Prognostic Significance of Pseudotime from Texture Parameters of FDG PET/CT in Locally Advanced Non-Small-Cell Lung Cancer with Tri-Modality Therapy

SIMPLE SUMMARY: Although texture parameters of F-18 fluorodeoxyglucose positron emission tomography/computed tomography images were known to associate tumor biology and clinical features, the types and implications of parameters are too various and complicated. To overcome the limitation of texture parameter, we attempted to produce a new simplified parameter from texture parameters of F-18 fluorodeoxyglucose positron emission tomography/computed tomography images in lung cancer patients using pseudotime analysis. Pseudotime analysis is a recently developed method to explore changes in cell or tissue characteristics based on transcriptomic expression. It is the first study to apply pseudotime analysis into radiomics dataset other than transcriptomics data. Herein, we demonstrated that pseudotime can be successfully estimated from texture parameters. In the aspect of prognostic prediction, pseudotime was an independent prognostic factor for overall survival in contrast to conventional parameters such as metabolic tumor volume and total lesion glycolysis. This study showed possibility of integrating various texture parameters into single parameter which reflects disease progression status. Pseudotime, as a concrete value of disease progression, is expected to be used in clinical field to evaluate disease and predict prognosis. ABSTRACT: Texture analysis provides image parameters from F-18 fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT). Although some parameters are associated with tumor biology and clinical features, the types and implications of these parameters are complicated. We applied pseudotime analysis, which has recently been used to estimate changes in individual sample characteristics, to texture parameters from FDG PET/CT images of locally advanced non-small-cell lung cancer (NSCLC) patients undergoing neoadjuvant concurrent chemoradiation therapy (CCRT) followed by surgery. Our subjects were 303 NSCLC patients who underwent pretherapeutic FDG PET/CT and tri-modality therapy. Texture parameters of the primary tumor were calculated from FDG PET/CT images acquired before neoadjuvant CCRT. Pseudotime analysis was performed using the PhenoPath tool. Clinicopathologic features including survival data were collected and survival analysis was performed to compare the prognostic significances of pseudotime parameters with those of conventional PET parameters. Pseudotime was successfully estimated from texture parameters. Normalized co-occurrence homogeneity, normalized co-occurrence inverse difference moment, and black–white symmetry showed positive correlations with pseudotime, short run emphasis, normalized co-occurrence dissimilarity, and short zone emphasis negative correlation. The maximum standardized uptake value (SUV) and mean SUV were not associated with overall survival. Pseudotime, metabolic tumor volume (MTV), and total lesion glycolysis (TLG) showed significant associations with overall survival. In contrast to MTV and TLG, pseudotime was an independent prognostic factor for overall survival. Various metabolic texture parameters can be integrated into a single parameter using pseudotime analysis. Pseudotime of the primary tumor, estimated from FDG PET/CT images, better predicts overall survival in locally advanced NSCLC patients treated with tri-modality therapy than conventional PET parameters.