Integration of pre-treatment computational radiomics, deep radiomics, and transcriptomics enhances soft-tissue sarcoma patient prognosis

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Abstract
Our objective was to capture subgroups of soft-tissue sarcoma (STS) using handcraft and deep radiomics approaches to understand their relationship with histopathology, gene-expression profiles, and metastatic relapse-free survival (MFS). We included all consecutive adults with newly diagnosed locally advanced STS (N = 225, 120 men, median age: 62 years) managed at our sarcoma reference center between 2008 and 2020, with contrast-enhanced baseline MRI. After MRI postprocessing, segmentation, and reproducibility assessment, 175 handcrafted radiomics features (h-RFs) were calculated. Convolutional autoencoder neural network (CAE) and half-supervised CAE (HSCAE) were trained in repeated cross-validation on representative contrast-enhanced slices to extract 1024 deep radiomics features (d-RFs). Gene-expression levels were calculated following RNA sequencing (RNAseq) of 110 untreated samples from the same cohort. Unsupervised classifications based on h-RFs, CAE, HSCAE, and RNAseq were built. The h-RFs, CAE, and HSCAE grouping were not associated with the transcriptomics groups but with prognostic radiological features known to correlate with lower survivals and higher grade and SARCULATOR groups (a validated prognostic clinical-histological nomogram). HSCAE and h-RF groups were also associated with MFS in multivariable Cox regressions. Combining HSCAE and transcriptomics groups significantly improved the prognostic performances compared to each group alone, according to the concordance index. The combined radiomic-transcriptomic group with worse MFS was characterized by the up-regulation of 707 genes and 292 genesets related to inflammation, hypoxia, apoptosis, and cell differentiation. Overall, subgroups of STS identified on pre-treatment MRI using handcrafted and deep radiomics were associated with meaningful clinical, histological, and radiological characteristics, and could strengthen the prognostic value of transcriptomics signatures.

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