A Machine Learning Model Based on PET/CT Radiomics and Clinical Characteristics Predicts Tumor Immune Profiles in Non-Small Cell Lung Cancer: A Retrospective Multicohort Study

The tumor immune microenvironment (TIME) phenotypes have been reported to mainly impact the efficacy of immunotherapy. Given the increasing use of immunotherapy in cancers, knowing an individual's TIME phenotypes could be helpful in screening patients who are more likely to respond to immunotherapy. Our study intended to establish, validate, and apply a machine learning model to predict TIME profiles in non-small cell lung cancer (NSCLC) by using 18F-FDG PET/CT radiomics and clinical characteristics.The RNA-seq data of 1145 NSCLC patients from The Cancer Genome Atlas (TCGA) cohort were analyzed. Then, 221 NSCLC patients from Daping Hospital (DPH) cohort received18F-FDG PET/CT scans before treatment and CD8 expression of the tumor samples were tested. The Artificial Intelligence Kit software was used to extract radiomic features of PET/CT images and develop a radiomics signature. The models were established by radiomics, clinical features, and radiomics-clinical combination, respectively, the performance of which was calculated by receiver operating curves (ROCs) and compared by DeLong test. Moreover, based on radiomics score (Rad-score) and clinical features, a nomogram was established. Finally, we applied the combined model to evaluate TIME phenotypes of NSCLC patients in The Cancer Imaging Archive (TCIA) cohort (n = 39).TCGA data showed CD8 expression could represent the TIME profiles in NSCLC. In DPH cohort, PET/CT radiomics model outperformed CT model (AUC: 0.907 vs. 0.861, P = 0.0314) to predict CD8 expression. Further, PET/CT radiomics-clinical combined model (AUC = 0.932) outperformed PET/CT radiomics model (AUC = 0.907, P = 0.0326) or clinical model (AUC = 0.868, P = 0.0036) to predict CD8 expression. In the TCIA cohort, the predicted CD8-high group had significantly higher immune scores and more activated immune pathways than the predicted CD8-low group (P = 0.0421).Our study indicates that 18F-FDG PET/CT radiomics-clinical combined model could be a clinically practical method to non-invasively detect the tumor immune status in NSCLCs.