NK Cell Activity in Smokers Screened for Lung Cancer

Lung cancer is the leading cause of cancer mortality in the United States. Despite
considerable clinical research in multi-modality cancer treatment, there has been no
significant decrease in lung cancer-specific mortality over the past three decades. The
recent results of the National Lung Screening Trial (NLST) established that screening
high-risk individuals using low-dose CT (LDCT) significantly reduces lung cancer-related
mortality. One caveat is that approximately 96% of the "positive" results in the NLST were
found not to be related to lung cancer. The difficulty in determining which subjects with
suspicious lesions should be biopsied or operated on could be alleviated by the development
of highly specific lung cancer biomarkers that could complement LDCT. Thus, novel,
complementary, non-invasive diagnostic tools with high sensitivity and specificity would
clearly be of enormous benefit to patients with a "positive" screening exam. This study will
look at measuring the activity of natural killer (NK) cells using the in vitro diagnostic
device NK Vue™ in a cohort of current and former smokers (n=100) who meet the criteria for
LDCT screening established by the National Comprehensive Cancer Network (NCCN) as a result of
the positive findings from the NLST. This project is aimed at measuring the NK cell activity,
which may eventually help in reducing false positive rates of LDCT screening, improve early
detection of lung cancer, and assist in risk assessment in patients with lung cancer. The
Investigators hypothesize that measurement of NK cell activity may be a useful tool for
assessing changes in immunosurveillance in patients with conditions or diseases where NK cell
activity has been shown to be reduced, such as lung cancer.

Objectives Specific Aim 1: To examine whether NK cell activity associates with two confirmed
risk factors: (1) presence of indeterminate lung nodule(s) and (2) smoking exposure after
controlling for potential confounders, including age, gender, body mass index (BMI), personal
history of any cancer, and family history of cancer.

Specific Aim 2 (Exploratory): In the study cohort, investigators expect approximately 45% of
patients having at least one indeterminate lung nodule. Among those with lung nodule(s),
investigators will examine whether NK cell activity associates with size of the largest lung
nodule after controlling for potential confounders, including smoking exposure, age, gender,
BMI, personal history of any cancer, and family history of cancer

Inclusion Criteria:

- At the time of registration, subjects must have a current or previous cumulative
cigarette smoking history of ≥ 20 pack years (packs per day multiplied by the number
of years smoked). If smoking history is between 20 and 29 pack years, subjects must
have an additional risk factor (i.e. radon exposure, occupational exposure, personal
history of smoking-associated cancer, family history of lung cancer in first-degree
relatives, COPD or pulmonary fibrosis).

- At the time of registration former smokers without additional risk factor(s) must have
quit smoking within the preceding 15 years.

- Subjects must be willing to provide blood samples as biospecimens for the study.

- At the time of registration, subjects must have recovered from the toxic effects of
prior therapy: ≥6 months (182 days) from the last dose of prior cytotoxic therapy.

- At the time of registration, subjects must have recovered from the effects of prior
pneumonia or acute respiratory infection treated by antibiotics by a physician: ≥12
weeks (84 days) from the first dose of antibiotics.

Exclusion Criteria:

- Medical or psychiatric condition precluding informed medical consent.

- Prior history of lung cancer.

- Treatment for or advisement by a physician of evidence of any cancer within the past
five years, with the exceptions of non-melanoma skin cancer and most in-situ
carcinomas. (Treatment for, or evidence of, melanoma or in-situ bladder/transition
cell carcinomas within the preceding five years renders the potential participant
ineligible.)