UK HealthCare Publications » Advances & Insights » Cancer »
A new test that looks at the immune system's response to the most common type of lung cancer accurately predicts the disease years before detection by CT scans, according to a recent study by University of Kentucky researchers.
The test could be a valuable tool for early detection of non-small cell lung cancer, significantly improving the patient's chances of survival.
The UK team, led by Dr. Edward A. Hirschowitz and Dr. Li Zhong, set out to explore the use of auto-antibody profiling as a means of lung cancer screening. The test they developed would better define who should get CT scans, which are costly and yield a high number of false positives when used in the general population. Their findings are published in the July 2006 issue of the Journal of Thoracic Oncology.
Cancerous cells express protein antigens that are alien to the body, leading the immune system to produce antibodies that attack the antigens. Such antibodies could be used as biologic markers for tumors, meaning the presence of the antibodies might signal the presence of cancer cells. However, developing a test that easily recognizes a particular set of antibodies specific to lung cancer has been elusive because such cancers produce hundreds of antigens and antibody reactions, none of which are universally present in all cases.
"Our goal was to look at corresponding antibodies that recognize these antigens in the early stages and use them as markers for lung cancer," Dr. Hirschowitz said. "The system we developed allowed us to sort through the millions of antigens and antibodies, identify those that correspond to cancer and define a combination that affords the best prediction of a sample being from a cancer patient or not."
The team was able to correctly identify nearly 90 percent of the cancer cases with very few false positives.
In applying a statistical combination of five of the most individually predictive markers, the team tested a group of 23 patients with early stage cancer and 23 subjects without a cancer diagnosis as a control. The team was able to correctly identify nearly 90 percent of the cancer cases with very few false positives. By comparison, CT screening has a false-positive rate of more than 40 percent.
The next step in the study was to test blood taken from lung cancer patients several years before their diagnosis. Using the five most predictive cancer markers, they tested 102 blood samples drawn from participants in the Mayo Clinic Lung Cancer Trial. The researchers found that the presence and amounts of the five antibodies in the blood predicted non-small cell lung cancer with about 85 percent accuracy. The data suggests that lung cancer may be present three to five years before reaching the size needed to be picked up by a CT scan, about 0.5 mm.
The new study was admittedly a small one, so UK is moving forward to confirm the results in a larger number of samples. 20/20 GeneSystems, Inc. is co-developing the multibiomarker blood test with the UK team using funding from the National Institutes of Health. For the next two years, researchers will work to develop the clinical application for the blood test.
"Our hope is that in another five years, this test will be available for doctors to use on high-risk patients," Dr. Zhong said.
In addition, he noted, more biomarkers identified by the research team may prove to be useful in pinpointing non-small cell lung cancer. There is also the possibility a similar test could be developed for small-cell lung cancer.
For more information, see:
• Kentucky Lung Cancer Research Program, Markey Cancer Center, UK HealthCare • What is cancer? Cancer overview • What causes cancer? • How is cancer diagnosed? • About clinical trials: information from the National Cancer Institute
For more information, or to make an appointment with a UK HealthCare physician, please call UK Health Connection at 1-800-333-8874.
Printable PDF (405 KB)
Lung cancer is the leading cause of cancer death for both men and women in the United States. Nearly 90 percent of the 170,000 people who develop the disease each year will die from it. That's more than the death rates from breast, prostate and colorectal cancers combined. In Kentucky, the incidence of this disease is 49 percent higher than the national rate.
"Outcomes for patients are poor because lung cancer usually is not diagnosed until the advanced stages."
Outcomes for patients are poor because lung cancer usually is not diagnosed until the advanced stages. Generally, there are no good screening tests for this disease. The use of X-rays, sputum samples and CT scans for screening hasn't been proven to decrease mortality. So it makes a lot of sense to develop a means of early detection when the disease is more amenable to curative surgery.
Since cigarette smoking is the major cause of lung cancer, our test would be used to prescreen patients who are 55 or older and have smoked for 20 years. If the biologic markers for non-small cell lung cancer are found, they could then undergo a series of CT scans and smoking cessation programs.
We chose non-small cell lung cancer for our testing because it accounts for 80 percent of all lung cancers. Small-cell lung cancers grow fast and spread early. Even detecting these tumors when they are very small won't change the outcome. By the time they show up on a CT scan, the cancer has already spread to other parts of the body. The average survival rate is six months.
Non-small cell lung cancer has an average five-year survival rate of only 40 percent. Generally, this type of cancer spreads to other parts of the body more slowly than small cell lung cancer. However, the majority of the tumors are not diagnosed until the advanced stages, in part because the patient is often asymptomatic but also because the early stage disease may not be picked up on a radiographic scan.
Lung cancer is a very heterogeneous disease. It doesn't make a lot of any one particular protein, or antigen. Prostate cancer, on the other hand, expresses very large amounts of PSA, or prostate specific antigen, which can be checked with a blood test.
No one particular lung cancer expresses 100 percent of all the known lung cancer antigens, so we decided to look at those made by 5 - 20 percent of all lung cancers. Our goal is to look at the corresponding antibodies the immune system develops in response to these antigens and use the antibodies as biologic markers for the presence of lung cancer.
"With this test, we may be able to identify people who are likely to develop cancer and get them to modify their lifestyle."
Today there are no therapies for treating the early stages of non-small cell lung cancer. It's too soon to do chemotherapy or surgery at that stage. Dietary supplements like selenium are probably the least harmful medications. Ultimately, as better drugs with fewer side effects are developed, we will be able to treat people who are at high risk for lung cancer before they actually develop the disease.
With this test, we may be able to identify people who are likely to develop cancer and get them to modify their lifestyle. The caveat here is that we are looking at smokers, and smokers use cigarettes as a crutch. The question is, will the test cause stress that leads them to keep smoking? Along with the effectiveness of the test, the FDA will want to know how patients will react to the results.
It certainly wouldn't be advisable to use the results of this test and give the patient chemotherapy or perform surgery without corresponding information that verifies the cancer. But if, at the very least, we give a patient extra health care maintenance as a result of this test, no harm has been done.
Dr. Hirschowitz is a specialist in pulmonary and critical care medicine on staff at the Markey Cancer Center and associate professor of internal medicine at the UK College of Medicine. He has a special interest in treating lung cancer.
Each issue of Advances & Insights summarizes an important piece of medical news, accompanied by commentary from a UK expert.
Subscribe here or call 859-257-1000 and provide your mailing address.
1000 S. Limestone
800-333-8874 (toll free)
connected with UK HealthCare. Become a fan of our Facebook and follow us on
Twitter and Youtube to stay up-to-date on community events, programs,
treatments, research, new physicians and more.
© University of Kentucky, Lexington, Kentucky, USA | An Equal Opportunity University