Bazan, J. G., Chang, P., Balog, R., Annalisa, D., Shaler, T., Lin, H., . . . Knox, S. J. (2013, 22-25 September). Novel human radiation exposure biomarker panel applicable for patient triage. Paper presented at the Annual Meeting of the American Society for Radiation Oncology (ASTRO ’13), Atlandta, GA.
To identify a panel of radiation-responsive plasma proteins that could be used in a point of care biological dosimeter to detect clinically significant levels of ionizing radiation exposure to facilitate appropriate triage of exposed individuals.
Patients undergoing preparation for non-myeloablative or myeloablative hematopoietic cell transplant using radiation therapy (RT) with either total lymphoid irradiation (TLI) or fractionated total body irradiation (fTBI) were eligible and recruited for this study. Plasma samples from healthy individuals and patients with potentially confounding conditions were also analyzed. The circulatory levels of a 17 candidate proteins were measured prior to initiation of RT and at several timepoints post-RT exposure. Paired and unpaired t-tests between dose and control groups were performed. Conditional inference trees were constructed based on combination panels of three or more proteins to evaluate the statistical significant differences between the non-RT and the RT groups.
A total of 151 patients (62 RT, 41 infection, 48 trauma) were enrolled on the study and the plasma from an additional 24 healthy controls were analyzed. Compared to controls, tenascin-C was upregulated and clusterin was down-regulated in patients receiving RT. Salivary amylase was also strongly radiation-responsive, with significant up-regulation in fTBI patients and slight downregulation in TLI patients compared to controls. A panel consisting of these three proteins could clearly distinguish the irradiated and control subject samples with 97% accuracy, a 0.5% false-negative rate and a 2% false-positive rate.
A panel of only three proteins (salivary amylase, tenascin-C, clusterin) is sufficient to accurately distinguish an individual that was exposed to low-levels of ionizing radiation from an unexposed person. These findings have significant implications in terms of being able to triage individuals in the case of unanticipated nuclear or radiological events.