Lung Subregion Partitioning by Incremental Dose Intervals Improves Omics-Based Prediction for Acute Radiation Pneumonitis in Non-Small-Cell Lung Cancer Patients

Simple Summary Acute radiation pneumonitis (ARP) is one of the common radiation toxicities in patients with non-small-cell lung cancer (NSCLC) treated by radiotherapy. The prediction for ARP can benefit clinical management and thereby improve the quality of life of patients. Markers derived from radiomics and dosiomics features can be adopted to predict ARP. Moreover, the features from lung subregions can improve the prediction for ARP compared to the whole lung region. The previous studies using lung subregion features for predicting ARP ignored the low-dose covered lung region. In this manuscript, we proposed an incremental-dose-interval-based lung subregion segmentation method by covering the low-dose lung region for ARP modeling and evaluated its effectiveness in improving ARP predictions using pre-treatment CT radiomics features and planning dose features for patients with NSCLC treated by radiotherapy. The performance among ARP models using features from our proposed lung subregion and the whole lung were compared for both multi-omics and single-omics. The results could provide insight into the subregion's ability to predict the ARP and could be useful in predicting the risk of radiation-induced toxicity. This manuscript and its results were neither published in any conferences nor journals. Purpose: To evaluate the effectiveness of features obtained from our proposed incremental-dose-interval-based lung subregion segmentation (IDLSS) for predicting grade >= 2 acute radiation pneumonitis (ARP) in lung cancer patients upon intensity-modulated radiotherapy (IMRT). (1) Materials and Methods: A total of 126 non-small-cell lung cancer patients treated with IMRT were retrospectively analyzed. Five lung subregions (SRs) were generated by the intersection of the whole lung (WL) and five sub-regions receiving incremental dose intervals. A total of 4610 radiomics features (RF) from pre-treatment planning computed tomographic (CT) and 213 dosiomics features (DF) were extracted. Six feature groups, including WL-RF, WL-DF, SR-RF, SR-DF, and the combined feature sets of WL-RDF and SR-RDF, were generated. Features were selected by using a variance threshold, followed by a Student t-test. Pearson's correlation test was applied to remove redundant features. Subsequently, Ridge regression was adopted to develop six models for ARP using the six feature groups. Thirty iterations of resampling were implemented to assess overall model performance by using the area under the Receiver-Operating-Characteristic curve (AUC), accuracy, precision, recall, and F1-score. (2) Results: The SR-RDF model achieved the best classification performance and provided significantly better predictability than the WL-RDF model in training cohort (Average AUC: 0.98 +/- 0.01 vs. 0.90 +/- 0.02, p < 0.001) and testing cohort (Average AUC: 0.88 +/- 0.05 vs. 0.80 +/- 0.04, p < 0.001). Similarly, predictability of the SR-DF model was significantly stronger than that of the WL-DF model in training cohort (Average AUC: 0.88 +/- 0.03 vs. 0.70 +/- 0.030, p < 0.001) and in testing cohort (Average AUC: 0.74 +/- 0.08 vs. 0.65 +/- 0.06, p < 0.001). By contrast, the SR-RF model significantly outperformed the WL-RF model only in the training set (Average AUC: 0.93 +/- 0.02 vs. 0.85 +/- 0.03, p < 0.001), but not in the testing set (Average AUC: 0.79 +/- 0.05 vs. 0.77 +/- 0.07, p = 0.13). (3) Conclusions: Our results demonstrated that the IDLSS method improved model performance for classifying ARP with grade >= 2 when using dosiomics or combined radiomics-dosiomics features.