Evaluation of Cell Changes in Blood and Tissue in Cancers of the Lung, Esophagus and Lung Lining

Prospective Evaluation of Genetic and Epigenetic Alterations in Patients With Thoracic Malignancies

Background:

• Chromatin is is the structural building block of a chromosome. It is found inside the nucleus of the cell and consists of a complex of DNA and protein.
• Cancers of the lung, pleura (lung lining) and esophagus show profound changes in chromatin structure that may affect the course of disease in participants.
• A better understanding of these diseases and the genetic changes associated with them may be helpful in developing new treatments for them.

Objectives:

• To medically evaluate individuals with potential (medically suspicious) or proven cancer of the lung, esophagus, pleura, mediastinum or chest wall, or cancers of other origin that have invaded the lung, and then, to determine eligibility for NCI investigational treatment studies for participants >18 years of age (adult participants only).
• To use clinically obtained biopsies (small pieces of tissue) of tumor and adjacent normal tissue from clinically indicated procedures (standard of care biopsy or surgery), as well as blood and urine samples, from participants with cancer of the lung, esophagus, pleura, mediastinum or chest wall, or cancers of other origin that have invaded the lung, for research into immune and cellular changes of these cancers. Study research includes genetic testing and the growth of laboratory cell lines from participant samples, to examine how genes change drug metabolism.
• To permit long-term follow-up of participants with cancer of the lung, esophagus, pleura, mediastinum or chest wall, or cancers of other origin that have invaded the lung, for natural history research on genetics and if the gene expression coincides with clinical response to patient anti-cancer therapies (treatment received at NCI or from participant's own physicians).

Eligibility:

• Individuals 2 years of age and older with potential (medically suspicious) or proven cancer of the lung, esophagus, pleura, mediastinum or chest wall, or cancers of other origin that have invaded the lung. Note: Individuals >= 2 years of age and under 18 years of age may only participate in research sample collection if the tissue acquisition is performed during a clinically indicated surgical procedure, and the sampling of tissue, blood or urine does NOT add risk to the clinically indicated procedures.
• Participants must have physical examination parameters within acceptable limits by standard of practice guidelines prior to clinically indicated surgical procedure (standard of care biopsy or surgery).

Design:

• All participants will undergo standard tests to evaluate the stage of their disease, and then, eligibility determination for NCI investigational treatment studies will be made for participants >18 years of age (adult participants only).

  • Participants >18 years of age (adult participants only) who are determined to be eligible for a treatment study at NCI are offered participation in that study. No investigational treatment is administered on this protocol.
  • Participants >= 2 years of age (all participants) may receive standard of care treatment at NCI or with their own physician if it is determined that standard of care surgery, radiation, or chemotherapy is more clinically appropriate for that participant's disease status.
  • Participants who receive standard of care biopsy or surgery (clinically indicated standard staging, surgical intervention, and follow up care) at the NIH Clinical Center are expected to return for a clinical examination visit post-procedure (for instance, 4 weeks after discharge from surgery). After recovery, participants will return to the NIH Clinical Center for study follow-up visits at intervals based on their clinical status (such as every 3 to 36 months) until the end of study participation.

• Blood and urine samples are collected from all participants for study research at baseline and study visits until the end of study participation. If participants have additional clinically indicated biopsies or surgeries, resected tissue may be collected for study research (as logistically appropriate).

• It is expected that up to 1,559 participants will be enrolled and followed long-term on this study.

Background:

• Lung and esophageal cancers as well as malignant pleural mesotheliomas exhibit epigenetic perturbations that may impact the clinical course of these neoplasms.
• To date, epigenetic alterations in primary thoracic malignancies and neoplasms metastatic to the chest have not been evaluated in a systematic, longitudinal manner.

Objectives:

• To permit evaluation of patients referred to the Thoracic Surgery Branch, NCI in order to identify individuals who will be suitable candidates for clinical research protocols.
• To use clinically obtained tumor and adjacent normal tissues as well as serum and urine samples from participants with primary or metastatic malignancies involving the lung, esophagus, pleura, and mediastinum to support preclinical research endeavors in the Thoracic Surgery Branch.
• To perform focused germline testing of genes modulating drug metabolism, possible future whole genome sequencing studies, possible ex vivo generation of autologous tumor cell lines and EBV-transformed B cell lines for research. Tumor tissue obtained during previous protocol participation and cryopreserved may undergo this process if the individual consents on this trial.
• To permit standard treatment for participants who are not eligible for investigational therapy on a current Thoracic Surgery protocol, but who present a novel and unique clinical training opportunity, or who manifest a clinical condition that requires immediate intervention to prevent compromise to the individual's well-being.
• To permit long term follow up of participants with thoracic malignancies including the collection of tissue and fluids to support preclinical research particularly to ascertain if gene expression and DNA methylation profiles coincide with response to therapy.

Eligibility:

• Individuals with potentially malignant or suspicious lesions or with biopsy proven, lung or esophageal cancers, malignant pleural mesotheliomas, mediastinal or chest wall neoplasms, thymoma/thymic neoplasms, or pulmonary metastases from cancers of nonthoracic origin.
• Individuals who have an ECOG performance score of 0-2.
• Participants must have physical examination parameters within acceptable limits by standard of practice guidelines prior to clinically indicated surgical procedure (biopsy or surgery).
• Age >= 2 years and older. Note: Individuals >= 2 years of age and under 18 years of age may only participate in research sample collection if the tissue acquisition is performed during a clinically indicated surgical procedure, and the sampling of tissue, blood or urine does not add risk to the clinically indicated procedures.

Design:

-This protocol is designed to:

--Facilitate screening of adult participants for investigational protocols in the Thoracic Surgery Branch, NCI. Adult participants will be screened to determine appropriate diagnostic and treatment interventions for their disease;

and

--As a tissue acquisition trial in which tissues will be obtained at the time of intervention from clinically indicated surgical procedures (i.e., standard of care biopsy or surgery) in order to enable evaluation of epigenetic events in primary and metastatic thoracic malignancies as an extension of ongoing laboratory research in the Thoracic Epigenetics Laboratory - including the establishment of tumor cell lines and EBVtransformed B cell lines to support immunologic evaluation of the participant's response to other clinical trials. Tissue, blood, and/or peritoneal/pleural effusion samples obtained during surgery/biopsy or clinic visits will be processed and either

stored for analysis or cultured for generation of tumor cell lines and EBV-transformed B cell lines for research.

• Where appropriate, participants will receive clinically indicated standard staging, surgical intervention, and follow up care. After recovery from the clinically indicated biopsy or surgery participants will continue to be followed on this study, and blood and urine samples may be collected for research purposes; tissue from further clinically indicated procedures may be collected as well when appropriate.
• No investigational treatment will be administered on this protocol. In circumstances approved by the Section Chief, a participant may be deemed ineligible for investigational therapy, yet may undergo standard of care treatment at the NIH Clinical Center on this study.
• It is anticipated that up to 1,559 participants will be enrolled and followed on this study.

• INCLUSION CRITERIA:

Individuals with potentially malignant or suspicious lesions, or with biopsy proven lung cancers or esophageal cancers, malignant pleural mesotheliomas, mediastinal or chest wall neoplasms, thymoma/thymic carcinomas, or thoracic metastases from cancers of non-thoracic origin.

Individuals must have an ECOG performance score of 0-2.

Participants must:

-Have physical examination parameters within acceptable limits by standard of practice guidelines prior to clinically indicated surgical procedure (e.g., biopsy or surgery),

and

-Be aware of the nature of his/her illness,

and

-Must be willing to undergo clinically indicated standard intervention that may include endoscopic biopsies of tumor and adjacent normal tissues (i.e., other tissue necessary to obtain negative margins per standard of care surgical processes) as a part of their standard of care treatment plan.

Participants must agree to provide blood and urine samples to support ongoing laboratory research endeavors pertaining to the epigenetics of thoracic malignancies.

Individuals must be 2 years of age or older. Note: Individuals >= 2 and < 18 years of age may only participate in research sample collection if the tissue acquisition is performed during a clinically indicated surgical procedure (e.g., biopsy or surgery), and the biospecimen sampling (e.g., blood, urine, [clinically indicated] resected tumor tissue) does not add risk to the clinically indicated procedures.

Ability of participant, their parents/guardians or legally authorized representative (LAR) to understand and the willingness to sign a written informed consent document.

EXCLUSION CRITERIA:

None.