This study will examine patients with non-small cell lung cancer metastasis, that is, the
distant spreading of tumors to the brain, and compare them with patients without brain
metastasis. The molecular and genetic events that permit tumor metastasis are not well
understood. There is intense investigation going on into the process in which tumor cells
escape the primary local tumor, spread to distant places in the body, and find and create
conditions that promote growth in those tissues. Metastasis of tumors such as lung cancer
to the brain is a common problem. Tumor cells will be analyzed with the use of microarrays.
A microarray is a tool for analyzing gene expression, consisting of a small membrane or
glass slide containing samples of many genes arranged in a regular pattern. The goal is to
identify a potential molecular signature. It is hoped that there will be discovery of why
some patients are more likely than others to develop a brain metastasis, which can have a
major negative effect on the quality of life and survival.
Patients 18 years of age with known or evidence by radiology of a non-small cell lung cancer
metastatic to the brain, either squamous cells or adenocarcinoma tumors, or those who have
had a removal of a brain tumor for diagnosis or treatment may be eligible for this study.
Participants will undergo the following procedures and tests:
- Craniotomy, that is, surgical opening of the skull, and removal of the brain tumor.
- Blood specimens taken from a central vein or artery before the operation, throughout as
needed, and for several days afterward, to measure blood chemistries, blood count, and
- Physical examination and imaging of the central nervous system before and after
- Urine or serum, or both, pregnancy test of women of childbearing potential.
Patients will also undergo blood tests at 3-month intervals after surgery for up to 5 years.
The purpose is to determine if there are tumor cells in the blood, which may explain how
they reached the brain.
Introduction: The molecular and genetic events that permit tumor metastasis are not well
understood. The process whereby tumor cells escape the primary, local tumor, spread to
distant sites in the body and find and create conditions conducive to growth in these
disparate tissues remains an area of intense investigation. Metastasis of epithelial
tumors, such as lung cancer, to the brain is a common problem, with significant consequences
with respect to neurological dysfunction and shortening of survival.
Objective: To study two subset of patients with non small cell lung cancer (NSCLC)
metastatic to the brain, to identify genes and proteins that facilitate metastasis.
Study Population: 78 patients with NSCLC (n=39 squamous cell (SQ), and n=39 adenocarcinoma
(AC) tumors) metastatic to the brain to compare with published microarray studies of
non-metastatic NSCLC patients with these tumor types as well as with one another to help
explain the differential trend toward metastasis in some patients with NSCLC and not others,
as well as the differential trend to brain metastasis in the AC subtype.
Anticipated Risks and Benefits: Less than minimal risk to the patients to sample tissue
already removed from the brain as part of medically-necessary surgery and to sample blood.
No direct benefit to the patient is expected.
Outcome Estimate and Potential Meaning for the Field: That this very detailed investigation
of the genes and proteins expressed differentially between the non-metastatic and metastatic
NSCLCs, as well as between SQ and AC subtypes will identify new or previously-unsuspected
targets for new therapies to either prevent the development of brain metastasis or to treat
brain metastases more effectively.
1. A patient with a known or with radiographic evidence of a NSCLC neoplasm metastatic
to the brain, either SQ or AC.
2. Medically-indicated (diagnostic and/or therapeutic) brain tumor resection.
3. Informed consent from female patient, age 18 or older. In general, patients less
than 18 years of age rarely have NSCLC metastatic to the brain.
1. Inability to provide informed consent prior to surgery.
2. Medical conditions that cannot be corrected prior to surgery that would be standard
contraindications for craniotomy (brain tumor patients).