Distinct patterns of the natural evolution of soft tissue sarcomas on pre-treatment MRIs captured with delta-radiomics correlate with gene expression profiles.

Abstract

Radiomics of soft tissue sarcomas (STS) is assumed to correlate with histologic and molecular tumor features, but radiogenomics analyses are lacking. Our aim was to identify if distinct patterns of natural evolution of STS obtained from consecutive pre-treatment MRIs are associated with differential gene expression (DGE) profiling in a pathway analysis. All patients with newly diagnosed STS treated in a curative intent in our sarcoma reference center between 2008 and 2019 and with two available pre-treatment contrast-enhanced MRIs were included in this retrospective study. Radiomics features (RFs) were extracted from fat-sat contrast-enhanced T1-weighted imaging. Log ratio and relative change in RFs were calculated and used to determine grouping of samples based on a consensus hierarchical clustering. DGE and oncogenesis pathway analysis were performed in the delta-radiomics groups identified in order to detect associations between delta-radiomics patterns and transcriptomics features of STS. Secondarily, the prognostic value of the delta-radiomics groups was investigated. Sixty-three patients were included (median age: 63 years, interquartile range: 52.5-70). The consensus clustering identified 3 reliable delta-radiomics patient groups (A, B, and C). On imaging, group B patients were characterized by increase in tumor heterogeneity, necrotic signal, infiltrative margins, peritumoral edema, and peritumoral enhancement before the treatment start (p value range: 0.0019-0.0244), and, molecularly, by downregulation of natural killer cell-mediated cytotoxicity genes and upregulation of Hedgehog and Hippo signaling pathways. Group A patients were characterized by morphological stability of pre-treatment MRI traits and no local relapse (log-rank p = 0.0277). This study highlights radiomics and transcriptomics convergence in STS. Proliferation and immune response inhibition were hyper-activated in the STS that were the most evolving on consecutive imaging. • Three consensual and stable delta-radiomics clusters were identified and captured the natural patterns of morphological evolution of STS on pre-treatment MRIs. • These 3 patterns were explainable and correlated with different well-known semantic radiological features with an ascending gradient of pejorative characteristics from the A group to C group to B group. • Gene expression profiling stressed distinct patterns of up/downregulated oncogenetic pathways in STS from B group in keeping with its most aggressive radiological evolution.