Cancer-Associated Macrophagelike (CAML) Cells to Enhance Detection of Early-Stage Lung Cancer and Relapse After Definitive Treatment
Abstract
Background: The National Lung Screening Trial (NLST), for which the Principal Investigator was a member of the endpoint verification committee, determined that low-dose CT screening could decrease lung cancer death by 20%. However, almost 25% of screened subjects were determined to have pulmonary nodules, with only 1.5% actually demonstrated to be malignant. This very high false positive rate results in several critical problems, including the requirement for further testing (scans, biopsies), the potential of loss to follow-up, the possibility of false negative biopsies, and resultant patient stress and anxiety. Nodules between from .8 and 3.0 cm have been described as “indeterminate” and represent a management challenge. Recently, we published preliminary data on the presence of CAMLs, which are specialized immune cells transiting the circulation of patients that have engulfed tumor cells or tumor material in a variety of malignancies, as well as their clinical use in tracking cancer progression and evolution in response to therapy. CAMLs are rarely found in healthy controls and are easily identified by filtration methods. We have completed preliminary assessments in lung, breast, and other cancers that indicate such cells occur at early stages of the disease and can indicate whether X-ray abnormalities are truly cancer versus benign tissues. Area of Emphasis: “Identify, develop, or optimize noninvasive or minimally invasive tools to improve the detection of the initial stages of lung cancer, such as, but not limited to, optimizing strategies for management of indeterminate nodules.” Hypothesis: CAMLs can substantially enrich for the presence of malignancy in the population of patients with pulmonary nodules. Impact: The proposed study would have substantial clinical impact in that it will provide critical data for validation of a methodology that would allow earlier intervention in patients with a high likelihood of having malignant nodules and avoid interventions in patients who have nodules that are less likely to harbor malignancy. This has the potential to both improve outcomes and decrease costs. Following completion of the trial and assuming that our preliminary results are confirmed, we anticipate rapid development of a commercially available test. Therefore, such testing could be available in approximately 5 years. Military Relevance: Military members have a high degree of pulmonary carcinogen exposure, both from tobacco and non-tobacco carcinogens (asbestos). In studies of Veterans, almost twice as many pulmonary nodules were seen as in the NLST. To ensure that patients from the Department of Veterans Affairs (VA) population are evaluated, we will enroll patients from the Philadelphia VA Medical Center. This is particularly important, as recent studies indicate that the VA (and likely military facilities as well) does not have adequate equipment or manpower to meet current screening recommendations. Therefore, an approach that uses a simple blood test to enrich for the patients that require more extensive diagnostic procedures would be particularly important.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Oct 29, 2018
- Source ID
- W81XWH1810196
Entities
People
- Martin Edelman
Organizations
- United States Army