Biomarkers play a significant role in screening for early lung cancer.
Military personnel, both active and veteran, have a high risk of lung cancer. To improve the rate of early detection of the disease, the Detection of Early Lung Cancer Among Military Personnel (DECAMP) Consortium has begun its first research protocol, with both the Boston University School of Medicine and ACRIN® playing key project roles.
DECAMP is a five-year, multicenter, multiphase project funded by a $13.6 million grant from the United States Department of Defense. Its aim is to develop novel technologies for the early detection of lung cancer. Specifically, the research has focused on the challenges identified in early detection of the disease, which were highlighted in the results of the National Lung Screening Trial (NLST), a collaborative effort between ACRIN and the National Cancer Institute's Lung Screening Study network.
Lung cancer continues to be the deadliest form of cancer both in the United States and the world, and the mortality rate has not changed during the past three decades. "Current lung cancer detection methods involve an invasive procedure that is often done only after symptoms occur, and by that time, the cancer has spread and is difficult to treat," notes DECAMP Co-principal Investigator Avrum Spira, MD, MSc, chief of the division of computational biomedicine within the department of medicine and associate professor of medicine, pathology, and bioinformatics at Boston University School of Medicine.
The outlook is even more discouraging within the population of military personnel and veterans, whose lung cancer rate is as much as two times higher than that of the general population. Studies have demonstrated significantly higher smoking rates among military personnel since the late 1990s, especially among deployed personnel, whose smoking rate is 50 percent higher than that of their nondeployed counterparts. In addition, exposure to radon, asbestos, depleted uranium, beryllium, fuel exhaust, and other battlefield emissions is also elevated among this population.
Lessons Learned From NLST
To determine whether screening a population at high risk for lung cancer with low-dose helical CT results in a mortality benefit, the eight-year NCI-funded NLST was conducted at 33 U.S. sites between 2002 and 2010 and compared low-dose helical CT with chest radiography in the screening of 53,456 older current and former heavy smokers. The study's findings of a 20 percent decrease in lung cancer mortality associated with CT scanning were tempered by an accompanying false-positive rate in which 37 percent of nodules considered positive for lung cancer on CT turned out to be noncancerous following more invasive follow-up. The study also highlighted the lack of effective biomarkers to identify the subset of smokers most likely to benefit from CT screening.
DECAMP Consortium Structure
Building on the NLST study, the DECAMP Consortium is pursuing the development and validation of molecular biomarkers to determine which of the many indeterminate lung nodules identified by CT are malignant in order to further refine the population at high-risk for lung cancer, thereby increasing screening efficacy, and to reduce the cost and morbidity associated with screening. Formulating and carrying out this research has necessitated bringing together leading academic groups in the field of lung cancer biomarker research, pathology laboratories with longstanding experience supporting biospeciman collection and storage, biostatistics groups highly regarded for data management and analysis, and clinical leaders with lung cancer diagnosis and management specialties at military and veteran hospitals across the country (see sidebar on page 27). Patients are enrolled in the trials at four military hospitals, seven VA hospitals, and one academic hospital.
“Lung cancer is the most lethal of all cancers, and this research could potentially lead to fewer people dying from the disease.” — Avrum Spira, MD, MSc
DECAMP Study 1
The primary aim of the first study, Diagnosis and Surveillance of Indeterminate Pulmonary Modules, is to determine the diagnostic accuracy of previously established gene-expression and protein biomarkers in the airway and blood to detect lung cancer. Secondary aims are to evaluate the value of the molecular biomarkers in relation to other clinical and imaging markers routinely used in the diagnostic workup of indeterminate pulmonary nodules and to develop a more robust, integrated model for diagnostic prediction.
Already underway, the study will enroll 500 current or former smokers, ages 50 years and older, diagnosed with an indeterminate pulmonary nodule by chest CT. Participants provide sputum, blood, urine, cells, and tissue biospecimens, which are stored for future studies. In addition, researchers conduct fiber-optic bronchoscopy to view the lung airways, collect a nodule tissue sample, and obtain brushings from the nose and throat and scrapings from the mouth. Participants are followed with clinical examinations and imaging for a two-year period. If surgery is advised, tissue from the tumor is collected for future trial use.
DECAMP Study 2
The goal of a second DECAMP study is to identify whether any of the minimally invasive or noninvasive molecular biomarkers developed in the high-risk lung cancer setting can predict which smokers, among those without symptoms or CT-identified abnormalities, are at risk for further development of lung cancer. The approximately 1,000 high-risk individuals to be recruited for this phase, which is still being developed, will receive follow-up examinations for four to five years in an effort to identify the subset of the screening-eligible population who might benefit most from annual CT scans and treatment with new therapies.
"The noninvasive methods we will work to develop will have the capability to distinguish between patients with or without lung cancer, as well as identify patients who show early signs of a higher risk for the disease," says Spira. "Lung cancer is the most lethal of all cancers, and this research could potentially lead to fewer people dying from the disease."
It Takes a Consortium
Identifying noninvasive ways to detect lung cancer early is a daunting undertaking, and the DECAMP Consortium is the largest collective of researchers dedicated to this objective. The sheer number of medical and scientific specialties, experts, and research sites involved makes close collaboration among the various trial components a major priority.
Mitchell D. Schnall, MD, PhD, FACR, Matthew J. Wilson Professor of Radiology at the University of Pennsylvania, and chair of ACRIN, who serves as co-principal investigator for these research efforts, says, "It has been exciting to see the DECAMP components come together to support this important research that builds upon what we learned from the NLST. The research personnel at the 12 designated participating sites have demonstrated much enthusiasm for getting their respective sites up and running and on to the next step of study participant accrual."
By Nancy Fredericks, MBA, and Julie Catagnus, MPH, ELS