Circulating Cell-Free DNA in Plasma/Serum of Lung Cancer Patients as a Potential Screening and Prognostic Tool

BACKGROUND: Evaluation of tumor-specific circulating DNA in plasma/serum is a promising noninvasive diagnostic and prognostic tool requiring only a blood sample, which circumvents the logistic difficulties associated with the use of invasive procedures for serial tumor samplings during screening of lung cancer. METHODS: We reviewed English-language reports published in the MEDLINE database that provided the results of qualitative and quantitative studies on circulating DNA in serum/plasma of lung cancer patients. We searched the bibliographies of the retrieved reports and reviews. Abstracts presented at the 2003, 2004, and 2005 annual meetings of the American Society of Clinical Oncology were also reviewed. RESULTS: More than 80 citations were retrieved, of which 33 met our criteria: 22 qualitative studies, and 11 quantitative studies. The studies varied in the choice of markers, frequency of alterations, sensitivities of used methodologies, sample sizes, treatment protocols, and prognostic correlates evaluated. CONCLUSIONS: The findings from the studies on serum/plasma DNA suggest that it would be possible to develop a simple blood test with high sensitivity and specificity that has potential for screening of high-risk individuals, for prognostic or staging purposes, and to be used as intermediate end-points of efficacy in chemo-prevention and therapeutic trials. However, further work is needed to identify additional biomarkers and to standardize present techniques for sample collection, processing, and analysis. Large prospective studies with long follow-ups are essential to eventually integrate blood marker-based assays into the clinical setting.