Clinico-biological-radiomics (CBR) based machine learning for improving the diagnostic accuracy of FDG-PET false-positive lymph nodes in lung cancer

Background The main problem of positron emission tomography/computed tomography (PET/CT) for lymph node (LN) staging is the high false positive rate (FPR). Thus, we aimed to explore a clinico-biological-radiomics (CBR) model via machine learning (ML) to reduce FPR and improve the accuracy for predicting the hypermetabolic mediastinal–hilar LNs status in lung cancer than conventional PET/CT. Methods A total of 260 lung cancer patients with hypermetabolic mediastinal–hilar LNs (SUVmax ≥ 2.5) were retrospectively reviewed. Patients were treated with surgery with systematic LN resection and pathologically divided into the LN negative (LN-) and positive (LN +) groups, and randomly assigned into the training ( n = 182) and test ( n = 78) sets. Preoperative CBR dataset containing 1738 multi-scale features was constructed for all patients. Prediction models for hypermetabolic LNs status were developed using the features selected by the supervised ML algorithms, and evaluated using the classical diagnostic indicators. Then, a nomogram was developed based on the model with the highest area under the curve (AUC) and the lowest FPR, and validated by the calibration plots. Results In total, 109 LN− and 151 LN + patients were enrolled in this study. 6 independent prediction models were developed to differentiate LN− from LN + patients using the selected features from clinico-biological-image dataset, radiomics dataset, and their combined CBR dataset, respectively. The DeLong test showed that the CBR Model containing all-scale features held the highest predictive efficiency and the lowest FPR among all of established models ( p < 0.05) in both the training and test sets (AUCs of 0.90 and 0.89, FPRs of 12.82% and 6.45%, respectively) ( p < 0.05). The quantitative nomogram based on CBR Model was validated to have a good consistency with actual observations. Conclusion This study presents an integrated CBR nomogram that can further reduce the FPR and improve the accuracy of hypermetabolic mediastinal–hilar LNs evaluation than conventional PET/CT in lung cancer, thereby greatly reducing the risk of overestimation and assisting for precision treatment.