Sensitivity of CT-derived radiomic features to extraction libraries and gray-level discretization in the context of immune biomarker discovery

Radiomics can predict patient outcomes by automatically extracting a large number of features from medical images. This study is aimed to investigate the sensitivity of radiomics features extracted from 2 different pipelines, namely, Pyradiomics and RaCat, as well as the impact of gray-level discretization on the discovery of immune checkpoint inhibitors (ICIs) biomarkers. A retrospective cohort of 164 non-small cell lung cancer patients administered with ICIs was used in this study. Radiomic features were extracted from the pre-treatment CT scans. Univariate models were used to assess the association of common radiomics features between 2 libraries with progression-free survival (PFS), programmed death ligand 1 (PD-L1), and tumour infiltrating lymphocytes (CD8 counts). In addition, we also examined the impact of gray-level discretization incorporated in Pyradiomics on the robustness of features across various clinical endpoints. We extracted 1224, 441 radiomic features using Pyradiomics and RaCat, respectively. Among these, 75 features were found to be common between the 2 libraries. Our analysis revealed that the directionality of association between radiomic features and clinical endpoints is highly dependent on the library. Notably, a larger number of Pyradiomics features were statistically associated with PFS, whereas RaCat features showed a stronger association with PD-L1 expression. Furthermore, intensity-based features were found to have a consistent association with clinical endpoints regardless of the gray-level discretization parameters in Pyradiomics-extracted features. This study highlights the heterogeneity of radiomics libraries and the gray-level discretization parameters that will impact the feature selection and predictive model development for biomarkers. Importantly, our work highlights the significance of standardizing radiomic features to facilitate translational studies that use imaging as an endpoint. Our study emphasizes the need to select stable CT-derived handcrafted features to build immunotherapy biomarkers, which is a necessary precursor for multi-institutional validation of imaging biomarkers.