global Cancer Trial Database for data and specimen collection