Ranking the most influential predictors of CT-based radiomics feature values in metastatic lung adenocarcinoma

To investigate which acquisition, post-processing, tumor, and patient characteristics contribute the most to the value of radiomics features (RFs) in lung adenocarcinoma in order to better understand and order the potential sources of bias in radiomics studies in a multivariate setting.This single-center retrospective study included all consecutive patients with newly-diagnosed lung adenocarcinoma treated between December 2016 and September 2018 who had pre-treatment contrast-enhanced CT-scan showing ≥ 2 target lesions per response evaluation criteria in solid tumors (RECIST) v1.1. All measurable lesions were manually segmented; 49 RFs were extracted using LIFEx v7.0.0. Afterwards, we reverted the usual radiomics approach (i.e., predicting a clinical outcome base on multiple RFs). To do so, for each RF, random forests and linear regression algorithms were trained using cross-validation to predict the RF value depending on the following variables: patient, mutational status, phase of CT-scan acquisition, discretization (binsize), lesion location, lesion volume, and best response obtained during the first line of treatment (partial response per RECIST vs other). The most important contributors to the value of reproducible RFs (intra-class correlation coefficient > 0.80) according to the best random forests model (selected via R-squared) were ranked.101 patients (median age: 62.3) were included, with a median of 5 target lesions per patient (range: 2-10) providing 466 segmented lesions. Twenty-nine RFs were reproducible. The most important predictors of the reproducible RFs values were, in order: tumor volume, binsize, tumor location, CT-scan phase, KRAS mutation, and treatment response (average importance: 61.7%, 57.4%, 8.1%, 3.3%, 3%, and 2.7%, respectively). The treatment response and KRAS and EGFR/ROS1/ALK mutational status remained independently correlated with the RF value for 64.3%, 32.1%, and 50% reproducible RFs, respectively.Tumor volume, location, acquisition and post-processing parameters should systematically be incorporated in radiomics-based modeling; however, most reproducible RFs do have significant relationships with mutational status and treatment response.