Abstract
BACKGROUND: Non-small cell lung cancer (NSCLC) is a complex disease characterized by diverse clinical, genetic, and histopathologic traits, necessitating personalized treatment approaches. While numerous biomarkers have been introduced for NSCLC prognostication, no single source of information can provide a comprehensive understanding of the disease. However, integrating biomarkers from multiple sources may offer a holistic view of the disease, enabling more accurate predictions. In this study, we present MetaPredictomics, a framework that integrates clinicopathologic data with PET/CT radiomics from the primary tumor and presumed healthy organs (referred to as "organomics") to predict postsurgical recurrence. PATIENTS AND METHODS: A fully automated deep learning-based segmentation model was employed to delineate 19 affected (whole lung and the affected lobe) and presumed healthy organs from CT images of the presurgical PET/CT scans of 145 NSCLC patients sourced from a publicly available data set. Using PyRadiomics, 214 features (107 from CT, 107 from PET) were extracted from the gross tumor volume (GTV) and each segmented organ. In addition, a clinicopathologic feature set was constructed, incorporating clinical characteristics, histopathologic data, gene mutation status, conventional PET imaging biomarkers, and patients' treatment history. GTV Radiomics, each of the organomics, and the clinicopathologic feature sets were each fed to a time-to-event prediction machine, based on glmboost, to establish first-level models. The risk scores obtained from the first-level models were then used as inputs for meta models developed using a stacked ensemble approach. Questing optimized performance, we assessed meta models established upon all combinations of first-level models with concordance index (C-index) ≥0.6. The performance of all the models was evaluated using the average C-index across a unique 3-fold cross-validation scheme for fair comparison. RESULTS: The clinicopathologic model outperformed other first-level models with a C-index of 0.67, followed closely by GTV radiomics model with C-index of 0.65. Among the organomics models, whole-lung and aorta models achieved top performance with a C-index of 0.65, while 12 organomics models achieved C-indices of ≥0.6. Meta models significantly outperformed the first-level models with the top 100 achieving C-indices between 0.703 and 0.731. The clinicopathologic, whole lung, esophagus, pancreas, and GTV models were the most frequently present models in the top 100 meta models with frequencies of 98, 71, 69, 62, and 61, respectively. CONCLUSIONS: In this study, we highlighted the value of maximizing the use of medical imaging for NSCLC recurrence prognostication by incorporating data from various organs, rather than focusing solely on the tumor and its immediate surroundings. This multisource integration proved particularly beneficial in the meta models, where combining clinicopathologic data with tumor radiomics and organomics models significantly enhanced recurrence prediction.