Radiogenomic Analysis of Locally Advanced Lung Cancer Based on CT Imaging and Intratreatment Changes in Cell-Free DNA
Kyle J Lafata, Michael N Corradetti, Junheng Gao, Corbin D Jacobs, Jingxi Weng, Yushi Chang, Chunhao Wang, Ace Hatch, Eric Xanthopoulos, Greg Jones, Chris R Kelsey, Fang-Fang Yin, Kyle J Lafata, Michael N Corradetti, Junheng Gao, Corbin D Jacobs, Jingxi Weng, Yushi Chang, Chunhao Wang, Ace Hatch, Eric Xanthopoulos, Greg Jones, Chris R Kelsey, Fang-Fang Yin
Abstract
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 TP53 mutations (P = .03) and changes in cfDNA concentration after 2 weeks of chemoradiation (P = .02). The radiomic features dissimilarity (hazard ratio [HR] = 0.56; P = .05), joint entropy (HR = 0.56; P = .04), sum entropy (HR = 0.53; P = .02), and normalized inverse difference (HR = 1.77; P = .05) were associated with overall survival. These results suggest heterogeneous and low-attenuating disease without a detectable ctDNA TP53 mutation was associated with early surges of cfDNA concentration in response to therapy and a generally better prognosis. Keywords: CT-Quantitative, Radiation Therapy, Lung, Computer Applications-3D, Oncology, Tumor Response, Outcomes Analysis Clinical trial registration no. NCT00921739 Supplemental material is available for this article. © RSNA, 2021.
Keywords: CT-Quantitative; Computer Applications-3D; Lung; Oncology; Outcomes Analysis; Radiation Therapy; Tumor Response.
Conflict of interest statement
Disclosures of Conflicts of Interest: K.J.L. disclosed no relevant relationships. M.N.C. disclosed no relevant relationships. J.G. disclosed no relevant relationships. C.D.J. Activities related to the present article: disclosed no relevant relationships. Activities not related to the present article: employed by Premera Blue Cross. Other relationships: disclosed no relevant relationships. J.W. disclosed no relevant relationships. Y.C. disclosed no relevant relationships. C.W. Activities related to the present article: disclosed no relevant relationships. Activities not related to the present article: employed by Duke University Medical Center. Other relationships: disclosed no relevant relationships. A.H. disclosed no relevant relationships. E.X. disclosed no relevant relationships. G.J. Activities related to the present article: disclosed no relevant relationships. Activities not related to the present article: employed by Inivata; has stock options issued as employee of Inivata. Other relationships: disclosed no relevant relationships. C.R.K. disclosed no relevant relationships. F.F.Y. Activities related to the present article: disclosed no relevant relationships. Activities not related to the present article: employed by Duke University Hospital; institution receives grant from Varian Medical Systems that is used for other work not related to this study. Other relationships: disclosed no relevant relationships.
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Source: PubMed