Whole lung radiomic features are associated with overall survival in patients with locally advanced non-small cell lung cancer treated with definitive radiotherapy

Background: Several studies have suggested that lung tissue heterogeneity is associated with overall survival (OS) in lung cancer. However, the quantitative relationship between the two remains unknown. The purpose of this study is to investigate the prognostic value of whole lung-based and tumor-based radiomics for OS in LA-NSCLC treated with definitive radiotherapy.

Methods: A total of 661 patients with LA-NSCLC treated with definitive radiotherapy in combination with chemotherapy were enrolled in this study, with 292 patients in the training set, 57 patients from the same hospital from January to December 2017 as an independent test set (test-set-1), 83 patients from a multi-institutional prospective clinical trial data set (RTOG0617) as test-set-2, and 229 patients from a Dutch radiotherapy center as test-set-3. Tumor-based radiomic features and whole lung-based radiomic features were extracted from primary tumor and whole lungs (excluding the primary tumor) delineations in planning CT images. Feature selection of radiomic features was done by the least absolute shrinkage (LASSO) method embedded with a Cox proportional hazards (CPH) model with 5-fold cross-internal validation, with 1000 bootstrap samples. Radiomics prognostic scores (RS) were calculated by CPH regression based on selected features. Three models based on a tumor RS, and a lung RS separately and their combinations were constructed. The Harrell concordance index (C-index) and calibration curves were used to evaluate the discrimination and calibration performance. Patients were stratified into high and low risk groups based on median RS, and a log-rank test was performed.

Results: The discrimination ability of lung- and tumor-based radiomics model was similar in terms of C-index, 0.69 vs. 0.68 in training set, 0.68 vs. 0.66 in test-set-1, 0.61 vs. 0.62 in test-set-2, 0.65 vs. 0.64 in test-set-3. The combination of tumor- and lung-based radiomics model performed best, with C-index of 0.71 in training set, 0.70 in test-set-1, 0.69 in test-set-2, and 0.68 in test-set-3. The calibration curve showed good agreement between predicted values and actual values. Patients were well stratified in training set, test-set-1 and test-set-3. In test-set-2, it was only whole lung-based RS that could stratify patients well and tumor-based RS performed bad.

Conclusion: Lung- and tumor-based radiomic features have the power to predict OS in LA-NSCLC. The combination of tumor- and lung-based radiomic features can achieve optimal performance.