Radiomics is a promising approach to identify patients at high risk of having pulmonary dysfunction caused by radiotherapy. This study aims to identify optimal radiomic input features for predicting pulmonary function. Forced expiratory volume in first second (FEV1) and forced vital capacity (FVC) were measured for 257 patients between 3 months prior to and 1 week after the first radiotherapy. FEV1/FVC ratio dichotomized at 70% was used as a target variable. Each patient had a radiotherapy planning CT and associated contours of gross tumor volume and left/right lungs. A total of 2,658 radiomic features were extracted and categorized into five levels: shape (S), first- (L1), second- (L2) and higher-order (L3) local texture, and global texture (G) features, as well as four multilevel groups: S+L1, S+L1+L2, S+L1+L2+L3, and S+L1+L2+L3+G. Nested cross-validation (NCV) was used to identify optimal input features. Cross-validated glmnet models optimized with unilevel or multilevel features were used to assess predictive performance on outer CV test sets. In unilevel analysis, the highest test AUC of 0.743±0.067 was obtained from NCV models optimized with L1 features. The best performance was achieved from NCV models optimized with S+L1+L2 features with AUC of 0.752±0.063. Paired Wilcoxon signed rank test results showed that AUC values of NCV models optimized with S, L2, L3, G or S+L1+L2+L3 features were statistically significantly different from those optimized with S+L1+L2 features (P<0.05). The multilevel analysis strategy will help to handle and optimize radiomic input features.
Surrogate-based tumor motion estimation and tracing methods are commonly used in radiotherapy despite the lack of continuous real time 3D tumor and surrogate data. In this study, we propose a method to simultaneously track the tumor and external surrogates with dynamic MRI, which allows us to evaluate their reproducible correlation. Four MRIcompatible fiducials are placed on the patient’s chest and upper abdomen, and multi-slice 2D cine MRIs are acquired to capture the lung and whole tumor, followed by two-slice 2D cine MRIs to simultaneously track the tumor and fiducials, all in sagittal orientation. A phase-binned 4D-MRI is first reconstructed from multi-slice MR images using body area as a respiratory surrogate and group-wise registration. The 4D-MRI provides 3D template volumes for different breathing phases. 3D tumor position is calculated by 3D-2D template matching in which 3D tumor templates in 4D-MRI reconstruction and the 2D cine MRIs from the two-slice tracking dataset are registered. 3D trajectories of the external surrogates are derived via matching a 3D geometrical model to the fiducial segmentations on the 2D cine MRIs. We tested our method on five lung cancer patients. Internal target volume from 4D-CT showed average sensitivity of 86.5% compared to the actual tumor motion for 5 min. 3D tumor motion correlated with the external surrogate signal, but showed a noticeable phase mismatch. The 3D tumor trajectory showed significant cycle-to-cycle variation, while the external surrogate was not sensitive enough to capture such variations. Additionally, there was significant phase mismatch between surrogate signals obtained from fiducials at different locations.