A radiomic-based predictive model of lung adenocarcinoma brain metastases and molecular subtypes.
Authors: Wu Xiancheng , Velez Maria A , Ak Murat , Tahon Nourel , Mamindla Priyadarshini , Peddagangireddy Vishal , Colen Rivka R. , Stabile Laura P. , Burns Timothy F. 
Published: June 2023

2014 Background: Non-small cell lung cancer (NSCLC) comprises the largest portion of brain metastases (BM) from solid cancer with 40% of patients developing BM during the course of their disease. There are currently no reliable prediction tools for identifying patients at risk for BM, especially in the early-stage setting where MRI screening is not performed. Furthermore, in the later stage setting, brain MRI are only performed annually. Therefore, there is a critical need to identify high-risk patients for BM that could benefit from MRI surveillance. Methods: We identified 162 lung adenocarcinoma (LUAD) patients with (N = 66) or without (N = 96) BM that had treatment-naïve CT scans with a segmentable lesion. The tumor, surrounding ground glass opacity and necrosis were segmented via 3D slicer to create a volume of interest for radiomic texture analysis and 400 features were extracted. The Least Absolute Shrinkage and Selection Operator (LASSO) logistic regression feature selection method was used to select the most relevant features and models were built using the machine learning method XGBoost classifier. Training and testing sets with random splitting was used for cross validation. We report the accuracy, sensitivity, specificity, and area under the curve (AUC) for each model. Results: Among the extracted features that LASSO deemed as most discriminative for development of BM, we identified the most relevant features using XGBoost that predicted BM with 79% accuracy, 83% sensitivity, 72% specificity, and 79% AUC ( p= 0.01) in the overall population. The addition of ground glass opacity and necrosis to the model did not significantly improve performance. Furthermore, the model distinguished those with metachronous vs synchronous BM with 84% accuracy, 83% sensitivity, 86% specificity, and 83% AUC ( p = 0.04). Our model held up across molecular subtypes ( EGFR and KRAS mutant). Importantly, the model was predictive in early-stage patients with 92% accuracy, 96% sensitivity, 83% specificity, and 95% AUC ( p= 0.0005). Moreover, our model predicted for high vs. low overall survival, and was BM-specific as it was not predictive of other sites of metastases. We further developed a model from the CT features that correctly classified KRAS mutant vs. KRAS wild type LUAD with 77% accuracy, 73% sensitivity, 80% specificity, and 80% AUC ( p= 0.002). Conclusions: Utilizing a radiomics approach, we were able to predict BM from primary lung CT features including in stage I and II disease, predict synchronous vs metachronous BM, and distinguish distinct molecular LUAD subtypes. We are currently validating our BM prediction model in a large independent cohort and developing models to classify targetable LUAD-BM molecular alterations utilizing brain MRI scans. These studies will identify patients that require MRI surveillance in the early-stage setting and more intensive surveillance in the late-stage setting for BM.