Robust radiogenomics approach to the identification of EGFR mutations among patients with NSCLC from three different countries using topologically invariant Betti numbers

PLoS One. 2021 Jan 11;16(1):e0244354. doi: 10.1371/journal.pone.0244354. eCollection 2021.

Abstract

Objectives: To propose a novel robust radiogenomics approach to the identification of epidermal growth factor receptor (EGFR) mutations among patients with non-small cell lung cancer (NSCLC) using Betti numbers (BNs).

Materials and methods: Contrast enhanced computed tomography (CT) images of 194 multi-racial NSCLC patients (79 EGFR mutants and 115 wildtypes) were collected from three different countries using 5 manufacturers' scanners with a variety of scanning parameters. Ninety-nine cases obtained from the University of Malaya Medical Centre (UMMC) in Malaysia were used for training and validation procedures. Forty-one cases collected from the Kyushu University Hospital (KUH) in Japan and fifty-four cases obtained from The Cancer Imaging Archive (TCIA) in America were used for a test procedure. Radiomic features were obtained from BN maps, which represent topologically invariant heterogeneous characteristics of lung cancer on CT images, by applying histogram- and texture-based feature computations. A BN-based signature was determined using support vector machine (SVM) models with the best combination of features that maximized a robustness index (RI) which defined a higher total area under receiver operating characteristics curves (AUCs) and lower difference of AUCs between the training and the validation. The SVM model was built using the signature and optimized in a five-fold cross validation. The BN-based model was compared to conventional original image (OI)- and wavelet-decomposition (WD)-based models with respect to the RI between the validation and the test.

Results: The BN-based model showed a higher RI of 1.51 compared with the models based on the OI (RI: 1.33) and the WD (RI: 1.29).

Conclusion: The proposed model showed higher robustness than the conventional models in the identification of EGFR mutations among NSCLC patients. The results suggested the robustness of the BN-based approach against variations in image scanner/scanning parameters.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Area Under Curve
  • Carcinoma, Non-Small-Cell Lung / diagnosis*
  • Carcinoma, Non-Small-Cell Lung / diagnostic imaging
  • Carcinoma, Non-Small-Cell Lung / genetics
  • ErbB Receptors / genetics
  • Female
  • Humans
  • Image Processing, Computer-Assisted / methods*
  • Japan
  • Lung Neoplasms / diagnosis*
  • Lung Neoplasms / diagnostic imaging
  • Lung Neoplasms / genetics
  • Malaysia
  • Male
  • Middle Aged
  • Mutation
  • ROC Curve
  • Support Vector Machine
  • Tomography, X-Ray Computed
  • United States

Substances

  • EGFR protein, human
  • ErbB Receptors

Grants and funding

This study was supported by a grant from Center for Clinical and Translational Research of Kyushu University Hospital and JSPS KAKENHI Grant Number 20K08084. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.