Machine learning-based prediction of microsatellite instability and high tumor mutation burden from contrast-enhanced computed tomography in endometrial cancers.

Journal: Scientific reports
PMID: 33082371

Abstract

To evaluate whether radiomic features from contrast-enhanced computed tomography (CE-CT) can identify DNA mismatch repair deficient (MMR-D) and/or tumor mutational burden-high (TMB-H) endometrial cancers (ECs). Patients who underwent targeted massively parallel sequencing of primary ECs between 2014 and 2018 and preoperative CE-CT were included (n = 150). Molecular subtypes of EC were assigned using DNA polymerase epsilon (POLE) hotspot mutations and immunohistochemistry-based p53 and MMR protein expression. TMB was derived from sequencing, with > 15.5 mutations-per-megabase as a cut-point to define TMB-H tumors. After radiomic feature extraction and selection, radiomic features and clinical variables were processed with the recursive feature elimination random forest classifier. Classification models constructed using the training dataset (n = 105) were then validated on the holdout test dataset (n = 45). Integrated radiomic-clinical classification distinguished MMR-D from copy number (CN)-low-like and CN-high-like ECs with an area under the receiver operating characteristic curve (AUROC) of 0.78 (95% CI 0.58-0.91). The model further differentiated TMB-H from TMB-low (TMB-L) tumors with an AUROC of 0.87 (95% CI 0.73-0.95). Peritumoral-rim radiomic features were most relevant to both classifications (p ≤ 0.044). Radiomic analysis achieved moderate accuracy in identifying MMR-D and TMB-H ECs directly from CE-CT. Radiomics may provide an adjunct tool to molecular profiling, especially given its potential advantage in the setting of intratumor heterogeneity.

Authors

  • Harini Veeraraghavan
    Department of Medical Physics, Memorial Sloan Kettering Cancer Center, New York, NY; veerarah@mskcc.org.
  • Claire F Friedman
    Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  • Deborah F DeLair
    Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  • Josip Ninčević
    Body Imaging Service, Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  • Yuki Himoto
    Body Imaging Service, Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  • Silvio G Bruni
    Body Imaging Service, Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  • Giovanni Cappello
    Body Imaging Service, Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  • Iva Petkovska
    Body Imaging Service, Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  • Stephanie Nougaret
    Body Imaging Service, Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  • Ines Nikolovski
    Body Imaging Service, Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  • Ahmet Zehir
    Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York.
  • Nadeem R Abu-Rustum
    Gynecology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  • Carol Aghajanian
    Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  • Dmitriy Zamarin
    Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  • Karen A Cadoo
    Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  • Luis A Diaz
    Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
  • Mario M Leitao
    Gynecology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  • Vicky Makker
    Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  • Robert A Soslow
    Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  • Jennifer J Mueller
    Gynecology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  • Britta Weigelt
    Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  • Yulia Lakhman
    Body Imaging Service, Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, USA. lakhmany@mskcc.org.

Keywords

External Resources

Popular Topics
Recent Journals