Multicentric development and evaluation of [ 18 F]FDG PET/CT and CT radiomic models to predict regional and/or distant recurrence in early-stage non-small cell lung cancer treated by stereotactic body radiation therapy

Purpose To develop machine learning models to predict regional and/or distant recurrence in patients with early-stage non-small cell lung cancer (ES-NSCLC) after stereotactic body radiation therapy (SBRT) using [ 18 F]FDG PET/CT and CT radiomics combined with clinical and dosimetric parameters. Methods We retrospectively collected 464 patients (60% for training and 40% for testing) from University Hospital of Liège and 63 patients from University Hospital of Brest (external testing set) with ES-NSCLC treated with SBRT between 2010 and 2020 and who had undergone pretreatment [ 18 F]FDG PET/CT and planning CT. Radiomic features were extracted using the PyRadiomics toolbox®. The ComBat harmonization method was applied to reduce the batch effect between centers. Clinical, radiomic, and combined models were trained and tested using a neural network approach to predict regional and/or distant recurrence. Results In the training ( n = 273) and testing sets ( n = 191 and n = 63), the clinical model achieved moderate performances to predict regional and/or distant recurrence with C -statistics from 0.53 to 0.59 (95% CI, 0.41, 0.67). The radiomic (original_firstorder_Entropy, original_gldm_LowGrayLevelEmphasis and original_glcm_DifferenceAverage) model achieved higher predictive ability in the training set and kept the same performance in the testing sets, with C -statistics from 0.70 to 0.78 (95% CI, 0.63, 0.88) while the combined model performs moderately well with C -statistics from 0.50 to 0.62 (95% CI, 0.37, 0.69). Conclusion Radiomic features extracted from pre-SBRT analog and digital [ 18 F]FDG PET/CT outperform clinical parameters in the prediction of regional and/or distant recurrence and to discuss an adjuvant systemic treatment in ES-NSCLC. Prospective validation of our models should now be carried out.