Radiogenomic Analysis of Locally Advanced Lung Cancer Based on CT Imaging and Intratreatment Changes in Cell-Free DNA.
Kyle J LafataMichael N CorradettiJunheng GaoCorbin D JacobsJingxi WengYushi ChangChunhao WangAce HatchEric XanthopoulosGreg JonesChris R KelseyFang-Fang YinPublished in: Radiology. Imaging cancer (2021)
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.
Keyphrases
- circulating tumor
- locally advanced
- radiation therapy
- rectal cancer
- neoadjuvant chemotherapy
- contrast enhanced
- cell free
- squamous cell carcinoma
- circulating tumor cells
- image quality
- dual energy
- high resolution
- phase ii study
- computed tomography
- clinical trial
- end stage renal disease
- chronic kidney disease
- positron emission tomography
- ejection fraction
- machine learning
- type diabetes
- radiation induced
- prognostic factors
- palliative care
- genome wide
- randomized controlled trial
- binding protein
- bone marrow
- phase ii
- single cell
- double blind
- mesenchymal stem cells
- data analysis
- free survival
- lymph node
- single molecule
- study protocol
- replacement therapy
- weight loss
- fluorescence imaging
- molecular dynamics simulations
- smoking cessation