Impact of image filtering and assessment of volume-confounding effects on CT radiomic features and derived survival models in non-small cell lung cancer.

Background: No evidence supports the choice of specific imaging filtering methodologies in radiomics. As the volume of the primary tumor is a well-recognized prognosticator, our purpose is to assess how filtering may impact the feature/volume dependency in computed tomography (CT) images of non-small cell lung cancer (NSCLC), and if such impact translates into differences in the performance of survival modeling. The role of lesion volume in model performances was also considered and discussed. Methods: Four-hundred seventeen CT images NSCLC patients were retrieved from the NSCLC-Radiomics public repository. Pre-processing and features extraction were implemented using Pyradiomics v3.0.1. Features showing high correlation with volume across original and filtered images were excluded. Cox proportional hazards (PH) with least absolute shrinkage and selection operator (LASSO) regularization and CatBoost models were built with and without volume, and their concordance (C-) indices were compared using Wilcoxon signed-ranked test. The Mann Whitney U test was used to assess model performances after stratification into two groups based on low- and high-volume lesions. Results: Radiomic models significantly outperformed models built on only clinical variables and volume. However, the exclusion/inclusion of volume did not generally alter the performances of radiomic models. Overall, performances were not substantially affected by the choice of either imaging filter (overall C-index 0.539-0.590 for Cox PH and 0.589-0.612 for CatBoost). The separation of patients with high-volume lesions resulted in significantly better performances in 2/10 and 7/10 cases for Cox PH and CatBoost models, respectively. Both low- and high-volume models performed significantly better with the inclusion of radiomic features (P<0.0001), but the improvement was largest in the high-volume group (+10.2% against +8.7% improvement for CatBoost models and +10.0% against +5.4% in Cox PH models). Conclusions: Radiomic features complement well-known prognostic factors such as volume, but their volume-dependency is high and should be managed with vigilance. The informative content of radiomic features may be diminished in small lesion volumes, which could limit the applicability of radiomics in early-stage NSCLC, where tumors tend to be small. Our results also suggest an advantage of CatBoost models over the Cox PH models.