Radiogenomic Analysis of Locally Advanced Lung Cancer Based on CT Imaging and Intratreatment Changes in Cell-Free DNA

The radiologic appearance of locally advanced lung cancer may be linked to molecular changes of the disease during treatment, but characteristics of this phenomenon are poorly understood. Radiomics, liquid biopsy of cell-free DNA (cfDNA), and next-generation sequencing of circulating tumor DNA (ctDNA) encode tumor-specific radiogenomic expression patterns that can be probed to study this problem. Preliminary findings are reported from a radiogenomic analysis of CT imaging, cfDNA, and ctDNA in 24 patients (median age, 64 years; range, 49-74 years) with stage III lung cancer undergoing chemoradiation on a prospective pilot study (NCT00921739) between September 2009 and September 2014. Unsupervised clustering of radiomic signatures resulted in two clusters that were associated with ctDNA mutations ( = .03) and changes in cfDNA concentration after 2 weeks of chemoradiation ( = .02). The radiomic features dissimilarity (hazard ratio [HR] = 0.56; = .05), joint entropy (HR = 0.56; = .04), sum entropy (HR = 0.53; = .02), and normalized inverse difference (HR = 1.77; = .05) were associated with overall survival. These results suggest heterogeneous and low-attenuating disease without a detectable ctDNA mutation was associated with early surges of cfDNA concentration in response to therapy and a generally better prognosis. CT-Quantitative, Radiation Therapy, Lung, Computer Applications-3D, Oncology, Tumor Response, Outcomes Analysis Clinical trial registration no. NCT00921739 © RSNA, 2021.