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

Background:

• Lung and esophageal cancers as well as malignant pleural mesotheliomas exhibit profound alterations in chromatin structure, which 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 manner.

Objectives:

• To permit evaluation of patients referred to the Thoracic Oncology Section, Surgery Branch, NCI in order to identify individuals who will be suitable candidates for clinical research protocols.
• To obtain biopsies during staging studies of tumor and adjacent normal tissues as well as serum and urine samples from patients with primary or metastatic malignancies involving the lung, esophagus, pleura, and mediastinum to support preclinical research endeavors in the Thoracic Oncology Section.
• To obtain blood, tumor tissue or malignant peritoneal/pleural effusions from patients with lung, esophageal, mediastinal, or chest wall malignancies for 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 patient consents on this trial.
• To permit standard treatment for patients who are not eligible for investigational therapy on a current Thoracic Oncology 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 patient’s well-being.
• To permit long term follow up of patients 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:

• Patients with radiographic evidence of, or histologically/cytologically proven, lung cancers or esophageal cancers, malignant pleural mesotheliomas, mediastinal or chest wall neoplasms, or pulmonary metastases from cancers of non-thoracic origin.
• Patients with concomitant intracranial metastases, which are potentially treatable by surgery and/or radiation therapy are eligible for study.
• Patients who have an ECOG performance score of 0-2.
• Patients under 18 years of age may participate if the tissue acquisition is performed during a clinically indicated surgical procedure, and the sampling of tissue, blood and urine does not add risk to the clinically indicated procedures.
• Patients must have coagulation parameters within acceptable limits by standard of practice guidelines prior to biopsy.

Design:

• This protocol is designed to:
  • facilitate screening of patients for investigational protocols in the Thoracic Oncology Section, Surgery Branch, NCI, and in doing so, obtain tissue samples to enable evaluation of epigenetic events in primary and metastatic thoracic malignancies, as an extension of ongoing laboratory research in the Thoracic Oncology laboratory.
  • allow for the establishment of tumor cell lines and EBV-transformed B cell lines to support immunologic evaluation of the patient’s response to other clinical trials.
• Patients will be screened to determine appropriate diagnostic and treatment interventions. Where appropriate, patients will receive staging and surgical intervention and necessary follow up care. Tissue, blood, and/or peritoneal/pleural effusion samples obtained during surgery/biopsy or clinic visit will be processed and either stored for analysis or cultured for generation of tumor cell lines and EBV-transformed B cell lines for research. After recovery from biopsy or surgery patients will continue to be followed, blood and urine samples will be collected as well as tissue when appropriate.
• No investigational treatment will be administered on this protocol. In circumstances approved by the Section Chief, a patient may be deemed ineligible for investigational therapy, yet may present a unique clinical training experience for Thoracic Oncology Section physicians and clinical associates, and undergo standard treatment.
• It is anticipated that the protocol will enroll 75 patients per year over 5 years for a total of 375 patients.

Eligibility Criteria

Inclusion Criteria

Patients with radiographic evidence of, or histologically/cytologically 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, are eligible for evaluation.

Patients with concomitant intracranial metastases, which are potentially treatable by surgery and/or radiation therapy are eligible for study.

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

Patients must be 18 years of age or older. Patients under 18 years of age may participate if the tissue acquisition is performed during a clinically indicated surgical procedure, and the sampling of tissue, blood and urine does not add risk to the clinically indicated procedures.

Patients must be aware of the neoplastic nature of his/her illness. The patient or parent must be willing to sign an Informed Consent, and undergo endoscopic biopsies of tumor and adjacent normal tissues, and provide blood (30cc) and urine (100cc) samples to support ongoing laboratory research endeavors pertaining to the thoracic malignancies.

Patients must have physical examination findings within acceptable limits by standard of practice guidelines prior to biopsy or surgery.

Patients must have lab values within the following parameters:

• ANC greater than or equal to 1000
• Platelet count greater than or equal to 75,000
• PT less than or equal to 16 or INR less than or equal to 2
• Creatinine less than 2.5 G/Dl
• Bilirubin less than or equal to 2 times upper limit of normal

Exclusion Criteria:

Candidates who do not meet the inclusion criteria