CDMRP 2012 Investigator Vignette

Title: Detection of Early Lung Cancer Among Military Personnel (DECAMP)

Investigator: Avrum Spira, M.D., M.Sc.; Boston University Medical Campus

In this grant we've put together a consortium called DECAMP or Detection of Early Lung Cancer among military personnel. It's a consortium of more than 14 centers in the United States. Most of them are military facilities and Veteran Administration Hospitals where patients are going to be recruited. And the goal of the whole consortium is to develop and validate early detection molecular biomarkers for lung cancer in the military personnel and veteran population.

Lung cancer is the number one killer of all cancers both here in the United States and the rest of the world. And that's true now with men and women. And-and the major reason for that is it's almost always detected at an advanced stage where cure is not possible. And I've said the main reason for that is we-it's a very difficult disease to detect. By the time someone presents with symptoms most often that disease has metastasized and therefore we can no longer cure it.

And we know it's associated with exposures to a number of toxins, so specifically cigarette smoke is known to be causative in lung carcinogenesis or lung cancer. We know that only about 10 to 15% of people who smoke will get lung cancer, but 90% of people in this country who get lung cancer have a history of smoking. And so this is a challenge for us; how do we identify that subset of people who have the exposure and are going to go on and get lung cancer?

And so, 2 years ago the Department of Defense came out with an initiative to fund groups that were developing early detection strategies for lung cancer. I work at the Veterans Hospital here in Boston; we see a tremendous burden of lung cancer among veterans and military personnel specifically they have much higher rates of smoking, they're exposed to other carcinogens during their service time, and we often again don't detect the disease early enough to cure it.

And so when this announcement came out from the Department of Defense that they wanted to fund research into the early detection of lung cancer among military personnel and veterans we thought it was a perfect fit since our lab for the last decade has been working on early detection of cancer and we thought we really want to push it into the military and veteran personnel.

So one of the reasons lung cancer is hard to detect early is it arises very deep in your lung and it's very hard to get access to that compartment. So what we've done in this proposal is we've decided to go after less invasive sites, specifically the cells that line your windpipe or your airway that are also exposed to all the toxins in cigarette smoke or any of the other carcinogens that a military person might be exposed to.

We then take those cells out and immediately put them onto a microarray where we can actually measure on a single assay the activity of all 20,000 genes in your cell in a simple two or three-day experiment and determine which genes are turned on and off secondary to that exposure and as a result of that whether you're at increased risk or decreased risk for going on to develop lung cancer.

And I think that's an incredibly innovative part of our proposal. I think the other really innovative piece is that we're combining molecular markers. So we're not only measuring one type of molecule in these cells, we're actually measuring four or five different types of molecular markers and looking to combine them into a single, early detection biomarker. And that's a very unique strategy. It's multidisciplinary in many ways.

This whole consortium in a sense is a marriage between leading groups that do molecular biomarkers for the early detection of lung cancer, including my own. And we have a number of groups through the country that are working with us, including Pierre Massion at Vanderbilt University, Steve Dubinett at UCLA, and a number of other good groups. And we've been marrying this-this early detection biomarker group with a very good clinical trials group called ACRIN, which is the American College of Radiology Imaging Network. It's run by a radiologist named Mitch Schnall and he's the co-principal investigator with me on this consortium. And what they're going to do is help build the infrastructure to collect and recruit all these patients and all the biosamples from 11 clinical sites. And that's an incredible undertaking.

And we're very fortunate that there was sufficient funding through this mechanism from the DoD to bring together a lot of the leading lung cancer groups that would normally compete for funding to work together under the same umbrella and try and put together all the molecular biomarkers in the same study and potentially create a better biomarker for the early detection of lung cancer.

And the infrastructure that we develop can be leveraged for future studies for decades to come. To have put together a cohort of this size that we're going to follow for 5 years here, really sets the stage to follow this cohort for many more years beyond the scope of this proposal and do additional types of clinical and translational studies. And that to me -that's actually the most exciting part of the whole DECAMP consortium.

If we're able to develop early detection biomarkers that can distinguish a benign nodule on a CT scan from a cancer that would have an immediate impact on the way we practice medicine and the way we evaluate people with abnormalities on the CTs.

I think the second impact is with screening, detecting people before they get lung cancer. If we had a way to identify people who are at higher risk years before they actually develop lung cancer, those are the people we could say you need to get CT scanned annually to be really closely watched and those are the people we could offer preventive therapy before they actually get lung cancer.

My true belief in my heart of hearts is this is a disease that we need to prevent. Once you get lung cancer it's incredibly hard to treat especially at a later stage. If we can get people before they get the disease and reverse their risk by giving them a medication or a drug that actually reverses the genomic abnormalities that are in these cells that is going to be ultimately the way to have the biggest bang for the buck with this disease. And that second project that we're doing gives us the ability to identify people before they get disease and therefore intervene at the earliest possible stage.