The Correlation between Plasma Circulating Tumor DNA and Radiographic Tumor Burden

Conventional blood-based biomarkers and radiographic imaging are excellent for use in monitoring different aspects of malignant disease, but given their specific shortcomings, their integration with other, complementary markers such as plasma circulating tumor DNA (ctDNA) will be beneficial toward a precision medicine- driven future. Plasma ctDNA analysis utilizes the measurement of cancer-specific molecular alterations in a variety of bodily fl uids released by dying tumor cells to monitor and profile response to therapy, and is being employed in several clinical scenarios. Plasma concentrations of ctDNA have been reported to correlate with tumor burden. However, the strength of this association is generally poor and highly variable, confounding the interpretation of longitudinal plasma ctDNA measurements in conjunction with routine radiographic assessments. Herein is discussed what is currently understood with respect to the fundamental characteristics of tumor growth that dictate plasma ctDNA concentrations, with a perspective on its interpretation in conjunction with radiographically determined tumor burden assessments. (J Mol Diagn 2024, 26: 952-961; https://doi.org/ 10.1016/j.jmoldx.2024.07.001)