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Multi-omics staging of locally advanced rectal cancer predicts treatment response: a pilot study

  • Ilaria Cicalini,
  • Antonio Maria Chiarelli,
  • Piero Chiacchiaretta,
  • David Perpetuini,
  • Consuelo Rosa,
  • Domenico Mastrodicasa,
  • Martina d’Annibale,
  • Stefano Trebeschi,
  • Francesco Lorenzo Serafini,
  • Giulio Cocco,
  • Marco Narciso,
  • Antonio Corvino,
  • Sebastiano Cinalli,
  • Domenico Genovesi,
  • Paola Lanuti,
  • Silvia Valentinuzzi,
  • Damiana Pieragostino,
  • Davide Brocco,
  • Regina G. H. Beets-Tan,
  • Nicola Tinari,
  • Stefano L. Sensi,
  • Liborio Stuppia,
  • Piero Del Boccio,
  • Massimo Caulo,
  • Andrea Delli Pizzi

摘要

Treatment response assessment of rectal cancer patients is a critical component of personalized cancer care and it allows to identify suitable candidates for organ-preserving strategies. This pilot study employed a novel multi-omics approach combining MRI-based radiomic features and untargeted metabolomics to infer treatment response at staging. The metabolic signature highlighted how tumor cell viability is predictively down-regulated, while the response to oxidative stress was up-regulated in responder patients, showing significantly reduced oxoproline values at baseline compared to non-responder patients (p-value < 10–4). Tumors with a high degree of texture homogeneity, as assessed by radiomics, were more likely to achieve a major pathological response (p-value < 10–3). A machine learning classifier was implemented to summarize the multi-omics information and discriminate responders and non-responders. Combining all available radiomic and metabolomic features, the classifier delivered an AUC of 0.864 (± 0.083, p-value < 10–3) with a best-point sensitivity of 90.9% and a specificity of 81.8%. Our results suggest that a multi-omics approach, integrating radiomics and metabolomic data, can enhance the predictive value of standard MRI and could help to avoid unnecessary surgical treatments and their associated long-term complications.